Full text data of ACTN2
ACTN2
[Confidence: low (only semi-automatic identification from reviews)]
Alpha-actinin-2 (Alpha-actinin skeletal muscle isoform 2; F-actin cross-linking protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Alpha-actinin-2 (Alpha-actinin skeletal muscle isoform 2; F-actin cross-linking protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P35609
ID ACTN2_HUMAN Reviewed; 894 AA.
AC P35609; B1ANE4; Q86TF4; Q86TI8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1994, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Alpha-actinin-2;
DE AltName: Full=Alpha-actinin skeletal muscle isoform 2;
DE AltName: Full=F-actin cross-linking protein;
GN Name=ACTN2;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=1339456;
RA Beggs A.H., Byers T.J., Knoll J.H.M., Boyce F.M., Bruns G.A.P.,
RA Kunkel L.M.;
RT "Cloning and characterization of two human skeletal muscle alpha-
RT actinin genes located on chromosomes 1 and 11.";
RL J. Biol. Chem. 267:9281-9288(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10548523; DOI=10.1006/bbrc.1999.1661;
RA Tiso N., Majetti M., Stanchi F., Rampazzo A., Zimbello R., Nava A.,
RA Danieli G.A.;
RT "Fine mapping and genomic structure of ACTN2, the human gene coding
RT for the sarcomeric isoform of alpha-actinin-2, expressed in skeletal
RT and cardiac muscle.";
RL Biochem. Biophys. Res. Commun. 265:256-259(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
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 INTERACTION WITH LDB3.
RX PubMed=10427098; DOI=10.1083/jcb.146.2.465;
RA Faulkner G., Pallavicini A., Formentin E., Comelli A., Ievolella C.,
RA Trevisan S., Bortoletto G., Scannapieco P., Salamon M., Mouly V.,
RA Valle G., Lanfranchi G.;
RT "ZASP: a new Z-band alternatively spliced PDZ-motif protein.";
RL J. Cell Biol. 146:465-475(1999).
RN [7]
RP INTERACTION WITH MYOZ1.
RX PubMed=10984498; DOI=10.1074/jbc.M007493200;
RA Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G.,
RA Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P.,
RA Valle G., Lanfranchi G.;
RT "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-
RT disc of skeletal muscle.";
RL J. Biol. Chem. 275:41234-41242(2000).
RN [8]
RP INTERACTION WITH MYOZ1 AND MYOZ2.
RX PubMed=11114196; DOI=10.1073/pnas.260501097;
RA Frey N., Richardson J.A., Olson E.N.;
RT "Calsarcins, a novel family of sarcomeric calcineurin-binding
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14632-14637(2000).
RN [9]
RP INTERACTION WITH MYOZ1, AND SUBCELLULAR LOCATION.
RX PubMed=11171996; DOI=10.1073/pnas.041609698;
RA Takada F., Vander Woude D.L., Tong H.-Q., Thompson T.G., Watkins S.C.,
RA Kunkel L.M., Beggs A.H.;
RT "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of
RT skeletal muscle Z lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1595-1600(2001).
RN [10]
RP INTERACTION WITH MYOZ3.
RX PubMed=11842093; DOI=10.1074/jbc.M200712200;
RA Frey N., Olson E.N.;
RT "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin
RT family, interacts with multiple Z-disc proteins.";
RL J. Biol. Chem. 277:13998-14004(2002).
RN [11]
RP INTERACTION WITH PARVB.
RX PubMed=15159419; DOI=10.1083/jcb.200308141;
RA Yamaji S., Suzuki A., Kanamori H., Mishima W., Yoshimi R.,
RA Takasaki H., Takabayashi M., Fujimaki K., Fujisawa S., Ohno S.,
RA Ishigatsubo Y.;
RT "Affixin interacts with alpha-actinin and mediates integrin signaling
RT for reorganization of F-actin induced by initial cell-substrate
RT interaction.";
RL J. Cell Biol. 165:539-551(2004).
RN [12]
RP INTERACTION WITH XIRP2.
RX PubMed=17046827; DOI=10.1074/jbc.M603244200;
RA Huang H.-T., Brand O.M., Mathew M., Ignatiou C., Ewen E.P.,
RA McCalmon S.A., Naya F.J.;
RT "Myomaxin is a novel transcriptional target of MEF2A that encodes a
RT Xin-related alpha-actinin-interacting protein.";
RL J. Biol. Chem. 281:39370-39379(2006).
RN [13]
RP INTERACTION WITH DST, AND SUBCELLULAR LOCATION.
RX PubMed=19932097; DOI=10.1016/j.yexcr.2009.11.010;
RA Steiner-Champliaud M.F., Schneider Y., Favre B., Paulhe F.,
RA Praetzel-Wunder S., Faulkner G., Konieczny P., Raith M., Wiche G.,
RA Adebola A., Liem R.K., Langbein L., Sonnenberg A., Fontao L.,
RA Borradori L.;
RT "BPAG1 isoform-b: complex distribution pattern in striated and heart
RT muscle and association with plectin and alpha-actinin.";
RL Exp. Cell Res. 316:297-313(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP UBIQUITINATION BY FBXL22.
RX PubMed=22972877; DOI=10.1161/CIRCRESAHA.112.271007;
RA Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D.,
RA Berger I.M., Wiemann S., Korn B., Koegl M., Backs J., Katus H.A.,
RA Rottbauer W., Frey N.;
RT "F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box
RT protein that regulates sarcomeric protein turnover and is essential
RT for maintenance of contractile function in vivo.";
RL Circ. Res. 111:1504-1516(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 391-637.
RX PubMed=10481917; DOI=10.1016/S0092-8674(00)81981-9;
RA Djinovic-Carugo K., Young P., Gautel M., Saraste M.;
RT "Structure of the alpha-actinin rod: molecular basis for cross-linking
RT of actin filaments.";
RL Cell 98:537-546(1999).
RN [17]
RP STRUCTURE BY NMR OF 823-894 IN COMPLEX WITH A TITIN Z-REPEAT.
RX PubMed=11573089; DOI=10.1038/nsb1001-853;
RA Atkinson R.A., Joseph C., Kelly G., Muskett F.W., Frenkiel T.A.,
RA Nietlispach D., Pastore A.;
RT "Ca2+-independent binding of an EF-hand domain to a novel motif in the
RT alpha-actinin-titin complex.";
RL Nat. Struct. Biol. 8:853-857(2001).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 274-746.
RX PubMed=11470434; DOI=10.1016/S0969-2126(01)00619-0;
RA Ylanne J., Scheffzek K., Young P., Saraste M.;
RT "Crystal structure of the alpha-actinin rod reveals an extensive
RT torsional twist.";
RL Structure 9:597-604(2001).
RN [19]
RP VARIANT CMD1AA ARG-9, AND VARIANT VAL-604.
