RBCC Red Blood Cell Collection

ACTG1 (ACTB, ACTG) [Confidence: low (only semi-automatic identification from reviews)]
Actin, cytoplasmic 2 (Gamma-actin; Actin, cytoplasmic 2, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P63261
ID ACTG_HUMAN Reviewed; 375 AA.
AC P63261; A8K7C2; P02571; P14104; P99022; Q5U032; Q96E67;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=Actin, cytoplasmic 2;
DE AltName: Full=Gamma-actin;
DE Contains:
DE RecName: Full=Actin, cytoplasmic 2, N-terminally processed;
GN Name=ACTG1; Synonyms=ACTB, ACTG;
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=3737401; DOI=10.1093/nar/14.13.5275;
RA Erba H.P., Gunning P., Kedes L.;
RT "Nucleotide sequence of the human gamma cytoskeletal actin mRNA:
RT anomalous evolution of vertebrate non-muscle actin genes.";
RL Nucleic Acids Res. 14:5275-5294(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2837653;
RA Erba H.P., Eddy R., Shows T., Kedes L., Gunning P.;
RT "Structure, chromosome location, and expression of the human gamma-
RT actin gene: differential evolution, location, and expression of the
RT cytoskeletal beta- and gamma-actin genes.";
RL Mol. Cell. Biol. 8:1775-1789(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell, Eye, Lung, Ovary, Placenta, Skin, and Uterus;
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 [6]
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 [7]
RP PROTEIN SEQUENCE OF 2-18; 29-37; 40-50; 85-113; 148-177; 184-191;
RP 197-206; 239-254; 292-312 AND 316-326, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT GLU-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 2-116; 119-210; 216-254 AND 291-372, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT GLU-2, METHYLATION AT HIS-73, AND
RP MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.,
RA Dozynkiewicz M., Norman J.C.;
RL Submitted (JUN-2009) to UniProtKB.
RN [9]
RP PROTEIN SEQUENCE OF 29-39; 85-113; 239-254 AND 292-312, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-375.
RX PubMed=3472224; DOI=10.1073/pnas.84.9.2575;
RA Chou C.C., Davis R.C., Fuller M.L., Slovin J.P., Wong A., Wright J.,
RA Kania S., Shaked R., Gatti R.A., Salser W.A.;
RT "Gamma-actin: unusual mRNA 3'-untranslated sequence conservation and
RT amino acid substitutions that may be cancer related.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2575-2579(1987).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLU-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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND GLU-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 [13]
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 [14]
RP VARIANTS DFNA20 ILE-89; MET-118; LEU-264 AND ALA-332.
RX PubMed=13680526; DOI=10.1086/379286;
RA Zhu M., Yang T., Wei S., DeWan A.T., Morell R.J., Elfenbein J.L.,
RA Fisher R.A., Leal S.M., Smith R.J.H., Friderici K.H.;
RT "Mutations in the gamma-actin gene (ACTG1) are associated with
RT dominant progressive deafness (DFNA20/26).";
RL Am. J. Hum. Genet. 73:1082-1091(2003).
RN [15]
RP VARIANT DFNA20 ILE-278.
RX PubMed=14684684; DOI=10.1136/jmg.40.12.879;
RA van Wijk E., Krieger E., Kemperman M.H., De Leenheer E.M.R.,
RA Huygen P.L.M., Cremers C.W.R.J., Cremers F.P.M., Kremer H.;
RT "A mutation in the gamma actin 1 (ACTG1) gene causes autosomal
RT dominant hearing loss (DFNA20/26).";
RL J. Med. Genet. 40:879-884(2003).
RN [16]
RP VARIANT DFNA20 ALA-370, AND CHARACTERIZATION OF VARIANT DFNA20
RP ALA-370.
RX PubMed=16773128; DOI=10.1038/sj.ejhg.5201670;
RA Rendtorff N.D., Zhu M., Fagerheim T., Antal T.L., Jones M.,
RA Teslovich T.M., Gillanders E.M., Barmada M., Teig E., Trent J.M.,
RA Friderici K.H., Stephan D.A., Tranebjaerg L.;
RT "A novel missense mutation in ACTG1 causes dominant deafness in a
RT Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among
RT families with hereditary hearing impairment.";
RL Eur. J. Hum. Genet. 14:1097-1105(2006).
RN [17]
RP VARIANT DFNA20 VAL-122.
RX PubMed=18804074; DOI=10.1016/S1673-8527(08)60075-2;
RA Liu P., Li H., Ren X., Mao H., Zhu Q., Zhu Z., Yang R., Yuan W.,
RA Liu J., Wang Q., Liu M.;
RT "Novel ACTG1 mutation causing autosomal dominant non-syndromic hearing
RT impairment in a Chinese family.";
RL J. Genet. Genomics 35:553-558(2008).
RN [18]
RP VARIANTS DFNA20 ASN-118 AND LYS-241.
RX PubMed=19477959; DOI=10.1093/hmg/ddp249;
RA Morin M., Bryan K.E., Mayo-Merino F., Goodyear R., Mencia A.,
RA Modamio-Hoybjor S., del Castillo I., Cabalka J.M., Richardson G.,
RA Moreno F., Rubenstein P.A., Moreno-Pelayo M.A.;
RT "In vivo and in vitro effects of two novel gamma-actin (ACTG1)
RT mutations that cause DFNA20/26 hearing impairment.";
RL Hum. Mol. Genet. 18:3075-3089(2009).
RN [19]
RP VARIANTS BRWS2 ILE-120; VAL-135; PHE-155; LYS-203; TRP-254 AND
RP TRP-256.
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.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-351292, EBI-351292;
CC P60709:ACTB; NbExp=3; IntAct=EBI-351292, EBI-353944;
CC Q9Y281:CFL2; NbExp=2; IntAct=EBI-351292, EBI-351218;
CC P40692:MLH1; NbExp=7; IntAct=EBI-351292, EBI-744248;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- PTM: The methylhistidine determined by Bienvenut et al is assumed
CC to be the tele-methylhistidine isomer by similarity to the mouse
CC ortholog.
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: Deafness, autosomal dominant, 20 (DFNA20) [MIM:604717]: A
CC form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner
CC ear, the nerve pathways to the brain, or the area of the brain
CC that receives sound information. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Baraitser-Winter syndrome 2 (BRWS2) [MIM:614583]: 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=Mendelian genes actin, gamma 1 (ACTG1);
