ID ACTN1_HUMAN Reviewed; 892 AA. AC P12814; B3V8S3; B4DHH3; B7TY16; Q1HE25; Q9BTN1; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 2. DT 27-MAR-2024, entry version 257. DE RecName: Full=Alpha-actinin-1; DE AltName: Full=Alpha-actinin cytoskeletal isoform; DE AltName: Full=F-actin cross-linking protein; DE AltName: Full=Non-muscle alpha-actinin-1; GN Name=ACTN1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=2780298; DOI=10.1093/nar/17.16.6725; RA Millake D.B., Blanchard A.D., Patel B., Critchley D.R.; RT "The cDNA sequence of a human placental alpha-actinin."; RL Nucleic Acids Res. 17:6725-6725(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2349951; RA Youssoufian H., McAfee M., Kwiatkowski D.J.; RT "Cloning and chromosomal localization of the human cytoskeletal alpha- RT actinin gene reveals linkage to the beta-spectrin gene."; RL Am. J. Hum. Genet. 47:62-71(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=18353764; DOI=10.1074/mcp.m700590-mcp200; RA Thorsen K., Sorensen K.D., Brems-Eskildsen A.S., Modin C., Gaustadnes M., RA Hein A.M., Kruhoffer M., Laurberg S., Borre M., Wang K., Brunak S., RA Krainer A.R., Torring N., Dyrskjot L., Andersen C.L., Orntoft T.F.; RT "Alternative splicing in colon, bladder, and prostate cancer identified by RT exon array analysis."; RL Mol. Cell. Proteomics 7:1214-1224(2008). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Tongue; RA Mancini U.M., Tajara E.H.; RT "A new mRNA isoform from ACTN1 gene."; RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RA Mansilla F., Orntoft T.F., Birkenkamp-Demtroeder K.; RT "Actinin alpha 1 alternative splicing variant."; RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 297-892 (ISOFORM 1). RX PubMed=2169343; RA Nishiyama M., Ozturk M., Frohlich M., Mafune K., Steele G. Jr., Wands J.R.; RT "Expression of human alpha-actinin in human hepatocellular carcinoma."; RL Cancer Res. 50:6291-6294(1990). RN [12] RP PROTEIN SEQUENCE OF 1-21. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [13] RP PROTEIN SEQUENCE OF 134-146. RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082; RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.; RT "Identification of the 70kD heat shock cognate protein (Hsc70) and alpha- RT actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes."; RL Biochem. Biophys. Res. Commun. 224:666-674(1996). RN [14] RP PROTEIN SEQUENCE OF 566-577; 727-738 AND 835-863, AND SUBCELLULAR LOCATION. RX PubMed=7750553; DOI=10.1016/0014-5793(95)00362-d; RA Dubernard V., Faucher D., Launay J.-M., Legrand C.; RT "Identification of the cytoskeletal protein alpha-actinin as a platelet RT thrombospondin-binding protein."; RL FEBS Lett. 364:109-114(1995). RN [15] RP INTERACTION WITH TTID. RX PubMed=10369880; DOI=10.1093/hmg/8.7.1329; RA Salmikangas P., Mykkaenen O.M., Groenholm M., Heiska L., Kere J., RA Carpen O.; RT "Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded RT by a candidate gene for limb-girdle muscular dystrophy."; RL Hum. Mol. Genet. 