RX PubMed=14567970; DOI=10.1016/S1096-7192(03)00142-2;
RA Mohapatra B., Jimenez S., Lin J.H., Bowles K.R., Coveler K.J.,
RA Marx J.G., Chrisco M.A., Murphy R.T., Lurie P.R., Schwartz R.J.,
RA Elliott P.M., Vatta M., McKenna W., Towbin J.A., Bowles N.E.;
RT "Mutations in the muscle LIM protein and alpha-actinin-2 genes in
RT dilated cardiomyopathy and endocardial fibroelastosis.";
RL Mol. Genet. Metab. 80:207-215(2003).
CC -!- FUNCTION: F-actin cross-linking protein which is thought to anchor
CC actin to a variety of intracellular structures. This is a bundling
CC protein.
CC -!- SUBUNIT: Homodimer; antiparallel. Also forms heterodimers with
CC ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts
CC via its C-terminal region with the LDB3 PDZ domain. Interacts with
CC XIRP2. Interacts with DST isoform 1 (via N-terminus). Interacts
CC with PARVB.
CC -!- INTERACTION:
CC Self; NbExp=8; IntAct=EBI-77797, EBI-77797;
CC Q61824:Adam12 (xeno); NbExp=3; IntAct=EBI-77797, EBI-77785;
CC P03950:ANG; NbExp=4; IntAct=EBI-77797, EBI-525291;
CC Q9UKG1:APPL1; NbExp=2; IntAct=EBI-77797, EBI-741243;
CC Q9NRI5:DISC1; NbExp=3; IntAct=EBI-77797, EBI-529989;
CC O75923:DYSF; NbExp=2; IntAct=EBI-77797, EBI-2799016;
CC P22460:KCNA5; NbExp=6; IntAct=EBI-77797, EBI-6426121;
CC P54296:MYOM2; NbExp=2; IntAct=EBI-77797, EBI-5357134;
CC Q8WZ42:TTN; NbExp=16; IntAct=EBI-77797, EBI-681210;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line.
CC Note=Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal
CC muscle.
CC -!- TISSUE SPECIFICITY: Expressed in both skeletal and cardiac muscle.
CC -!- PTM: Ubiquitinated by FBXL22, leading to proteasomal degradation.
CC -!- DISEASE: Cardiomyopathy, dilated 1AA (CMD1AA) [MIM:612158]: A
CC disorder characterized by ventricular dilation and impaired
CC systolic function, resulting in congestive heart failure and
CC arrhythmia. Patients are at risk of premature death. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the alpha-actinin family.
CC -!- SIMILARITY: Contains 1 actin-binding domain.
CC -!- SIMILARITY: Contains 2 CH (calponin-homology) domains.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SIMILARITY: Contains 4 spectrin repeats.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACTN2";
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DR EMBL; M86406; AAA51583.1; -; mRNA.
DR EMBL; M86804; AAA51584.1; -; Genomic_DNA.
DR EMBL; AJ249756; CAB61269.1; -; Genomic_DNA.
DR EMBL; AJ249757; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249758; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249759; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249760; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249761; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249762; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249763; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249764; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249765; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249766; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249767; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249768; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249769; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249770; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249771; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249772; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249773; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249774; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249775; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249776; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AL359185; CAH73201.1; -; Genomic_DNA.
DR EMBL; AL359921; CAH73201.1; JOINED; Genomic_DNA.
DR EMBL; AL359921; CAI13778.1; -; Genomic_DNA.
DR EMBL; AL359185; CAI13778.1; JOINED; Genomic_DNA.
DR EMBL; CH471098; EAW70064.1; -; Genomic_DNA.
DR EMBL; BC047901; AAH47901.2; -; mRNA.
DR EMBL; BC051770; AAH51770.2; -; mRNA.
DR PIR; A40199; FAHUA2.
DR RefSeq; NP_001094.1; NM_001103.3.
DR UniGene; Hs.498178; -.
DR PDB; 1H8B; NMR; -; A=823-894.
DR PDB; 1HCI; X-ray; 2.80 A; A/B=274-746.
DR PDB; 1QUU; X-ray; 2.50 A; A=391-637.
DR PDBsum; 1H8B; -.
DR PDBsum; 1HCI; -.
DR PDBsum; 1QUU; -.
DR ProteinModelPortal; P35609; -.
DR SMR; P35609; 35-261, 274-746, 751-894.
DR DIP; DIP-383N; -.
DR IntAct; P35609; 28.
DR MINT; MINT-145583; -.
DR STRING; 9606.ENSP00000355537; -.
DR PhosphoSite; P35609; -.
DR DMDM; 543742; -.
DR PaxDb; P35609; -.
DR PeptideAtlas; P35609; -.
DR PRIDE; P35609; -.
DR Ensembl; ENST00000366578; ENSP00000355537; ENSG00000077522.
DR GeneID; 88; -.
DR KEGG; hsa:88; -.
DR UCSC; uc001hyf.2; human.
DR CTD; 88; -.
DR GeneCards; GC01P236849; -.
DR HGNC; HGNC:164; ACTN2.
DR HPA; HPA006035; -.
DR HPA; HPA008315; -.
DR MIM; 102573; gene.
DR MIM; 612158; phenotype.
DR neXtProt; NX_P35609; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR PharmGKB; PA25; -.
DR eggNOG; COG5069; -.
DR HOGENOM; HOG000263418; -.
DR HOVERGEN; HBG050453; -.
DR InParanoid; P35609; -.
DR KO; K05699; -.
DR OrthoDB; EOG72C4ZJ; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR EvolutionaryTrace; P35609; -.
DR GeneWiki; Actinin,_alpha_2; -.
DR GenomeRNAi; 88; -.
DR NextBio; 327; -.
DR PRO; PR:P35609; -.
DR ArrayExpress; P35609; -.
DR Bgee; P35609; -.
DR CleanEx; HS_ACTN2; -.
DR Genevestigator; P35609; -.
DR GO; GO:0005884; C:actin filament; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; TAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IMP:UniProtKB.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0031143; C:pseudopodium; TAS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0051373; F:FATZ binding; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; TAS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0008307; F:structural constituent of muscle; TAS:ProtInc.
DR GO; GO:0030375; F:thyroid hormone receptor coactivator activity; IEA:Ensembl.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030035; P:microspike assembly; IDA:UniProtKB.
DR GO; GO:0030049; P:muscle filament sliding; TAS:Reactome.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IMP:BHF-UCL.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IMP:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:1901018; P:positive regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:BHF-UCL.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 2.
DR Gene3D; 1.10.418.10; -; 2.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014837; EF-hand_Ca_insen.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF08726; EFhand_Ca_insen; 1.
DR Pfam; PF00435; Spectrin; 4.
DR SMART; SM00033; CH; 2.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00150; SPEC; 3.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Calcium; Cardiomyopathy;
KW Complete proteome; Cytoplasm; Disease mutation; Metal-binding;
KW Polymorphism; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 894 Alpha-actinin-2.