CC Note=Leiden Open Variation Database (LOVD);
CC URL="http://www.lovd.nl/ACTG1";
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DR EMBL; X04098; CAA27723.1; -; mRNA.
DR EMBL; M19283; AAA51579.1; -; Genomic_DNA.
DR EMBL; AK291937; BAF84626.1; -; mRNA.
DR EMBL; BT019856; AAV38659.1; -; mRNA.
DR EMBL; BC000292; AAH00292.1; -; mRNA.
DR EMBL; BC001920; AAH01920.1; -; mRNA.
DR EMBL; BC007442; AAH07442.1; -; mRNA.
DR EMBL; BC009848; AAH09848.1; -; mRNA.
DR EMBL; BC010999; AAH10999.1; -; mRNA.
DR EMBL; BC012050; AAH12050.1; -; mRNA.
DR EMBL; BC015005; AAH15005.1; -; mRNA.
DR EMBL; BC015695; AAH15695.1; -; mRNA.
DR EMBL; BC015779; AAH15779.1; -; mRNA.
DR EMBL; BC018774; AAH18774.1; -; mRNA.
DR EMBL; BC053572; AAH53572.1; -; mRNA.
DR EMBL; M16247; AAA51580.1; -; mRNA.
DR PIR; A28098; ATHUG.
DR PIR; JC5818; JC5818.
DR RefSeq; NP_001186883.1; NM_001199954.1.
DR RefSeq; NP_001605.1; NM_001614.3.
DR UniGene; Hs.514581; -.
DR UniGene; Hs.713764; -.
DR ProteinModelPortal; P63261; -.
DR SMR; P63261; 6-375.
DR IntAct; P63261; 36.
DR MINT; MINT-4998686; -.
DR STRING; 9606.ENSP00000331514; -.
DR PhosphoSite; P63261; -.
DR DMDM; 54036678; -.
DR DOSAC-COBS-2DPAGE; P60709_OR_P63261; -.
DR DOSAC-COBS-2DPAGE; P63261; -.
DR OGP; P63261; -.
DR REPRODUCTION-2DPAGE; P63261; -.
DR SWISS-2DPAGE; P63261; -.
DR PRIDE; P63261; -.
DR DNASU; 71; -.
DR Ensembl; ENST00000331925; ENSP00000331514; ENSG00000184009.
DR Ensembl; ENST00000573283; ENSP00000458435; ENSG00000184009.
DR Ensembl; ENST00000575087; ENSP00000459124; ENSG00000184009.
DR Ensembl; ENST00000575842; ENSP00000458162; ENSG00000184009.
DR Ensembl; ENST00000576544; ENSP00000461672; ENSG00000184009.
DR Ensembl; ENST00000593601; ENSP00000470102; ENSG00000267807.
DR Ensembl; ENST00000597869; ENSP00000471522; ENSG00000267807.
DR Ensembl; ENST00000598366; ENSP00000470446; ENSG00000267807.
DR Ensembl; ENST00000601143; ENSP00000472125; ENSG00000267807.
DR Ensembl; ENST00000601845; ENSP00000469093; ENSG00000267807.
DR GeneID; 71; -.
DR KEGG; hsa:71; -.
DR UCSC; uc002kak.2; human.
DR CTD; 71; -.
DR GeneCards; GC17M079476; -.
DR H-InvDB; HIX0001479; -.
DR H-InvDB; HIX0199868; -.
DR HGNC; HGNC:144; ACTG1.
DR HPA; CAB013531; -.
DR HPA; HPA041264; -.
DR HPA; HPA041271; -.
DR MIM; 102560; gene.
DR MIM; 604717; phenotype.
DR MIM; 614583; phenotype.
DR neXtProt; NX_P63261; -.
DR Orphanet; 90635; Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
DR Orphanet; 2995; Baraitser-Winter syndrome.
DR PharmGKB; PA24468; -.
DR HOVERGEN; HBG003771; -.
DR InParanoid; P63261; -.
DR KO; K05692; -.
DR PhylomeDB; P63261; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P63261; -.
DR ChiTaRS; ACTG1; human.
DR GeneWiki; ACTG1; -.
DR GenomeRNAi; 71; -.
DR NextBio; 279; -.
DR PMAP-CutDB; P63261; -.
DR PRO; PR:P63261; -.
DR ArrayExpress; P63261; -.
DR Bgee; P63261; -.
DR CleanEx; HS_ACTB; -.
DR CleanEx; HS_ACTG1; -.
DR Genevestigator; P63261; -.
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:0031941; C:filamentous actin; IEA:Ensembl.
DR GO; GO:0030016; C:myofibril; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IC:UniProtKB.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0007411; P:axon guidance; 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 GO; GO:0045214; P:sarcomere organization; IEA:Ensembl.
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 Acetylation; ATP-binding; Complete proteome; Cytoplasm; Cytoskeleton;
KW Deafness; Direct protein sequencing; Disease mutation;
KW Mental retardation; Methylation; Non-syndromic deafness;
KW Nucleotide-binding; Oxidation; Polymorphism; Reference proteome.
FT CHAIN 1 375 Actin, cytoplasmic 2.
FT /FTId=PRO_0000367100.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 375 Actin, cytoplasmic 2, N-terminally
FT processed.
FT /FTId=PRO_0000000831.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylglutamate; in Actin, cytoplasmic
FT 2, N-terminally processed; partial.
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.
FT MOD_RES 84 84 N6-methyllysine.
FT VARIANT 89 89 T -> I (in DFNA20; dbSNP:rs28999111).
FT /FTId=VAR_032434.
FT VARIANT 118 118 K -> M (in DFNA20).
FT /FTId=VAR_032435.
FT VARIANT 118 118 K -> N (in DFNA20; dbSNP:rs267606630).
FT /FTId=VAR_067824.
FT VARIANT 120 120 T -> I (in BRWS2; dbSNP:rs281875325).
FT /FTId=VAR_067814.
FT VARIANT 122 122 I -> V (in DFNA20; dbSNP:rs281875330).
FT /FTId=VAR_067825.
FT VARIANT 135 135 A -> V (in BRWS2; dbSNP:rs11549190).
FT /FTId=VAR_067815.
FT VARIANT 155 155 S -> F (in BRWS2; dbSNP:rs281875326).
FT /FTId=VAR_067816.
FT VARIANT 160 160 T -> I (in dbSNP:rs11549206).
FT /FTId=VAR_048186.
FT VARIANT 203 203 T -> K (in BRWS2; dbSNP:rs281875327).
FT /FTId=VAR_067817.
FT VARIANT 241 241 E -> K (in DFNA20; dbSNP:rs267606631).
FT /FTId=VAR_067826.
FT VARIANT 243 243 P -> L (in dbSNP:rs11546899).
FT /FTId=VAR_055482.
FT VARIANT 254 254 R -> W (in BRWS2; dbSNP:rs281875328).
FT /FTId=VAR_067818.
FT VARIANT 256 256 R -> W (in BRWS2; dbSNP:rs281875329).
FT /FTId=VAR_067819.
FT VARIANT 264 264 P -> L (in DFNA20).
FT /FTId=VAR_032436.
FT VARIANT 278 278 T -> I (in DFNA20; dbSNP:rs28999112).
FT /FTId=VAR_032437.
FT VARIANT 332 332 P -> A (in DFNA20).
FT /FTId=VAR_032438.
FT VARIANT 370 370 V -> A (in DFNA20; restricts cell growth
FT at elevated temperature or under
FT hyperosmolar stress as measured in growth
FT assays with yeast expressing the
FT mutation).
FT /FTId=VAR_032439.
FT CONFLICT 316 316 E -> K (in Ref. 10; AAA51580).
FT CONFLICT 344 344 S -> F (in Ref. 10; AAA51580).
SQ SEQUENCE 375 AA; 41793 MW; 54D08F986964EFD5 CRC64;
MEEEIAALVI 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 102560
*RECORD*
*FIELD* NO
102560
*FIELD* TI
*102560 ACTIN, GAMMA-1; ACTG1
;;ACTIN, GAMMA; ACTG;;
CYTOSKELETAL GAMMA-ACTIN;;
ACTIN, CYTOPLASMIC, 2
read more*FIELD* TX

