Full text data of ACTB
ACTB
[Confidence: high (present in two of the MS resources)]
Actin, cytoplasmic 1 (Beta-actin; Actin, cytoplasmic 1, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Actin, cytoplasmic 1 (Beta-actin; Actin, cytoplasmic 1, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00021439
IPI00021439 Actin, cytoplasmic 1 Actin, cytoplasmic 1 membrane 8 17 17 12 15 8 15 11 154 n/a 7 7 2 7 n/a 3 3 2 16 17 cytoskeleton n/a found at its expected molecular weight found at molecular weight
IPI00021439 Actin, cytoplasmic 1 Actin, cytoplasmic 1 membrane 8 17 17 12 15 8 15 11 154 n/a 7 7 2 7 n/a 3 3 2 16 17 cytoskeleton n/a found at its expected molecular weight found at molecular weight
UniProt
P60709
ID ACTB_HUMAN Reviewed; 375 AA.
AC P60709; P02570; P70514; P99021; Q11211; Q64316; Q75MN2; Q96B34;
read moreAC Q96HG5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Actin, cytoplasmic 1;
DE AltName: Full=Beta-actin;
DE Contains:
DE RecName: Full=Actin, cytoplasmic 1, N-terminally processed;
GN Name=ACTB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6322116; DOI=10.1093/nar/12.3.1687;
RA Ponte P., Ng S.Y., Engel J., Gunning P., Kedes L.;
RT "Evolutionary conservation in the untranslated regions of actin mRNAs:
RT DNA sequence of a human beta-actin cDNA.";
RL Nucleic Acids Res. 12:1687-1696(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2994062; DOI=10.1073/pnas.82.18.6133;
RA Nakajima-Iijima S., Hamada H., Reddy P., Kakunaga T.;
RT "Molecular structure of the human cytoplasmic beta-actin gene:
RT interspecies homology of sequences in the introns.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6133-6137(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1734024; DOI=10.1083/jcb.116.4.933;
RA Ohmori H., Toyama S., Toyama S.;
RT "Direct proof that the primary site of action of cytochalasin on cell
RT motility processes is actin.";
RL J. Cell Biol. 116:933-941(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Kidney, Muscle, Pancreas, Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-28.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP PROTEIN SEQUENCE OF 2-18; 29-37; 40-50; 85-95; 148-177; 184-191;
RP 197-206; 292-312 AND 316-326, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ASP-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 19-62; 85-113; 184-191; 197-206; 216-254; 291-312;
RP 316-326 AND 360-372, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 252-375.
RX PubMed=6842590; DOI=10.1016/0022-2836(83)90117-1;
RA Hanukoglu I., Tanese N., Fuchs E.;
RT "Complementary DNA sequence of a human cytoplasmic actin. Interspecies
RT divergence of 3' non-coding regions.";
RL J. Mol. Biol. 163:673-678(1983).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH RAN; XPO6 AND PFN1, AND INTERACTION
RP WITH XPO6.
RX PubMed=14592989; DOI=10.1093/emboj/cdg565;
RA Stueven T., Hartmann E., Goerlich D.;
RT "Exportin 6: a novel nuclear export receptor that is specific for
RT profilin.actin complexes.";
RL EMBO J. 22:5928-5940(2003).
RN [12]
RP INTERACTION WITH EMD.
RX PubMed=15328537; DOI=10.1371/journal.pbio.0020231;
RA Holaska J.M., Kowalski A.K., Wilson K.L.;
RT "Emerin caps the pointed end of actin filaments: evidence for an actin
RT cortical network at the nuclear inner membrane.";
RL PLoS Biol. 2:1354-1362(2004).
RN [13]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [14]
RP INTERACTION WITH GCSAM.
RX PubMed=17823310; DOI=10.1182/blood-2007-04-087775;
RA Lu X., Chen J., Malumbres R., Cubedo Gil E., Helfman D.M.,
RA Lossos I.S.;
RT "HGAL, a lymphoma prognostic biomarker, interacts with the
RT cytoskeleton and mediates the effects of IL-6 on cell migration.";
RL Blood 110:4268-4277(2007).
RN [15]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.M600346-MCP200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [16]
RP IDENTIFICATION IN THE BAF COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=18765789; DOI=10.1101/gad.471408;
RA Lange M., Kaynak B., Forster U.B., Toenjes M., Fischer J.J., Grimm C.,
RA Schlesinger J., Just S., Dunkel I., Krueger T., Mebus S., Lehrach H.,
RA Lurz R., Gobom J., Rottbauer W., Abdelilah-Seyfried S., Sperling S.;
RT "Regulation of muscle development by DPF3, a novel histone acetylation
RT and methylation reader of the BAF chromatin remodeling complex.";
RL Genes Dev. 22:2370-2384(2008).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ASP-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP INTERACTION WITH ERBB2.
RX PubMed=21555369; DOI=10.1158/0008-5472.CAN-10-3504;
RA Li L.Y., Chen H., Hsieh Y.H., Wang Y.N., Chu H.J., Chen Y.H.,
RA Chen H.Y., Chien P.J., Ma H.T., Tsai H.C., Lai C.C., Sher Y.P.,
RA Lien H.C., Tsai C.H., Hung M.C.;
RT "Nuclear ErbB2 enhances translation and cell growth by activating
RT transcription of ribosomal RNA genes.";
RL Cancer Res. 71:4269-4279(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND ASP-2, AND MASS
RP SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP VARIANT DYTJ TRP-183, AND CHARACTERIZATION OF VARIANT DYTJ TRP-183.
RX PubMed=16685646; DOI=10.1086/504271;
RA Procaccio V., Salazar G., Ono S., Styers M.L., Gearing M., Davila A.,
RA Jimenez R., Juncos J., Gutekunst C.-A., Meroni G., Fontanella B.,
RA Sontag E., Sontag J.-M., Faundez V., Wainer B.H.;
RT "A mutation of beta -actin that alters depolymerization dynamics is
RT associated with autosomal dominant developmental malformations,
RT deafness, and dystonia.";
RL Am. J. Hum. Genet. 78:947-960(2006).
RN [21]
RP IDENTIFICATION IN THE MLL5-L COMPLEX.
RX PubMed=19377461; DOI=10.1038/nature07954;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
RT granulopoiesis.";
RL Nature 459:455-459(2009).
RN [22]
RP METHYLATION AT LYS-84, AND DEMETHYLATION BY ALKBH4.
RX PubMed=23673617; DOI=10.1038/ncomms2863;
RA Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B.,
RA Niu Y., Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z.,
RA He C., Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.;
RT "ALKBH4-dependent demethylation of actin regulates actomyosin
RT dynamics.";
RL Nat. Commun. 4:1832-1832(2013).
RN [23]
RP VARIANTS BRWS1 ASP-12; VAL-65; CYS-196 AND HIS-196.
RX PubMed=22366783; DOI=10.1038/ng.1091;
RA Riviere J.B., van Bon B.W., Hoischen A., Kholmanskikh S.S.,
RA O'Roak B.J., Gilissen C., Gijsen S., Sullivan C.T., Christian S.L.,
RA Abdul-Rahman O.A., Atkin J.F., Chassaing N., Drouin-Garraud V.,
RA Fry A.E., Fryns J.P., Gripp K.W., Kempers M., Kleefstra T.,
RA Mancini G.M., Nowaczyk M.J., van Ravenswaaij-Arts C.M., Roscioli T.,
RA Marble M., Rosenfeld J.A., Siu V.M., de Vries B.B., Shendure J.,
RA Verloes A., Veltman J.A., Brunner H.G., Ross M.E., Pilz D.T.,
RA Dobyns W.B.;
RT "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-
RT Winter syndrome.";
RL Nat. Genet. 44:440-444(2012).
CC -!- FUNCTION: Actins are highly conserved proteins that are involved
CC in various types of cell motility and are ubiquitously expressed
CC in all eukaryotic cells.
CC -!- SUBUNIT: Polymerization of globular actin (G-actin) leads to a
CC structural filament (F-actin) in the form of a two-stranded helix.
CC Each actin can bind to 4 others. Identified in a IGF2BP1-dependent
CC mRNP granule complex containing untranslated mRNAs. Component of
CC the BAF complex, which includes at least actin (ACTB), ARID1A,
CC ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B,
CC SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1,
CC and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or
CC SMARCD3/BAF60C. In muscle cells, the BAF complex also contains
CC DPF3. Found in a complex with XPO6, Ran, ACTB and PFN1. Component
CC of the MLL5-L complex, at least composed of KMT2E/MLL5, STK38,
CC PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with XPO6
CC and EMD. Interacts with ERBB2. Interacts with GCSAM.
CC -!- INTERACTION:
CC P63261:ACTG1; NbExp=3; IntAct=EBI-353944, EBI-351292;
CC Q9Y281:CFL2; NbExp=3; IntAct=EBI-353944, EBI-351218;
CC P04626:ERBB2; NbExp=10; IntAct=EBI-353944, EBI-641062;
CC Q8TCJ0-2:FBXO25; NbExp=3; IntAct=EBI-353944, EBI-6264551;
CC P11142:HSPA8; NbExp=2; IntAct=EBI-353944, EBI-351896;
CC Q8K4J6:Mkl1 (xeno); NbExp=3; IntAct=EBI-353944, EBI-8291665;
CC O14950:MYL12B; NbExp=3; IntAct=EBI-353944, EBI-1642165;
CC P14598:NCF1; NbExp=3; IntAct=EBI-353944, EBI-395044;
CC Q92636:NSMAF; NbExp=2; IntAct=EBI-353944, EBI-2947053;
CC P37802:TAGLN2; NbExp=3; IntAct=EBI-353944, EBI-1056740;
CC P63104:YWHAZ; NbExp=3; IntAct=EBI-353944, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs.
CC -!- PTM: ISGylated.
CC -!- PTM: Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or
CC MICAL3) to form methionine sulfoxide promotes actin filament
CC depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form.
CC The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote
CC actin repolymerization (By similarity).
CC -!- PTM: Monomethylation at Lys-84 (K84me1) regulates actin-myosin
CC interaction and actomyosin-dependent processes. Demethylation by
CC ALKBH4 is required for maintaining actomyosin dynamics supporting
CC normal cleavage furrow ingression during cytokinesis and cell
CC migration.
CC -!- DISEASE: Dystonia, juvenile-onset (DYTJ) [MIM:607371]: A form of
CC dystonia with juvenile onset. Dystonia is defined by the presence
CC of sustained involuntary muscle contraction, often leading to
CC abnormal postures. Patients with juvenile-onset dystonia manifest
CC progressive, generalized, dopa-unresponsive dystonia,
CC developmental malformations and sensory hearing loss. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Baraitser-Winter syndrome 1 (BRWS1) [MIM:243310]: A rare
CC developmental disorder characterized by the combination of
CC congenital ptosis, high-arched eyebrows, hypertelorism, ocular
CC colobomata, and a brain malformation consisting of anterior-
CC predominant lissencephaly. Other typical features include
CC postnatal short stature and microcephaly, intellectual disability,
CC seizures, and hearing loss. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In vertebrates 3 main groups of actin isoforms,
CC alpha, beta and gamma have been identified. The alpha actins are
CC found in muscle tissues and are a major constituent of the
CC contractile apparatus. The beta and gamma actins coexist in most
CC cell types as components of the cytoskeleton and as mediators of
CC internal cell motility.
CC -!- SIMILARITY: Belongs to the actin family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ACTBID42959ch7p22.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/actb/";
CC -!- WEB RESOURCE: Name=Mendelian genes actin, beta (ACTB); Note=Leiden
CC Open Variation Database (LOVD);
CC URL="http://www.lovd.nl/ACTB";
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DR EMBL; X00351; CAA25099.1; -; mRNA.
DR EMBL; M10277; AAA51567.1; -; Genomic_DNA.
DR EMBL; X63432; CAA45026.1; -; mRNA.
DR EMBL; AY582799; AAS79319.1; -; Genomic_DNA.
DR EMBL; AC006483; AAP22343.1; -; Genomic_DNA.
DR EMBL; BC001301; AAH01301.1; -; mRNA.
DR EMBL; BC002409; AAH02409.1; -; mRNA.
DR EMBL; BC004251; AAH04251.1; -; mRNA.
DR EMBL; BC008633; AAH08633.1; -; mRNA.
DR EMBL; BC012854; AAH12854.1; -; mRNA.
DR EMBL; BC013380; AAH13380.1; -; mRNA.
DR EMBL; BC014861; AAH14861.1; -; mRNA.
DR EMBL; BC016045; AAH16045.1; -; mRNA.
DR EMBL; V00478; CAA23745.1; -; mRNA.
DR PIR; A25168; ATHUB.
DR RefSeq; NP_001092.1; NM_001101.3.
DR RefSeq; XP_005249875.1; XM_005249818.1.
DR UniGene; Hs.520640; -.
DR PDB; 3BYH; EM; 12.00 A; A=2-375.
DR PDB; 3D2U; X-ray; 2.21 A; C/G=170-178.
DR PDB; 3LUE; EM; -; A/B/C/D/E/F/G/H/I/J=2-375.
DR PDBsum; 3BYH; -.
DR PDBsum; 3D2U; -.
DR PDBsum; 3LUE; -.
DR ProteinModelPortal; P60709; -.
DR SMR; P60709; 6-375.
DR DIP; DIP-29686N; -.
DR IntAct; P60709; 165.
DR MINT; MINT-220312; -.
DR ChEMBL; CHEMBL2062353; -.
DR PhosphoSite; P60709; -.
DR DMDM; 46397333; -.
DR DOSAC-COBS-2DPAGE; P60709; -.
DR DOSAC-COBS-2DPAGE; P60709_OR_P63261; -.
DR REPRODUCTION-2DPAGE; P60709; -.
DR SWISS-2DPAGE; P60709; -.
DR UCD-2DPAGE; P60709; -.
DR PaxDb; P60709; -.
DR PeptideAtlas; P60709; -.
DR PRIDE; P60709; -.
DR DNASU; 60; -.
DR Ensembl; ENST00000331789; ENSP00000349960; ENSG00000075624.
DR GeneID; 60; -.
DR KEGG; hsa:60; -.
DR UCSC; uc003soq.4; human.
DR CTD; 60; -.
DR GeneCards; GC07M005566; -.
DR HGNC; HGNC:132; ACTB.
DR HPA; CAB002621; -.