8:1329-1336(1999). RN [16] RP INTERACTION WITH 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 proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 97:14632-14637(2000). RN [17] RP PHOSPHORYLATION AT TYR-12. RX PubMed=11369769; DOI=10.1074/jbc.m101678200; RA Izaguirre G., Aguirre L., Hu Y.P., Lee H.Y., Schlaepfer D.D., RA Aneskievich B.J., Haimovich B.; RT "The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on RT its actin-binding domain by the focal adhesion kinase."; RL J. Biol. Chem. 276:28676-28685(2001). RN [18] RP INTERACTION WITH LPP. RX PubMed=12615977; DOI=10.1242/jcs.00309; RA Li B., Zhuang L., Reinhard M., Trueb B.; RT "The lipoma preferred partner LPP interacts with alpha-actinin."; RL J. Cell Sci. 116:1359-1366(2003). RN [19] RP INTERACTION WITH DDN. RX PubMed=16464232; DOI=10.1111/j.1471-4159.2006.03679.x; RA Kremerskothen J., Kindler S., Finger I., Veltel S., Barnekow A.; RT "Postsynaptic recruitment of Dendrin depends on both dendritic mRNA RT transport and synaptic anchoring."; RL J. Neurochem. 96:1659-1666(2006). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-95; LYS-195 AND LYS-676, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [21] 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., Buerckstuemmer T., RA 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 [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-6, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471 AND SER-677, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [25] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 30-253. RX PubMed=16698282; DOI=10.1016/j.jsb.2006.01.013; RA Borrego-Diaz E., Kerff F., Lee S.H., Ferron F., Li Y., Dominguez R.; RT "Crystal structure of the actin-binding domain of alpha-actinin 1: RT evaluating two competing actin-binding models."; RL J. Struct. Biol. 155:230-238(2006). RN [26] RP VARIANTS BDPLT15 LYS-32; GLN-46; ILE-105; LYS-225; TRP-738 AND GLN-752, RP VARIANT TRP-197, AND CHARACTERIZATION OF VARIANTS BDPLT15 LYS-32 AND RP ILE-105. RX PubMed=23434115; DOI=10.1016/j.ajhg.2013.01.015; RA Kunishima S., Okuno Y., Yoshida K., Shiraishi Y., Sanada M., Muramatsu H., RA Chiba K., Tanaka H., Miyazaki K., Sakai M., Ohtake M., Kobayashi R., RA Iguchi A., Niimi G., Otsu M., Takahashi Y., Miyano S., Saito H., Kojima S., RA Ogawa S.; RT "ACTN1 mutations cause congenital macrothrombocytopenia."; RL Am. J. Hum. Genet. 92:431-438(2013). RN [27] RP VARIANT BDPLT15 GLN-46, CHARACTERIZATION OF VARIANT BDPLT15 GLN-46, AND RP SUBCELLULAR LOCATION. RX PubMed=24069336; DOI=10.1371/journal.pone.0074728; RA Gueguen P., Rouault K., Chen J.M., Raguenes O., Fichou Y., Hardy E., RA Gobin E., Pan-Petesch B., Kerbiriou M., Trouve P., Marcorelles P., RA Abgrall J.F., Le Marechal C., Ferec C.; RT "A missense mutation in the alpha-actinin 1 gene (ACTN1) is the cause of RT autosomal dominant macrothrombocytopenia in a large French family."; RL PLoS ONE 8:E74728-E74728(2013). 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. Interacts with MYOZ2, TTID and LPP CC (PubMed:10369880, PubMed:11114196, PubMed:12615977). Interacts with DDN CC (PubMed:16464232). Interacts with PSD. Interacts with MICALL2 (By CC similarity). Interacts with DNM2 and CTTN. Interacts with PDLIM1. CC Interacts with PDLIM2. Interacts with PDLIM4 (via PDZ domain) (By CC similarity). {ECO:0000250|UniProtKB:Q7TPR4, CC ECO:0000250|UniProtKB:Q9Z1P2, ECO:0000269|PubMed:10369880, CC ECO:0000269|PubMed:11114196, ECO:0000269|PubMed:12615977, CC ECO:0000269|PubMed:16464232}. CC -!