DESCRIPTION

Actins are a family of highly conserved cytoskeletal proteins that play
fundamental roles in nearly all aspects of eukaryotic cell biology. The
ability of a cell to divide, move, endocytose, generate contractile
force, and maintain shape is reliant upon functional actin-based
structures. Actin isoforms are grouped according to expression patterns:
muscle actins predominate in striated and smooth muscle (e.g., ACTA1,
102610, and ACTA2, 102620, respectively), whereas the 2 cytoplasmic
nonmuscle actins, gamma-actin (ACTG1) and beta-actin (ACTB; 102630), are
found in all cells (Sonnemann et al., 2006).

CLONING

Using chick beta-actin cDNA as probe, Gunning et al. (1983) cloned
beta-actin and gamma-actin from a fibroblast cDNA library. They noted
that the N-terminal methionine is posttranslationally removed from the
mature beta-actin and gamma-actin proteins.

Erba et al. (1986) presented the complete sequence of gamma-actin mRNA.
They noted that gamma- and beta-actin differ by only 4 amino acids at
their conserved N-terminal ends.

By screening a promyelocytic leukemia cell line cDNA library with
chicken beta-actin, Chou et al. (1987) cloned human gamma-actin. The
deduced protein contains 375 amino acids. Northern blot analysis of
human fetal tissues detected highest expression of a 2.35-kb transcript
in brain and kidney, with weaker expression in liver and trophoblasts.
High expression was also detected in a human hepatoma cell line.
Expression of gamma-actin increased during macrophage differentiation in
a neuroblastoma cell line.

By Northern blot analysis of mouse tissues, Erba et al. (1988) detected
high gamma-actin expression in lung, kidney, and testis, moderate
expression in brain, low expression in stomach, and very low expression
in liver, heart, and muscle.

GENE FUNCTION

Leisel et al. (1999) used pure components of the actin cytoskeleton to
reconstitute sustained movement in Listeria and Shigella in vitro.
Actin-based propulsion was driven by the free energy released by ATP
hydrolysis linked to actin polymerization and did not require myosin
(see 601478). In addition to actin and activated Arp2/3 complex (see
604221), actin depolymerizing factor and capping protein (see 601571)
were also required for motility as they maintained a high steady-state
level of G-actin, (monomeric, or globular, actin) which controls the
rate of unidirectional growth of actin filaments at the surface of the
bacterium. The movement was more effective when profilin (see 176590),
alpha-actinin (see 102575), and, in the case of Listeria, VASP (601703)
were also included.

Tzima et al. (2000) showed that annexin V (ANXA5; 131230) bound
filamentous actin (F-actin) and gamma-actin, but not beta-actin, in
activated human platelets.

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 G-actin
inhibited both basal and stimulated PLD1 activity, whereas 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.

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.