DR HPA; HPA041264; -.
DR HPA; HPA041271; -.
DR MIM; 102630; gene.
DR MIM; 243310; phenotype.
DR MIM; 607371; phenotype.
DR neXtProt; NX_P60709; -.
DR Orphanet; 2995; Baraitser-Winter syndrome.
DR Orphanet; 79107; Developmental malformations - deafness - dystonia.
DR PharmGKB; PA24457; -.
DR eggNOG; COG5277; -.
DR HOVERGEN; HBG003771; -.
DR InParanoid; P60709; -.
DR KO; K05692; -.
DR OMA; NGIADRM; -.
DR OrthoDB; EOG72RMZ1; -.
DR PhylomeDB; P60709; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P60709; -.
DR ChiTaRS; ACTB; human.
DR EvolutionaryTrace; P60709; -.
DR GeneWiki; Beta-actin; -.
DR GenomeRNAi; 60; -.
DR NextBio; 253; -.
DR PRO; PR:P60709; -.
DR ArrayExpress; P60709; -.
DR Bgee; P60709; -.
DR CleanEx; HS_ACTB; -.
DR Genevestigator; P60709; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0070688; C:MLL5-L complex; IDA:UniProtKB.
DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB.
DR GO; GO:0051084; P:'de novo' posttranslational protein folding; TAS:Reactome.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR InterPro; IPR004000; Actin-related.
DR InterPro; IPR020902; Actin/actin-like_CS.
DR InterPro; IPR004001; Actin_CS.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR PROSITE; PS00406; ACTINS_1; 1.
DR PROSITE; PS00432; ACTINS_2; 1.
DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW Cytoskeleton; Deafness; Direct protein sequencing; Disease mutation;
KW Dystonia; Mental retardation; Methylation; Nucleotide-binding;
KW Oxidation; Polymorphism; Reference proteome; Ubl conjugation.
FT CHAIN 1 375 Actin, cytoplasmic 1.
FT /FTId=PRO_0000367073.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 375 Actin, cytoplasmic 1, N-terminally
FT processed.
FT /FTId=PRO_0000000771.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylaspartate; in Actin, cytoplasmic
FT 1, N-terminally processed.
FT MOD_RES 44 44 Methionine (R)-sulfoxide (By similarity).
FT MOD_RES 47 47 Methionine (R)-sulfoxide (By similarity).
FT MOD_RES 73 73 Tele-methylhistidine (By similarity).
FT MOD_RES 84 84 N6-methyllysine.
FT VARIANT 12 12 N -> D (in BRWS1; dbSNP:rs281875331).
FT /FTId=VAR_067810.
FT VARIANT 65 65 L -> V (in BRWS1; dbSNP:rs281875332).
FT /FTId=VAR_067811.
FT VARIANT 183 183 R -> W (in DYTJ; modifies cell response
FT to latrunculin A).
FT /FTId=VAR_030026.
FT VARIANT 196 196 R -> C (in BRWS1; dbSNP:rs281875333).
FT /FTId=VAR_067812.
FT VARIANT 196 196 R -> H (in BRWS1; dbSNP:rs281875334).
FT /FTId=VAR_067813.
FT VARIANT 243 243 P -> L (in dbSNP:rs11546899).
FT /FTId=VAR_048185.
FT CONFLICT 97 97 A -> P (in Ref. 6; AAH16045).
FT CONFLICT 116 116 R -> L (in Ref. 6; AAH12854).
SQ SEQUENCE 375 AA; 41737 MW; 6AFD05CA94E360E2 CRC64;
MDDDIAALVV DNGSGMCKAG FAGDDAPRAV FPSIVGRPRH QGVMVGMGQK DSYVGDEAQS
KRGILTLKYP IEHGIVTNWD DMEKIWHHTF YNELRVAPEE HPVLLTEAPL NPKANREKMT
QIMFETFNTP AMYVAIQAVL SLYASGRTTG IVMDSGDGVT HTVPIYEGYA LPHAILRLDL
AGRDLTDYLM KILTERGYSF TTTAEREIVR DIKEKLCYVA LDFEQEMATA ASSSSLEKSY
ELPDGQVITI GNERFRCPEA LFQPSFLGME SCGIHETTFN SIMKCDVDIR KDLYANTVLS
GGTTMYPGIA DRMQKEITAL APSTMKIKII APPERKYSVW IGGSILASLS TFQQMWISKQ
EYDESGPSIV HRKCF
//
ID ACTB_HUMAN Reviewed; 375 AA.
AC P60709; P02570; P70514; P99021; Q11211; Q64316; Q75MN2; Q96B34;
read moreAC Q96HG5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 22-JAN-2014, entry version 125.
DE RecName: Full=Actin, cytoplasmic 1;
DE AltName: Full=Beta-actin;
DE Contains:
DE RecName: Full=Actin, cytoplasmic 1, N-terminally processed;
GN Name=ACTB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6322116; DOI=10.1093/nar/12.3.1687;
RA Ponte P., Ng S.Y., Engel J., Gunning P., Kedes L.;
RT "Evolutionary conservation in the untranslated regions of actin mRNAs:
RT DNA sequence of a human beta-actin cDNA.";
RL Nucleic Acids Res. 12:1687-1696(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2994062; DOI=10.1073/pnas.82.18.6133;
RA Nakajima-Iijima S., Hamada H., Reddy P., Kakunaga T.;
RT "Molecular structure of the human cytoplasmic beta-actin gene:
RT interspecies homology of sequences in the introns.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6133-6137(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1734024; DOI=10.1083/jcb.116.4.933;
RA Ohmori H., Toyama S., Toyama S.;
RT "Direct proof that the primary site of action of cytochalasin on cell
RT motility processes is actin.";
RL J. Cell Biol. 116:933-941(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Kidney, Muscle, Pancreas, Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-28.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP PROTEIN SEQUENCE OF 2-18; 29-37; 40-50; 85-95; 148-177; 184-191;
RP 197-206; 292-312 AND 316-326, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ASP-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 19-62; 85-113; 184-191; 197-206; 216-254; 291-312;
RP 316-326 AND 360-372, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 252-375.
RX PubMed=6842590; DOI=10.1016/0022-2836(83)90117-1;
RA Hanukoglu I., Tanese N., Fuchs E.;
RT "Complementary DNA sequence of a human cytoplasmic actin. Interspecies
RT divergence of 3' non-coding regions.";
RL J. Mol. Biol. 163:673-678(1983).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH RAN; XPO6 AND PFN1, AND INTERACTION
RP WITH XPO6.
RX PubMed=14592989; DOI=10.1093/emboj/cdg565;
RA Stueven T., Hartmann E., Goerlich D.;
RT "Exportin 6: a novel nuclear export receptor that is specific for
RT profilin.actin complexes.";
RL EMBO J. 22:5928-5940(2003).
RN [12]
RP INTERACTION WITH EMD.
RX PubMed=15328537; DOI=10.1371/journal.pbio.0020231;
RA Holaska J.M., Kowalski A.K., Wilson K.L.;
RT "Emerin caps the pointed end of actin filaments: evidence for an actin
RT cortical network at the nuclear inner membrane.";
RL PLoS Biol. 2:1354-1362(2004).
RN [13]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [14]
RP INTERACTION WITH GCSAM.
RX PubMed=17823310; DOI=10.1182/blood-2007-04-087775;
RA Lu X., Chen J., Malumbres R., Cubedo Gil E., Helfman D.M.,
RA Lossos I.S.;
RT "HGAL, a lymphoma prognostic biomarker, interacts with the
RT cytoskeleton and mediates the effects of IL-6 on cell migration.";
RL Blood 110:4268-4277(2007).
RN [15]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.M600346-MCP200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [16]
RP IDENTIFICATION IN THE BAF COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=18765789; DOI=10.1101/gad.471408;
RA Lange M., Kaynak B., Forster U.B., Toenjes M., Fischer J.J., Grimm C.,
RA Schlesinger J., Just S., Dunkel I., Krueger T., Mebus S., Lehrach H.,
RA Lurz R., Gobom J., Rottbauer W., Abdelilah-Seyfried S., Sperling S.;
RT "Regulation of muscle development by DPF3, a novel histone acetylation
RT and methylation reader of the BAF chromatin remodeling complex.";
RL Genes Dev. 22:2370-2384(2008).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ASP-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP INTERACTION WITH ERBB2.
RX PubMed=21555369; DOI=10.1158/0008-5472.CAN-10-3504;
RA Li L.Y., Chen H., Hsieh Y.H., Wang Y.N., Chu H.J., Chen Y.H.,
RA Chen H.Y., Chien P.J., Ma H.T., Tsai H.C., Lai C.C., Sher Y.P.,
RA Lien H.C., Tsai C.H., Hung M.C.;
RT "Nuclear ErbB2 enhances translation and cell growth by activating
RT transcription of ribosomal RNA genes.";
RL Cancer Res. 71:4269-4279(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND ASP-2, AND MASS
RP SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP VARIANT DYTJ TRP-183, AND CHARACTERIZATION OF VARIANT DYTJ TRP-183.
RX PubMed=16685646; DOI=10.1086/504271;
RA Procaccio V., Salazar G., Ono S., Styers M.L., Gearing M., Davila A.,
RA Jimenez R., Juncos J., Gutekunst C.-A., Meroni G., Fontanella B.,
RA Sontag E., Sontag J.-M., Faundez V., Wainer B.H.;
RT "A mutation of beta -actin that alters depolymerization dynamics is
RT associated with autosomal dominant developmental malformations,
RT deafness, and dystonia.";
RL Am. J. Hum. Genet. 78:947-960(2006).
RN [21]
RP IDENTIFICATION IN THE MLL5-L COMPLEX.
RX PubMed=19377461; DOI=10.1038/nature07954;
RA Fujiki R., Chikanishi T., Hashiba W., Ito H., Takada I., Roeder R.G.,
RA Kitagawa H., Kato S.;
RT "GlcNAcylation of a histone methyltransferase in retinoic-acid-induced
RT granulopoiesis.";
RL Nature 459:455-459(2009).
RN [22]
RP METHYLATION AT LYS-84, AND DEMETHYLATION BY ALKBH4.
RX PubMed=23673617; DOI=10.1038/ncomms2863;
RA Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B.,
RA Niu Y., Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z.,
RA He C., Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.;
RT "ALKBH4-dependent demethylation of actin regulates actomyosin
RT dynamics.";
RL Nat. Commun. 4:1832-1832(2013).
RN [23]
RP VARIANTS BRWS1 ASP-12; VAL-65; CYS-196 AND HIS-196.
RX PubMed=22366783; DOI=10.1038/ng.1091;
RA Riviere J.B., van Bon B.W., Hoischen A., Kholmanskikh S.S.,
RA O'Roak B.J., Gilissen C., Gijsen S., Sullivan C.T., Christian S.L.,
RA Abdul-Rahman O.A., Atkin J.F., Chassaing N., Drouin-Garraud V.,
RA Fry A.E., Fryns J.P., Gripp K.W., Kempers M., Kleefstra T.,
RA Mancini G.M., Nowaczyk M.J., van Ravenswaaij-Arts C.M., Roscioli T.,
RA Marble M., Rosenfeld J.A., Siu V.M., de Vries B.B., Shendure J.,
RA Verloes A., Veltman J.A., Brunner H.G., Ross M.E., Pilz D.T.,
RA Dobyns W.B.;
RT "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-
RT Winter syndrome.";
RL Nat. Genet. 44:440-444(2012).
CC -!- FUNCTION: Actins are highly conserved proteins that are involved
CC in various types of cell motility and are ubiquitously expressed
CC in all eukaryotic cells.
CC -!- SUBUNIT: Polymerization of globular actin (G-actin) leads to a
CC structural filament (F-actin) in the form of a two-stranded helix.
CC Each actin can bind to 4 others. Identified in a IGF2BP1-dependent
CC mRNP granule complex containing untranslated mRNAs. Component of
CC the BAF complex, which includes at least actin (ACTB), ARID1A,
CC ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B,
CC SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1,
CC and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or
CC SMARCD3/BAF60C. In muscle cells, the BAF complex also contains
CC DPF3. Found in a complex with XPO6, Ran, ACTB and PFN1. Component
CC of the MLL5-L complex, at least composed of KMT2E/MLL5, STK38,
CC PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Interacts with XPO6
CC and EMD. Interacts with ERBB2. Interacts with GCSAM.
CC -!- INTERACTION:
CC P63261:ACTG1; NbExp=3; IntAct=EBI-353944, EBI-351292;
CC Q9Y281:CFL2; NbExp=3; IntAct=EBI-353944, EBI-351218;
CC P04626:ERBB2; NbExp=10; IntAct=EBI-353944, EBI-641062;
CC Q8TCJ0-2:FBXO25; NbExp=3; IntAct=EBI-353944, EBI-6264551;
CC P11142:HSPA8; NbExp=2; IntAct=EBI-353944, EBI-351896;
CC Q8K4J6:Mkl1 (xeno); NbExp=3; IntAct=EBI-353944, EBI-8291665;
CC O14950:MYL12B; NbExp=3; IntAct=EBI-353944, EBI-1642165;
CC P14598:NCF1; NbExp=3; IntAct=EBI-353944, EBI-395044;
CC Q92636:NSMAF; NbExp=2; IntAct=EBI-353944, EBI-2947053;
CC P37802:TAGLN2; NbExp=3; IntAct=EBI-353944, EBI-1056740;
CC P63104:YWHAZ; NbExp=3; IntAct=EBI-353944, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Note=Localized in
CC cytoplasmic mRNP granules containing untranslated mRNAs.
CC -!- PTM: ISGylated.
CC -!- PTM: Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or
CC MICAL3) to form methionine sulfoxide promotes actin filament
CC depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form.
CC The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote
CC actin repolymerization (By similarity).
CC -!- PTM: Monomethylation at Lys-84 (K84me1) regulates actin-myosin
CC interaction and actomyosin-dependent processes. Demethylation by
CC ALKBH4 is required for maintaining actomyosin dynamics supporting
CC normal cleavage furrow ingression during cytokinesis and cell
CC migration.
