Entry sw:ACTN3_HUMAN

ID   ACTN3_HUMAN             Reviewed;         901 AA.
AC   Q08043; A6NP77; Q4KKV2;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   25-NOV-2008, sequence version 2.
DT   30-NOV-2016, entry version 157.
DE   RecName: Full=Alpha-actinin-3;
DE   AltName: Full=Alpha-actinin skeletal muscle isoform 3;
DE   AltName: Full=F-actin cross-linking protein;
GN   Name=ACTN3;
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], AND VARIANTS GLN-523; ARG-628 AND ARG-776.
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLN-523; ARG-628
RP   AND ARG-776.
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   [4]
RP   TISSUE SPECIFICITY, AND POLYMORPHISM.
RX   PubMed=11440986; DOI=10.1093/hmg/10.13.1335;
RA   Mills M., Yang N., Weinberger R., Vander Woude D.L., Beggs A.H.,
RA   Easteal S., North K.N.;
RT   "Differential expression of the actin-binding proteins, alpha-actinin-
RT   2 and -3, in different species: implications for the evolution of
RT   functional redundancy.";
RL   Hum. Mol. Genet. 10:1335-1346(2001).
RN   [5]
RP   INTERACTION WITH MYOZ1.
RX   PubMed=11171996; DOI=10.1073/pnas.98.4.1595;
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   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.M111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C.,
RA   Meinnel T., Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-273.
RX   PubMed=15808860; DOI=10.1016/j.jmb.2005.01.002;
RA   Franzot G., Sjoblom B., Gautel M., Djinovic Carugo K.;
RT   "The crystal structure of the actin binding domain from alpha-actinin
RT   in its closed conformation: structural insight into phospholipid
RT   regulation of alpha-actinin.";
RL   J. Mol. Biol. 348:151-165(2005).
RN   [8]
RP   VARIANT GLN-523, AND POLYMORPHISM.
RX   PubMed=10192379; DOI=10.1038/7675;
RA   North K.N., Yang N., Wattanasirichaigoon D., Mills M., Easteal S.,
RA   Beggs A.H.;
RT   "A common nonsense mutation results in alpha-actinin-3 deficiency in
RT   the general population.";
RL   Nat. Genet. 21:353-354(1999).
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       ACTN2. Interacts with MYOZ1. {ECO:0000269|PubMed:11171996}.
CC   -!- INTERACTION:
CC       P12814:ACTN1; NbExp=4; IntAct=EBI-2880652, EBI-351710;
CC   -!- TISSUE SPECIFICITY: Expressed only in a subset of type 2 skeletal
CC       muscle fibers. {ECO:0000269|PubMed:11440986}.
CC   -!- POLYMORPHISM: About 18% of the world population lack a functional
CC       ACTN3 due to a stop codon polymorphism at position 577. The
CC       absence of a functional ACTN3 expression is not correlated with a
CC       disease state [MIM:102574].
CC   -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 actin-binding domain. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 2 CH (calponin-homology) domains.
CC       {ECO:0000255|PROSITE-ProRule:PRU00044}.
CC   -!- SIMILARITY: Contains 2 EF-hand domains. {ECO:0000255|PROSITE-
CC       ProRule:PRU00448}.
CC   -!- SIMILARITY: Contains 4 spectrin repeats. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AP002748; Type=Miscellaneous discrepancy; Note=According to the human genome assembly there is a stop codon in position 577 which is only found in 18% of the world population.; Evidence={ECO:0000305};
DR   EMBL; M86407; AAA51585.1; -; mRNA.
DR   EMBL; AP002748; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC099647; AAH99647.1; -; mRNA.
DR   EMBL; BC099649; AAH99649.1; -; mRNA.
DR   PIR; B40199; FAHUA3.
DR   RefSeq; NP_001095.2; NM_001104.3.
DR   RefSeq; NP_001245300.2; NM_001258371.2.
DR   UniGene; Hs.654432; -.
DR   UniGene; Hs.737862; -.
DR   PDB; 1TJT; X-ray; 2.19 A; A=26-273.
DR   PDB; 1WKU; X-ray; 1.60 A; A/B=26-273.
DR   PDB; 3LUE; EM; -; K/L/M/N/O/P/Q/R/S/T=42-150.
DR   PDBsum; 1TJT; -.
DR   PDBsum; 1WKU; -.
DR   PDBsum; 3LUE; -.
DR   ProteinModelPortal; Q08043; -.
DR   SMR; Q08043; -.
DR   BioGrid; 106604; 22.
DR   IntAct; Q08043; 32.
DR   MINT; MINT-269455; -.
DR   iPTMnet; Q08043; -.
DR   PhosphoSitePlus; Q08043; -.
DR   SwissPalm; Q08043; -.
DR   DMDM; 215273967; -.
DR   EPD; Q08043; -.
DR   MaxQB; Q08043; -.
DR   PeptideAtlas; Q08043; -.
DR   PRIDE; Q08043; -.