BIOCHEMICAL FEATURES

- Crystal Structure

Otterbein et al. (2001) determined the crystal structure at
1.54-angstrom resolution of actin in the ADP state modified to block
polymerization. Compared with ATP-actin structures from complexes with
deoxyribonuclease I (125505), profilin, and gelsolin (137350), monomeric
ADP-actin is characterized by a marked conformational change in
subdomain 2.

GENE STRUCTURE

Erba et al. (1988) determined that the ACTG1 gene contains 6 exons. The
5-prime flanking region contains TATA and CCAAT boxes, an SRF
(600589)-binding site, and 5 SP1 (189906)-binding sites. The ACTB gene
has a structure similar to that of ACTG1, suggesting that ACTB and ACTG1
arose by duplication of a common ancestor.

MAPPING

Erba et al. (1988) demonstrated that the human gamma-actin gene is
located on chromosome 17 by Southern analysis of DNA from human-mouse
somatic cell hybrids. Hybridization of the probe to the genome of a
human-mouse cell hybrid containing a 17;9 translocation indicated that
the gene is located in the region 17p11-qter.

Ueyama et al. (1996) mapped the ACTG1 gene to 17q25 and 3 ACTG
pseudogenes to other chromosomes.

MOLECULAR GENETICS

- DFNA20/26

Zhu et al. (2003) identified 4 families segregating an autosomal
dominant progressive sensorineural hearing loss, designated DFNA20 or
DFNA26 (see 604717), that had been linked to 17q25.3. They narrowed the
critical interval containing the causative gene to approximately 2
million bp between markers D17S914 and D17S668, and sequenced
cochlear-expressed genes within this interval in affected family
members. In all 4 families, they identified missense mutations in highly
conserved actin domains of the ACTG1 gene (102560.0001-102560.0004).
Much of the specialized ultrastructural organization of the cells in the
cochlea was based on the actin cytoskeleton. Zhu et al. (2003) noted
that many of the mutations known to cause either syndromic or
nonsyndromic deafness occur in genes that interact with actin. They
stated that this was the first description of a mutation in
cytoskeletal, or nonmuscle, actin.

In 19 affected individuals of a large Norwegian family reported by Teig
(1968), Rendtorff et al. (2006) identified a heterozygous mutation in
the ACTG1 gene (102560.0006). No mutations in the ACTG1 gene were
identified in 19 additional Norwegian and Danish families with autosomal
dominant hearing loss, suggesting that it is not a frequent cause in
this population.

- Baraitser-Winter Syndrome 2

Riviere et al. (2012) reported 8 patients with Baraitser-Winter syndrome
(BRWS2; 614582) with heterozygous missense mutations in the ACTG1 gene.
Seven of 8 of these patients were proven to have de novo mutations. One
mutation was recurrent in 3 patients, a ser-to-phe substitution at codon
155 (S155F; 102560.0009). All the others had novel missense mutations
(102560.0010-102560.0014). Congenital or later-onset progressive hearing
loss is a common feature of Baraitser-Winter syndrome, and Riviere et
al. (2012) suggested that Baraitser-Winter syndrome represents the
severe end of a spectrum of cytoplasmic actin-associated phenotypes that
begins with Baraitser-Winter syndrome and extends to nonsyndromic
hearing loss.

ANIMAL MODEL

To study the role of ACTG1 in skeletal muscle development and avoid the
near-certain embryonic lethality of conventional Actg1 knockout,
Sonnemann et al. (2006) conditionally ablated Actg1 expression in mouse
skeletal muscle. Although muscle development proceeded normally,
Actg1-knockout mice presented with overt muscle weakness accompanied by
a progressive pattern of muscle fiber necrosis and regeneration. The
phenotype resembled human centronuclear myopathies, which are typically
associated with perturbations in enzyme activity, muscle development, or
excitation-contraction coupling.

*FIELD* AV
.0001
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, THR89ILE

In 17 affected members of a family segregating autosomal dominant
progressive sensorineural hearing loss (604717), Zhu et al. (2003)
identified a 340C-T transition in exon 3 of the processed ACTG1 mRNA,
resulting in a thr89-to-ile (T89I) substitution in subdomain 1. The
mutation is in an alpha helix that is thought to participate in the
binding of fimbrin (PLS3; 300131), a bundling protein. This amino acid
is perfectly conserved in cytoplasmic actin, in species ranging from
nematodes to mammals. The mutation was not identified in 220 control
chromosomes.

.0002
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, LYS118MET

In 8 affected members of a family segregating autosomal dominant
progressive sensorineural hearing loss (604717), Zhu et al. (2003)
identified a lys118-to-met (K118M) mutation in exon 3 of the ACTG1 gene.
The substitution occurs in subdomain 1 of the protein near the fimbrin
(PLS3; 300131)-binding domain. The family had been reported by Yang and
Smith (2000).

.0003
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, PRO332ALA

In 8 affected members of a family segregating autosomal dominant
progressive sensorineural hearing loss (604717), Zhu et al. (2003)
identified a pro332-to-ala (P332A) missense mutation in the ACTG1 gene.
The family had been reported by Yang and Smith (2000). P332A is in a
3-amino acid loop in subdomain 3 of the protein; this loop may be part
of the primary contact site for myosin.

.0004
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, PRO264LEU

In 11 affected members of a family segregating autosomal dominant
progressive sensorineural hearing loss (604717) reported by DeWan et al.
(2003), Zhu et al. (2003) identified a pro264-to-leu (P264L) missense
mutation in the gamma-actin gene. P264L is in a proposed hydrophobic
plug for interstrand interactions in subdomain 4 of the protein, near
the actin self-assembly site. Affected members had an early age at onset
and rapid progression of hearing loss.

.0005
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, THR278ILE

In a Dutch family with autosomal dominant deafness linked to the DFNA20
region (604717), Van Wijk et al. (2003) found that affected members had
an 833C-T transition in exon 5 of the ACTG1 gene, resulting in a
thr278-to-ile (T278I) substitution. The mutation was identified in helix
9 of the modeled protein structure and was predicted to have a small but
significant effect on the gamma-1 actin structure owing to its close
proximity to a methionine residue at position 313 in helix 11. The
authors suggested that the mutation would interfere with actin
polymerization.