FT /FTId=PRO_0000073435.
FT DOMAIN 1 254 Actin-binding.
FT DOMAIN 38 142 CH 1.
FT DOMAIN 151 254 CH 2.
FT REPEAT 281 391 Spectrin 1.
FT REPEAT 401 506 Spectrin 2.
FT REPEAT 516 627 Spectrin 3.
FT REPEAT 637 740 Spectrin 4.
FT DOMAIN 753 788 EF-hand 1.
FT DOMAIN 789 824 EF-hand 2.
FT CA_BIND 766 777 1; possibly ancestral.
FT CA_BIND 802 813 2; possibly ancestral.
FT VARIANT 9 9 Q -> R (in CMD1AA; dbSNP:rs121434525).
FT /FTId=VAR_054628.
FT VARIANT 604 604 M -> V (in dbSNP:rs35997569).
FT /FTId=VAR_033487.
FT HELIX 275 294
FT HELIX 296 303
FT STRAND 311 313
FT TURN 314 317
FT HELIX 318 329
FT HELIX 331 340
FT TURN 341 343
FT HELIX 344 347
FT TURN 351 356
FT HELIX 364 366
FT STRAND 368 370
FT HELIX 371 382
FT HELIX 393 416
FT TURN 417 419
FT HELIX 420 425
FT HELIX 428 430
FT HELIX 434 470
FT HELIX 476 536
FT TURN 537 540
FT TURN 548 550
FT HELIX 551 562
FT HELIX 564 588
FT HELIX 604 632
FT TURN 666 669
FT HELIX 672 704
FT HELIX 716 741
FT HELIX 828 838
FT STRAND 843 845
FT HELIX 847 853
FT HELIX 856 865
FT HELIX 881 888
SQ SEQUENCE 894 AA; 103854 MW; 7F612C1C3B3E2299 CRC64;
MNQIEPGVQY NYVYDEDEYM IQEEEWDRDL LLDPAWEKQQ RKTFTAWCNS HLRKAGTQIE
NIEEDFRNGL KLMLLLEVIS GERLPKPDRG KMRFHKIANV NKALDYIASK GVKLVSIGAE
EIVDGNVKMT LGMIWTIILR FAIQDISVEE TSAKEGLLLW CQRKTAPYRN VNIQNFHTSW
KDGLGLCALI HRHRPDLIDY SKLNKDDPIG NINLAMEIAE KHLDIPKMLD AEDIVNTPKP
DERAIMTYVS CFYHAFAGAE QAETAANRIC KVLAVNQENE RLMEEYERLA SELLEWIRRT
IPWLENRTPE KTMQAMQKKL EDFRDYRRKH KPPKVQEKCQ LEINFNTLQT KLRISNRPAF
MPSEGKMVSD IAGAWQRLEQ AEKGYEEWLL NEIRRLERLE HLAEKFRQKA STHETWAYGK
EQILLQKDYE SASLTEVRAL LRKHEAFESD LAAHQDRVEQ IAAIAQELNE LDYHDAVNVN
DRCQKICDQW DRLGTLTQKR REALERMEKL LETIDQLHLE FAKRAAPFNN WMEGAMEDLQ
DMFIVHSIEE IQSLITAHEQ FKATLPEADG ERQSIMAIQN EVEKVIQSYN IRISSSNPYS
TVTMDELRTK WDKVKQLVPI RDQSLQEELA RQHANERLRR QFAAQANAIG PWIQNKMEEI
ARSSIQITGA LEDQMNQLKQ YEHNIINYKN NIDKLEGDHQ LIQEALVFDN KHTNYTMEHI
RVGWELLLTT IARTINEVET QILTRDAKGI TQEQMNEFRA SFNHFDRRKN GLMDHEDFRA
CLISMGYDLG EAEFARIMTL VDPNGQGTVT FQSFIDFMTR ETADTDTAEQ VIASFRILAS
DKPYILAEEL RRELPPDQAQ YCIKRMPAYS GPGSVPGALD YAAFSSALYG ESDL
//
ID ACTN2_HUMAN Reviewed; 894 AA.
AC P35609; B1ANE4; Q86TF4; Q86TI8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1994, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Alpha-actinin-2;
DE AltName: Full=Alpha-actinin skeletal muscle isoform 2;
DE AltName: Full=F-actin cross-linking protein;
GN Name=ACTN2;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=1339456;
RA Beggs A.H., Byers T.J., Knoll J.H.M., Boyce F.M., Bruns G.A.P.,
RA Kunkel L.M.;
RT "Cloning and characterization of two human skeletal muscle alpha-
RT actinin genes located on chromosomes 1 and 11.";
RL J. Biol. Chem. 267:9281-9288(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10548523; DOI=10.1006/bbrc.1999.1661;
RA Tiso N., Majetti M., Stanchi F., Rampazzo A., Zimbello R., Nava A.,
RA Danieli G.A.;
RT "Fine mapping and genomic structure of ACTN2, the human gene coding
RT for the sarcomeric isoform of alpha-actinin-2, expressed in skeletal
RT and cardiac muscle.";
RL Biochem. Biophys. Res. Commun. 265:256-259(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
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 INTERACTION WITH LDB3.
RX PubMed=10427098; DOI=10.1083/jcb.146.2.465;
RA Faulkner G., Pallavicini A., Formentin E., Comelli A., Ievolella C.,
RA Trevisan S., Bortoletto G., Scannapieco P., Salamon M., Mouly V.,
RA Valle G., Lanfranchi G.;
RT "ZASP: a new Z-band alternatively spliced PDZ-motif protein.";
RL J. Cell Biol. 146:465-475(1999).
RN [7]
RP INTERACTION WITH MYOZ1.
RX PubMed=10984498; DOI=10.1074/jbc.M007493200;
RA Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G.,
RA Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P.,
RA Valle G., Lanfranchi G.;
RT "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-
RT disc of skeletal muscle.";
RL J. Biol. Chem. 275:41234-41242(2000).
RN [8]
RP INTERACTION WITH MYOZ1 AND MYOZ2.
RX PubMed=11114196; DOI=10.1073/pnas.260501097;
RA Frey N., Richardson J.A., Olson E.N.;
RT "Calsarcins, a novel family of sarcomeric calcineurin-binding
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14632-14637(2000).
RN [9]
RP INTERACTION WITH MYOZ1, AND SUBCELLULAR LOCATION.
RX PubMed=11171996; DOI=10.1073/pnas.041609698;
RA Takada F., Vander Woude D.L., Tong H.-Q., Thompson T.G., Watkins S.C.,
RA Kunkel L.M., Beggs A.H.;
RT "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of
RT skeletal muscle Z lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1595-1600(2001).
RN [10]
RP INTERACTION WITH MYOZ3.
