ID   ACTN1_MOUSE             Reviewed;         892 AA.
AC   Q7TPR4;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   02-SEP-2026, entry version 188.
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Olfactory epithelium;
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   [2]
RP   SUBCELLULAR LOCATION.
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   [3]
RP   INTERACTION WITH PSD, AND SUBCELLULAR LOCATION.
RX   PubMed=17298598; DOI=10.1111/j.1460-9568.2007.05345.x;
RA   Sakagami H., Honma T., Sukegawa J., Owada Y., Yanagisawa T., Kondo H.;
RT   "Somatodendritic localization of EFA6A, a guanine nucleotide exchange
RT   factor for ADP-ribosylation factor 6, and its possible interaction with
RT   alpha-actinin in dendritic spines.";
RL   Eur. J. Neurosci. 25:618-628(2007).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC   Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   INTERACTION WITH MICALL2, AND SUBCELLULAR LOCATION.
RX   PubMed=23100251; DOI=10.1074/jbc.m112.383653;
RA   Sakane A., Abdallah A.A., Nakano K., Honda K., Ikeda W., Nishikawa Y.,
RA   Matsumoto M., Matsushita N., Kitamura T., Sasaki T.;
RT   "Rab13 small G protein and junctional Rab13-binding protein (JRAB)
RT   orchestrate actin cytoskeletal organization during epithelial junctional
RT   development.";
RL   J. Biol. Chem. 287:42455-42468(2012).
RN   [6]
RP   MUTAGENESIS OF GLN-32 AND VAL-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).
CC   -!- FUNCTION: F-actin cross-linking protein which is thought to anchor
CC       actin to a variety of intracellular structures. Association with IGSF8
CC       regulates the immune synapse formation and is required for efficient T-
CC       cell activation. {ECO:0000250|UniProtKB:P12814}.
CC   -!- SUBUNIT: Homodimer; antiparallel. Interacts with MYOZ2, TTID and LPP.
CC       Interacts with DDN (By similarity). Interacts with PSD
CC       (PubMed:17298598). Interacts with MICALL2 (PubMed:23100251). Interacts
CC       with DNM2 and CTTN. Interacts with PDLIM1. Interacts with PDLIM2.
CC       Interacts with PDLIM4 (via PDZ domain) (By similarity). Interacts with
CC       IGSF8 (By similarity). {ECO:0000250|UniProtKB:P12814,
CC       ECO:0000250|UniProtKB:Q9Z1P2, ECO:0000269|PubMed:17298598,
CC       ECO:0000269|PubMed:23100251}.
CC   -!- INTERACTION:
CC       Q7TPR4; Q8K4E0: Alms1; NbExp=4; IntAct=EBI-774010, EBI-6272972;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC       {ECO:0000269|PubMed:23100251}. Cytoplasm, myofibril, sarcomere, Z line
CC       {ECO:0000269|PubMed:11114196}. Cell membrane
CC       {ECO:0000250|UniProtKB:P12814}. Cell junction
CC       {ECO:0000250|UniProtKB:Q9Z1P2}. Cell projection, ruffle
CC       {ECO:0000269|PubMed:17298598}. Note=Colocalizes with MYOZ2 and PPP3CA
CC       at the Z-line of heart and skeletal muscle (PubMed:11114196).
CC       Colocalizes with PSD in membrane ruffles and central reticular
CC       structures (PubMed:17298598). {ECO:0000269|PubMed:11114196,
CC       ECO:0000269|PubMed:17298598}.
CC   -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}.
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DR   EMBL; BC054830; AAH54830.1; -; mRNA.
DR   CCDS; CCDS26011.1; -.
DR   RefSeq; NP_598917.1; NM_134156.3.
DR   PDB; 6C0A; NMR; -; A=822-892.
DR   AlphaFoldDB; Q7TPR4; -.
DR   SMR; Q7TPR4; -.
DR   BioGRID; 224977; 40.
DR   CORUM; Q7TPR4; -.
DR   FunCoup; Q7TPR4; 1518.
DR   IntAct; Q7TPR4; 19.
DR   MINT; Q7TPR4; -.
DR   STRING; 10090.ENSMUSP00000021554; -.
DR   CarbonylDB; Q7TPR4; -.
DR   GlyGen; Q7TPR4; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q7TPR4; -.
DR   PhosphoSitePlus; Q7TPR4; -.