.0006
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, VAL370ALA

In 19 affected members of a large Norwegian family with autosomal
dominant DFNA20 (604717), Rendtorff et al. (2006) identified a
heterozygous 1109T-C transition in exon 6 of the ACTG1 gene, resulting
in a val370-to-ala (V370A) substitution in a highly conserved region.
Functional expression studies in yeast showed that the mutant protein
suppressed growth; computer modeling suggested that the V370A
substitution impaired hydrophobic interactions and destabilized the
position of the C-terminal tail of the protein. The family had
originally been reported by Teig (1968).

.0007
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, LYS118ASN

In a Spanish father and daughter with autosomal dominant deafness
(604717), Morin et al. (2009) identified heterozygosity for a 354G-C
transversion in exon 3 of the ACTG1 gene, resulting in a lys118-to-asn
(K118N) substitution in subdomain 1. The mutation was not found in 100
normal unrelated Spanish controls. Both father and daughter showed
bilateral, symmetric, progressive sensorineural hearing loss at mid and
high frequencies of postlingual onset. The daughter had onset in the
third decade, and the father had even later onset. Morin et al. (2009)
showed that the K118N mutation had a very mild effect in yeast. In
transiently transfected NIH3T3 cells, K118N-mutant actin was normally
incorporated into cytoskeleton structures, although cytoplasmic
aggregates were also observed indicating an element of abnormality
caused by the K118N mutation in vivo. Gene-gun mediated expression of
K118N mutant in mouse cochlear hair cells resulted in no gross
alteration in cytoskeletal structures or the morphology of stereocilia.
Morin et al. (2009) supported the hypothesis that the postlingual and
progressive nature of the DFNA20/26 hearing loss may be the result of a
progressive deterioration of the hair cell cytoskeleton over time.

.0008
DEAFNESS, AUTOSOMAL DOMINANT 20
ACTG1, GLU241LYS

In 4 affected members of a Spanish family with autosomal dominant
deafness (604717), Morin et al. (2009) identified heterozygosity for a
721G-A transition in exon 4 of the ACTG1 gene, resulting in a
glu241-to-lys (E241K) substitution in subdomain 4. The mutation was not
found in 100 normal unrelated Spanish controls. The affected members
were referred for hearing loss at school age, with the earliest
individual referred at age 6 years. All showed postlingual, bilateral,
symmetric, progressive sensorineural hearing loss at mid and high
frequencies. In yeast, the E241K mutation resulted in a severe phenotype
characterized by a highly compromised ability to grow on glycerol as a
carbon source, an aberrant multivacuolar pattern, and deposition of
thick F-actin bundles randomly in the cell. The latter feature is
consistent with the unusual tendency of the E241K mutant to form bundles
in vitro, although this propensity to bundle was neutralized by
tropomyosin (TPM1; 191010) and the E241K filament bundles were
hypersensitive to severing in the presence of cofilin (CFL1; 601442). In
transiently transfected NIH3T3 cells, E241K-mutant actin was normally
incorporated into cytoskeleton structures, although cytoplasmic
aggregates were also observed indicating an element of abnormality
caused by the mutations in vivo. Gene-gun mediated expression of the
E241K mutant in mouse cochlear hair cells resulted in no gross
alteration in cytoskeletal structures or the morphology of stereocilia.
Morin et al. (2009) supported the hypothesis that the postlingual and
progressive nature of the DFNA20/26 hearing loss may be the result of a
progressive deterioration of the hair cell cytoskeleton over time.

.0009
BARAITSER-WINTER SYNDROME 2
ACTG1, SER155PHE

In 3 unrelated individuals with Baraitser-Winter syndrome-2 (BRWS2;
614583), Riviere et al. (2012) identified a heterozygous C-to-T
transition at nucleotide 464 of the ACTG1 gene, resulting in a
ser-to-phe substitution at codon 155 (S155F). This mutation was proven
to have occurred de novo in 2 of the 3; in the third, parental DNA was
not available. One of these 3 patients, LP98-096, was reported by
Baraitser and Winter (1988). This mutation was not identified in 224
control exomes. Riviere et al. (2012) studied lymphoblastoid cell lines
from individuals carrying the S155F mutation and demonstrated that these
had increased F-actin content and multiple, anomalous F-actin-rich
filopodia-like protrusions compared to control cells, resulting in
increased cell perimeter. Cell lines also showed increased sensitivity
to treatment with latrunculin A.

.0010
BARAITSER-WINTER SYNDROME 2
ACTG1, THR120ILE

Riviere et al. (2012) reported a single individual with Baraitser-Winter
syndrome-2 (BRWS2; 614583) carrying a de novo heterozygous mutation in
ACTG1, a C-to-T transition at nucleotide 359 resulting in a thr-to-ile
substitution at codon 120 (T120I). This mutation was not observed in 244
other exomes sequenced.

.0011
BARAITSER-WINTER SYNDROME 2
ACTG1, ALA135VAL

In an individual with Baraitser-Winter syndrome-2 (BRWS2; 614583),
Riviere et al. (2012) identified a heterozygous C-to-T transition at
nucleotide 404 of the ACTG1 gene, resulting in an ala-to-val
substitution at codon 135 (A135V). This mutation occurred de novo in the
patient and was not observed in 192 other exomes sequenced.

.0012
BARAITSER-WINTER SYNDROME 2
ACTG1, THR203LYS

In an individual with Baraitser-Winter syndrome-2 (BRWS2; 614583),
Riviere et al. (2012) identified a heterozygous C-to-A transversion at
nucleotide 608 of the ACTG1 gene, resulting in an thr-to-lys
substitution at codon 203 (T203K). This mutation occurred de novo in the
patient and was not observed in 203 other exomes sequenced.

