ID   ACTN2_MOUSE             Reviewed;         894 AA.
AC   Q9JI91; G3UW84;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 2.
DT   27-MAR-2024, entry version 188.
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   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 [MRNA].
RC   TISSUE=Skeletal muscle;
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-2 and
RT   -3, in different species: implications for the evolution of functional
RT   redundancy.";
RL   Hum. Mol. Genet. 10:1335-1346(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   INTERACTION WITH ADAM12.
RX   PubMed=10788519; DOI=10.1074/jbc.275.18.13933;
RA   Galliano M.-F., Huet C., Frygelius J., Polgren A., Wewer U.M., Engvall E.;
RT   "Binding of ADAM12, a marker of skeletal muscle regeneration, to the
RT   muscle-specific actin-binding protein, alpha-actinin-2, is required for
RT   myoblast fusion.";
RL   J. Biol. Chem. 275:13933-13939(2000).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-237, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, and Lung;
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   [6]
RP   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., Borradori L.;
RT   "BPAG1 isoform-b: complex distribution pattern in striated and heart muscle
RT   and association with plectin and alpha-actinin.";
RL   Exp. Cell Res. 316:297-313(2010).
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. Also forms heterodimers with ACTN3.
CC       Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C-
CC       terminal region with the LDB3 PDZ domain. Interacts with XIRP2.
CC       Interacts with DST (via N-terminus). Interacts with PARVB. Interacts
CC       with SYNPO2 (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:P35609}.
CC   -!- INTERACTION:
CC       Q9JI91; P11798: Camk2a; NbExp=3; IntAct=EBI-299169, EBI-400384;
CC       Q9JI91; Q01097: Grin2b; NbExp=2; IntAct=EBI-299169, EBI-400125;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC       {ECO:0000269|PubMed:19932097}. Note=Colocalizes with MYOZ1 and FLNC at
CC       the Z-lines of skeletal muscle.
CC   -!- PTM: Ubiquitinated by FBXL22, leading to proteasomal degradation.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}.
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DR   EMBL; AF248643; AAF76325.1; -; mRNA.
DR   EMBL; AC154523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466588; EDL32304.1; -; Genomic_DNA.
DR   CCDS; CCDS26239.1; -.
DR   RefSeq; NP_150371.4; NM_033268.4.
DR   AlphaFoldDB; Q9JI91; -.
DR   BMRB; Q9JI91; -.
DR   SMR; Q9JI91; -.
DR   BioGRID; 197950; 25.
DR   IntAct; Q9JI91; 12.
DR   MINT; Q9JI91; -.
DR   STRING; 10090.ENSMUSP00000067708; -.
DR   GlyGen; Q9JI91; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9JI91; -.
DR   PhosphoSitePlus; Q9JI91; -.
DR   EPD; Q9JI91; -.
DR   jPOST; Q9JI91; -.
DR   MaxQB; Q9JI91; -.
DR   PaxDb; 10090-ENSMUSP00000067708; -.
DR   PeptideAtlas; Q9JI91; -.
DR   ProteomicsDB; 285719; -.
DR   Pumba; Q9JI91; -.
DR   Antibodypedia; 1323; 495 antibodies from 39 providers.
DR   DNASU; 11472; -.
DR   Ensembl; ENSMUST00000064204.14; ENSMUSP00000067708.8; ENSMUSG00000052374.17.
DR   Ensembl; ENSMUST00000168193.8; ENSMUSP00000129609.2; ENSMUSG00000052374.17.
DR   GeneID; 11472; -.
DR   KEGG; mmu:11472; -.
DR   UCSC; uc007pli.1; mouse.
DR   AGR; MGI:109192; -.
DR   CTD; 88; -.
DR   MGI; MGI:109192; Actn2.
DR   VEuPathDB; HostDB:ENSMUSG00000052374; -.
DR   eggNOG; KOG0035; Eukaryota.
DR   GeneTree; ENSGT00940000153968; -.
DR   HOGENOM; CLU_005217_1_0_1; -.
DR   InParanoid; Q9JI91; -.
DR   OMA; VRYDNGY; -.
DR   OrthoDB; 2872403at2759; -.
DR   PhylomeDB; Q9JI91; -.
DR   TreeFam; TF352676; -.
DR   Reactome; R-MMU-114608; Platelet degranulation.
DR   Reactome; R-MMU-390522; Striated Muscle Contraction.
DR   Reactome; R-MMU-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   BioGRID-ORCS; 11472; 3 hits in 78 CRISPR screens.
DR   ChiTaRS; Actn2; mouse.
DR   PRO; PR:Q9JI91; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; Q9JI91; Protein.
DR   Bgee; ENSMUSG00000052374; Expressed in soleus muscle and 129 other cell types or tissues.
DR   ExpressionAtlas; Q9JI91; baseline and differential.
DR   GO; GO:0030054; C:cell junction; IBA:GO_Central.
DR   GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR   GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR   GO; GO:0030175; C:filopodium; ISO:MGI.
DR   GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0098871; C:postsynaptic actin cytoskeleton; ISO:MGI.
DR   GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI.
DR   GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:MGI.
DR   GO; GO:0030017; C:sarcomere; IDA:MGI.
DR   GO; GO:0005865; C:striated muscle thin filament; TAS:MGI.