CC -!- DISEASE: Dystonia, juvenile-onset (DYTJ) [MIM:607371]: A form of
CC dystonia with juvenile onset. Dystonia is defined by the presence
CC of sustained involuntary muscle contraction, often leading to
CC abnormal postures. Patients with juvenile-onset dystonia manifest
CC progressive, generalized, dopa-unresponsive dystonia,
CC developmental malformations and sensory hearing loss. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- DISEASE: Baraitser-Winter syndrome 1 (BRWS1) [MIM:243310]: A rare
CC developmental disorder characterized by the combination of
CC congenital ptosis, high-arched eyebrows, hypertelorism, ocular
CC colobomata, and a brain malformation consisting of anterior-
CC predominant lissencephaly. Other typical features include
CC postnatal short stature and microcephaly, intellectual disability,
CC seizures, and hearing loss. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In vertebrates 3 main groups of actin isoforms,
CC alpha, beta and gamma have been identified. The alpha actins are
CC found in muscle tissues and are a major constituent of the
CC contractile apparatus. The beta and gamma actins coexist in most
CC cell types as components of the cytoskeleton and as mediators of
CC internal cell motility.
CC -!- SIMILARITY: Belongs to the actin family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ACTBID42959ch7p22.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/actb/";
CC -!- WEB RESOURCE: Name=Mendelian genes actin, beta (ACTB); Note=Leiden
CC Open Variation Database (LOVD);
CC URL="http://www.lovd.nl/ACTB";
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DR EMBL; X00351; CAA25099.1; -; mRNA.
DR EMBL; M10277; AAA51567.1; -; Genomic_DNA.
DR EMBL; X63432; CAA45026.1; -; mRNA.
DR EMBL; AY582799; AAS79319.1; -; Genomic_DNA.
DR EMBL; AC006483; AAP22343.1; -; Genomic_DNA.
DR EMBL; BC001301; AAH01301.1; -; mRNA.
DR EMBL; BC002409; AAH02409.1; -; mRNA.
DR EMBL; BC004251; AAH04251.1; -; mRNA.
DR EMBL; BC008633; AAH08633.1; -; mRNA.
DR EMBL; BC012854; AAH12854.1; -; mRNA.
DR EMBL; BC013380; AAH13380.1; -; mRNA.
DR EMBL; BC014861; AAH14861.1; -; mRNA.
DR EMBL; BC016045; AAH16045.1; -; mRNA.
DR EMBL; V00478; CAA23745.1; -; mRNA.
DR PIR; A25168; ATHUB.
DR RefSeq; NP_001092.1; NM_001101.3.
DR RefSeq; XP_005249875.1; XM_005249818.1.
DR UniGene; Hs.520640; -.
DR PDB; 3BYH; EM; 12.00 A; A=2-375.
DR PDB; 3D2U; X-ray; 2.21 A; C/G=170-178.
DR PDB; 3LUE; EM; -; A/B/C/D/E/F/G/H/I/J=2-375.
DR PDBsum; 3BYH; -.
DR PDBsum; 3D2U; -.
DR PDBsum; 3LUE; -.
DR ProteinModelPortal; P60709; -.
DR SMR; P60709; 6-375.
DR DIP; DIP-29686N; -.
DR IntAct; P60709; 165.
DR MINT; MINT-220312; -.
DR ChEMBL; CHEMBL2062353; -.
DR PhosphoSite; P60709; -.
DR DMDM; 46397333; -.
DR DOSAC-COBS-2DPAGE; P60709; -.
DR DOSAC-COBS-2DPAGE; P60709_OR_P63261; -.
DR REPRODUCTION-2DPAGE; P60709; -.
DR SWISS-2DPAGE; P60709; -.
DR UCD-2DPAGE; P60709; -.
DR PaxDb; P60709; -.
DR PeptideAtlas; P60709; -.
DR PRIDE; P60709; -.
DR DNASU; 60; -.
DR Ensembl; ENST00000331789; ENSP00000349960; ENSG00000075624.
DR GeneID; 60; -.
DR KEGG; hsa:60; -.
DR UCSC; uc003soq.4; human.
DR CTD; 60; -.
DR GeneCards; GC07M005566; -.
DR HGNC; HGNC:132; ACTB.
DR HPA; CAB002621; -.
DR HPA; HPA041264; -.
DR HPA; HPA041271; -.
DR MIM; 102630; gene.
DR MIM; 243310; phenotype.
DR MIM; 607371; phenotype.
DR neXtProt; NX_P60709; -.
DR Orphanet; 2995; Baraitser-Winter syndrome.
DR Orphanet; 79107; Developmental malformations - deafness - dystonia.
DR PharmGKB; PA24457; -.
DR eggNOG; COG5277; -.
DR HOVERGEN; HBG003771; -.
DR InParanoid; P60709; -.
DR KO; K05692; -.
DR OMA; NGIADRM; -.
DR OrthoDB; EOG72RMZ1; -.
DR PhylomeDB; P60709; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P60709; -.
DR ChiTaRS; ACTB; human.
DR EvolutionaryTrace; P60709; -.
DR GeneWiki; Beta-actin; -.
DR GenomeRNAi; 60; -.
DR NextBio; 253; -.
DR PRO; PR:P60709; -.
DR ArrayExpress; P60709; -.
DR Bgee; P60709; -.
DR CleanEx; HS_ACTB; -.
DR Genevestigator; P60709; -.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0070688; C:MLL5-L complex; IDA:UniProtKB.
DR GO; GO:0035267; C:NuA4 histone acetyltransferase complex; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:UniProtKB.
DR GO; GO:0051084; P:'de novo' posttranslational protein folding; TAS:Reactome.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR InterPro; IPR004000; Actin-related.
DR InterPro; IPR020902; Actin/actin-like_CS.
DR InterPro; IPR004001; Actin_CS.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR PROSITE; PS00406; ACTINS_1; 1.
DR PROSITE; PS00432; ACTINS_2; 1.
DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm;
KW Cytoskeleton; Deafness; Direct protein sequencing; Disease mutation;
KW Dystonia; Mental retardation; Methylation; Nucleotide-binding;
KW Oxidation; Polymorphism; Reference proteome; Ubl conjugation.
FT CHAIN 1 375 Actin, cytoplasmic 1.
FT /FTId=PRO_0000367073.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 375 Actin, cytoplasmic 1, N-terminally
FT processed.
FT /FTId=PRO_0000000771.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylaspartate; in Actin, cytoplasmic
FT 1, N-terminally processed.
FT MOD_RES 44 44 Methionine (R)-sulfoxide (By similarity).
FT MOD_RES 47 47 Methionine (R)-sulfoxide (By similarity).
FT MOD_RES 73 73 Tele-methylhistidine (By similarity).
FT MOD_RES 84 84 N6-methyllysine.
FT VARIANT 12 12 N -> D (in BRWS1; dbSNP:rs281875331).
FT /FTId=VAR_067810.
FT VARIANT 65 65 L -> V (in BRWS1; dbSNP:rs281875332).
FT /FTId=VAR_067811.
FT VARIANT 183 183 R -> W (in DYTJ; modifies cell response
FT to latrunculin A).
FT /FTId=VAR_030026.
FT VARIANT 196 196 R -> C (in BRWS1; dbSNP:rs281875333).
FT /FTId=VAR_067812.
FT VARIANT 196 196 R -> H (in BRWS1; dbSNP:rs281875334).
FT /FTId=VAR_067813.
FT VARIANT 243 243 P -> L (in dbSNP:rs11546899).
FT /FTId=VAR_048185.
FT CONFLICT 97 97 A -> P (in Ref. 6; AAH16045).
FT CONFLICT 116 116 R -> L (in Ref. 6; AAH12854).
SQ SEQUENCE 375 AA; 41737 MW; 6AFD05CA94E360E2 CRC64;
MDDDIAALVV DNGSGMCKAG FAGDDAPRAV FPSIVGRPRH QGVMVGMGQK DSYVGDEAQS
KRGILTLKYP IEHGIVTNWD DMEKIWHHTF YNELRVAPEE HPVLLTEAPL NPKANREKMT
QIMFETFNTP AMYVAIQAVL SLYASGRTTG IVMDSGDGVT HTVPIYEGYA LPHAILRLDL
AGRDLTDYLM KILTERGYSF TTTAEREIVR DIKEKLCYVA LDFEQEMATA ASSSSLEKSY
ELPDGQVITI GNERFRCPEA LFQPSFLGME SCGIHETTFN SIMKCDVDIR KDLYANTVLS
GGTTMYPGIA DRMQKEITAL APSTMKIKII APPERKYSVW IGGSILASLS TFQQMWISKQ
EYDESGPSIV HRKCF
//
MIM
102630
*RECORD*
*FIELD* NO
102630
*FIELD* TI
*102630 ACTIN, BETA; ACTB
;;BETA-ACTIN;;
ACTIN, CYTOPLASMIC, 1
*FIELD* TX
CLONING
read more
From studies of the amino acid sequence of cytoplasmic and muscle
actins, Vandekerckhove and Weber (1978) concluded that mammalian
cytoplasmic actins are the products of 2 different genes and differ by
many amino acids from muscle actin. In a neoplastic cell line resulting
from treatment of cultured human diploid fibroblasts with a chemical
mutagen, Leavitt et al. (1982) observed a mutant form of beta actin.
Toyama and Toyama (1984) isolated and characterized lines of KB cells
resistant to cytochalasin B. They found that one resistant line had an
alteration in beta-actin. Such cells bound less cytochalasin B than did
parental KB cells. The authors suggested that the primary site of action
of cytochalasin B on cell motility processes is beta-actin.
Using chick beta-actin cDNA as probe, Gunning et al. (1983) cloned
beta-actin and gamma-actin (ACTG1; 102560) from a fibroblast cDNA
library. They noted that the N-terminal methionine is
posttranslationally removed from the mature beta- and gamma-actin
proteins.
MAPPING
Ng et al. (1985) assigned the ACTB gene to 7pter-q22 by Southern blot
analysis of DNA from somatic cell hybrids. Habets et al. (1992)
generated hybrids that harbor only specific regions of human chromosome
7 and assigned the ACTB locus to 7p15-p12.
Ueyama et al. (1996) used fluorescence in situ hybridization to map ACTB
to 7p22. By PCR of somatic cell hybrid DNAs, they mapped 4 ACTB
pseudogenes to other chromosomes.
GENE FUNCTION
Interaction of phospholipase D (see PLD1; 602382) with actin
microfilaments regulates cell proliferation, vesicle trafficking, and
secretion. Kusner et al. (2002) found that highly purified globular
actin (G-actin) inhibited both basal and stimulated PLD1 activity,
whereas filamentous actin (F-actin) had the opposite effect.
Actin-induced modulation of PLD1 activity was independent of the
activating stimulus. The effects of actin on PLD1 were isoform specific:
human platelet actin, which exists in a 5:1 ratio of beta- and
gamma-actin, was only 45% as potent and 40% as efficacious as rabbit
skeletal muscle alpha-actin.
Localization of beta-actin mRNA to sites of active actin polymerization
modulates cell migration during embryogenesis, differentiation, and
possibly carcinogenesis. This localization requires the oncofetal
protein ZBP1 (608288), which binds to a conserved 54-nucleotide element
in the 3-prime untranslated region of the beta-actin mRNA known as the
'zipcode.' ZBP1 promotes translocation of the beta-actin transcript to
actin-rich protrusions in primary fibroblasts and neurons. Huttelmaier
et al. (2005) showed that chicken ZBP1 modulates the translation of
beta-actin mRNA. ZBP1 associates with the beta-actin transcript in the
nucleus and prevents premature translation in the cytoplasm by blocking
translation initiation. Translation occurs only when the ZBP1-RNA
complex reaches its destination at the periphery of the cell. At the
endpoint of mRNA transport, the protein kinase Src (190090) promotes
translation by phosphorylating a key tyrosine residue in ZBP1 that is
required for binding to RNA. These sequential events provide both
temporal and spatial control over beta-actin mRNA translation, which is
important for cell migration and neurite outgrowth.
In immunoprecipitation studies of embryonic fibroblasts from wildtype
and knockout mice deficient in the arginylation enzyme Ate1 (607103),
Karakozova et al. (2006) found that approximately 40% of intracellular
beta-actin is arginylated in vivo. In both wildtype and Ate1-null cells
beta-actin was stable, suggesting that arginylation does not induce
beta-actin degradation. Karakozova et al. (2006) found that arginylation
of beta-actin regulates cell motility. The majority of Ate1-null cells
appeared smaller than wildtype cells and were apparently unable to form
a lamella during movement along the substrate. In addition, Ate1-null
cells exhibited apparent defects in ruffling activity and cortical flow.
Karakozova et al. (2006) concluded that arginylation of beta-actin
apparently represents a critical step in the actin N-terminal processing
needed for actin functioning in vivo.
Nitric oxide (NO) is a paracrine mediator of vascular and platelet
function that is produced in the vasculature by NO synthase-3 (NOS3;
163729). Using human platelets, Ji et al. (2007) demonstrated that
polymerization of beta-actin regulated the activation state of NOS3, and
hence NO formation, by altering its binding to heat-shock protein-90
(HSP90, or HSPCA; 140571). NOS3 bound the globular, but not the
filamentous, form of beta-actin, and the affinity of NOS3 for globular
beta-actin was, in turn, increased by HSP90. Formation of this ternary
complex of NOS3, globular beta-actin, and HSP90 increased NOS activity
and cyclic GMP, an index of bioactive NO, and increased the rate of
HSP90 degradation, thus limiting NOS3 activation. Ji et al. (2007)
concluded that beta-actin regulates NO formation and signaling in
platelets.
The mammalian cytoskeletal proteins beta- and gamma-actin are highly
homologous, but only beta-actin is N-terminally arginylated in vivo,
which regulates its function. Zhang et al. (2010) examined the metabolic
fate of exogenously expressed arginylated and nonarginylated actin
isoforms. Arginylated gamma-actin, unlike beta-actin, was highly
unstable and was selectively ubiquitinated and degraded in vivo. This
instability was regulated by the differences in the nucleotide coding
sequence between the 2 actin isoforms, which conferred different
translation rates. Gamma-actin was translated more slowly than
beta-actin, and this slower processing resulted in the exposure of a
normally hidden lysine residue for ubiquitination, leading to the
preferential degradation of gamma-actin upon arginylation. Zhang et al.
(2010) suggested that this degradation mechanism, coupled to nucleotide
coding sequence, may regulate protein arginylation in vivo.