RX PubMed=11842093; DOI=10.1074/jbc.M200712200;
RA Frey N., Olson E.N.;
RT "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin
RT family, interacts with multiple Z-disc proteins.";
RL J. Biol. Chem. 277:13998-14004(2002).
RN [11]
RP INTERACTION WITH PARVB.
RX PubMed=15159419; DOI=10.1083/jcb.200308141;
RA Yamaji S., Suzuki A., Kanamori H., Mishima W., Yoshimi R.,
RA Takasaki H., Takabayashi M., Fujimaki K., Fujisawa S., Ohno S.,
RA Ishigatsubo Y.;
RT "Affixin interacts with alpha-actinin and mediates integrin signaling
RT for reorganization of F-actin induced by initial cell-substrate
RT interaction.";
RL J. Cell Biol. 165:539-551(2004).
RN [12]
RP INTERACTION WITH XIRP2.
RX PubMed=17046827; DOI=10.1074/jbc.M603244200;
RA Huang H.-T., Brand O.M., Mathew M., Ignatiou C., Ewen E.P.,
RA McCalmon S.A., Naya F.J.;
RT "Myomaxin is a novel transcriptional target of MEF2A that encodes a
RT Xin-related alpha-actinin-interacting protein.";
RL J. Biol. Chem. 281:39370-39379(2006).
RN [13]
RP INTERACTION WITH DST, AND SUBCELLULAR LOCATION.
RX PubMed=19932097; DOI=10.1016/j.yexcr.2009.11.010;
RA Steiner-Champliaud M.F., Schneider Y., Favre B., Paulhe F.,
RA Praetzel-Wunder S., Faulkner G., Konieczny P., Raith M., Wiche G.,
RA Adebola A., Liem R.K., Langbein L., Sonnenberg A., Fontao L.,
RA Borradori L.;
RT "BPAG1 isoform-b: complex distribution pattern in striated and heart
RT muscle and association with plectin and alpha-actinin.";
RL Exp. Cell Res. 316:297-313(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP UBIQUITINATION BY FBXL22.
RX PubMed=22972877; DOI=10.1161/CIRCRESAHA.112.271007;
RA Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D.,
RA Berger I.M., Wiemann S., Korn B., Koegl M., Backs J., Katus H.A.,
RA Rottbauer W., Frey N.;
RT "F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box
RT protein that regulates sarcomeric protein turnover and is essential
RT for maintenance of contractile function in vivo.";
RL Circ. Res. 111:1504-1516(2012).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 391-637.
RX PubMed=10481917; DOI=10.1016/S0092-8674(00)81981-9;
RA Djinovic-Carugo K., Young P., Gautel M., Saraste M.;
RT "Structure of the alpha-actinin rod: molecular basis for cross-linking
RT of actin filaments.";
RL Cell 98:537-546(1999).
RN [17]
RP STRUCTURE BY NMR OF 823-894 IN COMPLEX WITH A TITIN Z-REPEAT.
RX PubMed=11573089; DOI=10.1038/nsb1001-853;
RA Atkinson R.A., Joseph C., Kelly G., Muskett F.W., Frenkiel T.A.,
RA Nietlispach D., Pastore A.;
RT "Ca2+-independent binding of an EF-hand domain to a novel motif in the
RT alpha-actinin-titin complex.";
RL Nat. Struct. Biol. 8:853-857(2001).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 274-746.
RX PubMed=11470434; DOI=10.1016/S0969-2126(01)00619-0;
RA Ylanne J., Scheffzek K., Young P., Saraste M.;
RT "Crystal structure of the alpha-actinin rod reveals an extensive
RT torsional twist.";
RL Structure 9:597-604(2001).
RN [19]
RP VARIANT CMD1AA ARG-9, AND VARIANT VAL-604.
RX PubMed=14567970; DOI=10.1016/S1096-7192(03)00142-2;
RA Mohapatra B., Jimenez S., Lin J.H., Bowles K.R., Coveler K.J.,
RA Marx J.G., Chrisco M.A., Murphy R.T., Lurie P.R., Schwartz R.J.,
RA Elliott P.M., Vatta M., McKenna W., Towbin J.A., Bowles N.E.;
RT "Mutations in the muscle LIM protein and alpha-actinin-2 genes in
RT dilated cardiomyopathy and endocardial fibroelastosis.";
RL Mol. Genet. Metab. 80:207-215(2003).
CC -!- FUNCTION: F-actin cross-linking protein which is thought to anchor
CC actin to a variety of intracellular structures. This is a bundling
CC protein.
CC -!- SUBUNIT: Homodimer; antiparallel. Also forms heterodimers with
CC ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts
CC via its C-terminal region with the LDB3 PDZ domain. Interacts with
CC XIRP2. Interacts with DST isoform 1 (via N-terminus). Interacts
CC with PARVB.
CC -!- INTERACTION:
CC Self; NbExp=8; IntAct=EBI-77797, EBI-77797;
CC Q61824:Adam12 (xeno); NbExp=3; IntAct=EBI-77797, EBI-77785;
CC P03950:ANG; NbExp=4; IntAct=EBI-77797, EBI-525291;
CC Q9UKG1:APPL1; NbExp=2; IntAct=EBI-77797, EBI-741243;
CC Q9NRI5:DISC1; NbExp=3; IntAct=EBI-77797, EBI-529989;
CC O75923:DYSF; NbExp=2; IntAct=EBI-77797, EBI-2799016;
CC P22460:KCNA5; NbExp=6; IntAct=EBI-77797, EBI-6426121;
CC P54296:MYOM2; NbExp=2; IntAct=EBI-77797, EBI-5357134;
CC Q8WZ42:TTN; NbExp=16; IntAct=EBI-77797, EBI-681210;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line.
CC Note=Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal
CC muscle.
CC -!- TISSUE SPECIFICITY: Expressed in both skeletal and cardiac muscle.
CC -!- PTM: Ubiquitinated by FBXL22, leading to proteasomal degradation.
CC -!- DISEASE: Cardiomyopathy, dilated 1AA (CMD1AA) [MIM:612158]: A
CC disorder characterized by ventricular dilation and impaired
CC systolic function, resulting in congestive heart failure and
CC arrhythmia. Patients are at risk of premature death. Note=The
CC disease is caused by mutations affecting the gene represented in
CC this entry.
CC -!- SIMILARITY: Belongs to the alpha-actinin family.
CC -!- SIMILARITY: Contains 1 actin-binding domain.
CC -!- SIMILARITY: Contains 2 CH (calponin-homology) domains.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- SIMILARITY: Contains 4 spectrin repeats.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACTN2";
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DR EMBL; M86406; AAA51583.1; -; mRNA.
DR EMBL; M86804; AAA51584.1; -; Genomic_DNA.
DR EMBL; AJ249756; CAB61269.1; -; Genomic_DNA.
