ACTN1_MOUSE
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 03-AUG-2022, entry version 170.
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, Spleen,
RC 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. This is a bundling
CC protein (By similarity). {ECO:0000250}.
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).
CC {ECO:0000250|UniProtKB:P12814, ECO:0000250|UniProtKB:Q9Z1P2,
CC ECO:0000269|PubMed:17298598, 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:Q9Z1P2}. 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_134156.2.
DR PDB; 6C0A; NMR; -; A=822-892.
DR PDBsum; 6C0A; -.
DR AlphaFoldDB; Q7TPR4; -.
DR SMR; Q7TPR4; -.
DR BioGRID; 224977; 38.
DR CORUM; Q7TPR4; -.
DR IntAct; Q7TPR4; 19.
DR MINT; Q7TPR4; -.
DR STRING; 10090.ENSMUSP00000021554; -.
DR CarbonylDB; Q7TPR4; -.
DR iPTMnet; Q7TPR4; -.
DR PhosphoSitePlus; Q7TPR4; -.
DR SwissPalm; Q7TPR4; -.
DR CPTAC; non-CPTAC-3764; -.
DR EPD; Q7TPR4; -.
DR jPOST; Q7TPR4; -.
DR MaxQB; Q7TPR4; -.
DR PaxDb; Q7TPR4; -.
DR PeptideAtlas; Q7TPR4; -.
DR PRIDE; Q7TPR4; -.
DR ProteomicsDB; 285718; -.
DR Antibodypedia; 51; 497 antibodies from 39 providers.
DR DNASU; 109711; -.
DR Ensembl; ENSMUST00000021554; ENSMUSP00000021554; ENSMUSG00000015143.
DR GeneID; 109711; -.
DR KEGG; mmu:109711; -.
DR UCSC; uc007oap.2; mouse.
DR CTD; 87; -.
DR MGI; MGI:2137706; Actn1.
DR VEuPathDB; HostDB:ENSMUSG00000015143; -.
DR eggNOG; KOG0035; Eukaryota.
DR GeneTree; ENSGT00940000155548; -.
DR InParanoid; Q7TPR4; -.
DR OMA; QRFENVN; -.
DR OrthoDB; 543832at2759; -.
DR PhylomeDB; Q7TPR4; -.
DR TreeFam; TF352676; -.
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-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013418; RHOBTB2 GTPase cycle.
DR Reactome; R-MMU-9035034; RHOF GTPase cycle.
DR BioGRID-ORCS; 109711; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Actn1; mouse.
DR PRO; PR:Q7TPR4; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q7TPR4; protein.
DR Bgee; ENSMUSG00000015143; Expressed in vestibular membrane of cochlear duct and 259 other tissues.
DR ExpressionAtlas; Q7TPR4; baseline and differential.
DR Genevisible; Q7TPR4; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:MGI.
DR GO; GO:0030863; C:cortical cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
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:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:MGI.
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:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0099186; F:structural constituent of postsynapse; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
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:MGI.
DR GO; GO:0007015; P:actin filament organization; ISO:MGI.
DR GO; GO:0030865; P:cortical cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; ISO:MGI.
DR GO; GO:0055001; P:muscle cell development; IBA:GO_Central.
DR GO; GO:0030220; P:platelet formation; ISO:MGI.
DR GO; GO:0036344; P:platelet morphogenesis; ISO:MGI.
DR CDD; cd00014; CH; 2.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00176; SPEC; 2.
DR Gene3D; 1.10.418.10; -; 2.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
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 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; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
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