DR   SwissPalm; Q7TPR4; -.
DR   CPTAC; non-CPTAC-3764; -.
DR   jPOST; Q7TPR4; -.
DR   PaxDb; 10090-ENSMUSP00000021554; -.
DR   PeptideAtlas; Q7TPR4; -.
DR   ProteomicsDB; 285718; -.
DR   Pumba; Q7TPR4; -.
DR   Antibodypedia; 51; 495 antibodies from 41 providers.
DR   DNASU; 109711; -.
DR   Ensembl; ENSMUST00000021554.16; ENSMUSP00000021554.9; ENSMUSG00000015143.16.
DR   GeneID; 109711; -.
DR   KEGG; mmu:109711; -.
DR   UCSC; uc007oap.2; mouse.
DR   AGR; MGI:2137706; -.
DR   CTD; 87; -.
DR   MGI; MGI:2137706; Actn1.
DR   VEuPathDB; HostDB:ENSMUSG00000015143; -.
DR   eggNOG; KOG0035; Eukaryota.
DR   GeneTree; ENSGT00940000155548; -.
DR   InParanoid; Q7TPR4; -.
DR   OMA; QQRWITV; -.
DR   OrthoDB; 10017054at2759; -.
DR   PhylomeDB; Q7TPR4; -.
DR   Reactome; R-MMU-114608; Platelet degranulation.
DR   Reactome; R-MMU-446388; Regulation of cytoskeletal remodeling and cell spreading by IPP complex components.
DR   Reactome; R-MMU-9013418; RHOBTB2 GTPase cycle.
DR   Reactome; R-MMU-9035034; RHOF GTPase cycle.
DR   BioGRID-ORCS; 109711; 3 hits in 80 CRISPR screens.
DR   CD-CODE; CE726F99; Postsynaptic density.
DR   PRO; PR:Q7TPR4; -.
DR   Proteomes; UP000000589; Chromosome 12.
DR   RNAct; Q7TPR4; protein.
DR   Bgee; ENSMUSG00000015143; Expressed in vestibular membrane of cochlear duct and 263 other cell types or tissues.
DR   ExpressionAtlas; Q7TPR4; baseline and differential.
DR   GO; GO:0005884; C:actin filament; IEA:Ensembl.
DR   GO; GO:0070161; C:anchoring junction; ISS:UniProtKB.
DR   GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR   GO; GO:0030054; C:cell junction; ISO:GO_Central.
DR   GO; GO:0005911; C:cell-cell junction; ISO:GO_Central.
DR   GO; GO:0030864; C:cortical actin cytoskeleton; ISO:GO_Central.
DR   GO; GO:0030863; C:cortical cytoskeleton; TAS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISO:GO_Central.
DR   GO; GO:0005856; C:cytoskeleton; ISO:GO_Central.
DR   GO; GO:0043197; C:dendritic spine; ISO:GO_Central.
DR   GO; GO:0032127; C:dense core granule membrane; TAS:UniProtKB.
DR   GO; GO:0005916; C:fascia adherens; IDA:MGI.
DR   GO; GO:0005925; C:focal adhesion; ISO:GO_Central.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098871; C:postsynaptic actin cytoskeleton; ISO:GO_Central.
DR   GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR   GO; GO:0030017; C:sarcomere; IDA:MGI.
DR   GO; GO:0030141; C:secretory granule; NAS:UniProtKB.
DR   GO; GO:0001725; C:stress fiber; ISO:GO_Central.
DR   GO; GO:0045202; C:synapse; ISO:GO_Central.
DR   GO; GO:0030018; C:Z disc; IDA:MGI.
DR   GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0005519; F:cytoskeletal regulatory protein binding; ISO:GO_Central.
DR   GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR   GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0099186; F:structural constituent of postsynapse; ISO:GO_Central.
DR   GO; GO:0003713; F:transcription coactivator activity; ISO:GO_Central.
DR   GO; GO:0044325; F:transmembrane transporter binding; ISO:GO_Central.
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; IDA:UniProtKB.
DR   GO; GO:0051639; P:actin filament network formation; ISO:GO_Central.
DR   GO; GO:0007015; P:actin filament organization; ISO:GO_Central.
DR   GO; GO:0030865; P:cortical cytoskeleton organization; TAS:UniProtKB.
DR   GO; GO:0048041; P:focal adhesion assembly; ISO:GO_Central.