DR EMBL; AJ249757; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249758; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249759; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249760; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249761; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249762; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249763; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249764; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249765; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249766; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249767; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249768; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249769; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249770; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249771; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249772; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249773; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249774; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249775; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AJ249776; CAB61269.1; JOINED; Genomic_DNA.
DR EMBL; AL359185; CAH73201.1; -; Genomic_DNA.
DR EMBL; AL359921; CAH73201.1; JOINED; Genomic_DNA.
DR EMBL; AL359921; CAI13778.1; -; Genomic_DNA.
DR EMBL; AL359185; CAI13778.1; JOINED; Genomic_DNA.
DR EMBL; CH471098; EAW70064.1; -; Genomic_DNA.
DR EMBL; BC047901; AAH47901.2; -; mRNA.
DR EMBL; BC051770; AAH51770.2; -; mRNA.
DR PIR; A40199; FAHUA2.
DR RefSeq; NP_001094.1; NM_001103.3.
DR UniGene; Hs.498178; -.
DR PDB; 1H8B; NMR; -; A=823-894.
DR PDB; 1HCI; X-ray; 2.80 A; A/B=274-746.
DR PDB; 1QUU; X-ray; 2.50 A; A=391-637.
DR PDBsum; 1H8B; -.
DR PDBsum; 1HCI; -.
DR PDBsum; 1QUU; -.
DR ProteinModelPortal; P35609; -.
DR SMR; P35609; 35-261, 274-746, 751-894.
DR DIP; DIP-383N; -.
DR IntAct; P35609; 28.
DR MINT; MINT-145583; -.
DR STRING; 9606.ENSP00000355537; -.
DR PhosphoSite; P35609; -.
DR DMDM; 543742; -.
DR PaxDb; P35609; -.
DR PeptideAtlas; P35609; -.
DR PRIDE; P35609; -.
DR Ensembl; ENST00000366578; ENSP00000355537; ENSG00000077522.
DR GeneID; 88; -.
DR KEGG; hsa:88; -.
DR UCSC; uc001hyf.2; human.
DR CTD; 88; -.
DR GeneCards; GC01P236849; -.
DR HGNC; HGNC:164; ACTN2.
DR HPA; HPA006035; -.
DR HPA; HPA008315; -.
DR MIM; 102573; gene.
DR MIM; 612158; phenotype.
DR neXtProt; NX_P35609; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR PharmGKB; PA25; -.
DR eggNOG; COG5069; -.
DR HOGENOM; HOG000263418; -.
DR HOVERGEN; HBG050453; -.
DR InParanoid; P35609; -.
DR KO; K05699; -.
DR OrthoDB; EOG72C4ZJ; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR EvolutionaryTrace; P35609; -.
DR GeneWiki; Actinin,_alpha_2; -.
DR GenomeRNAi; 88; -.
DR NextBio; 327; -.
DR PRO; PR:P35609; -.
DR ArrayExpress; P35609; -.
DR Bgee; P35609; -.
DR CleanEx; HS_ACTN2; -.
DR Genevestigator; P35609; -.
DR GO; GO:0005884; C:actin filament; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; TAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IMP:UniProtKB.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0031143; C:pseudopodium; TAS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0051373; F:FATZ binding; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; TAS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0008307; F:structural constituent of muscle; TAS:ProtInc.
DR GO; GO:0030375; F:thyroid hormone receptor coactivator activity; IEA:Ensembl.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0030035; P:microspike assembly; IDA:UniProtKB.
DR GO; GO:0030049; P:muscle filament sliding; TAS:Reactome.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IMP:BHF-UCL.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IMP:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:1901018; P:positive regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IDA:BHF-UCL.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:BHF-UCL.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 2.
DR Gene3D; 1.10.418.10; -; 2.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014837; EF-hand_Ca_insen.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF08726; EFhand_Ca_insen; 1.
DR Pfam; PF00435; Spectrin; 4.
DR SMART; SM00033; CH; 2.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00150; SPEC; 3.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Calcium; Cardiomyopathy;
KW Complete proteome; Cytoplasm; Disease mutation; Metal-binding;
KW Polymorphism; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 894 Alpha-actinin-2.
FT /FTId=PRO_0000073435.
FT DOMAIN 1 254 Actin-binding.
FT DOMAIN 38 142 CH 1.
FT DOMAIN 151 254 CH 2.
FT REPEAT 281 391 Spectrin 1.
FT REPEAT 401 506 Spectrin 2.
FT REPEAT 516 627 Spectrin 3.
FT REPEAT 637 740 Spectrin 4.
FT DOMAIN 753 788 EF-hand 1.
FT DOMAIN 789 824 EF-hand 2.
FT CA_BIND 766 777 1; possibly ancestral.
FT CA_BIND 802 813 2; possibly ancestral.
FT VARIANT 9 9 Q -> R (in CMD1AA; dbSNP:rs121434525).
FT /FTId=VAR_054628.
FT VARIANT 604 604 M -> V (in dbSNP:rs35997569).
FT /FTId=VAR_033487.