- INTERACTION: CC P12814; P35609: ACTN2; NbExp=3; IntAct=EBI-351710, EBI-77797; CC P12814; Q08043: ACTN3; NbExp=3; IntAct=EBI-351710, EBI-2880652; CC P12814; Q92624: APPBP2; NbExp=3; IntAct=EBI-351710, EBI-743771; CC P12814; Q96QS3: ARX; NbExp=2; IntAct=EBI-351710, EBI-11107474; CC P12814; Q9NWQ9: C14orf119; NbExp=3; IntAct=EBI-351710, EBI-725606; CC P12814; Q13936: CACNA1C; NbExp=2; IntAct=EBI-351710, EBI-1038838; CC P12814; Q8NA61: CBY2; NbExp=3; IntAct=EBI-351710, EBI-741724; CC P12814; P63172: DYNLT1; NbExp=3; IntAct=EBI-351710, EBI-1176455; CC P12814; P05198: EIF2S1; NbExp=3; IntAct=EBI-351710, EBI-1056162; CC P12814; Q7L775: EPM2AIP1; NbExp=6; IntAct=EBI-351710, EBI-6255981; CC P12814; O95257: GADD45G; NbExp=3; IntAct=EBI-351710, EBI-448202; CC P12814; Q9Y223: GNE; NbExp=3; IntAct=EBI-351710, EBI-4291090; CC P12814; Q8NC69: KCTD6; NbExp=3; IntAct=EBI-351710, EBI-2511344; CC P12814; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-351710, EBI-739832; CC P12814; Q8IY33: MICALL2; NbExp=6; IntAct=EBI-351710, EBI-2555563; CC P12814; A0A0S2Z4Y0: MYOT; NbExp=3; IntAct=EBI-351710, EBI-16430371; CC P12814; Q9NP98: MYOZ1; NbExp=4; IntAct=EBI-351710, EBI-744402; CC P12814; Q9NPC6: MYOZ2; NbExp=11; IntAct=EBI-351710, EBI-746712; CC P12814; Q6ZUT1: NKAPD1; NbExp=3; IntAct=EBI-351710, EBI-3920396; CC P12814; P00973: OAS1; NbExp=4; IntAct=EBI-351710, EBI-3932815; CC P12814; P00973-2: OAS1; NbExp=3; IntAct=EBI-351710, EBI-12081862; CC P12814; P50479: PDLIM4; NbExp=3; IntAct=EBI-351710, EBI-372861; CC P12814; Q9BYB0: SHANK3; NbExp=2; IntAct=EBI-351710, EBI-1752330; CC P12814; P12931: SRC; NbExp=2; IntAct=EBI-351710, EBI-621482; CC P12814; Q8N3V7: SYNPO; NbExp=2; IntAct=EBI-351710, EBI-352936; CC P12814; Q9H987-2: SYNPO2L; NbExp=3; IntAct=EBI-351710, EBI-12082116; CC P12814; Q8WZ42: TTN; NbExp=2; IntAct=EBI-351710, EBI-681210; CC P12814; P10599: TXN; NbExp=3; IntAct=EBI-351710, EBI-594644; CC P12814; O75604: USP2; NbExp=3; IntAct=EBI-351710, EBI-743272; CC P12814; B2R8Y4; NbExp=3; IntAct=EBI-351710, EBI-10175581; CC P12814; Q8VC66: Ssx2ip; Xeno; NbExp=3; IntAct=EBI-351710, EBI-6654049; CC P12814; PRO_0000037577 [P27958]; Xeno; NbExp=7; IntAct=EBI-351710, EBI-6904388; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:24069336, ECO:0000269|PubMed:7750553}. Cytoplasm, CC myofibril, sarcomere, Z line {ECO:0000269|PubMed:7750553}. Cell CC membrane {ECO:0000250|UniProtKB:Q9Z1P2}. Cell junction CC {ECO:0000250|UniProtKB:Q9Z1P2}. Cell projection, ruffle CC {ECO:0000250|UniProtKB:Q7TPR4}. Note=Colocalizes with MYOZ2 and PPP3CA CC at the Z-line of heart and skeletal muscle. Colocalizes with PSD in CC membrane ruffles and central reticular structures. CC {ECO:0000250|UniProtKB:Q7TPR4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P12814-1; Sequence=Displayed; CC Name=2; CC IsoId=P12814-2; Sequence=VSP_041264; CC Name=3; CC IsoId=P12814-3; Sequence=VSP_043525; CC Name=4; CC IsoId=P12814-4; Sequence=VSP_041264, VSP_047763; CC -!- DISEASE: Bleeding disorder, platelet-type, 15 (BDPLT15) [MIM:615193]: CC An autosomal dominant form of macrothrombocytopenia. Affected CC individuals usually have no or only mild bleeding tendency, such as CC epistaxis. Laboratory studies show decreased numbers of large platelets CC and anisocytosis, but the platelets show no in vitro functional CC abnormalities. {ECO:0000269|PubMed:23434115, CC ECO:0000269|PubMed:24069336}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X15804; CAA33803.1; -; mRNA. DR EMBL; M95178; AAA51582.1; -; mRNA. DR EMBL; EU716325; ACE62922.1; -; mRNA. DR EMBL; DQ496098; ABF50047.1; -; mRNA. DR EMBL; FJ410030; ACJ24535.1; -; mRNA. DR