DR   Ensembl; ENST00000513398; ENSP00000426797; ENSG00000248746.
DR   GeneID; 89; -.
DR   KEGG; hsa:89; -.
DR   UCSC; uc021qlz.4; human.
DR   CTD; 89; -.
DR   DisGeNET; 89; -.
DR   GeneCards; ACTN3; -.
DR   HGNC; HGNC:165; ACTN3.
DR   HPA; HPA006035; -.
DR   MIM; 102574; gene+phenotype.
DR   neXtProt; NX_Q08043; -.
DR   OpenTargets; ENSG00000248746; -.
DR   PharmGKB; PA24485; -.
DR   GeneTree; ENSGT00760000118813; -.
DR   HOVERGEN; HBG050453; -.
DR   InParanoid; Q08043; -.
DR   KO; K05699; -.
DR   PhylomeDB; Q08043; -.
DR   Reactome; R-HSA-373753; Nephrin interactions.
DR   Reactome; R-HSA-390522; Striated Muscle Contraction.
DR   EvolutionaryTrace; Q08043; -.
DR   GeneWiki; ACTN3; -.
DR   GenomeRNAi; 89; -.
DR   PRO; PR:Q08043; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   CleanEx; HS_ACTN3; -.
DR   ExpressionAtlas; Q08043; baseline and differential.
DR   Genevisible; Q08043; HS.
DR   GO; GO:0005884; C:actin filament; TAS:ProtInc.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR   GO; GO:0005925; C:focal adhesion; IMP:UniProtKB.
DR   GO; GO:0005622; C:intracellular; IDA:UniProtKB.
DR   GO; GO:0031143; C:pseudopodium; TAS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0005178; F:integrin binding; TAS:UniProtKB.
DR   GO; GO:0044325; F:ion channel binding; IPI:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; TAS:UniProtKB.
DR   GO; GO:0008307; F:structural constituent of muscle; TAS:ProtInc.
DR   GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR   GO; GO:0030049; P:muscle filament sliding; TAS:Reactome.
DR   GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISS:UniProtKB.
DR   GO; GO:0045820; P:negative regulation of glycolytic process; ISS:UniProtKB.
DR   GO; GO:0090324; P:negative regulation of oxidative phosphorylation; ISS:UniProtKB.
DR   GO; GO:1904025; P:positive regulation of glucose catabolic process to lactate via pyruvate; ISS:UniProtKB.
DR   GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; ISS:UniProtKB.
DR   GO; GO:1903715; P:regulation of aerobic respiration; ISS:UniProtKB.
DR   GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR   GO; GO:0014728; P:regulation of the force of skeletal muscle contraction; ISS:UniProtKB.
DR   GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:UniProtKB.
DR   GO; GO:0014732; P:skeletal muscle atrophy; ISS:UniProtKB.
DR   GO; GO:0014883; P:transition between fast and slow fiber; ISS:UniProtKB.
DR   CDD; cd00014; CH; 2.
DR   CDD; cd00051; EFh; 1.
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; 2.
DR   SUPFAM; SSF47473; SSF47473; 1.
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; Acetylation; Actin-binding; Calcium; Complete proteome;
KW   Metal-binding; Polymorphism; Reference proteome; Repeat.
FT   CHAIN         1    901       Alpha-actinin-3.
FT                                /FTId=PRO_0000073438.
FT   DOMAIN        1    261       Actin-binding.
FT   DOMAIN       45    149       CH 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00044}.
FT   DOMAIN      158    261       CH 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00044}.
FT   REPEAT      288    398       Spectrin 1.
FT   REPEAT      408    513       Spectrin 2.
FT   REPEAT      523    634       Spectrin 3.
FT   REPEAT      644    747       Spectrin 4.
FT   DOMAIN      760    795       EF-hand 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00448}.
FT   DOMAIN      796    831       EF-hand 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00448}.
FT   CA_BIND     773    784       1; possibly ancestral.
FT   CA_BIND     809    820       2; possibly ancestral.
FT   MOD_RES       1      1       N-acetylmethionine.
FT                                {ECO:0000244|PubMed:22223895}.
FT   VARIANT     523    523       R -> Q (in dbSNP:rs1671064).
FT                                {ECO:0000269|PubMed:10192379,
FT                                ECO:0000269|PubMed:1339456,
FT                                ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_012705.
FT   VARIANT     628    628       C -> R (in dbSNP:rs618838).
FT                                {ECO:0000269|PubMed:1339456,
FT                                ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_047528.
FT   VARIANT     635    635       E -> A (in dbSNP:rs2229456).
FT                                /FTId=VAR_033488.
FT   VARIANT     776    776       Q -> R (in dbSNP:rs540874).
FT                                {ECO:0000269|PubMed:1339456,
FT                                ECO:0000269|PubMed:15489334}.
FT                                /FTId=VAR_047529.
FT   HELIX        43     59       {ECO:0000244|PDB:1WKU}.
FT   HELIX        60     62       {ECO:0000244|PDB:1WKU}.