FT HELIX 275 294
FT HELIX 296 303
FT STRAND 311 313
FT TURN 314 317
FT HELIX 318 329
FT HELIX 331 340
FT TURN 341 343
FT HELIX 344 347
FT TURN 351 356
FT HELIX 364 366
FT STRAND 368 370
FT HELIX 371 382
FT HELIX 393 416
FT TURN 417 419
FT HELIX 420 425
FT HELIX 428 430
FT HELIX 434 470
FT HELIX 476 536
FT TURN 537 540
FT TURN 548 550
FT HELIX 551 562
FT HELIX 564 588
FT HELIX 604 632
FT TURN 666 669
FT HELIX 672 704
FT HELIX 716 741
FT HELIX 828 838
FT STRAND 843 845
FT HELIX 847 853
FT HELIX 856 865
FT HELIX 881 888
SQ SEQUENCE 894 AA; 103854 MW; 7F612C1C3B3E2299 CRC64;
MNQIEPGVQY NYVYDEDEYM IQEEEWDRDL LLDPAWEKQQ RKTFTAWCNS HLRKAGTQIE
NIEEDFRNGL KLMLLLEVIS GERLPKPDRG KMRFHKIANV NKALDYIASK GVKLVSIGAE
EIVDGNVKMT LGMIWTIILR FAIQDISVEE TSAKEGLLLW CQRKTAPYRN VNIQNFHTSW
KDGLGLCALI HRHRPDLIDY SKLNKDDPIG NINLAMEIAE KHLDIPKMLD AEDIVNTPKP
DERAIMTYVS CFYHAFAGAE QAETAANRIC KVLAVNQENE RLMEEYERLA SELLEWIRRT
IPWLENRTPE KTMQAMQKKL EDFRDYRRKH KPPKVQEKCQ LEINFNTLQT KLRISNRPAF
MPSEGKMVSD IAGAWQRLEQ AEKGYEEWLL NEIRRLERLE HLAEKFRQKA STHETWAYGK
EQILLQKDYE SASLTEVRAL LRKHEAFESD LAAHQDRVEQ IAAIAQELNE LDYHDAVNVN
DRCQKICDQW DRLGTLTQKR REALERMEKL LETIDQLHLE FAKRAAPFNN WMEGAMEDLQ
DMFIVHSIEE IQSLITAHEQ FKATLPEADG ERQSIMAIQN EVEKVIQSYN IRISSSNPYS
TVTMDELRTK WDKVKQLVPI RDQSLQEELA RQHANERLRR QFAAQANAIG PWIQNKMEEI
ARSSIQITGA LEDQMNQLKQ YEHNIINYKN NIDKLEGDHQ LIQEALVFDN KHTNYTMEHI
RVGWELLLTT IARTINEVET QILTRDAKGI TQEQMNEFRA SFNHFDRRKN GLMDHEDFRA
CLISMGYDLG EAEFARIMTL VDPNGQGTVT FQSFIDFMTR ETADTDTAEQ VIASFRILAS
DKPYILAEEL RRELPPDQAQ YCIKRMPAYS GPGSVPGALD YAAFSSALYG ESDL
//
MIM
102573
*RECORD*
*FIELD* NO
102573
*FIELD* TI
*102573 ACTININ, ALPHA-2; ACTN2
*FIELD* TX
CLONING
Alpha-actinin is an actin-binding protein with multiple roles in
read moredifferent cell types. In nonmuscle cells, the cytoskeletal isoform is
found along microfilament bundles and adherens-type junctions, where it
is involved in binding actin to the membrane (see ACTN1; 102575). In
contrast, skeletal, cardiac, and smooth muscle isoforms are localized to
the Z disc and analogous dense bodies, where they help anchor the
myofibrillar actin filaments. Beggs et al. (1992) characterized 2 human
muscle-specific alpha-actinin genes, ACTN2 and ACTN3 (102574). They
identified 3 ACTN2 transcripts that differed only in their use of
polyadenylation signals. The deduced 894-amino acid protein has a
calculated molecular mass of about 104 kD. ACTN2 has an N-terminal
actin-binding domain of about 250 amino acids, followed by 4 central
repeats and 2 EF-hand motifs near the C terminus. Northern blot analysis
of mouse tissues detected Actn2 expression in skeletal muscle and heart,
but not in brain, liver, kidney, or small intestine. Two major ACTN2
bands were detected in human fetal skeletal muscle.
Seto et al. (2011) stated that the central repeats of ACTN2 are spectrin
(see 182860)-like repeats that form a rod domain.
MAPPING
Using somatic cell hybrids, Beggs et al. (1992) mapped the ACTN2 and
ACTN3 genes to chromosomes 1 and 11, respectively. In situ hybridization
placed the ACTN2 locus at 1q42-q43. Beggs et al. (1992) identified a
polymorphic (CA)n repeat within the ACTN2 gene and used it to position
the ACTN2 gene on the CEPH linkage map of chromosome 1.
Mills et al. (2001) mapped the 4 murine actinin orthologs, which were
all located at evolutionarily conserved syntenic regions for the 4 human
genes.
GENE FUNCTION
Mills et al. (2001) observed that murine Actn2 and Actn3 were
differentially expressed, spatially and temporally, during embryonic
development and, in contrast to humans, alpha-actinin-2 expression did
not completely overlap with alpha-actinin-3 in postnatal skeletal
muscle, suggesting independent function.
Seto et al. (2011) found that expression of Actn2 was upregulated in
Actn3 -/- mouse extensor digitorum longus muscle such that the total
sarcomeric content of alpha-actinin was unchanged. Actn3 -/- muscle was
susceptible to contraction-induced damage compared with wildtype. The
Z-disc proteins Zasp (LDB3; 605906), titin (TTN; 188840), and vinculin
(VCL; 193065) bound more avidly to Actn2 than to Actn3, suggesting a
biochemical basis for altered mechanics and fragility in Actn3 -/-
muscle.
MOLECULAR GENETICS
In a 7-year-old girl who died of dilated cardiomyopathy (CMD1AA; 612158)
and was negative for mutation in 8 known cardiomyopathy genes, Mohapatra
et al. (2003) identified heterozygosity for a missense mutation in the
ACTN2 gene (Q9R; 102573.0001).
ANIMAL MODEL
Mutations in the dystrophin gene (DMD; 300377) result in Duchenne
muscular dystrophy. Dystrophin is a multidomain protein that functions
to stabilize the sarcolemmal membrane during muscle contraction.
Dystrophin shares considerable homology with alpha-actinin. To explore
the hypothesis that the dystrophin rod domain acts as a spacer region,
Harper et al. (2002) expressed a chimeric micro-dystrophin transgene
containing the 4-repeat rod domain of alpha-actinin-2 in mdx mice. The
transgene was incapable of correcting the morphologic pathology of the
mdx mouse, but still functioned to assemble the dystrophin-glycoprotein
complex at the membrane and provided some protection from
contraction-induced injury. The authors concluded that different
spectrin-like repeats are not equivalent, and proposed that the
dystrophin rod domain is not merely a spacer but likely contributes an
important mechanical role to overall dystrophin function.
*FIELD* AV
.0001
CARDIOMYOPATHY, DILATED, 1AA (1 family)
ACTN2, GLN9ARG
In a 7-year-old girl who died of dilated cardiomyopathy (CMD1AA;
612158), Mohapatra et al. (2003) identified heterozygosity for a 26A-G
transition in exon 1 of the ACTN2 gene, resulting in a substitution of
arg for the conserved residue gln9 (Q9R). The mutation was not found in
the unaffected mother or in 200 controls; DNA was not available from the
father, who had died from idiopathic CMD at 42 years of age.
*FIELD* RF
1. Beggs, A. H.; Byers, T. J.; Knoll, J. H. M.; Boyce, F. M.; Bruns,
G. A. P.; Kunkel, L. M.: Cloning and characterization of two human
skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. J.
Biol. Chem. 267: 9281-9288, 1992.
2. Beggs, A. H.; Phillips, H. A.; Kozman, H.; Mulley, J. C.; Wilton,
S. D.; Kunkel, L. M.; Laing, N. G.: A (CA)n repeat polymorphism for
the human skeletal muscle alpha-actinin gene ACTN2 and its localization
on the linkage map of chromosome 1. Genomics 13: 1314-1315, 1992.
3. Harper, S. Q.; Crawford, R. W.; DellRusso, C.; Chamberlain, J.
S.: Spectrin-like repeats from dystrophin and alpha-actinin-2 are
not functionally interchangeable. Hum. Molec. Genet. 11: 1807-1815,
2002.
4. Mills, M. A.; Yang, N.; Weinberger, R. P.; Vander Woude, D. L.;
Beggs, A. H.; Easteal, S.; North, K. N.: Differential expression
of the actin-binding proteins, alpha-actinin-2 and -3, in different
species: implications for the evolution of functional redundancy. Hum.
