ACTN2_MOUSE
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 03-AUG-2022, entry version 179.
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; 24.
DR IntAct; Q9JI91; 12.
DR MINT; Q9JI91; -.
DR STRING; 10090.ENSMUSP00000067708; -.
DR iPTMnet; Q9JI91; -.
DR PhosphoSitePlus; Q9JI91; -.
DR EPD; Q9JI91; -.
DR jPOST; Q9JI91; -.
DR MaxQB; Q9JI91; -.
DR PaxDb; Q9JI91; -.
DR PeptideAtlas; Q9JI91; -.
DR PRIDE; Q9JI91; -.
DR ProteomicsDB; 285719; -.
DR Antibodypedia; 1323; 405 antibodies from 39 providers.
DR DNASU; 11472; -.
DR Ensembl; ENSMUST00000064204; ENSMUSP00000067708; ENSMUSG00000052374.
DR Ensembl; ENSMUST00000168193; ENSMUSP00000129609; ENSMUSG00000052374.
DR GeneID; 11472; -.
DR KEGG; mmu:11472; -.
DR UCSC; uc007pli.1; mouse.
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; IMILVDP; -.
DR OrthoDB; 543832at2759; -.
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 73 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 127 other tissues.
DR ExpressionAtlas; Q9JI91; baseline and differential.
DR Genevisible; Q9JI91; MM.
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; ISO:MGI.
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; 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:1901017; P:negative regulation of potassium ion transmembrane transporter activity; ISO: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:1901018; P:positive regulation of potassium ion transmembrane transporter activity; ISO:MGI.
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; cd00014; CH; 2.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00176; SPEC; 1.
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; 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; 3.
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 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