FT   TURN         69     75       {ECO:0000244|PDB:1WKU}.
FT   HELIX        77     87       {ECO:0000244|PDB:1WKU}.
FT   HELIX       100    115       {ECO:0000244|PDB:1WKU}.
FT   TURN        116    118       {ECO:0000244|PDB:1WKU}.
FT   HELIX       126    131       {ECO:0000244|PDB:1WKU}.
FT   HELIX       134    149       {ECO:0000244|PDB:1WKU}.
FT   TURN        150    152       {ECO:0000244|PDB:1WKU}.
FT   HELIX       160    172       {ECO:0000244|PDB:1WKU}.
FT   STRAND      182    184       {ECO:0000244|PDB:1WKU}.
FT   HELIX       185    187       {ECO:0000244|PDB:1WKU}.
FT   HELIX       191    200       {ECO:0000244|PDB:1WKU}.
FT   TURN        202    204       {ECO:0000244|PDB:1TJT}.
FT   HELIX       207    209       {ECO:0000244|PDB:1WKU}.
FT   HELIX       215    229       {ECO:0000244|PDB:1WKU}.
FT   HELIX       238    243       {ECO:0000244|PDB:1WKU}.
FT   STRAND      244    246       {ECO:0000244|PDB:1WKU}.
FT   HELIX       249    265       {ECO:0000244|PDB:1WKU}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       796    831       iprf:EF_HAND_2 [T]
FT   MYHIT       159    264       ipfam:CH [T]
FT   MYHIT       764    792       ismart:EFh [T]
FT   MYHIT       831    897       ipfam:EFhand_Ca_insen [T]
FT   MYHIT       121    145       ipat:ACTININ_2 [T]
FT   MYHIT       760    795       iprf:EF_HAND_2 [T]
FT   MYHIT       158    261       iprf:CH [T]
FT   MYHIT       408    512       ipfam:Spectrin [T]
FT   MYHIT       411    512       ismart:SPEC [T]
FT   MYHIT        47     56       ipat:ACTININ_1 [T]
FT   MYHIT        46    149       ipfam:CH [T]
FT   MYHIT       160    259       ismart:CH [T]
FT   MYHIT       800    828       ismart:EFh [T]
FT   MYHIT        45    149       iprf:CH [T]
FT   MYHIT       526    633       ismart:SPEC [T]
FT   MYHIT        47    147       ismart:CH [T]
FT   MYHIT       524    634       ipfam:Spectrin [T]
FT   MYHIT       288    397       ipfam:Spectrin [T]
FT   MYHIT       645    746       ipfam:Spectrin [T]
SQ   SEQUENCE   901 AA;  103241 MW;  C49B7885E7E1EDA7 CRC64;
     MMMVMQPEGL GAGEGRFAGG GGGGEYMEQE EDWDRDLLLD PAWEKQQRKT FTAWCNSHLR
     KAGTQIENIE EDFRNGLKLM LLLEVISGER LPRPDKGKMR FHKIANVNKA LDFIASKGVK
     LVSIGAEEIV DGNLKMTLGM IWTIILRFAI QDISVEETSA KEGLLLWCQR KTAPYRNVNV
     QNFHTSWKDG LALCALIHRH RPDLIDYAKL RKDDPIGNLN TAFEVAEKYL DIPKMLDAED
     IVNTPKPDEK AIMTYVSCFY HAFAGAEQAE TAANRICKVL AVNQENEKLM EEYEKLASEL
     LEWIRRTVPW LENRVGEPSM SAMQRKLEDF RDYRRLHKPP RIQEKCQLEI NFNTLQTKLR
     LSHRPAFMPS EGKLVSDIAN AWRGLEQVEK GYEDWLLSEI RRLQRLQHLA EKFRQKASLH
     EAWTRGKEEM LSQRDYDSAL LQEVRALLRR HEAFESDLAA HQDRVEHIAA LAQELNELDY
     HEAASVNSRC QAICDQWDNL GTLTQKRRDA LERMEKLLET IDRLQLEFAR RAAPFNNWLD
     GAVEDLQDVW LVHSVEETQS LLTAHDQFKA TLPEADRERG AIMGIQGEIQ KICQTYGLRP
     CSTNPYITLS PQDINTKWDM VRKLVPSCDQ TLQEELARQQ VNERLRRQFA AQANAIGPWI
     QAKVEEVGRL AAGLAGSLEE QMAGLRQQEQ NIINYKTNID RLEGDHQLLQ ESLVFDNKHT
     VYSMEHIRVG WEQLLTSIAR TINEVENQVL TRDAKGLSQE QLNEFRASFN HFDRKQNGMM
     EPDDFRACLI SMGYDLGEVE FARIMTMVDP NAAGVVTFQA FIDFMTRETA ETDTTEQVVA
     SFKILAGDKN YITPEELRRE LPAKQAEYCI RRMVPYKGSG APAGALDYVA FSSALYGESD
     L
//