Molec. Genet. 10: 1335-1346, 2001.
5. Mohapatra, B.; Jimenez, S.; Lin, J. H.; Bowles, K. R.; Coveler,
K. J.; Marx, J. G.; Chrisco, M. A.; Murphy, R. T.; Lurie, P. R.; Schwartz,
R. J.; Elliott, P. M.; Vatta, M.; McKenna, W.; Towbin, J. A.; Bowles,
N. E.: Mutations in the muscle LIM protein and alpha-actinin-2 genes
in dilated cardiomyopathy and endocardial fibroelastosis. Molec.
Genet. Metab. 80: 207-215, 2003.
6. Seto, J. T.; Lek, M.; Quinlan, K. G. R.; Houweling, P. J.; Zheng,
X. F.; Garton, F.; MacArthur, D. G.; Raftery, J. M.; Garvey, S. M.;
Hauser, M. A.; Yang, N.; Head, S. I.; North, K. N.: Deficiency of
alpha-actinin-3 is associated with increased susceptibility to contraction-induced
damage and skeletal muscle remodeling. Hum. Molec. Genet. 20: 2914-2927,
2011.
*FIELD* CN
Patricia A. Hartz - updated: 4/10/2013
Marla J. F. O'Neill - updated: 6/30/2008
George E. Tiller - updated: 7/3/2003
George E. Tiller - updated: 11/12/2001
*FIELD* CD
Victor A. McKusick: 8/14/1992
*FIELD* ED
carol: 11/04/2013
carol: 8/5/2013
mgross: 4/10/2013
terry: 7/3/2008
alopez: 7/1/2008
alopez: 6/30/2008
terry: 6/30/2008
cwells: 7/3/2003
alopez: 11/21/2001
cwells: 11/20/2001
cwells: 11/12/2001
carol: 10/13/1992
carol: 9/9/1992
carol: 8/14/1992
*RECORD*
*FIELD* NO
102573
*FIELD* TI
*102573 ACTININ, ALPHA-2; ACTN2
*FIELD* TX
CLONING
Alpha-actinin is an actin-binding protein with multiple roles in
read moredifferent cell types. In nonmuscle cells, the cytoskeletal isoform is
found along microfilament bundles and adherens-type junctions, where it
is involved in binding actin to the membrane (see ACTN1; 102575). In
contrast, skeletal, cardiac, and smooth muscle isoforms are localized to
the Z disc and analogous dense bodies, where they help anchor the
myofibrillar actin filaments. Beggs et al. (1992) characterized 2 human
muscle-specific alpha-actinin genes, ACTN2 and ACTN3 (102574). They
identified 3 ACTN2 transcripts that differed only in their use of
polyadenylation signals. The deduced 894-amino acid protein has a
calculated molecular mass of about 104 kD. ACTN2 has an N-terminal
actin-binding domain of about 250 amino acids, followed by 4 central
repeats and 2 EF-hand motifs near the C terminus. Northern blot analysis
of mouse tissues detected Actn2 expression in skeletal muscle and heart,
but not in brain, liver, kidney, or small intestine. Two major ACTN2
bands were detected in human fetal skeletal muscle.
Seto et al. (2011) stated that the central repeats of ACTN2 are spectrin
(see 182860)-like repeats that form a rod domain.
MAPPING
Using somatic cell hybrids, Beggs et al. (1992) mapped the ACTN2 and
ACTN3 genes to chromosomes 1 and 11, respectively. In situ hybridization
placed the ACTN2 locus at 1q42-q43. Beggs et al. (1992) identified a
polymorphic (CA)n repeat within the ACTN2 gene and used it to position
the ACTN2 gene on the CEPH linkage map of chromosome 1.
Mills et al. (2001) mapped the 4 murine actinin orthologs, which were
all located at evolutionarily conserved syntenic regions for the 4 human
genes.
GENE FUNCTION
Mills et al. (2001) observed that murine Actn2 and Actn3 were
differentially expressed, spatially and temporally, during embryonic
development and, in contrast to humans, alpha-actinin-2 expression did
not completely overlap with alpha-actinin-3 in postnatal skeletal
muscle, suggesting independent function.
Seto et al. (2011) found that expression of Actn2 was upregulated in
Actn3 -/- mouse extensor digitorum longus muscle such that the total
sarcomeric content of alpha-actinin was unchanged. Actn3 -/- muscle was
susceptible to contraction-induced damage compared with wildtype. The
Z-disc proteins Zasp (LDB3; 605906), titin (TTN; 188840), and vinculin
(VCL; 193065) bound more avidly to Actn2 than to Actn3, suggesting a
biochemical basis for altered mechanics and fragility in Actn3 -/-
muscle.
MOLECULAR GENETICS
In a 7-year-old girl who died of dilated cardiomyopathy (CMD1AA; 612158)
and was negative for mutation in 8 known cardiomyopathy genes, Mohapatra
et al. (2003) identified heterozygosity for a missense mutation in the
ACTN2 gene (Q9R; 102573.0001).
ANIMAL MODEL
Mutations in the dystrophin gene (DMD; 300377) result in Duchenne
muscular dystrophy. Dystrophin is a multidomain protein that functions
to stabilize the sarcolemmal membrane during muscle contraction.
Dystrophin shares considerable homology with alpha-actinin. To explore
the hypothesis that the dystrophin rod domain acts as a spacer region,
Harper et al. (2002) expressed a chimeric micro-dystrophin transgene
containing the 4-repeat rod domain of alpha-actinin-2 in mdx mice. The
transgene was incapable of correcting the morphologic pathology of the
mdx mouse, but still functioned to assemble the dystrophin-glycoprotein
complex at the membrane and provided some protection from
contraction-induced injury. The authors concluded that different
spectrin-like repeats are not equivalent, and proposed that the
dystrophin rod domain is not merely a spacer but likely contributes an
important mechanical role to overall dystrophin function.
*FIELD* AV
.0001
CARDIOMYOPATHY, DILATED, 1AA (1 family)
ACTN2, GLN9ARG
In a 7-year-old girl who died of dilated cardiomyopathy (CMD1AA;
612158), Mohapatra et al. (2003) identified heterozygosity for a 26A-G
transition in exon 1 of the ACTN2 gene, resulting in a substitution of
arg for the conserved residue gln9 (Q9R). The mutation was not found in
the unaffected mother or in 200 controls; DNA was not available from the
father, who had died from idiopathic CMD at 42 years of age.
*FIELD* RF
1. Beggs, A. H.; Byers, T. J.; Knoll, J. H. M.; Boyce, F. M.; Bruns,
G. A. P.; Kunkel, L. M.: Cloning and characterization of two human
skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. J.
Biol. Chem. 267: 9281-9288, 1992.