Glinka et al. (2010) noted that the beta-actin mRNA binding protein
HNRNPR (607201) has been identified as a partner of the survival motor
neuron protein (SMN1; 600354) that is deficient in spinal muscular
atrophy. They reported that hnRNPR and beta-actin mRNA colocalized in
axons. Recombinant hnRNPR interacted directly with the 3-prime UTR of
beta-actin mRNA. Suppression of hnRNPR in developing zebrafish embryos
resulted in reduced axon growth in spinal motor neurons, without any
alteration in motor neuron survival. ShRNA-mediated knockdown in
isolated embryonic mouse motor neurons reduced beta-actin mRNA
translocation to the axonal growth cone, which was paralleled by reduced
axon elongation. Dendrite growth and neuronal survival were not affected
by hnRNPR depletion in these neurons. The loss of beta-actin mRNA in
axonal growth cones of hnRNPR-depleted motor neurons resembled that
observed in Smn-deficient motor neurons, a model for the human disease
spinal muscular atrophy. In particular, hnRNPR-depleted motor neurons
also exhibited defects in presynaptic clustering of voltage-gated
calcium channels. Glinka et al. (2010) suggested that hnRNPR-mediated
axonal beta-actin mRNA translocation may play an essential physiologic
role in axon growth and presynaptic differentiation.
- Pseudogenes
Ng et al. (1985, 1985) showed that there are about 20 pseudogenes widely
distributed in the genome. ACTBP1 is on Xq13-q22; ACTBP2, on chromosome
5; ACTBP3, on chromosome 18; ACTBP4, on chromosome 5 and ACTBP5, on
7q22-7qter. All have been mapped in somatic cell hybrids by use of DNA
clones.
MOLECULAR GENETICS
- Juvenile-Onset Dystonia
In the monozygotic twins reported by Gearing et al. (2002) with
juvenile-onset dystonia (607371), Procaccio et al. (2006) identified a
point mutation in the beta-actin gene that resulted in
arginine-to-tryptophan substitution at position 183 (102630.0001). The
disease phenotype included developmental midline malformations, sensory
hearing loss, and a delayed-onset generalized dystonia syndrome.
Cellular studies of a lymphoblastoid cell line obtained from an affected
patient demonstrated morphologic abnormalities of the actin cytoskeleton
and altered actin depolymerization dynamics in response to latrunculin
A, an actin monomer-sequestering drug. Resistance to latrunculin A was
also observed in NIH 3T3 cells expressing the mutant actin. These
findings suggested that mutations in nonmuscle actins may be associated
with a broad spectrum of developmental malformations and/or neurologic
abnormalities such as dystonia.
Riviere et al. (2012) suggested that this report should be interpreted
with caution given the absence of replication studies and unavailability
of parental DNA.
- Baraitser-Winter Syndrome 1
Riviere et al. (2012) identified heterozygous missense mutations in 10
of 18 patients with Baraitser-Winter syndrome-1 (BRWS1; 243310). In all
cases where parental DNA was available the mutation was shown to have
occurred de novo. Seven of the 10 patients carried a recurrent
arg196-to-his mutation (102630.0002). One carried a different mutation
at the same codon, arg196-to-cys (102630.0003), and the other 2 patients
carried different de novo missense mutations in the ACTB gene.
In a 7-year-old girl with atypical Baraitser-Winter syndrome-1, who did
not exhibit lissencephaly or seizures, Johnston et al. (2013) identified
a de novo missense mutation in the ACTB gene (E117K; 102630.0006).
*FIELD* AV
.0001
DYSTONIA, JUVENILE-ONSET
ACTB, ARG183TRP
In the twins with juvenile-onset dystonia (607371) originally described
by Gearing et al. (2002), Procaccio et al. (2006) detected a
heterozygous arg183-to-trp (R183W) mutation in the ACTB gene. The amino
acid substitution was the result of a 547C-T transition in exon 4. The
constellation of malformations exhibited by the patients resembled Opitz
syndrome (300000), but no mutations were found in the MID1 gene (300552)
and no evidence was found for involvement of genes causing the autosomal
form of Opitz syndrome. No mutations in ACTB were identified in the
mother and 2 half brothers. Paternal samples were not available for
analysis.
Riviere et al. (2012) suggested that this report should be interpreted
with caution given the absence of replication studies and unavailability
of parental DNA.
.0002
BARAITSER-WINTER SYNDROME 1
ACTB, ARG196HIS
In 7 of 10 patients with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a heterozygous G-to-A transition at
nucleotide 587 of the ACTB gene, resulting in an arg-to-his substitution
at codon 196 (R196H). In 2 patients from whom parental DNA was available
the mutation was determined to have occurred de novo. This mutation was
not identified in 212 other exomes. Lymphoblastoid cell lines
established from patients carrying this mutation had greatly increased
F-actin content and multiple, anomalous F-actin-rich, filopodia-like
protrusions compared to control cells, resulting in an increased cell
perimeter.
One of the patients found by Riviere et al. (2012) to carry the R196H
mutation had been described by Fryns and Aftimos (2000) as patient 1 in
the original report of Fryns-Aftimos syndrome (606155).
.0003
BARAITSER-WINTER SYNDROME 1
ACTB, ARG196CYS
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a heterozygous C-to-T transition at
nucleotide 586 of the ACTB gene, resulting in an arg-to-cys substitution
at codon 196 (R196C). This mutation was not found in 214 other exomes.
.0004
BARAITSER-WINTER SYNDROME 1
ACTB, LEU65VAL
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a de novo mutation, a heterozygous
C-to-G transversion at nucleotide 193 of the ACTB gene resulting in a
leu-to-val substitution at codon 65 (L65V). This mutation was not
identified in 244 other exomes.
.0005
BARAITSER-WINTER SYNDROME 1
ACTB, ASN12ASP
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a de novo mutation, a heterozygous
A-to-G transition at nucleotide 34 of the ACTB gene resulting in an
asn-to-asp substitution at codon 12 (N12D). This mutation was not
identified in 24 other exomes.
.0006
BARAITSER-WINTER SYNDROME 1, ATYPICAL
ACTB, GLU117LYS
In a 7-year-old girl with atypical Baraitser-Winter syndrome-1 (243310),
who had microcephaly, intellectual disability, and facial dysmorphism
but no lissencephaly or seizures, Johnston et al. (2013) identified
heterozygosity for a de novo c.349G-A transition in the ACTB gene,
resulting in a glu117-to-lys (E117K) substitution. The mutation was not
present in either of her unaffected parents. Patient lymphocytes
demonstrated significantly decreased ability to adhere to a
fibronectin-coated surface and formed few actin-rich protrusions
compared to the parents' lymphocytes. Studies in yeast showed virtually
complete loss of normal polarization of the cytoskeleton with the
mutant, and mutant cells were almost completely resistant to the
depolymerizing agent latrunculin A, suggesting that E117K might result
in strengthened actin monomer-monomer interactions and increased
filament stability.
*FIELD* SA
Erba et al. (1988); Kedes et al. (1985); Nakajima-Iijima et al. (1985)
*FIELD* RF
1. Erba, H. P.; Eddy, R.; Shows, T.; Kedes, L.; Gunning, P.: Structure,
chromosome location, and expression of the human gamma-actin gene:
differential evolution, location, and expression of the cytoskeletal
beta- and gamma-actin genes. Molec. Cell. Biol. 8: 1775-1789, 1988.
2. Fryns, J.-P.; Aftimos, S.: New MR/MCA syndrome with distinct facial
appearance and general habitus, broad and webbed neck, hypoplastic
inverted nipples, epilepsy, and pachygyria of the frontal lobes. (Letter) J.
Med. Genet. 37: 460-462, 2000.
3. Gearing, M.; Juncos, J. L.; Procaccio, V.; Gutekunst, C.-A.; Marino-Rodriguez,
E. M.; Gyure, K. A.; Ono, S.; Santoianni, R.; Krawiecki, N. S.; Wallace,
D. C.; Wainer, B. H.: Aggregation of actin and cofilin in identical
twins with juvenile-onset dystonia. Ann. Neurol. 52: 465-476, 2002.
4. Glinka, M.; Herrmann, T.; Funk, N.; Havlicek, S.; Rossoll, W.;
Winkler, C.; Sendtner, M.: The heterogeneous nuclear ribonucleoprotein-R
is necessary for axonal beta-actin mRNA translocation in spinal motor
neurons. Hum. Molec. Genet. 19: 1951-1966, 2010.
5. Gunning, P.; Ponte, P.; Okayama, H.; Engel, J.; Blau, H.; Kedes,
L.: Isolation and characterization of full-length cDNA clones for
human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic
actins have an amino-terminal cysteine that is subsequently removed. Molec.
Cell. Biol. 3: 787-795, 1983.
6. Habets, G. G. M.; van der Kammen, R. A.; Willemsen, V.; Balemans,
M.; Wiegant, J.; Collard, J. G.: Sublocalization of an invasion-inducing
locus and other genes on human chromosome 7. Cytogenet. Cell Genet. 60:
200-205, 1992.
7. Huttelmaier, S.; Zenklusen, D.; Lederer, M.; Dictenberg, J.; Lorenz,
M.; Meng, X.; Bassell, G. J.; Condeelis, J.; Singer, R. H.: Spatial
regulation of beta-actin translation by Src-dependent phosphorylation
of ZBP1. Nature 438: 512-515, 2005.
8. Ji, Y.; Ferracci, G.; Warley, A.; Ward, M.; Leung, K.-Y.; Samsuddin,
S.; Leveque, C.; Queen, L.; Reebye, V.; Pal, P.; Gkaliagkousi, E.;
Seager, M.; Ferro, A.: Beta-actin regulates platelet nitric oxide
synthase 3 activity through interaction with heat shock protein 90. Proc.
Nat. Acad. Sci. 104: 8839-8844, 2007.
9. Johnston, J. J.; Wen, K.-K.; Keppler-Noreuil, K.; McKane, M.; Maiers,
J. L.; Greiner, A.; Sapp, J. C.; NIH Intramural Sequencing Center;
DeMali K. A.; Rubenstein, P. A.; Biesecker, L. G.: Functional analysis
of a de novo ACTB mutation in a patient with atypical Baraitser-Winter
syndrome. Hum. Mutat. 34: 1242-1249, 2013.
10. Karakozova, M.; Kozak, M.; Wong, C. C. L.; Bailey, A. O.; Yates,
J. R, III; Mogilner, A.; Zebroski, H.; Kashina, A.: Arginylation
of beta-actin regulates actin cytoskeleton and cell motility. Science 313:
192-196, 2006.
11. Kedes, L.; Ng, S.-Y.; Lin, C.-S.; Gunning, P.; Eddy, R.; Shows,
T.; Leavitt, J.: The human beta-actin multigene family. Trans. Assoc.
Am. Phys. 98: 42-46, 1985.
12. Kusner, D. J.; Barton, J. A.; Wen, K.-K.; Wang, X.; Rubenstein,
P. A.; Iyer, S. S.: Regulation of phospholipase D activity by actin:
actin exerts bidirectional modulation of mammalian phospolipase (sic)
D activity in a polymerization-dependent, isoform-specific manner. J.
Biol. Chem. 277: 50683-50692, 2002.
13. Leavitt, J.; Bushar, G.; Kakunaga, T.; Hamada, H.; Hirakawa, T.;
Goldman, D.; Merril, C.: Variations in expression of mutant beta-actin
accompanying incremental increases in human fibroblast tumorigenicity. Cell 28:
259-268, 1982.
14. Nakajima-Iijima, S.; Hamada, H.; Reddy, P.; Kakunaga, T.: Molecular
structure of the human cytoplasmic beta-actin gene; interspecies homology
of sequences in the introns. Proc. Nat. Acad. Sci. 82: 6133-6137,
1985.
15. Ng, S.-Y.; Gunning, P.; Eddy, R.; Ponte, P.; Leavitt, J.; Kedes,
L.; Shows, T.: Chromosome 7 assignment of the human beta-actin functional
gene (ACTB) and the chromosomal dispersion of pseudogenes. (Abstract) Cytogenet.
Cell Genet. 40: 712 only, 1985.
16. Ng, S.-Y.; Gunning, P.; Eddy, R.; Ponte, P.; Leavitt, J.; Shows,
T.; Kedes, L.: Evolution of the functional human beta-actin gene
and its multi-pseudogene family: conservation of the noncoding regions
and chromosomal dispersion of pseudogenes. Molec. Cell. Biol. 5:
2720-2732, 1985.
17. Procaccio, V.; Salazar, G.; Ono, S.; Styers, M. L.; Gearing, M.;
Davila, A.; Jimenez, R.; Juncos, J.; Gutekunst, C.-A.; Meroni, G.;
Fontanella, B.; Sontag, E.; Sontag, J. M.; Faundez, V.; Wainer, B.
H.: A mutation of beta-actin that alters depolymerization dynamics
is associated with autosomal dominant developmental malformations,
deafness, and dystonia. Am. J. Hum. Genet. 78: 947-960, 2006.
18. Riviere, J.-B.; van Bon, B. W. M.; Hoischen, A.; Kholmanskikh,
S. S.; O'Roak, B. J.; Gilissen, C.; Gijsen, S.; Sullivan, C. T.; Christian,
S. L.; Abdul-Rahman, O. A.; Atkin, J. F.; Chassaing, N.; and 21 others
: De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter
syndrome. Nature Genet. 44: 440-444, 2012.
19. Toyama, S.; Toyama, S.: A variant form of beta-actin in a mutant
of KB cells resistant to cytochalasin B. Cell 37: 609-614, 1984.
20. Ueyama, H.; Inazawa, J.; Nishino, H.; Ohkubo, I.; Miwa, T.: FISH
localization of human cytoplasmic actin genes ACTB to 7p22 and ACTG1
to 17q25 and characterization of related pseudogenes. Cytogenet.
Cell Genet. 74: 221-224, 1996.
21. Vandekerckhove, J.; Weber, K.: Mammalian cytoplasmic actins are
the products of at least two genes and differ in primary structure
in at least 25 identified positions from skeletal muscle actins. Proc.
Nat. Acad. Sci. 75: 1106-1110, 1978.