EMBL; BT007207; AAP35871.1; -; mRNA. DR EMBL; AK295099; BAG58135.1; -; mRNA. DR EMBL; AL117694; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471061; EAW80975.1; -; Genomic_DNA. DR EMBL; BC003576; AAH03576.1; -; mRNA. DR EMBL; BC015766; AAH15766.1; -; mRNA. DR EMBL; X55187; CAA38970.1; -; mRNA. DR CCDS; CCDS45129.1; -. [P12814-2] DR CCDS; CCDS45130.1; -. [P12814-3] DR CCDS; CCDS9792.1; -. [P12814-1] DR PIR; S05503; FAHUAA. DR RefSeq; NP_001093.1; NM_001102.3. [P12814-1] DR RefSeq; NP_001123476.1; NM_001130004.1. [P12814-3] DR RefSeq; NP_001123477.1; NM_001130005.1. [P12814-2] DR PDB; 2EYI; X-ray; 1.70 A; A=30-253. DR PDB; 2EYN; X-ray; 1.80 A; A=30-253. DR PDB; 2N8Y; NMR; -; A=743-892. DR PDB; 2N8Z; NMR; -; A=743-892. DR PDBsum; 2EYI; -. DR PDBsum; 2EYN; -. DR PDBsum; 2N8Y; -. DR PDBsum; 2N8Z; -. DR AlphaFoldDB; P12814; -. DR SMR; P12814; -. DR BioGRID; 106602; 308. DR CORUM; P12814; -. DR DIP; DIP-33184N; -. DR IntAct; P12814; 127. DR MINT; P12814; -. DR STRING; 9606.ENSP00000377941; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB06773; Human calcitonin. DR CarbonylDB; P12814; -. DR GlyCosmos; P12814; 1 site, 2 glycans. DR GlyGen; P12814; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; P12814; -. DR MetOSite; P12814; -. DR PhosphoSitePlus; P12814; -. DR SwissPalm; P12814; -. DR BioMuta; ACTN1; -. DR DMDM; 46397817; -. DR OGP; P12814; -. DR EPD; P12814; -. DR jPOST; P12814; -. DR MassIVE; P12814; -. DR MaxQB; P12814; -. DR PaxDb; 9606-ENSP00000377941; -. DR PeptideAtlas; P12814; -. DR PRIDE; P12814; -. DR ProteomicsDB; 52871; -. [P12814-1] DR ProteomicsDB; 52872; -. [P12814-2] DR ProteomicsDB; 52873; -. [P12814-3] DR ProteomicsDB; 6259; -. DR Pumba; P12814; -. DR Antibodypedia; 51; 546 antibodies from 39 providers. DR DNASU; 87; -. DR Ensembl; ENST00000193403.10; ENSP00000193403.6; ENSG00000072110.16. [P12814-1] DR Ensembl; ENST00000394419.9; ENSP00000377941.4; ENSG00000072110.16. [P12814-3] DR Ensembl; ENST00000438964.6; ENSP00000414272.2; ENSG00000072110.16. [P12814-2] DR Ensembl; ENST00000538545.6; ENSP00000439828.2; ENSG00000072110.16. [P12814-4] DR GeneID; 87; -. DR KEGG; hsa:87; -. DR MANE-Select; ENST00000394419.9; ENSP00000377941.4; NM_001130004.2; NP_001123476.1. [P12814-3] DR UCSC; uc001xkl.4; human. [P12814-1] DR AGR; HGNC:163; -. DR CTD; 87; -. DR DisGeNET; 87; -. DR GeneCards; ACTN1; -. DR HGNC; HGNC:163; ACTN1. DR HPA; ENSG00000072110; Tissue enhanced (smooth). DR MalaCards; ACTN1; -. DR MIM; 102575; gene. DR MIM; 615193; phenotype. DR neXtProt; NX_P12814; -. DR OpenTargets; ENSG00000072110; -. DR Orphanet; 140957; Autosomal dominant macrothrombocytopenia. DR PharmGKB; PA24; -. DR VEuPathDB; HostDB:ENSG00000072110; -. DR eggNOG; KOG0035; Eukaryota. DR GeneTree; ENSGT00940000155548; -. DR HOGENOM; CLU_005217_1_1_1; -. DR InParanoid; P12814; -. DR OMA; CYEGVEV; -. DR OrthoDB; 2872403at2759; -. DR PhylomeDB; P12814; -. DR TreeFam; TF352676; -. DR PathwayCommons; P12814; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-3000170; Syndecan interactions. DR Reactome; R-HSA-373753; Nephrin family interactions. DR Reactome; R-HSA-446388; Regulation of cytoskeletal remodeling and cell spreading by IPP complex components. DR Reactome; R-HSA-9013405; RHOD GTPase cycle. DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle. DR Reactome; R-HSA-9035034; RHOF GTPase cycle. DR SignaLink; P12814; -. DR