.0013
BARAITSER-WINTER SYNDROME 2
ACTG1, ARG254TRP

In an individual with Baraitser-Winter syndrome-2 (BRWS2; 614583),
Riviere et al. (2012) identified a heterozygous C-to-T transition at
nucleotide 760 of the ACTG1 gene, resulting in an arg-to-trp
substitution at codon 254 (R254W). This mutation occurred de novo in the
patient and was not observed in 195 other exomes sequenced.

.0014
BARAITSER-WINTER SYNDROME 2
ACTG1, ARG256TRP

In an individual with Baraitser-Winter syndrome-2 (BRWS2; 614583),
Riviere et al. (2012) identified a heterozygous C-to-T transition at
nucleotide 766 of the ACTG1 gene, resulting in an arg-to-trp
substitution at codon 256 (R256W). This mutation occurred de novo in the
patient and was not observed in 184 other exomes sequenced.

*FIELD* RF
1. Baraitser, M.; Winter, R. M.: Iris coloboma, ptosis, hypertelorism,
and mental retardation: a new syndrome. J. Med. Genet. 25: 41-43,
1988.

2. Chou, C.-C.; Davis, R. C.; Fuller, M. L.; Slovin, J. P.; Wong,
A.; Wright, J.; Kania, S.; Shaked, R.; Gatti, R. A.; Salser, W. A.
: Gamma-actin: unusual mRNA 3-prime-untranslated sequence conservation
and amino acid substitutions that may be cancer related. Proc. Nat.
Acad. Sci. 84: 2575-2579, 1987.

3. DeWan, A. T.; Parrado, A. R.; Leal, S. M.: A second kindred linked
to DFNA20 (17q25.3) reduces the genetic interval. Clin. Genet. 63:
39-45, 2003.

4. 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.

5. Erba, H. P.; Gunning, P.; Kedes, L.: Nucleotide sequence of the
human gamma cytoskeletal actin mRNA: anomalous evolution of vertebrate
non-muscle actin genes. Nucleic Acids Res. 14: 5275-5294, 1986.

6. 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.

7. 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.

8. Leisel, T. P.; Boujemaa, R.; Pantaloni, D.; Carlier, M.-F.: Reconstitution
of actin-based motility of Listeria and Shigella using pure proteins. Nature 401:
613-616, 1999.

9. Morin, M.; Bryan, K. E.; Mayo-Merino, F.; Goodyear, R.; Mencia,
A.; Modamio-Hoybjor, S.; del Castillo, I.; Cabalka, J. M.; Richardson,
G.; Moreno, F.; Rubenstein, P. A.; Moreno-Pelayo, M. A.: In vivo
and in vitro effects of two novel gamma-actin (ACTG1) mutations that
cause DFNA20/26 hearing impairment. Hum. Molec. Genet. 18: 3075-3089,
2009.

10. Otterbein, L. R.; Graceffa, P.; Dominguez, R.: The crystal structure
of uncomplexed actin in the ADP state. Science 293: 708-711, 2001.

11. Rendtorff, N. D.; Zhu, M.; Fagerheim, T.; Antal, T. L.; Jones,
M.; Teslovich, T. M.; Gillanders, E. M.; Barmada, M.; Teig, E.; Trent,
J. M.; Friderici, K. H.; Stephan, D. A.; Tranebjaerg, L.: A novel
missense mutation in ACTG1 causes dominant deafness in a Norwegian
DFNA20/26 family, but ACTG1 mutations are not frequent among families
with hereditary hearing impairment. Europ. J. Hum. Genet. 14: 1097-1105,
2006.

12. 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.

13. Sonnemann, K. J.; Fitzsimons, D. P.; Patel, J. R.; Liu, Y.; Schneider,
M. F.; Moss, R. L.; Ervasti, J. M.: Cytoplasmic gamma-actin is not
required for skeletal muscle development but its absence leads to
a progressive myopathy. Dev. Cell 11: 387-397, 2006.

14. Teig, E.: Hereditary progressive perceptive deafness in a family
of 72 patients. Acta Otolaryng. 65: 365-372, 1968.

15. Tzima, E.; Trotter, P. J.; Orchard, M. A.; Walker, J. H.: Annexin
V relocates to the platelet cytoskeleton upon activation and binds
to a specific isoform of actin. J. Biochem. 267: 4720-4730, 2000.

16. 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.

17. van Wijk, E.; Krieger, E.; Kemperman, M. H.; De Leenheer, E. M.
R.; Huygen, P. L. M.; Cremers, C. W. R. J.; Cremers, F. P. M.; Kremer,
H.: A mutation in the gamma actin 1 (ACTG1) gene causes autosomal
dominant hearing loss (DFNA20/26). J. Med. Genet. 40: 879-884, 2003.

18. Yang, T.; Smith, R.: A novel locus DFNA26 maps to chromosome
17q25 in two unrelated families with progressive autosomal dominant
hearing loss. (Abstract) Am. J. Hum. Genet. 67 (suppl. 2): 300 only,
2000.

19. 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.

20. Zhu, M.; Yang, T.; Wei, S.; DeWan, A. T.; Morell, R. J.; Elfenbein,
J. L.; Fisher, R. A.; Leal, S. M.; Smith, R. J. H.; Friderici, K.
H.: Mutations in the gamma-actin gene (ACTG1) are associated with
dominant progressive deafness (DFNA20/26). Am. J. Hum. Genet. 73:
1082-1091, 2003.