22. Zhang, F.; Saha, S.; Shabalina, S. A.; Kashina, A.: Differential
arginylation of actin isoforms is regulated by coding sequence-dependent
degradation. Science 329: 1534-1537, 2010.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/7/2013
George E. Tiller - updated: 8/14/2013
Ada Hamosh - updated: 4/18/2012
Ada Hamosh - updated: 11/2/2010
Patricia A. Hartz - updated: 5/29/2008
Patricia A. Hartz - updated: 1/16/2008
Patricia A. Hartz - updated: 10/4/2006
Ada Hamosh - updated: 8/7/2006
Victor A. McKusick - updated: 5/15/2006
Ada Hamosh - updated: 1/30/2006
Mark H. Paalman - edited: 4/18/1997
Mark H. Paalman - edited: 4/10/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 10/07/2013
tpirozzi: 10/7/2013
carol: 8/15/2013
tpirozzi: 8/15/2013
tpirozzi: 8/14/2013
carol: 1/2/2013
alopez: 4/20/2012
alopez: 4/19/2012
terry: 4/18/2012
alopez: 11/9/2010
terry: 11/2/2010
carol: 4/28/2010
mgross: 6/2/2008
terry: 5/29/2008
mgross: 1/25/2008
terry: 1/16/2008
mgross: 10/11/2006
terry: 10/4/2006
alopez: 8/9/2006
terry: 8/7/2006
alopez: 5/17/2006
terry: 5/15/2006
alopez: 1/31/2006
terry: 1/30/2006
mark: 4/18/1997
jenny: 4/10/1997
terry: 1/13/1997
carol: 7/1/1993
supermim: 3/16/1992
carol: 2/29/1992
supermim: 3/20/1990
ddp: 10/26/1989
carol: 5/18/1988
*RECORD*
*FIELD* NO
102630
*FIELD* TI
*102630 ACTIN, BETA; ACTB
;;BETA-ACTIN;;
ACTIN, CYTOPLASMIC, 1
*FIELD* TX
CLONING
read more
From studies of the amino acid sequence of cytoplasmic and muscle
actins, Vandekerckhove and Weber (1978) concluded that mammalian
cytoplasmic actins are the products of 2 different genes and differ by
many amino acids from muscle actin. In a neoplastic cell line resulting
from treatment of cultured human diploid fibroblasts with a chemical
mutagen, Leavitt et al. (1982) observed a mutant form of beta actin.
Toyama and Toyama (1984) isolated and characterized lines of KB cells
resistant to cytochalasin B. They found that one resistant line had an
alteration in beta-actin. Such cells bound less cytochalasin B than did
parental KB cells. The authors suggested that the primary site of action
of cytochalasin B on cell motility processes is beta-actin.
Using chick beta-actin cDNA as probe, Gunning et al. (1983) cloned
beta-actin and gamma-actin (ACTG1; 102560) from a fibroblast cDNA
library. They noted that the N-terminal methionine is
posttranslationally removed from the mature beta- and gamma-actin
proteins.
MAPPING
Ng et al. (1985) assigned the ACTB gene to 7pter-q22 by Southern blot
analysis of DNA from somatic cell hybrids. Habets et al. (1992)
generated hybrids that harbor only specific regions of human chromosome
7 and assigned the ACTB locus to 7p15-p12.
Ueyama et al. (1996) used fluorescence in situ hybridization to map ACTB
to 7p22. By PCR of somatic cell hybrid DNAs, they mapped 4 ACTB
pseudogenes to other chromosomes.
GENE FUNCTION
Interaction of phospholipase D (see PLD1; 602382) with actin
microfilaments regulates cell proliferation, vesicle trafficking, and
secretion. Kusner et al. (2002) found that highly purified globular
actin (G-actin) inhibited both basal and stimulated PLD1 activity,
whereas filamentous actin (F-actin) had the opposite effect.
Actin-induced modulation of PLD1 activity was independent of the
activating stimulus. The effects of actin on PLD1 were isoform specific:
human platelet actin, which exists in a 5:1 ratio of beta- and
gamma-actin, was only 45% as potent and 40% as efficacious as rabbit
skeletal muscle alpha-actin.
Localization of beta-actin mRNA to sites of active actin polymerization
modulates cell migration during embryogenesis, differentiation, and
possibly carcinogenesis. This localization requires the oncofetal
protein ZBP1 (608288), which binds to a conserved 54-nucleotide element
in the 3-prime untranslated region of the beta-actin mRNA known as the
'zipcode.' ZBP1 promotes translocation of the beta-actin transcript to
actin-rich protrusions in primary fibroblasts and neurons. Huttelmaier
et al. (2005) showed that chicken ZBP1 modulates the translation of
beta-actin mRNA. ZBP1 associates with the beta-actin transcript in the
nucleus and prevents premature translation in the cytoplasm by blocking
translation initiation. Translation occurs only when the ZBP1-RNA
complex reaches its destination at the periphery of the cell. At the
endpoint of mRNA transport, the protein kinase Src (190090) promotes
translation by phosphorylating a key tyrosine residue in ZBP1 that is
required for binding to RNA. These sequential events provide both
temporal and spatial control over beta-actin mRNA translation, which is
important for cell migration and neurite outgrowth.
In immunoprecipitation studies of embryonic fibroblasts from wildtype
and knockout mice deficient in the arginylation enzyme Ate1 (607103),
Karakozova et al. (2006) found that approximately 40% of intracellular
beta-actin is arginylated in vivo. In both wildtype and Ate1-null cells
beta-actin was stable, suggesting that arginylation does not induce
beta-actin degradation. Karakozova et al. (2006) found that arginylation
of beta-actin regulates cell motility. The majority of Ate1-null cells
appeared smaller than wildtype cells and were apparently unable to form
a lamella during movement along the substrate. In addition, Ate1-null
cells exhibited apparent defects in ruffling activity and cortical flow.
Karakozova et al. (2006) concluded that arginylation of beta-actin
apparently represents a critical step in the actin N-terminal processing
needed for actin functioning in vivo.
Nitric oxide (NO) is a paracrine mediator of vascular and platelet
function that is produced in the vasculature by NO synthase-3 (NOS3;
163729). Using human platelets, Ji et al. (2007) demonstrated that
polymerization of beta-actin regulated the activation state of NOS3, and
hence NO formation, by altering its binding to heat-shock protein-90
(HSP90, or HSPCA; 140571). NOS3 bound the globular, but not the
filamentous, form of beta-actin, and the affinity of NOS3 for globular
beta-actin was, in turn, increased by HSP90. Formation of this ternary
complex of NOS3, globular beta-actin, and HSP90 increased NOS activity
and cyclic GMP, an index of bioactive NO, and increased the rate of
HSP90 degradation, thus limiting NOS3 activation. Ji et al. (2007)
concluded that beta-actin regulates NO formation and signaling in
platelets.
The mammalian cytoskeletal proteins beta- and gamma-actin are highly
homologous, but only beta-actin is N-terminally arginylated in vivo,
which regulates its function. Zhang et al. (2010) examined the metabolic
fate of exogenously expressed arginylated and nonarginylated actin
isoforms. Arginylated gamma-actin, unlike beta-actin, was highly
unstable and was selectively ubiquitinated and degraded in vivo. This
instability was regulated by the differences in the nucleotide coding
sequence between the 2 actin isoforms, which conferred different
translation rates. Gamma-actin was translated more slowly than
beta-actin, and this slower processing resulted in the exposure of a
normally hidden lysine residue for ubiquitination, leading to the
preferential degradation of gamma-actin upon arginylation. Zhang et al.
(2010) suggested that this degradation mechanism, coupled to nucleotide
coding sequence, may regulate protein arginylation in vivo.
Glinka et al. (2010) noted that the beta-actin mRNA binding protein
HNRNPR (607201) has been identified as a partner of the survival motor
neuron protein (SMN1; 600354) that is deficient in spinal muscular
atrophy. They reported that hnRNPR and beta-actin mRNA colocalized in
axons. Recombinant hnRNPR interacted directly with the 3-prime UTR of
beta-actin mRNA. Suppression of hnRNPR in developing zebrafish embryos
resulted in reduced axon growth in spinal motor neurons, without any
alteration in motor neuron survival. ShRNA-mediated knockdown in
isolated embryonic mouse motor neurons reduced beta-actin mRNA
translocation to the axonal growth cone, which was paralleled by reduced
axon elongation. Dendrite growth and neuronal survival were not affected
by hnRNPR depletion in these neurons. The loss of beta-actin mRNA in
axonal growth cones of hnRNPR-depleted motor neurons resembled that
observed in Smn-deficient motor neurons, a model for the human disease
spinal muscular atrophy. In particular, hnRNPR-depleted motor neurons
also exhibited defects in presynaptic clustering of voltage-gated
calcium channels. Glinka et al. (2010) suggested that hnRNPR-mediated
axonal beta-actin mRNA translocation may play an essential physiologic
role in axon growth and presynaptic differentiation.
- Pseudogenes
Ng et al. (1985, 1985) showed that there are about 20 pseudogenes widely
distributed in the genome. ACTBP1 is on Xq13-q22; ACTBP2, on chromosome
5; ACTBP3, on chromosome 18; ACTBP4, on chromosome 5 and ACTBP5, on
7q22-7qter. All have been mapped in somatic cell hybrids by use of DNA
clones.
MOLECULAR GENETICS
- Juvenile-Onset Dystonia
In the monozygotic twins reported by Gearing et al. (2002) with
juvenile-onset dystonia (607371), Procaccio et al. (2006) identified a
point mutation in the beta-actin gene that resulted in
arginine-to-tryptophan substitution at position 183 (102630.0001). The
disease phenotype included developmental midline malformations, sensory
hearing loss, and a delayed-onset generalized dystonia syndrome.
Cellular studies of a lymphoblastoid cell line obtained from an affected
patient demonstrated morphologic abnormalities of the actin cytoskeleton
and altered actin depolymerization dynamics in response to latrunculin
A, an actin monomer-sequestering drug. Resistance to latrunculin A was
also observed in NIH 3T3 cells expressing the mutant actin. These
findings suggested that mutations in nonmuscle actins may be associated
with a broad spectrum of developmental malformations and/or neurologic
abnormalities such as dystonia.
Riviere et al. (2012) suggested that this report should be interpreted
with caution given the absence of replication studies and unavailability
of parental DNA.
- Baraitser-Winter Syndrome 1
Riviere et al. (2012) identified heterozygous missense mutations in 10
of 18 patients with Baraitser-Winter syndrome-1 (BRWS1; 243310). In all
cases where parental DNA was available the mutation was shown to have
occurred de novo. Seven of the 10 patients carried a recurrent
arg196-to-his mutation (102630.0002). One carried a different mutation
at the same codon, arg196-to-cys (102630.0003), and the other 2 patients
carried different de novo missense mutations in the ACTB gene.
In a 7-year-old girl with atypical Baraitser-Winter syndrome-1, who did
not exhibit lissencephaly or seizures, Johnston et al. (2013) identified
a de novo missense mutation in the ACTB gene (E117K; 102630.0006).
*FIELD* AV
.0001
DYSTONIA, JUVENILE-ONSET
ACTB, ARG183TRP
In the twins with juvenile-onset dystonia (607371) originally described
by Gearing et al. (2002), Procaccio et al. (2006) detected a
heterozygous arg183-to-trp (R183W) mutation in the ACTB gene. The amino
acid substitution was the result of a 547C-T transition in exon 4. The
constellation of malformations exhibited by the patients resembled Opitz
syndrome (300000), but no mutations were found in the MID1 gene (300552)
and no evidence was found for involvement of genes causing the autosomal
form of Opitz syndrome. No mutations in ACTB were identified in the
mother and 2 half brothers. Paternal samples were not available for
analysis.
Riviere et al. (2012) suggested that this report should be interpreted
with caution given the absence of replication studies and unavailability
of parental DNA.
.0002
BARAITSER-WINTER SYNDROME 1
ACTB, ARG196HIS
In 7 of 10 patients with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a heterozygous G-to-A transition at
nucleotide 587 of the ACTB gene, resulting in an arg-to-his substitution
at codon 196 (R196H). In 2 patients from whom parental DNA was available
the mutation was determined to have occurred de novo. This mutation was
not identified in 212 other exomes. Lymphoblastoid cell lines
established from patients carrying this mutation had greatly increased
F-actin content and multiple, anomalous F-actin-rich, filopodia-like
protrusions compared to control cells, resulting in an increased cell
perimeter.
One of the patients found by Riviere et al. (2012) to carry the R196H
mutation had been described by Fryns and Aftimos (2000) as patient 1 in
the original report of Fryns-Aftimos syndrome (606155).
.0003
BARAITSER-WINTER SYNDROME 1
ACTB, ARG196CYS
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a heterozygous C-to-T transition at
nucleotide 586 of the ACTB gene, resulting in an arg-to-cys substitution
at codon 196 (R196C). This mutation was not found in 214 other exomes.
.0004
BARAITSER-WINTER SYNDROME 1
ACTB, LEU65VAL
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a de novo mutation, a heterozygous
C-to-G transversion at nucleotide 193 of the ACTB gene resulting in a
leu-to-val substitution at codon 65 (L65V). This mutation was not
identified in 244 other exomes.
.0005
BARAITSER-WINTER SYNDROME 1
ACTB, ASN12ASP
In an individual with Baraitser-Winter syndrome-1 (BRWS1; 243310),
Riviere et al. (2012) identified a de novo mutation, a heterozygous
A-to-G transition at nucleotide 34 of the ACTB gene resulting in an
asn-to-asp substitution at codon 12 (N12D). This mutation was not
identified in 24 other exomes.
.0006
BARAITSER-WINTER SYNDROME 1, ATYPICAL
ACTB, GLU117LYS
In a 7-year-old girl with atypical Baraitser-Winter syndrome-1 (243310),
who had microcephaly, intellectual disability, and facial dysmorphism
but no lissencephaly or seizures, Johnston et al. (2013) identified
heterozygosity for a de novo c.349G-A transition in the ACTB gene,
resulting in a glu117-to-lys (E117K) substitution. The mutation was not
present in either of her unaffected parents. Patient lymphocytes
demonstrated significantly decreased ability to adhere to a
fibronectin-coated surface and formed few actin-rich protrusions
compared to the parents' lymphocytes. Studies in yeast showed virtually
complete loss of normal polarization of the cytoskeleton with the
mutant, and mutant cells were almost completely resistant to the
depolymerizing agent latrunculin A, suggesting that E117K might result
in strengthened actin monomer-monomer interactions and increased
filament stability.