SIGNOR; P12814; -. DR BioGRID-ORCS; 87; 17 hits in 1163 CRISPR screens. DR ChiTaRS; ACTN1; human. DR EvolutionaryTrace; P12814; -. DR GeneWiki; Actinin,_alpha_1; -. DR GenomeRNAi; 87; -. DR Pharos; P12814; Tbio. DR PRO; PR:P12814; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P12814; Protein. DR Bgee; ENSG00000072110; Expressed in blood vessel layer and 207 other cell types or tissues. DR ExpressionAtlas; P12814; baseline and differential. DR GO; GO:0005903; C:brush border; IEA:Ensembl. DR GO; GO:0030054; C:cell junction; IBA:GO_Central. DR GO; GO:0042995; C:cell projection; IDA:UniProtKB. DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB. DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0031143; C:pseudopodium; TAS:UniProtKB. DR GO; GO:0001726; C:ruffle; IDA:UniProtKB. DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB. DR GO; GO:0030018; C:Z disc; IDA:UniProtKB. DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0099186; F:structural constituent of postsynapse; IDA:SynGO. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB. DR GO; GO:0017166; F:vinculin binding; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central. DR GO; GO:0051017; P:actin filament bundle assembly; IEA:Ensembl. DR GO; GO:0051639; P:actin filament network formation; IMP:UniProtKB. DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB. DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB. DR GO; GO:0055001; P:muscle cell development; IBA:GO_Central. DR GO; GO:0030220; P:platelet formation; IMP:UniProtKB. DR GO; GO:0036344; P:platelet morphogenesis; IMP:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB. DR CDD; cd21214; CH_ACTN_rpt1; 1. DR CDD; cd21216; CH_ACTN_rpt2; 1. DR CDD; cd00051; EFh; 1. DR CDD; cd00176; SPEC; 2. DR Gene3D; 1.20.58.60; -; 4. DR Gene3D; 1.10.418.10; Calponin-like domain; 2. DR Gene3D; 1.10.238.10; EF-hand; 2. DR InterPro; IPR001589; Actinin_actin-bd_CS. DR InterPro; IPR001715; CH_dom. DR InterPro; IPR036872; CH_dom_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR014837; EF-hand_Ca_insen. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR018159; Spectrin/alpha-actinin. DR InterPro; IPR002017; Spectrin_repeat. DR PANTHER; PTHR11915:SF434; ALPHA-ACTININ-1; 1. DR PANTHER; PTHR11915; SPECTRIN/FILAMIN RELATED CYTOSKELETAL PROTEIN; 1. DR Pfam; PF00307; CH; 2. DR Pfam; PF13405; EF-hand_6; 1. DR Pfam; PF08726; EFhand_Ca_insen; 1. DR Pfam; PF00435; Spectrin; 4. DR SMART; SM00033; CH; 2. DR SMART; SM00054; EFh; 2. DR SMART; SM01184; efhand_Ca_insen; 1. DR SMART; SM00150; SPEC; 3. DR SUPFAM; SSF47576; Calponin-homology domain, CH-domain; 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF46966; Spectrin repeat; 4. DR PROSITE; PS00019; ACTININ_1; 1. DR PROSITE; PS00020; ACTININ_2; 1. DR PROSITE; PS50021; CH; 2. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 2. DR Genevisible; P12814; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Actin-binding; Alternative splicing; Calcium; KW Cell junction; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Disease variant; Membrane; Metal-binding; KW Phosphoprotein; Reference proteome; Repeat. FT CHAIN 1..892 FT /note="Alpha-actinin-1" FT /id="PRO_0000073431" FT DOMAIN 31..135 FT /note="Calponin-homology (CH) 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT DOMAIN 144..250 FT /note="Calponin-homology (CH) 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044" FT