2. Beggs, A. H.; Phillips, H. A.; Kozman, H.; Mulley, J. C.; Wilton,
S. D.; Kunkel, L. M.; Laing, N. G.: A (CA)n repeat polymorphism for
the human skeletal muscle alpha-actinin gene ACTN2 and its localization
on the linkage map of chromosome 1. Genomics 13: 1314-1315, 1992.
3. Harper, S. Q.; Crawford, R. W.; DellRusso, C.; Chamberlain, J.
S.: Spectrin-like repeats from dystrophin and alpha-actinin-2 are
not functionally interchangeable. Hum. Molec. Genet. 11: 1807-1815,
2002.
4. Mills, M. A.; Yang, N.; Weinberger, R. P.; Vander Woude, D. L.;
Beggs, A. H.; Easteal, S.; North, K. N.: Differential expression
of the actin-binding proteins, alpha-actinin-2 and -3, in different
species: implications for the evolution of functional redundancy. Hum.
Molec. Genet. 10: 1335-1346, 2001.
5. Mohapatra, B.; Jimenez, S.; Lin, J. H.; Bowles, K. R.; Coveler,
K. J.; Marx, J. G.; Chrisco, M. A.; Murphy, R. T.; Lurie, P. R.; Schwartz,
R. J.; Elliott, P. M.; Vatta, M.; McKenna, W.; Towbin, J. A.; Bowles,
N. E.: Mutations in the muscle LIM protein and alpha-actinin-2 genes
in dilated cardiomyopathy and endocardial fibroelastosis. Molec.
Genet. Metab. 80: 207-215, 2003.
6. Seto, J. T.; Lek, M.; Quinlan, K. G. R.; Houweling, P. J.; Zheng,
X. F.; Garton, F.; MacArthur, D. G.; Raftery, J. M.; Garvey, S. M.;
Hauser, M. A.; Yang, N.; Head, S. I.; North, K. N.: Deficiency of
alpha-actinin-3 is associated with increased susceptibility to contraction-induced
damage and skeletal muscle remodeling. Hum. Molec. Genet. 20: 2914-2927,
2011.
*FIELD* CN
Patricia A. Hartz - updated: 4/10/2013
Marla J. F. O'Neill - updated: 6/30/2008
George E. Tiller - updated: 7/3/2003
George E. Tiller - updated: 11/12/2001
*FIELD* CD
Victor A. McKusick: 8/14/1992
*FIELD* ED
carol: 11/04/2013
carol: 8/5/2013
mgross: 4/10/2013
terry: 7/3/2008
alopez: 7/1/2008
alopez: 6/30/2008
terry: 6/30/2008
cwells: 7/3/2003
alopez: 11/21/2001
cwells: 11/20/2001
cwells: 11/12/2001
carol: 10/13/1992
carol: 9/9/1992
carol: 8/14/1992
MIM
612158
*RECORD*
*FIELD* NO
612158
*FIELD* TI
#612158 CARDIOMYOPATHY, DILATED, 1AA; CMD1AA
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moredilated cardiomyopathy-1AA (CMD1AA) is caused by heterozygous mutation
in the gene encoding alpha-actinin-2 (ACTN2; 102573) on chromosome 1q43.
One such family has been reported.
For a general phenotypic description and a discussion of genetic
heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
CLINICAL FEATURES
Mohapatra et al. (2003) reported a 7-year-old girl who died of dilated
cardiomyopathy (CMD) only a few weeks after the onset of symptoms. At
autopsy, marked dilation of both ventricles, myocyte hypertrophy, and
interstitial fibrosis were noted; there were no viral genomic sequences
on PCR analysis of cardiac tissue or histologic evidence of myocarditis.
Her father had died of acute-onset idiopathic CMD at 42 years of age.
MOLECULAR GENETICS
In a 7-year-old girl who died of dilated cardiomyopathy and was negative
for mutation in 8 known cardiomyopathy genes, Mohapatra et al. (2003)
identified heterozygosity for a missense mutation at a conserved residue
in the ACTN2 gene (102573.0001). The mutation was not found in the
mother or in 200 controls; DNA was unavailable from the deceased father.
*FIELD* RF
1. Mohapatra, B.; Jimenez, S.; Lin, J. H.; Bowles, K. R.; Coveler,
K. J.; Marx, J. G.; Chrisco, M. A.; Murphy, R. T.; Lurie, P. R.; Schwartz,
R. J.; Elliott, P. M.; Vatta, M.; McKenna, W.; Towbin, J. A.; Bowles,
N. E.: Mutations in the muscle LIM protein and alpha-actinin-2 genes
in dilated cardiomyopathy and endocardial fibroelastosis. Molec.
Genet. Metab. 80: 207-215, 2003.
*FIELD* CD
Marla J. F. O'Neill: 6/30/2008
*FIELD* ED
carol: 11/08/2013
alopez: 6/30/2008
*RECORD*
*FIELD* NO
612158
*FIELD* TI
#612158 CARDIOMYOPATHY, DILATED, 1AA; CMD1AA
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moredilated cardiomyopathy-1AA (CMD1AA) is caused by heterozygous mutation
in the gene encoding alpha-actinin-2 (ACTN2; 102573) on chromosome 1q43.
One such family has been reported.
For a general phenotypic description and a discussion of genetic
heterogeneity of dilated cardiomyopathy, see CMD1A (115200).
CLINICAL FEATURES
Mohapatra et al. (2003) reported a 7-year-old girl who died of dilated
cardiomyopathy (CMD) only a few weeks after the onset of symptoms. At
autopsy, marked dilation of both ventricles, myocyte hypertrophy, and
interstitial fibrosis were noted; there were no viral genomic sequences
on PCR analysis of cardiac tissue or histologic evidence of myocarditis.
Her father had died of acute-onset idiopathic CMD at 42 years of age.
MOLECULAR GENETICS
In a 7-year-old girl who died of dilated cardiomyopathy and was negative
for mutation in 8 known cardiomyopathy genes, Mohapatra et al. (2003)
identified heterozygosity for a missense mutation at a conserved residue
in the ACTN2 gene (102573.0001). The mutation was not found in the
mother or in 200 controls; DNA was unavailable from the deceased father.
*FIELD* RF
1. Mohapatra, B.; Jimenez, S.; Lin, J. H.; Bowles, K. R.; Coveler,
K. J.; Marx, J. G.; Chrisco, M. A.; Murphy, R. T.; Lurie, P. R.; Schwartz,
R. J.; Elliott, P. M.; Vatta, M.; McKenna, W.; Towbin, J. A.; Bowles,
N. E.: Mutations in the muscle LIM protein and alpha-actinin-2 genes
in dilated cardiomyopathy and endocardial fibroelastosis. Molec.
Genet. Metab. 80: 207-215, 2003.
*FIELD* CD
Marla J. F. O'Neill: 6/30/2008
*FIELD* ED
carol: 11/08/2013
alopez: 6/30/2008