*FIELD* CN
Ada Hamosh - updated: 4/18/2012
Ada Hamosh - updated: 11/2/2010
George E. Tiller - updated: 6/28/2010
Cassandra L. Kniffin - updated: 11/3/2006
Patricia A. Hartz - updated: 10/4/2006
Natalie E. Krasikov - updated: 3/30/2004
Victor A. McKusick - updated: 10/27/2003
Ada Hamosh - updated: 8/14/2001
Ada Hamosh - updated: 10/12/1999

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
alopez: 04/19/2012
terry: 4/18/2012
alopez: 11/9/2010
terry: 11/2/2010
wwang: 7/16/2010
terry: 6/28/2010
wwang: 5/7/2009
terry: 8/6/2007
alopez: 7/25/2007
terry: 7/24/2007
carol: 11/3/2006
ckniffin: 11/3/2006
mgross: 10/11/2006
terry: 10/4/2006
carol: 4/8/2004
terry: 3/30/2004
carol: 10/28/2003
terry: 10/27/2003
alopez: 8/17/2001
terry: 8/14/2001
mgross: 10/15/1999
alopez: 10/12/1999
mark: 3/20/1997
terry: 1/13/1997
supermim: 3/16/1992
carol: 7/3/1991
carol: 3/19/1991
supermim: 3/20/1990
ddp: 10/26/1989
root: 6/3/1988

MIM 604717
*RECORD*
*FIELD* NO
604717
*FIELD* TI
#604717 DEAFNESS, AUTOSOMAL DOMINANT 20; DFNA20
;;DFNA26
*FIELD* TX
A number sign (#) is used with this entry because this form of autosomal
read moredominant progressive sensorineural hearing loss, DFNA20/26, is caused by
mutation in the gamma-actin gene (ACTG1; 102560) on chromosome 17q25.3.

CLINICAL FEATURES

Morell et al. (2000) reported a 3-generation family living in the U.S.
Midwest in which some members had a bilateral, sloping, progressive,
sensorineural hearing loss, first evident at 6,000 and 8,000 Hz. It was
identified in some family members in the early teens but was clearly
evident by the early twenties. The degree of hearing loss increased with
age, and threshold shifts were seen at all frequencies.

DeWan et al. (2003) described another U.S. family in which affected
members had sloping audiograms with mid- and high-frequency hearing
loss, which progressed to hearing loss that affected all frequencies.
Mean age at onset of hearing impairment was 13.2 years, with a standard
deviation of 4.6 years.

Rendtorff et al. (2006) provided follow-up of a large Norwegian family
originally reported by Teig (1968) with autosomal dominant sensorineural
hearing loss spanning 7 generations. Age at onset was in the first or
second decade of life. Hearing loss first affected high frequencies and
progressed to involve all frequencies. Audiograms showed a sloping
configuration with age, resulting in profound hearing loss. The rate of
progression was variable, but most affected members in this family
needed a hearing aid by age 20 years.

MAPPING

Using a genomewide screen, Morell et al. (2000) demonstrated linkage of
the disorder, designated DFNA20, to chromosome 17q25. By haplotype
analysis, they refined the DFNA20 critical region to 12 cM between
D17S1806 and D17S668. Morell et al. (2000) noted that the mouse mutation
jackson-shaker (js), which causes deafness and circling behavior, maps
to a region of chromosome 11 that has homology with human 17q25.

Yang and Smith (2000) reported 2 unrelated American families with
progressive autosomal dominant hearing loss that mapped to chromosome
17q25. They designated the locus DFNA26.

DeWan et al. (2003) found significant linkage to 17q25.3 (maximum
2-point lod score of 6.32) in a U.S. family with hearing loss. The
authors concluded that DFNA20 and DFNA26 are probably the same or
allelic disorders. They also noted that Usher syndrome type 1G (USH1G;
606943) maps to the same region and may be allelic.

MOLECULAR GENETICS

In affected members of 4 families with autosomal dominant progressive
sensorineural hearing loss (DFNA20/DFNA26), Zhu et al. (2003) identified
heterozygous mutations in highly conserved regions of the ACTG1 gene
(102560.0001-102560.0004). Three of the families had been reported by
Yang and Smith (2000) and DeWan et al. (2003). The findings established
that DFNA20 and DFNA26 are identical.

In affected members of a Dutch family with autosomal dominant deafness
linked to the 17q25 region, Van Wijk et al. (2003) identified a mutation
in the ACTG1 gene (102560.0005).

In 19 affected individuals of a large Norwegian family reported by Teig
(1968), Rendtorff et al. (2006) identified a heterozygous mutation in
the ACTG1 gene (102560.0006).

Morin et al. (2009) reported 2 Spanish families with autosomal deafness
and identified heterozygous mutations (102560.0007 and 102560.0008,
respectively) in the ACTG1 gene.

*FIELD* RF
1. DeWan, A. T.; Parrado, A. R.; Leal, S. M.: A second kindred linked
to DFNA20 (17q25.3) reduces the genetic interval. Clin. Genet. 63:
39-45, 2003.

2. Morell, R. J.; Friderici, K. H.; Wei, S.; Elfenbein, J. L.; Friedman,
T. B.; Fisher, R. A.: A new locus for late-onset, progressive, hereditary
hearing loss DFNA20 maps to 17q25. Genomics 63: 1-6, 2000.

3. Morin, M.; Bryan, K. E.; Mayo-Merino, F.; Goodyear, R.; Mencia,
A.; Modamio-Hoybjor, S.; del Castillo, I.; Cabalka, J. M.; Richardson,
G.; Moreno, F.; Rubenstein, P. A.; Moreno-Pelayo, M. A.: In vivo
and in vitro effects of two novel gamma-actin (ACTG1) mutations that
cause DFNA20/26 hearing impairment. Hum. Molec. Genet. 18: 3075-3089,
2009.

4. Rendtorff, N. D.; Zhu, M.; Fagerheim, T.; Antal, T. L.; Jones,
M.; Teslovich, T. M.; Gillanders, E. M.; Barmada, M.; Teig, E.; Trent,
J. M.; Friderici, K. H.; Stephan, D. A.; Tranebjaerg, L.: A novel
missense mutation in ACTG1 causes dominant deafness in a Norwegian
DFNA20/26 family, but ACTG1 mutations are not frequent among families
with hereditary hearing impairment. Europ. J. Hum. Genet. 14: 1097-1105,
2006.