DR   GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR   GO; GO:0051015; F:actin filament binding; IDA:MGI.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IDA:UniProtKB.
DR   GO; GO:0051373; F:FATZ binding; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0030274; F:LIM domain binding; IPI:MGI.
DR   GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:MGI.
DR   GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISO:MGI.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR   GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:MGI.
DR   GO; GO:0031432; F:titin binding; ISO:MGI.
DR   GO; GO:0070080; F:titin Z domain binding; ISO:MGI.
DR   GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR   GO; GO:0051695; P:actin filament uncapping; ISO:MGI.
DR   GO; GO:0055013; P:cardiac muscle cell development; IMP:UniProtKB.
DR   GO; GO:0048041; P:focal adhesion assembly; ISO:MGI.
DR   GO; GO:0030035; P:microspike assembly; ISO:MGI.
DR   GO; GO:0055001; P:muscle cell development; IBA:GO_Central.
DR   GO; GO:0006936; P:muscle contraction; TAS:MGI.
DR   GO; GO:0043267; P:negative regulation of potassium ion transport; ISO:MGI.
DR   GO; GO:2000009; P:negative regulation of protein localization to cell surface; ISO:MGI.
DR   GO; GO:0086097; P:phospholipase C-activating angiotensin-activated signaling pathway; ISO:MGI.
DR   GO; GO:2001259; P:positive regulation of cation channel activity; IMP:UniProtKB.
DR   GO; GO:2001137; P:positive regulation of endocytic recycling; IMP:UniProtKB.
DR   GO; GO:0043268; P:positive regulation of potassium ion transport; ISO:MGI.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR   GO; GO:0042391; P:regulation of membrane potential; ISO:MGI.
DR   GO; GO:0045214; P:sarcomere organization; ISO:MGI.
DR   CDD; cd21214; CH_ACTN_rpt1; 1.
DR   CDD; cd21216; CH_ACTN_rpt2; 1.
DR   CDD; cd00051; EFh; 1.
DR   CDD; cd00176; SPEC; 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; IPR002048; EF_hand_dom.
DR   InterPro; IPR018159; Spectrin/alpha-actinin.
DR   InterPro; IPR002017; Spectrin_repeat.
DR   PANTHER; PTHR11915:SF429; ALPHA-ACTININ-2; 1.
DR   PANTHER; PTHR11915; SPECTRIN/FILAMIN RELATED CYTOSKELETAL PROTEIN; 1.
DR   Pfam; PF00307; CH; 2.
DR   Pfam; PF13499; EF-hand_7; 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; PS50222; EF_HAND_2; 2.
DR   Genevisible; Q9JI91; MM.
PE   1: Evidence at protein level;
KW   Actin-binding; Calcium; Cytoplasm; Metal-binding; Phosphoprotein;
KW   Reference proteome; Repeat; Ubl conjugation.
FT   CHAIN           1..894
FT                   /note="Alpha-actinin-2"
FT                   /id="PRO_0000073436"
FT   DOMAIN          38..142
FT                   /note="Calponin-homology (CH) 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT   DOMAIN          151..257
FT                   /note="Calponin-homology (CH) 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT   REPEAT          281..391
FT                   /note="Spectrin 1"
FT   REPEAT          401..506
FT                   /note="Spectrin 2"
FT   REPEAT          516..627
FT                   /note="Spectrin 3"
FT   REPEAT          637..740
FT                   /note="Spectrin 4"
FT   DOMAIN          753..788
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          789..824
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   REGION          1..254
FT                   /note="Actin-binding"
FT   BINDING         766
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000305"
FT   BINDING         770
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000305"
FT   BINDING         777
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000305"
FT   BINDING         802
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000305"
FT   BINDING         804
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000305"
FT   BINDING         808
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         237
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CONFLICT        272
FT                   /note="V -> G (in Ref. 1; AAF76325)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        358
FT                   /note="P -> A (in Ref. 1; AAF76325)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        375
FT                   /note="W -> C (in Ref. 1; AAF76325)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        705
FT                   /note="A -> G (in Ref. 1; AAF76325)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        732
FT                   /note="A -> G (in Ref. 1; AAF76325)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        753
FT                   /note="E -> K (in Ref. 1; AAF76325)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   894 AA;  103834 MW;  79FCDC9C85B3949C 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 REALERTEKL LETIDQLHLE FAKRAAPFNN WMEGAMEDLQ
     DMFIVHSIEE IQSLITAHEQ FKATLPEADG ERQSILAIQN EVEKVIQSYS IRISSSNPYS
     TVTMDELRNK WDKVKQLVPV RDQSLQEELA RQHANERLRR QFAAQANAIG PWIQNKMEEI
     ARSSIQITGA LEDQMNQLKQ YEHNIINYKN NIDKLEGDHQ LIQEALVFDN KHTNYTMEHI
     RVGWELLLTT IARTINEVET QILTRDAKGI TQEQMNEFRA SFNHFDRRKN GLMDHEDFRA
     CLISMGYDLG EAEFARIMTL VDPNGQGTVT FQSFIDFMTR ETADTDTAEQ VIASFRILAS
     DKPYILAEEL RRELPPDQAQ YCIKRMPPYS GPGSVPGALD YTAFSSALYG ESDL
//