*FIELD* SA
Erba et al. (1988); Kedes et al. (1985); Nakajima-Iijima et al. (1985)
*FIELD* RF
1. Erba, H. P.; Eddy, R.; Shows, T.; Kedes, L.; Gunning, P.: Structure,
chromosome location, and expression of the human gamma-actin gene:
differential evolution, location, and expression of the cytoskeletal
beta- and gamma-actin genes. Molec. Cell. Biol. 8: 1775-1789, 1988.
2. Fryns, J.-P.; Aftimos, S.: New MR/MCA syndrome with distinct facial
appearance and general habitus, broad and webbed neck, hypoplastic
inverted nipples, epilepsy, and pachygyria of the frontal lobes. (Letter) J.
Med. Genet. 37: 460-462, 2000.
3. Gearing, M.; Juncos, J. L.; Procaccio, V.; Gutekunst, C.-A.; Marino-Rodriguez,
E. M.; Gyure, K. A.; Ono, S.; Santoianni, R.; Krawiecki, N. S.; Wallace,
D. C.; Wainer, B. H.: Aggregation of actin and cofilin in identical
twins with juvenile-onset dystonia. Ann. Neurol. 52: 465-476, 2002.
4. Glinka, M.; Herrmann, T.; Funk, N.; Havlicek, S.; Rossoll, W.;
Winkler, C.; Sendtner, M.: The heterogeneous nuclear ribonucleoprotein-R
is necessary for axonal beta-actin mRNA translocation in spinal motor
neurons. Hum. Molec. Genet. 19: 1951-1966, 2010.
5. Gunning, P.; Ponte, P.; Okayama, H.; Engel, J.; Blau, H.; Kedes,
L.: Isolation and characterization of full-length cDNA clones for
human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic
actins have an amino-terminal cysteine that is subsequently removed. Molec.
Cell. Biol. 3: 787-795, 1983.
6. Habets, G. G. M.; van der Kammen, R. A.; Willemsen, V.; Balemans,
M.; Wiegant, J.; Collard, J. G.: Sublocalization of an invasion-inducing
locus and other genes on human chromosome 7. Cytogenet. Cell Genet. 60:
200-205, 1992.
7. Huttelmaier, S.; Zenklusen, D.; Lederer, M.; Dictenberg, J.; Lorenz,
M.; Meng, X.; Bassell, G. J.; Condeelis, J.; Singer, R. H.: Spatial
regulation of beta-actin translation by Src-dependent phosphorylation
of ZBP1. Nature 438: 512-515, 2005.
8. Ji, Y.; Ferracci, G.; Warley, A.; Ward, M.; Leung, K.-Y.; Samsuddin,
S.; Leveque, C.; Queen, L.; Reebye, V.; Pal, P.; Gkaliagkousi, E.;
Seager, M.; Ferro, A.: Beta-actin regulates platelet nitric oxide
synthase 3 activity through interaction with heat shock protein 90. Proc.
Nat. Acad. Sci. 104: 8839-8844, 2007.
9. Johnston, J. J.; Wen, K.-K.; Keppler-Noreuil, K.; McKane, M.; Maiers,
J. L.; Greiner, A.; Sapp, J. C.; NIH Intramural Sequencing Center;
DeMali K. A.; Rubenstein, P. A.; Biesecker, L. G.: Functional analysis
of a de novo ACTB mutation in a patient with atypical Baraitser-Winter
syndrome. Hum. Mutat. 34: 1242-1249, 2013.
10. Karakozova, M.; Kozak, M.; Wong, C. C. L.; Bailey, A. O.; Yates,
J. R, III; Mogilner, A.; Zebroski, H.; Kashina, A.: Arginylation
of beta-actin regulates actin cytoskeleton and cell motility. Science 313:
192-196, 2006.
11. Kedes, L.; Ng, S.-Y.; Lin, C.-S.; Gunning, P.; Eddy, R.; Shows,
T.; Leavitt, J.: The human beta-actin multigene family. Trans. Assoc.
Am. Phys. 98: 42-46, 1985.
12. Kusner, D. J.; Barton, J. A.; Wen, K.-K.; Wang, X.; Rubenstein,
P. A.; Iyer, S. S.: Regulation of phospholipase D activity by actin:
actin exerts bidirectional modulation of mammalian phospolipase (sic)
D activity in a polymerization-dependent, isoform-specific manner. J.
Biol. Chem. 277: 50683-50692, 2002.
13. Leavitt, J.; Bushar, G.; Kakunaga, T.; Hamada, H.; Hirakawa, T.;
Goldman, D.; Merril, C.: Variations in expression of mutant beta-actin
accompanying incremental increases in human fibroblast tumorigenicity. Cell 28:
259-268, 1982.
14. Nakajima-Iijima, S.; Hamada, H.; Reddy, P.; Kakunaga, T.: Molecular
structure of the human cytoplasmic beta-actin gene; interspecies homology
of sequences in the introns. Proc. Nat. Acad. Sci. 82: 6133-6137,
1985.
15. Ng, S.-Y.; Gunning, P.; Eddy, R.; Ponte, P.; Leavitt, J.; Kedes,
L.; Shows, T.: Chromosome 7 assignment of the human beta-actin functional
gene (ACTB) and the chromosomal dispersion of pseudogenes. (Abstract) Cytogenet.
Cell Genet. 40: 712 only, 1985.
16. Ng, S.-Y.; Gunning, P.; Eddy, R.; Ponte, P.; Leavitt, J.; Shows,
T.; Kedes, L.: Evolution of the functional human beta-actin gene
and its multi-pseudogene family: conservation of the noncoding regions
and chromosomal dispersion of pseudogenes. Molec. Cell. Biol. 5:
2720-2732, 1985.
17. Procaccio, V.; Salazar, G.; Ono, S.; Styers, M. L.; Gearing, M.;
Davila, A.; Jimenez, R.; Juncos, J.; Gutekunst, C.-A.; Meroni, G.;
Fontanella, B.; Sontag, E.; Sontag, J. M.; Faundez, V.; Wainer, B.
H.: A mutation of beta-actin that alters depolymerization dynamics
is associated with autosomal dominant developmental malformations,
deafness, and dystonia. Am. J. Hum. Genet. 78: 947-960, 2006.
18. Riviere, J.-B.; van Bon, B. W. M.; Hoischen, A.; Kholmanskikh,
S. S.; O'Roak, B. J.; Gilissen, C.; Gijsen, S.; Sullivan, C. T.; Christian,
S. L.; Abdul-Rahman, O. A.; Atkin, J. F.; Chassaing, N.; and 21 others
: De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter
syndrome. Nature Genet. 44: 440-444, 2012.
19. Toyama, S.; Toyama, S.: A variant form of beta-actin in a mutant
of KB cells resistant to cytochalasin B. Cell 37: 609-614, 1984.
20. Ueyama, H.; Inazawa, J.; Nishino, H.; Ohkubo, I.; Miwa, T.: FISH
localization of human cytoplasmic actin genes ACTB to 7p22 and ACTG1
to 17q25 and characterization of related pseudogenes. Cytogenet.
Cell Genet. 74: 221-224, 1996.
21. Vandekerckhove, J.; Weber, K.: Mammalian cytoplasmic actins are
the products of at least two genes and differ in primary structure
in at least 25 identified positions from skeletal muscle actins. Proc.
Nat. Acad. Sci. 75: 1106-1110, 1978.
22. Zhang, F.; Saha, S.; Shabalina, S. A.; Kashina, A.: Differential
arginylation of actin isoforms is regulated by coding sequence-dependent
degradation. Science 329: 1534-1537, 2010.
*FIELD* CN
Marla J. F. O'Neill - updated: 10/7/2013
George E. Tiller - updated: 8/14/2013
Ada Hamosh - updated: 4/18/2012
Ada Hamosh - updated: 11/2/2010
Patricia A. Hartz - updated: 5/29/2008
Patricia A. Hartz - updated: 1/16/2008
Patricia A. Hartz - updated: 10/4/2006
Ada Hamosh - updated: 8/7/2006
Victor A. McKusick - updated: 5/15/2006
Ada Hamosh - updated: 1/30/2006
Mark H. Paalman - edited: 4/18/1997
Mark H. Paalman - edited: 4/10/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 10/07/2013
tpirozzi: 10/7/2013
carol: 8/15/2013
tpirozzi: 8/15/2013
tpirozzi: 8/14/2013
carol: 1/2/2013
alopez: 4/20/2012
alopez: 4/19/2012
terry: 4/18/2012
alopez: 11/9/2010
terry: 11/2/2010
carol: 4/28/2010
mgross: 6/2/2008
terry: 5/29/2008
mgross: 1/25/2008
terry: 1/16/2008
mgross: 10/11/2006
terry: 10/4/2006
alopez: 8/9/2006
terry: 8/7/2006
alopez: 5/17/2006
terry: 5/15/2006
alopez: 1/31/2006
terry: 1/30/2006
mark: 4/18/1997
jenny: 4/10/1997
terry: 1/13/1997
carol: 7/1/1993
supermim: 3/16/1992
carol: 2/29/1992
supermim: 3/20/1990
ddp: 10/26/1989
carol: 5/18/1988
MIM
243310
*RECORD*
*FIELD* NO
243310
*FIELD* TI
#243310 BARAITSER-WINTER SYNDROME 1; BRWS1
;;IRIS COLOBOMA WITH PTOSIS, HYPERTELORISM, AND MENTAL RETARDATION
read more*FIELD* TX
A number sign (#) is used with this entry because Baraitser-Winter
syndrome-1 (BRWS1) is caused by heterozygous mutation in the ACTB gene
(102630) on chromosome 7p22-p12.
DESCRIPTION
Baraitser-Winter syndrome is a rare but well-defined developmental
disorder recognized by the combination of congenital ptosis, high-arched
eyebrows, hypertelorism, ocular colobomata, and a brain malformation
consisting of anterior-predominant lissencephaly. Other typical features
include postnatal short stature and microcephaly, intellectual
disability, seizures, and hearing loss (summary by Riviere et al.,
2012).
- Genetic Heterogeneity of Baraitser-Winter Syndrome
Baraitser-Winter syndrome-2 (BRWS2; 614583) is caused by heterozygous
mutation in the ACTG1 gene (102560) on chromosome 17q25.3.
CLINICAL FEATURES
In a girl with unrelated parents, Baraitser and Winter (1988) described
a seemingly distinct syndrome of iris coloboma, bilateral ptosis,
hypertelorism, broad nasal bridge, prominent epicanthal folds, short
stature, and mental retardation. This report also contained the
description of sibs with similar features who, based on a comparison of
phenotypic features and inheritance patterns, Riviere et al. (2012)
suggested did not have Baraitser-Winter syndrome.
Riviere et al. (2012) reported on 10 children with Baraitser-Winter
syndrome and mutations in the ACTB gene. Six of the 10 had short
stature; 6 of 9 evaluated had postnatal microcephaly; all 9 evaluated
had intellectual disability and seizures, and 4 of 8 had hearing loss; 8
of 10 had trigonocephaly; all 10 had hypertelorism and congenital
ptosis, and 9 had high-arched eyebrows. Colobomata of the iris or retina
were present in 6 of 10 and all 8 for whom data were available had
anterior-to-posterior gradient lissencephaly of the pachygyria or
pachygyria-band type. Neither familial recurrence nor consanguinity had
been observed in any families, including the 18 reported by them, and no
pathogenic copy-number variants had been detected using chromosome
microarrays.
- Phenotypic Overlap with Fryns-Aftimos Syndrome
Riviere et al. (2012) noted substantial phenotypic overlap between
Baraitser-Winter syndrome and some patients with Fryns-Aftimos syndrome
(606155), including trigonocephaly, hypertelorism, congenital ptosis,
high-arched eyebrows, broad nose, and low-set posteriorly rotated
malformed ears; both have predominantly proximal contractures and a
cortical malformation. One subject (11-11287), reported as patient 1 in
the original report of Fryns and Aftimos (2000), was found by Riviere et
al. (2012) to carry a mutation in the ACTB gene (102630.0002).
- Phenotypic Overlap with Dubowitz Syndrome
Johnston et al. (2013) described a 7-year-old girl with microcephaly,
dysmorphic facial features, and intellectual disability, who was
initially given a clinical diagnosis of Dubowitz syndrome (223370). At
birth she was noted to have low-set ears, unilateral ptosis, low
anterior hairline, and mild hypertrichosis. MRI of the brain at age 34
months was normal as was renal ultrasound and skeletal survey.
Examination at age 4.5 years showed metopic ridging with apparent
microcephaly and hoarse voice. Craniofacial findings included asymmetric
positioning of the globes with left ptosis, short palpebral fissures,
and apparent widely spaced eyes; posteriorly rotated ears with
abnormally shaped pinnae; broad nasal root, long columella, and alae
nasae flaring; prominent tongue, wide mouth, and bifid uvula. Limb
findings included distally placed thumbs, small thenar eminence,
camptodactlyly of digits 3, 4, and 5, and prominent fingertip pads. At
age 7 years age, she was noted to have obsessive-compulsive behaviors
and hyperactivity as well as severe myopia in her right eye, optic nerve
asymmetry, and mild conductive hearing loss. Left vertical talus had
been treated. Upon discovery of a mutation in the ACTB gene (see
MOLECULAR GENETICS), her diagnosis was changed to atypical
Baraitser-Winter syndrome, given the absence of some of the
characteristic findings of BRWS including lissencephaly, seizures, and
iris/retinal coloboma.
INHERITANCE
Riviere et al. (2012) reported that, with one exception, all reported
patients with Baraitser-Winter syndrome have been sporadic. They
considered it likely that the sibs included in the original report
(Baraitser and Winter, 1988) did not have Baraitser-Winter syndrome (see
HISTORY).
CYTOGENETICS
Pallotta (1991) reported this phenotype in a 6-year-old male with a
pericentric inversion of chromosome 2: inv(2)(p12q14). The chromosomal
rearrangement had been inherited from his mother, who was phenotypically
normal. They pointed to a case reported by Ayme et al. (1979) in which a
similar phenotype was associated with a similar pericentric inversion.
Again, the mother, who was phenotypically normal, had the same
chromosomal rearrangement. The possibility that an odd number of
crossovers in the 'inversion loops' of chromosome 2 caused a very small
duplication or deletion of chromosomal material in the affected
offspring was raised by Pallotta (1991).