REPEAT 274..384 FT /note="Spectrin 1" FT REPEAT 394..499 FT /note="Spectrin 2" FT REPEAT 509..620 FT /note="Spectrin 3" FT REPEAT 630..733 FT /note="Spectrin 4" FT DOMAIN 746..781 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 787..822 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT REGION 1..247 FT /note="Actin-binding" FT REGION 274..733 FT /note="Interaction with DDN" FT /evidence="ECO:0000269|PubMed:16464232" FT BINDING 759 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 761 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 763 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 765 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 770 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 6 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 12 FT /note="Phosphotyrosine; by FAK1" FT /evidence="ECO:0000269|PubMed:11369769" FT MOD_RES 95 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 195 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 471 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 676 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 677 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 890 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1P2" FT VAR_SEQ 761..787 FT /note="DHSGTLGPEEFKACLISLGYDIGNDPQ -> KKTGMMDTDDFRACLISMGYN FT M (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:18353764, ECO:0000303|Ref.5" FT /id="VSP_041264" FT VAR_SEQ 787 FT /note="Q -> QKKTGMMDTDDFRACLISMGYNM (in isoform 3)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_043525" FT VAR_SEQ 840 FT /note="K -> KLQEGGKMQTAHAAFTPPGFAAVSGRAALRLLDFAAFLTTLSSQ FT (in isoform 4)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_047763" FT VARIANT 32 FT /note="Q -> K (in BDPLT15; the mutation dominantly affects FT the actin filament assembly likely resulting in abnormal FT cytoskeletal organization; dbSNP:rs387907346)" FT /evidence="ECO:0000269|PubMed:23434115" FT /id="VAR_069910" FT VARIANT 46 FT /note="R -> Q (in BDPLT15; disorganization of the actin and FT alpha-actinin 1 filaments; dbSNP:rs387907348)" FT /evidence="ECO:0000269|PubMed:23434115, FT ECO:0000269|PubMed:24069336" FT /id="VAR_069911" FT VARIANT 105 FT /note="V -> I (in BDPLT15; the mutation dominantly affects FT the actin filament assembly likely resulting in abnormal FT cytoskeletal organization; dbSNP:rs387907345)" FT /evidence="ECO:0000269|PubMed:23434115" FT /id="VAR_069912" FT VARIANT 197 FT /note="R -> W (in dbSNP:rs904887313)" FT /evidence="ECO:0000269|PubMed:23434115" FT /id="VAR_069913" FT VARIANT 225 FT /note="E -> K (in BDPLT15; dbSNP:rs387907350)" FT /evidence="ECO:0000269|PubMed:23434115" FT /id="VAR_069914" FT VARIANT 707 FT /note="N -> T (in dbSNP:rs7157661)" FT /id="VAR_053883" FT VARIANT 738 FT /note="R -> W (in BDPLT15; dbSNP:rs387907349)" FT /evidence="ECO:0000269|PubMed:23434115" FT /id="VAR_069915" FT VARIANT 752 FT /note="R -> Q (in BDPLT15; dbSNP:rs387907347)" FT /evidence="ECO:0000269|PubMed:23434115" FT /id="VAR_069916" FT VARIANT 868 FT /note="T -> S (in dbSNP:rs11557769)" FT /id="VAR_053884" FT CONFLICT 317 FT /note="R -> L (in Ref. 11; CAA38970)" FT /evidence="ECO:0000305" FT CONFLICT 321 FT /note="R -> H (in Ref. 7; BAG58135)" FT /evidence="ECO:0000305" FT CONFLICT 424 FT /note="T -> A (in Ref. 7; BAG58135)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="Q -> L (in Ref. 11; CAA38970)" FT /evidence="ECO:0000305" FT CONFLICT 630..631 FT /note="RL -> SV (in Ref. 1; CAA33803)" FT /evidence="ECO:0000305" FT CONFLICT 654..656 FT /note="GRI -> ARF (in Ref. 11; CAA38970)" FT /evidence="ECO:0000305" FT CONFLICT 674 FT /note="Y -> D (in Ref. 11; CAA38970)" FT /evidence="ECO:0000305" FT CONFLICT 778 FT /note="L -> S (in Ref. 11; CAA38970)" FT /evidence="ECO:0000305" FT HELIX 30..45 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 46..48 FT /evidence="ECO:0007829|PDB:2EYI" FT TURN 55..61 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 63..73 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 86..102 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 112..116 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 120..135 FT /evidence="ECO:0007829|PDB:2EYI" FT TURN 136..138 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 146..158 FT /evidence="ECO:0007829|PDB:2EYI" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 177..186 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 188..190 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 201..215 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 224..229 FT /evidence="ECO:0007829|PDB:2EYI" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 235..249 FT /evidence="ECO:0007829|PDB:2EYI" FT HELIX 745..751 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 754..757 FT /evidence="ECO:0007829|PDB:2N8Y" FT STRAND 763..766 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 768..774 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 775..778 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 788..798 FT /evidence="ECO:0007829|PDB:2N8Y" FT STRAND 803..807 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 809..816 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 818..820 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 826..830 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 832..837 FT /evidence="ECO:0007829|PDB:2N8Y" FT STRAND 841..844 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 845..851 FT /evidence="ECO:0007829|PDB:2N8Y" FT HELIX 855..863 FT /evidence="ECO:0007829|PDB:2N8Y" FT STRAND 864..867 FT /evidence="ECO:0007829|PDB:2N8Y" FT STRAND 869..872 FT /evidence="ECO:0007829|PDB:2N8Y" FT STRAND 876..881 FT /evidence="ECO:0007829|PDB:2N8Y" FT TURN 884..888 FT /evidence="ECO:0007829|PDB:2N8Y" SQ SEQUENCE 892 AA; 103058 MW; 6DA3E4D1A0289519 CRC64; MDHYDSQQTN DYMQPEEDWD RDLLLDPAWE KQQRKTFTAW CNSHLRKAGT QIENIEEDFR DGLKLMLLLE VISGERLAKP ERGKMRVHKI SNVNKALDFI ASKGVKLVSI GAEEIVDGNV KMTLGMIWTI ILRFAIQDIS VEETSAKEGL LLWCQRKTAP YKNVNIQNFH ISWKDGLGFC ALIHRHRPEL IDYGKLRKDD PLTNLNTAFD VAEKYLDIPK MLDAEDIVGT ARPDEKAIMT YVSSFYHAFS GAQKAETAAN RICKVLAVNQ ENEQLMEDYE KLASDLLEWI RRTIPWLENR VPENTMHAMQ QKLEDFRDYR RLHKPPKVQE KCQLEINFNT LQTKLRLSNR PAFMPSEGRM VSDINNAWGC LEQVEKGYEE WLLNEIRRLE RLDHLAEKFR QKASIHEAWT DGKEAMLRQK DYETATLSEI KALLKKHEAF ESDLAAHQDR VEQIAAIAQE LNELDYYDSP SVNARCQKIC DQWDNLGALT QKRREALERT EKLLETIDQL YLEYAKRAAP FNNWMEGAME DLQDTFIVHT IEEIQGLTTA HEQFKATLPD ADKERLAILG IHNEVSKIVQ TYHVNMAGTN PYTTITPQEI NGKWDHVRQL VPRRDQALTE EHARQQHNER LRKQFGAQAN VIGPWIQTKM EEIGRISIEM HGTLEDQLSH LRQYEKSIVN YKPKIDQLEG DHQLIQEALI FDNKHTNYTM EHIRVGWEQL LTTIARTINE VENQILTRDA KGISQEQMNE FRASFNHFDR DHSGTLGPEE FKACLISLGY DIGNDPQGEA EFARIMSIVD PNRLGVVTFQ AFIDFMSRET ADTDTADQVM ASFKILAGDK NYITMDELRR ELPPDQAEYC IARMAPYTGP DSVPGALDYM SFSTALYGES DL //