DR   GO; GO:0055001; P:muscle cell development; IBA:GO_Central.
DR   GO; GO:0030220; P:platelet formation; ISO:GO_Central.
DR   GO; GO:0036344; P:platelet morphogenesis; ISO:GO_Central.
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   FunFam; 1.10.238.10:FF:000004; Actinin alpha 1; 1.
DR   FunFam; 1.10.418.10:FF:000001; Actinin alpha 1; 1.
DR   FunFam; 1.20.58.60:FF:000004; Actinin alpha 1; 1.
DR   FunFam; 1.20.58.60:FF:000005; Actinin alpha 1; 1.
DR   FunFam; 1.10.418.10:FF:000005; Actinin alpha 4; 1.
DR   FunFam; 1.10.238.10:FF:000018; Actinin, alpha 1; 1.
DR   FunFam; 1.20.58.60:FF:000002; Actinin, alpha 1; 1.
DR   FunFam; 1.20.58.60:FF:000003; Actinin, alpha 1; 1.
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; 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; 2.
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   PDBsum; 6C0A; -.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Actin-binding; Calcium; Cell junction;
KW   Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Membrane;
KW   Metal-binding; Phosphoprotein; Reference proteome; Repeat.
FT   CHAIN           1..892
FT                   /note="Alpha-actinin-1"
FT                   /id="PRO_0000073432"
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:0000250"
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:0000250|UniProtKB:P12814"
FT   MOD_RES         6
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         12
FT                   /note="Phosphotyrosine; by FAK1"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         95
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         195
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         471
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         676
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         677
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P12814"
FT   MOD_RES         890
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z1P2"
FT   MUTAGEN         32
FT                   /note="Q->K: Shows less organization of the circumferential
FT                   actin-filament network compared to controls."
FT                   /evidence="ECO:0000269|PubMed:23434115"
FT   MUTAGEN         105
FT                   /note="V->I: Shows less organization of the circumferential
FT                   actin-filament network compared to controls."
FT                   /evidence="ECO:0000269|PubMed:23434115"
FT   HELIX           826..837
FT                   /evidence="ECO:0007829|PDB:6C0A"
FT   STRAND          841..844
FT                   /evidence="ECO:0007829|PDB:6C0A"
FT   HELIX           845..851
FT                   /evidence="ECO:0007829|PDB:6C0A"
FT   HELIX           854..863
FT                   /evidence="ECO:0007829|PDB:6C0A"
FT   STRAND          869..871
FT                   /evidence="ECO:0007829|PDB:6C0A"
FT   STRAND          876..879
FT                   /evidence="ECO:0007829|PDB:6C0A"
FT   HELIX           880..887
FT                   /evidence="ECO:0007829|PDB:6C0A"
SQ   SEQUENCE   892 AA;  103068 MW;  652DA065A5F38E7C CRC64;
     MDHYDSQQTN DYMQPEEDWD RDLLLDPAWE KQQRKTFTAW CNSHLRKAGT QIENIEEDFR
     DGLKLMLLLE VISGERLAKP ERGKMRVHKI SNVNKALDFI ASKGVKLVSI GAEEIVDGNV
     KMTLGMIWTI ILRFAIQDIS VEETSAKEGL LLWCQRKTAP YKNVNIQNFH ISWKDGLGFC
     ALIHRHRPEL IDYGKLRKDD PLTNLNTAFD VAERFLDIPK MLDAEDIVGT ARPDEKAIMT
     YVSSFYHAFS GAQKAETAAN RICKVLAVNQ ENEQLMEDYE KLASDLLEWI RRTIPWLENR
     VPENTMHAMQ QKLEDFRDYR RLHKPPKVQE KCQLEINFNT LQTKLRLSNR PAFMPSEGRM
     VSDINNAWGC LEQAEKGYEE 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 YKPKIDQLEC DHQLIQEALI FDNKHTNYNM EHIRVGWEQL
     LTTIARTINE VENQILTRDA KGISQEQMNE FRASFNHFDR DHSGTLGPEE FKACLISLGY
     DIGNDPQGEA EFARIMSIVD PNRLGVVTFQ AFIDFMSRET ADTDTADQVM ASFKILAGDK
     NYITEDELRR ELPPDQAEYC IARMAPYAGP DSVPGALDYM SFSTALYGES DL
//