Ramer et al. (1995) reported that 2 of 9 children, most of whom shared
the features of shallow orbits, ptosis, coloboma, trigonocephaly, gyral
malformations, and mental and growth retardation, had identical
pericentric inversions involving 2p12-q14. Ramer et al. (1995) noted
that the PAX8 gene (167415) maps to 2q12-q14, a site coincident with the
distal breakpoint of the inversions identified in the children reported
by Ayme et al. (1979) and Pallotta (1991).
MOLECULAR GENETICS
Riviere et al. (2012) performed whole-exome sequencing in 3
proband-parent trios and identified de novo missense changes in the
cytoplasmic actin-coding genes ACTB and ACTG1 (102560) in 1 and 2
probands, respectively. The ACTB mutation in the proband was a missense
mutation, arg196-to-his (R196H; 102630.0002), that was also found in 6
of 15 additional affected individuals. Three additional de novo missense
mutations were identified in the ACTB gene in that cohort.
In a 7-year-old girl with microcephaly, dysmorphic facial features
including ptosis and low-set ears, and intellectual disability, who was
initially given a clinical diagnosis of Dubowitz syndrome (223370),
Johnston et al. (2013) identified a de novo missense mutation in the
ACTB gene (E117K; 102630.0006) and concluded that the patient had an
atypical form of Baraitser-Winter syndrome without lissencephaly,
seizures, or iris/retinal coloboma.
HISTORY
Two of the children reported by Baraitser and Winter (1988) were sibs,
which is consistent with autosomal recessive inheritance but does not
exclude a submicroscopic abnormality of chromosome structure. Sib
occurrence with apparently normal parents may also represent germinal
mosaicism in one parent.
Riviere et al. (2012) reviewed the only report of affected sibs,
patients 1 and 2 of Baraitser and Winter (1988), a brother and sister
born to unrelated Asian parents. These patients both had iris
colobomata, but both had normal head size and normal metopic region with
no trigonocephaly, as well as normal ears and hearing. Brain imaging was
not performed. Riviere et al. (2012) remarked that this family was lost
to follow-up, and a cryptic chromosomal imbalance was not excluded.
Considering their findings, Riviere et al. (2012) concluded that these 2
sibs should probably not be considered as having Baraitser-Winter
syndrome. Patient 3 of the original report was found to have a mutation
in the ACTG1 gene (102560.0009).
*FIELD* RF
1. Ayme, S.; Mattei, M. G.; Mattei, J. F.; Giraud, F.: Abnormal childhood
phenotypes associated with the same balanced chromosome rearrangements
as in the parents. Hum. Genet. 48: 7-12, 1979.
2. Baraitser, M.; Winter, R. M.: Iris coloboma, ptosis, hypertelorism,
and mental retardation: a new syndrome. J. Med. Genet. 25: 41-43,
1988.
3. Fryns, J.-P.; Aftimos, S.: New MR/MCA syndrome with distinct facial
appearance and general habitus, broad and webbed neck, hypoplastic
inverted nipples, epilepsy, and pachygyria of the frontal lobes. (Letter) J.
Med. Genet. 37: 460-462, 2000.
4. Johnston, J. J.; Wen, K.-K.; Keppler-Noreuil, K.; McKane, M.; Maiers,
J. L.; Greiner, A.; Sapp, J. C.; NIH Intramural Sequencing Center;
Rubenstein, P. A.; Biesecker, L. G.: Functional analysis of a de
novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome. Hum.
Mutat. 34: 1242-1249, 2013.
5. Pallotta, R.: Iris coloboma, ptosis, hypertelorism, and mental
retardation: a new syndrome possibly localised on chromosome 2. J.
Med. Genet. 28: 342-344, 1991.
6. Ramer, J. C.; Lin, A. E.; Dobyns, W. B.; Winter, R.; Ayme, S.;
Pallotta, R.; Ladda, R. L.: Previously apparently undescribed syndrome:
shallow orbits, ptosis, coloboma, trigonocephaly, gyral malformations,
and mental and growth retardation. Am. J. Med. Genet. 57: 403-409,
1995.
7. Riviere, J.-B.; van Bon, B. W. M.; Hoischen, A.; Kholmanskikh,
S. S.; O'Roak, B. J.; Gilissen, C.; Gijsen, S.; Sullivan, C. T.; Christian,
S. L.; Abdul-Rahman, O. A.; Atkin, J. F.; Chassaing, N.; and 21 others
: De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter
syndrome. Nature Genet. 44: 440-444, 2012.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GROWTH:
[Height];
Short stature;
Height in childhood <5th percentile;
[Weight];
Weight in childhood <5th percentile;
[Other];
Postnatal growth retardation
HEAD AND NECK:
[Head];
Metopic ridging;
Trigonocephaly;
Microcephaly;
[Face];
Long philtrum;
[Ears];
Low-set ears;
Overfolded helices;
Hearing loss, sensorineural;
[Eyes];
Ptosis;
Hypertelorism;
Prominent epicanthal folds;
Iris coloboma;
Chorioretinal coloboma;
[Nose];
Broad nasal bridge;
Short nose;
[Mouth];
Thin upper lip;
Large mouth;
[Neck];
Short neck
CARDIOVASCULAR:
[Heart];
Bicuspid aortic valve;
Aortic stenosis;
[Vascular];
Patent ductus arteriosus
GENITOURINARY:
[External genitalia, male];
Small penis;
[Internal genitalia, male];
Cryptorchidism
SKIN, NAILS, HAIR:
[Hair];
Low posterior hair line
NEUROLOGIC:
[Central nervous system];
Developmental delay;
Hypotonia;
Seizures;
Agenesis of corpus callosum;
Focal pachygyria;
Lissencephaly
LABORATORY ABNORMALITIES:
chromosome inversion - inv2(p12q14) in 2 patients
MOLECULAR BASIS:
Caused by mutation in the beta actin gene (ACTB, 102630.0002)
*FIELD* CN
Ada Hamosh - updated: 05/15/2012
Kelly A. Przylepa - revised: 2/22/2007
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 05/15/2012
ckniffin: 5/22/2007
joanna: 3/2/2007
joanna: 2/22/2007
*FIELD* CN
Marla J. F. O'Neill - updated: 10/7/2013
Ada Hamosh - updated: 4/18/2012
*FIELD* CD
Victor A. McKusick: 2/23/1988
*FIELD* ED
carol: 10/07/2013
tpirozzi: 10/7/2013
alopez: 4/19/2012
terry: 4/18/2012
carol: 4/6/2012
mark: 7/16/1995
mimadm: 2/19/1994
supermim: 3/16/1992
carol: 6/18/1991
carol: 6/10/1991
supermim: 3/20/1990
*RECORD*
*FIELD* NO
243310
*FIELD* TI
#243310 BARAITSER-WINTER SYNDROME 1; BRWS1
;;IRIS COLOBOMA WITH PTOSIS, HYPERTELORISM, AND MENTAL RETARDATION
read more*FIELD* TX
A number sign (#) is used with this entry because Baraitser-Winter
syndrome-1 (BRWS1) is caused by heterozygous mutation in the ACTB gene
(102630) on chromosome 7p22-p12.
DESCRIPTION
Baraitser-Winter syndrome is a rare but well-defined developmental
disorder recognized by the combination of congenital ptosis, high-arched
eyebrows, hypertelorism, ocular colobomata, and a brain malformation
consisting of anterior-predominant lissencephaly. Other typical features
include postnatal short stature and microcephaly, intellectual
disability, seizures, and hearing loss (summary by Riviere et al.,
2012).
- Genetic Heterogeneity of Baraitser-Winter Syndrome
Baraitser-Winter syndrome-2 (BRWS2; 614583) is caused by heterozygous
mutation in the ACTG1 gene (102560) on chromosome 17q25.3.
CLINICAL FEATURES
In a girl with unrelated parents, Baraitser and Winter (1988) described
a seemingly distinct syndrome of iris coloboma, bilateral ptosis,
hypertelorism, broad nasal bridge, prominent epicanthal folds, short
stature, and mental retardation. This report also contained the
description of sibs with similar features who, based on a comparison of
phenotypic features and inheritance patterns, Riviere et al. (2012)
suggested did not have Baraitser-Winter syndrome.
Riviere et al. (2012) reported on 10 children with Baraitser-Winter
syndrome and mutations in the ACTB gene. Six of the 10 had short
stature; 6 of 9 evaluated had postnatal microcephaly; all 9 evaluated
had intellectual disability and seizures, and 4 of 8 had hearing loss; 8
of 10 had trigonocephaly; all 10 had hypertelorism and congenital
ptosis, and 9 had high-arched eyebrows. Colobomata of the iris or retina
were present in 6 of 10 and all 8 for whom data were available had
anterior-to-posterior gradient lissencephaly of the pachygyria or
pachygyria-band type. Neither familial recurrence nor consanguinity had
been observed in any families, including the 18 reported by them, and no
pathogenic copy-number variants had been detected using chromosome
microarrays.
- Phenotypic Overlap with Fryns-Aftimos Syndrome
Riviere et al. (2012) noted substantial phenotypic overlap between
Baraitser-Winter syndrome and some patients with Fryns-Aftimos syndrome
(606155), including trigonocephaly, hypertelorism, congenital ptosis,
high-arched eyebrows, broad nose, and low-set posteriorly rotated
malformed ears; both have predominantly proximal contractures and a
cortical malformation. One subject (11-11287), reported as patient 1 in
the original report of Fryns and Aftimos (2000), was found by Riviere et
al. (2012) to carry a mutation in the ACTB gene (102630.0002).
- Phenotypic Overlap with Dubowitz Syndrome
Johnston et al. (2013) described a 7-year-old girl with microcephaly,
dysmorphic facial features, and intellectual disability, who was
initially given a clinical diagnosis of Dubowitz syndrome (223370). At
birth she was noted to have low-set ears, unilateral ptosis, low
anterior hairline, and mild hypertrichosis. MRI of the brain at age 34
months was normal as was renal ultrasound and skeletal survey.
Examination at age 4.5 years showed metopic ridging with apparent
microcephaly and hoarse voice. Craniofacial findings included asymmetric
positioning of the globes with left ptosis, short palpebral fissures,
and apparent widely spaced eyes; posteriorly rotated ears with
abnormally shaped pinnae; broad nasal root, long columella, and alae
nasae flaring; prominent tongue, wide mouth, and bifid uvula. Limb
findings included distally placed thumbs, small thenar eminence,
camptodactlyly of digits 3, 4, and 5, and prominent fingertip pads. At
age 7 years age, she was noted to have obsessive-compulsive behaviors
and hyperactivity as well as severe myopia in her right eye, optic nerve
asymmetry, and mild conductive hearing loss. Left vertical talus had
been treated. Upon discovery of a mutation in the ACTB gene (see
MOLECULAR GENETICS), her diagnosis was changed to atypical
Baraitser-Winter syndrome, given the absence of some of the
characteristic findings of BRWS including lissencephaly, seizures, and
iris/retinal coloboma.
INHERITANCE
Riviere et al. (2012) reported that, with one exception, all reported
patients with Baraitser-Winter syndrome have been sporadic. They
considered it likely that the sibs included in the original report
(Baraitser and Winter, 1988) did not have Baraitser-Winter syndrome (see
HISTORY).
CYTOGENETICS
Pallotta (1991) reported this phenotype in a 6-year-old male with a
pericentric inversion of chromosome 2: inv(2)(p12q14). The chromosomal
rearrangement had been inherited from his mother, who was phenotypically
normal. They pointed to a case reported by Ayme et al. (1979) in which a
similar phenotype was associated with a similar pericentric inversion.
Again, the mother, who was phenotypically normal, had the same
chromosomal rearrangement. The possibility that an odd number of
crossovers in the 'inversion loops' of chromosome 2 caused a very small
duplication or deletion of chromosomal material in the affected
offspring was raised by Pallotta (1991).
Ramer et al. (1995) reported that 2 of 9 children, most of whom shared
the features of shallow orbits, ptosis, coloboma, trigonocephaly, gyral
malformations, and mental and growth retardation, had identical
pericentric inversions involving 2p12-q14. Ramer et al. (1995) noted
that the PAX8 gene (167415) maps to 2q12-q14, a site coincident with the
distal breakpoint of the inversions identified in the children reported
by Ayme et al. (1979) and Pallotta (1991).
MOLECULAR GENETICS
Riviere et al. (2012) performed whole-exome sequencing in 3
proband-parent trios and identified de novo missense changes in the
cytoplasmic actin-coding genes ACTB and ACTG1 (102560) in 1 and 2
probands, respectively. The ACTB mutation in the proband was a missense
mutation, arg196-to-his (R196H; 102630.0002), that was also found in 6
of 15 additional affected individuals. Three additional de novo missense
mutations were identified in the ACTB gene in that cohort.
In a 7-year-old girl with microcephaly, dysmorphic facial features
including ptosis and low-set ears, and intellectual disability, who was
initially given a clinical diagnosis of Dubowitz syndrome (223370),
Johnston et al. (2013) identified a de novo missense mutation in the
ACTB gene (E117K; 102630.0006) and concluded that the patient had an
atypical form of Baraitser-Winter syndrome without lissencephaly,
seizures, or iris/retinal coloboma.
HISTORY
Two of the children reported by Baraitser and Winter (1988) were sibs,
which is consistent with autosomal recessive inheritance but does not
exclude a submicroscopic abnormality of chromosome structure. Sib
occurrence with apparently normal parents may also represent germinal
mosaicism in one parent.
Riviere et al. (2012) reviewed the only report of affected sibs,
patients 1 and 2 of Baraitser and Winter (1988), a brother and sister
born to unrelated Asian parents. These patients both had iris
colobomata, but both had normal head size and normal metopic region with
no trigonocephaly, as well as normal ears and hearing. Brain imaging was
not performed. Riviere et al. (2012) remarked that this family was lost
to follow-up, and a cryptic chromosomal imbalance was not excluded.
Considering their findings, Riviere et al. (2012) concluded that these 2
sibs should probably not be considered as having Baraitser-Winter
syndrome. Patient 3 of the original report was found to have a mutation
in the ACTG1 gene (102560.0009).
*FIELD* RF
1. Ayme, S.; Mattei, M. G.; Mattei, J. F.; Giraud, F.: Abnormal childhood
phenotypes associated with the same balanced chromosome rearrangements
as in the parents. Hum. Genet. 48: 7-12, 1979.
2. Baraitser, M.; Winter, R. M.: Iris coloboma, ptosis, hypertelorism,
and mental retardation: a new syndrome. J. Med. Genet. 25: 41-43,
1988.