5. Teig, E.: Hereditary progressive perceptive deafness in a family
of 72 patients. Acta Otolaryngol. 65: 365-372, 1968.

6. van Wijk, E.; Krieger, E.; Kemperman, M. H.; De Leenheer, E. M.
R.; Huygen, P. L. M.; Cremers, C. W. R. J.; Cremers, F. P. M.; Kremer,
H.: A mutation in the gamma actin 1 (ACTG1) gene causes autosomal
dominant hearing loss (DFNA20/26). J. Med. Genet. 40: 879-884, 2003.

7. Yang, T.; Smith, R.: A novel locus DFNA26 maps to chromosome 17q25
in two unrelated families with progressive autosomal dominant hearing
loss. (Abstract) Am. J. Hum. Genet. 67 (suppl. 2): 300 only, 2000.

8. Zhu, M.; Yang, T.; Wei, S.; DeWan, A. T.; Morell, R. J.; Elfenbein,
J. L.; Fisher, R. A.; Leal, S. M.; Smith, R. J. H.; Friderici, K.
H.: Mutations in the gamma-actin gene (ACTG1) are associated with
dominant progressive deafness (DFNA20/26). Am. J. Hum. Genet. 73:
1082-1091, 2003.

*FIELD* CS
INHERITANCE:
Autosomal dominant

HEAD AND NECK:
[Ears];
Hearing loss, sensorineural, bilateral, progressive;
Hearing loss begins with loss of high frequencies;
Audiogram shows sloping configuration;
Deafness, profound, by 6th decade

MISCELLANEOUS:
Onset in first or second decades;
Variable rate of progression

MOLECULAR BASIS:
Caused by mutation in the gamma-1 actin gene (ACTG1, 102560.0001)

*FIELD* CD
Cassandra L. Kniffin: 11/3/2006

*FIELD* ED
joanna: 05/22/2007
ckniffin: 11/3/2006

*FIELD* CN
George E. Tiller - updated: 6/28/2010
Cassandra L. Kniffin - updated: 11/3/2006
Natalie E. Krasikov - updated: 3/30/2004
Victor A. McKusick - updated: 10/27/2003
Victor A. McKusick - updated: 2/10/2003

*FIELD* CD
Victor A. McKusick: 3/22/2000

*FIELD* ED
wwang: 07/16/2010
terry: 6/28/2010
wwang: 6/2/2009
carol: 11/3/2006
ckniffin: 11/3/2006
carol: 4/8/2004
terry: 3/30/2004
carol: 10/28/2003
terry: 10/27/2003
tkritzer: 7/11/2003
carol: 2/24/2003
tkritzer: 2/20/2003
terry: 2/10/2003
carol: 3/22/2000

MIM 614583
*RECORD*
*FIELD* NO
614583
*FIELD* TI
#614583 BARAITSER-WINTER SYNDROME 2; BRWS2
*FIELD* TX
A number sign (#) is used with this entry because Baraitser-Winter
read moresyndrome-2 (BRWS2) is caused by heterozygous mutation in the ACTG1 gene
(102560) on chromosome 17q25.3.

For a phenotypic description and a discussion of genetic heterogeneity
of Baraitser-Winter syndrome, see BRWS1 (243310).

CLINICAL FEATURES

Riviere et al. (2012) reported 8 patients with Baraitser-Winter
syndrome-2. Three of 7 of those examined had short stature; 4 of 7 had
postnatal microcephaly; all 5 patients evaluated had intellectual
disability; 5 of 6 had hearing loss; and 7 of 8 had seizures. Seven of 7
had trigonocephaly; 7 of 8 had hypertelorism; 7 of 7 had high-arched
eyebrows; and 8 of 8 had ptosis. Five of 7 had iris or retinal coloboma
and 7 of 7 patients evaluated had anterior-to-posterior gradient
lissencephaly of the pachygyria or pachygyria-band type.

INHERITANCE

Riviere et al. (2012) reported that, with one exception, all patients
with Baraitser-Winter syndrome have been sporadic. The only report of
affected sibs involved patients 1 and 2 in the original report
(Baraitser and Winter, 1988), and further analysis of phenotypic
features led Riviere et al. (2012) to consider these individuals, lost
to follow-up, as not having Baraitser-Winter syndrome.

MOLECULAR GENETICS

Riviere et al. (2012) reported 8 patients with Baraitser-Winter syndrome
carrying heterozygous missense mutations in the ACTG1 gene; in 7
patients the mutation was proven to have occurred de novo. One mutation
was recurrent in 3 patients, a ser-to-phe substitution at codon 155
(102560.0009). One of these 3, LP98-096, was originally reported by
Baraitser and Winter (1988) as patient 3. All the others had novel
missense mutations. Autosomal dominant progressive nonsyndromic hearing
loss (DFNA20/26; 604717) is also caused by mutations in ACTG1, and
congenital or later-onset progressive hearing loss is a common feature
of Baraitser-Winter syndrome, suggesting partially overlapping
pathogenic mechanisms for Baraitser-Winter syndrome and DFNA20/26.
Riviere et al. (2012) suggested that Baraitser-Winter syndrome
represents the severe end of a spectrum of cytoplasmic actin-associated
phenotypes that begins with Baraitser-Winter syndrome and extends to
nonsyndromic hearing loss.

*FIELD* RF
1. Baraitser, M.; Winter, R. M.: Iris coloboma, ptosis, hypertelorism,
and mental retardation: a new syndrome. J. Med. Genet. 25: 41-43,
1988.

2. 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* CD
Ada Hamosh: 4/19/2012

*FIELD* ED
terry: 05/08/2012
alopez: 4/19/2012