3. Fryns, J.-P.; Aftimos, S.: New MR/MCA syndrome with distinct facial
appearance and general habitus, broad and webbed neck, hypoplastic
inverted nipples, epilepsy, and pachygyria of the frontal lobes. (Letter) J.
Med. Genet. 37: 460-462, 2000.
4. Johnston, J. J.; Wen, K.-K.; Keppler-Noreuil, K.; McKane, M.; Maiers,
J. L.; Greiner, A.; Sapp, J. C.; NIH Intramural Sequencing Center;
Rubenstein, P. A.; Biesecker, L. G.: Functional analysis of a de
novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome. Hum.
Mutat. 34: 1242-1249, 2013.
5. Pallotta, R.: Iris coloboma, ptosis, hypertelorism, and mental
retardation: a new syndrome possibly localised on chromosome 2. J.
Med. Genet. 28: 342-344, 1991.
6. Ramer, J. C.; Lin, A. E.; Dobyns, W. B.; Winter, R.; Ayme, S.;
Pallotta, R.; Ladda, R. L.: Previously apparently undescribed syndrome:
shallow orbits, ptosis, coloboma, trigonocephaly, gyral malformations,
and mental and growth retardation. Am. J. Med. Genet. 57: 403-409,
1995.
7. Riviere, J.-B.; van Bon, B. W. M.; Hoischen, A.; Kholmanskikh,
S. S.; O'Roak, B. J.; Gilissen, C.; Gijsen, S.; Sullivan, C. T.; Christian,
S. L.; Abdul-Rahman, O. A.; Atkin, J. F.; Chassaing, N.; and 21 others
: De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter
syndrome. Nature Genet. 44: 440-444, 2012.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GROWTH:
[Height];
Short stature;
Height in childhood <5th percentile;
[Weight];
Weight in childhood <5th percentile;
[Other];
Postnatal growth retardation
HEAD AND NECK:
[Head];
Metopic ridging;
Trigonocephaly;
Microcephaly;
[Face];
Long philtrum;
[Ears];
Low-set ears;
Overfolded helices;
Hearing loss, sensorineural;
[Eyes];
Ptosis;
Hypertelorism;
Prominent epicanthal folds;
Iris coloboma;
Chorioretinal coloboma;
[Nose];
Broad nasal bridge;
Short nose;
[Mouth];
Thin upper lip;
Large mouth;
[Neck];
Short neck
CARDIOVASCULAR:
[Heart];
Bicuspid aortic valve;
Aortic stenosis;
[Vascular];
Patent ductus arteriosus
GENITOURINARY:
[External genitalia, male];
Small penis;
[Internal genitalia, male];
Cryptorchidism
SKIN, NAILS, HAIR:
[Hair];
Low posterior hair line
NEUROLOGIC:
[Central nervous system];
Developmental delay;
Hypotonia;
Seizures;
Agenesis of corpus callosum;
Focal pachygyria;
Lissencephaly
LABORATORY ABNORMALITIES:
chromosome inversion - inv2(p12q14) in 2 patients
MOLECULAR BASIS:
Caused by mutation in the beta actin gene (ACTB, 102630.0002)
*FIELD* CN
Ada Hamosh - updated: 05/15/2012
Kelly A. Przylepa - revised: 2/22/2007
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 05/15/2012
ckniffin: 5/22/2007
joanna: 3/2/2007
joanna: 2/22/2007
*FIELD* CN
Marla J. F. O'Neill - updated: 10/7/2013
Ada Hamosh - updated: 4/18/2012
*FIELD* CD
Victor A. McKusick: 2/23/1988
*FIELD* ED
carol: 10/07/2013
tpirozzi: 10/7/2013
alopez: 4/19/2012
terry: 4/18/2012
carol: 4/6/2012
mark: 7/16/1995
mimadm: 2/19/1994
supermim: 3/16/1992
carol: 6/18/1991
carol: 6/10/1991
supermim: 3/20/1990
MIM
607371
*RECORD*
*FIELD* NO
607371
*FIELD* TI
#607371 DYSTONIA, JUVENILE-ONSET
*FIELD* TX
A number sign (#) is used with this entry because the phenotype can be
read morecaused by mutation in the beta-actin gene (ACTB; 102630).
CLINICAL FEATURES
Gearing et al. (2002) reported the cases of male twins with the onset at
age 12 years of rapidly progressive, dopa-unresponsive generalized
dystonia. They found extensive neurologic involvement of the cortex and
basal ganglia of a novel type suggesting that these identical twins
suffered from a degenerative disorder not previously characterized. The
dystonic manifestations in adolescence were heralded by early bulbar
signs that suggested a widespread disorder. The twins were born with
cleft lip and palate requiring multiple repairs. They were small for
age, and their limbs were small in relation to the rest of their bodies.
Skeletal abnormalities included high foreheads, hypoplastic scapulas,
and externally rotated hips. By age 10 years, they began developing
kyphoscoliosis and severe antecolis. Achalasia presented at age 2 years,
requiring surgical repair in 1 twin. One twin developed spontaneous
cataracts, aggravated later by trauma; by age 10 years, he was blind in
1 eye and had limited vision in the other. Vision in the other twin was
not affected. Sensorineural hearing loss in both twins resulted in
functional deafness by age 4 years, significantly affecting their speech
development. Cognition was mildly subnormal but stable until the last
few years. Genetic, metabolic, and imaging studies ruled out known
causes of dystonia. Death occurred at ages 21 and 22 years.
- Neuropathologic Findings
The brains of the twins reported by Gearing et al. (2002) were
macroscopically unremarkable. The most striking findings on microscopic
examination were (1) eosinophilic, rod-like cytoplasmic inclusions in
neocortical and thalamic neurons that were actin depolymerizing
factor/cofilin-immunoreactive but only rarely actin-positive; and (2)
abundant eosinophilic spherical structures in the striatum that were
strongly actin- and actin depolarizing factor/cofilin-positive. Gearing
et al. (2002) stated that aggregation of actin had not previously been
reported as the predominant feature in any neurodegenerative disease.
They suggested that this neuropathologic change associated with dystonia
may represent a new degenerative mechanism involving actin. Since actin
is a ubiquitous constituent of the cytoskeletal system the presence of
congenital anomalies and developmental abnormalities may be explained by
systemic involvement.
MOLECULAR GENETICS
In the monozygotic twins reported by Gearing et al. (2002), Procaccio et
al. (2006) identified a heterozygous missense mutation, arg183 to trp
(102630.0001), in the beta-actin gene as the cause of the neurologic
syndrome.
*FIELD* RF
1. Gearing, M.; Juncos, J. L.; Procaccio, V.; Gutekunst, C.-A.; Marino-Rodriguez,
E. M.; Gyure, K. A.; Ono, S.; Santoianni, R.; Krawiecki, N. S.; Wallace,
D. C.; Wainer, B. H.: Aggregation of actin and cofilin in identical
twins with juvenile-onset dystonia. Ann. Neurol. 52: 465-476, 2002.
2. Procaccio, V.; Salazar, G.; Ono, S.; Styers, M. L.; Gearing, M.;
Davila, A.; Jimenez, R.; Juncos, J.; Gutekunst, C.-A.; Meroni, G.;
Fontanella, B.; Sontag, E.; Sontag, J. M.; Faundez, V.; Wainer, B.
H.: A mutation of beta-actin that alters depolymerization dynamics
is associated with autosomal dominant developmental malformations,
deafness, and dystonia. Am. J. Hum. Genet. 78: 947-960, 2006.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GROWTH:
[Weight];
Low birth weight;
[Other];
Small for age
HEAD AND NECK:
[Head];
High forehead;
[Ears];
Sensorineural hearing loss;
[Eyes];
Cataracts;
Limited vision;
[Mouth];
Cleft lip;
Cleft palate
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Hypoplastic scapulae
ABDOMEN:
[Gastrointestinal];
Achalasia
SKELETAL:
[Spine];
Kyphoscoliosis;
Antecolis;
[Pelvis];
Externally rotated hips
NEUROLOGIC:
[Central nervous system];
Developmental delay, mild;
Dystonia, generalized, dopa-unresponsive;
Subnormal cognition;
Actin depolymerizing factor/cofilin-immunoreactive eosinophilic rod-like
cytoplasmic inclusions in neocortical and thalamic neurons;
Actin- and actin depolymerizing factor/cofilin-immunoreactive eosinophilic
spherical structures in the striatum
MISCELLANEOUS:
Onset of dystonia at 12 years
MOLECULAR BASIS:
Caused by mutation in the beta-actin gene (ACTB, 102630.0001).
*FIELD* CN
Joanna S. Amberger - updated: 07/11/2006
*FIELD* CD
Cassandra L. Kniffin: 11/20/2002
*FIELD* ED
joanna: 07/11/2006
alopez: 5/17/2006
ckniffin: 11/20/2002
*FIELD* CN
Victor A. McKusick - updated: 5/15/2006
*FIELD* CD
Victor A. McKusick: 11/20/2002
*FIELD* ED
alopez: 05/17/2006
terry: 5/15/2006
carol: 11/20/2002
ckniffin: 11/20/2002
*RECORD*
*FIELD* NO
607371
*FIELD* TI
#607371 DYSTONIA, JUVENILE-ONSET
*FIELD* TX
A number sign (#) is used with this entry because the phenotype can be
read morecaused by mutation in the beta-actin gene (ACTB; 102630).
CLINICAL FEATURES
Gearing et al. (2002) reported the cases of male twins with the onset at
age 12 years of rapidly progressive, dopa-unresponsive generalized
dystonia. They found extensive neurologic involvement of the cortex and
basal ganglia of a novel type suggesting that these identical twins
suffered from a degenerative disorder not previously characterized. The
dystonic manifestations in adolescence were heralded by early bulbar
signs that suggested a widespread disorder. The twins were born with
cleft lip and palate requiring multiple repairs. They were small for
age, and their limbs were small in relation to the rest of their bodies.
Skeletal abnormalities included high foreheads, hypoplastic scapulas,
and externally rotated hips. By age 10 years, they began developing
kyphoscoliosis and severe antecolis. Achalasia presented at age 2 years,
requiring surgical repair in 1 twin. One twin developed spontaneous
cataracts, aggravated later by trauma; by age 10 years, he was blind in
1 eye and had limited vision in the other. Vision in the other twin was
not affected. Sensorineural hearing loss in both twins resulted in
functional deafness by age 4 years, significantly affecting their speech
development. Cognition was mildly subnormal but stable until the last
few years. Genetic, metabolic, and imaging studies ruled out known
causes of dystonia. Death occurred at ages 21 and 22 years.
- Neuropathologic Findings
The brains of the twins reported by Gearing et al. (2002) were
macroscopically unremarkable. The most striking findings on microscopic
examination were (1) eosinophilic, rod-like cytoplasmic inclusions in
neocortical and thalamic neurons that were actin depolymerizing
factor/cofilin-immunoreactive but only rarely actin-positive; and (2)
abundant eosinophilic spherical structures in the striatum that were
strongly actin- and actin depolarizing factor/cofilin-positive. Gearing
et al. (2002) stated that aggregation of actin had not previously been
reported as the predominant feature in any neurodegenerative disease.
They suggested that this neuropathologic change associated with dystonia
may represent a new degenerative mechanism involving actin. Since actin
is a ubiquitous constituent of the cytoskeletal system the presence of
congenital anomalies and developmental abnormalities may be explained by
systemic involvement.
MOLECULAR GENETICS
In the monozygotic twins reported by Gearing et al. (2002), Procaccio et
al. (2006) identified a heterozygous missense mutation, arg183 to trp
(102630.0001), in the beta-actin gene as the cause of the neurologic
syndrome.
*FIELD* RF
1. Gearing, M.; Juncos, J. L.; Procaccio, V.; Gutekunst, C.-A.; Marino-Rodriguez,
E. M.; Gyure, K. A.; Ono, S.; Santoianni, R.; Krawiecki, N. S.; Wallace,
D. C.; Wainer, B. H.: Aggregation of actin and cofilin in identical
twins with juvenile-onset dystonia. Ann. Neurol. 52: 465-476, 2002.
2. Procaccio, V.; Salazar, G.; Ono, S.; Styers, M. L.; Gearing, M.;
Davila, A.; Jimenez, R.; Juncos, J.; Gutekunst, C.-A.; Meroni, G.;
Fontanella, B.; Sontag, E.; Sontag, J. M.; Faundez, V.; Wainer, B.
H.: A mutation of beta-actin that alters depolymerization dynamics
is associated with autosomal dominant developmental malformations,
deafness, and dystonia. Am. J. Hum. Genet. 78: 947-960, 2006.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GROWTH:
[Weight];
Low birth weight;
[Other];
Small for age
HEAD AND NECK:
[Head];
High forehead;
[Ears];
Sensorineural hearing loss;
[Eyes];
Cataracts;
Limited vision;
[Mouth];
Cleft lip;
Cleft palate
CHEST:
[Ribs, sternum, clavicles, and scapulae];
Hypoplastic scapulae
ABDOMEN:
[Gastrointestinal];
Achalasia
SKELETAL:
[Spine];
Kyphoscoliosis;
Antecolis;
[Pelvis];
Externally rotated hips
NEUROLOGIC:
[Central nervous system];
Developmental delay, mild;
Dystonia, generalized, dopa-unresponsive;
Subnormal cognition;
Actin depolymerizing factor/cofilin-immunoreactive eosinophilic rod-like
cytoplasmic inclusions in neocortical and thalamic neurons;
Actin- and actin depolymerizing factor/cofilin-immunoreactive eosinophilic
spherical structures in the striatum
MISCELLANEOUS:
Onset of dystonia at 12 years
MOLECULAR BASIS:
Caused by mutation in the beta-actin gene (ACTB, 102630.0001).
*FIELD* CN
Joanna S. Amberger - updated: 07/11/2006
*FIELD* CD
Cassandra L. Kniffin: 11/20/2002
*FIELD* ED
joanna: 07/11/2006
alopez: 5/17/2006
ckniffin: 11/20/2002
*FIELD* CN
Victor A. McKusick - updated: 5/15/2006
*FIELD* CD
Victor A. McKusick: 11/20/2002
*FIELD* ED
alopez: 05/17/2006
terry: 5/15/2006
carol: 11/20/2002
ckniffin: 11/20/2002