CSRP3_MOUSE
ID CSRP3_MOUSE Reviewed; 194 AA.
AC P50462;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Cysteine and glycine-rich protein 3;
DE AltName: Full=Cysteine-rich protein 3;
DE Short=CRP3;
DE AltName: Full=LIM domain protein, cardiac;
DE AltName: Full=Muscle LIM protein;
GN Name=Csrp3; Synonyms=Clp, Mlp;
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 STRAIN=MF1; TISSUE=Mandible;
RX PubMed=8773898;
RA Harrod G.V., Kettunen P.J., Jowett A.K.;
RT "Murine MLP: cloning and expression in the embryonic head.";
RL J. Craniofac. Genet. Dev. Biol. 16:65-73(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ;
RA Hashimoto N., Ogashiwa M.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=129/Sv;
RX PubMed=9039266; DOI=10.1016/s0092-8674(00)81878-4;
RA Arber S., Hunter J.J., Ross J. Jr., Hongo M., Sansig G., Borg J.,
RA Perriard J.C., Chien K.R., Caroni P.;
RT "MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural
RT organization, dilated cardiomyopathy, and heart failure.";
RL Cell 88:393-403(1997).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15665106; DOI=10.1073/pnas.0405488102;
RA Heineke J., Ruetten H., Willenbockel C., Gross S.C., Naguib M.,
RA Schaefer A., Kempf T., Hilfiker-Kleiner D., Caroni P., Kraft T.,
RA Kaiser R.A., Molkentin J.D., Drexler H., Wollert K.C.;
RT "Attenuation of cardiac remodeling after myocardial infarction by muscle
RT LIM protein-calcineurin signaling at the sarcomeric Z-disc.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1655-1660(2005).
RN [6]
RP INTERACTION WITH GLRX3 AND PPP3CA, AND SUBCELLULAR LOCATION.
RX PubMed=18258855; DOI=10.1161/circresaha.107.165985;
RA Jeong D., Kim J.M., Cha H., Oh J.G., Park J., Yun S.H., Ju E.S., Jeon E.S.,
RA Hajjar R.J., Park W.J.;
RT "PICOT attenuates cardiac hypertrophy by disrupting calcineurin-NFAT
RT signaling.";
RL Circ. Res. 102:711-719(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95 AND SER-111, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, 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 [8]
RP MUTAGENESIS OF TRP-4, AND INTERACTION WITH TCAP.
RX PubMed=20044516; DOI=10.1161/circresaha.109.206243;
RA Knoll R., Kostin S., Klede S., Savvatis K., Klinge L., Stehle I.,
RA Gunkel S., Kotter S., Babicz K., Sohns M., Miocic S., Didie M., Knoll G.,
RA Zimmermann W.H., Thelen P., Bickeboller H., Maier L.S., Schaper W.,
RA Schaper J., Kraft T., Tschope C., Linke W.A., Chien K.R.;
RT "A common MLP (muscle LIM protein) variant is associated with
RT cardiomyopathy.";
RL Circ. Res. 106:695-704(2010).
RN [9]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=27353086; DOI=10.1038/ncomms12120;
RA Lange S., Gehmlich K., Lun A.S., Blondelle J., Hooper C., Dalton N.D.,
RA Alvarez E.A., Zhang X., Bang M.L., Abassi Y.A., Dos Remedios C.G.,
RA Peterson K.L., Chen J., Ehler E.;
RT "MLP and CARP are linked to chronic PKCalpha signalling in dilated
RT cardiomyopathy.";
RL Nat. Commun. 7:12120-12120(2016).
CC -!- FUNCTION: Positive regulator of myogenesis. Acts as cofactor for
CC myogenic bHLH transcription factors such as MYOD1, and probably MYOG
CC and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform
CC E47 complex and may promote formation of a functional MYOD1:TCF3
CC isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays
CC a crucial and specific role in the organization of cytosolic structures
CC in cardiomyocytes. Could play a role in mechanical stretch sensing. May
CC be a scaffold protein that promotes the assembly of interacting
CC proteins at Z-line structures. It is essential for calcineurin
CC anchorage to the Z line. Required for stress-induced calcineurin-NFAT
CC activation (PubMed:9039266, PubMed:15665106). The role in regulation of
CC cytoskeleton dynamics by association with CFL2 is reported
CC conflictingly. Proposed to contribute to the maintenance of muscle cell
CC integrity through an actin-based mechanism. Can directly bind to actin
CC filaments, cross-link actin filaments into bundles without polarity
CC selectivity and protect them from dilution- and cofilin-mediated
CC depolymerization; the function seems to involve its self-association
CC (By similarity). In vitro can inhibit PKC/PRKCA activity. Proposed to
CC be involved in cardiac stress signaling by down-regulating excessive
CC PKC/PRKCA signaling (PubMed:27353086). {ECO:0000250|UniProtKB:P50461,
CC ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:15665106,
CC ECO:0000269|PubMed:27353086, ECO:0000269|PubMed:9039266}.
CC -!- SUBUNIT: Self-associates. Oligomeric in the cytoplasm and monomeric in
CC the nucleus. Homooligomers preferentially form along the actin
CC cytoskeleton (By similarity). Interacts with TCAP (PubMed:20044516).
CC Interacts with LDHD, MYOD1, MYOG, ACTN2, NRAP, MYF6 (By similarity).
CC Interacts (via N-terminus)D with GLRX3 (via C-terminus) and PPP3CA;
CC GLRX3 and calcineurin compete for interaction with CSRP3
CC (PubMed:18258855). Interacts with CFL2; the stoichiometry influences F-
CC actin depolymerization and possibly two molecules of CFL2 can interact
CC with one molecule of CSRP3 resulting in the highest functional impact;
CC the interaction is stronger with phosphorylated CFL2 (By similarity).
CC {ECO:0000250|UniProtKB:P50461, ECO:0000250|UniProtKB:P50463,
CC ECO:0000269|PubMed:18258855, ECO:0000269|PubMed:20044516}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P50463}. Cytoplasm
CC {ECO:0000269|PubMed:18258855}. Cytoplasm, cytoskeleton {ECO:0000305}.
CC Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:18258855}.
CC Cytoplasm, myofibril, sarcomere {ECO:0000250|UniProtKB:P50461}.
CC Note=Nucleocytoplasmic shuttling protein (By similarity). Mainly
CC cytoplasmic. In the Z line, found associated with GLRX3 (via C-
CC terminus). {ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:18258855}.
CC -!- DOMAIN: LIM zinc-binding domain 1 is required for self-association. LIM
CC zinc-binding domain 1 and LIM zinc-binding domain 2 both are required
CC for optimal actin-bundling activity. LIM zinc-binding domain 1 mediates
CC binding to MYOD1. LIM zinc-binding domain 2 mediates binding to SPTB.
CC {ECO:0000250|UniProtKB:P50461, ECO:0000250|UniProtKB:P50463}.
CC -!- PTM: Phosphorylated by PKC/PRKCA. {ECO:0000250|UniProtKB:P50461}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice developed dilated cardiomyopathy with
CC hypertrophy and heart failure after birth. Ultrastructural analysis
CC revealed a dramatic disruption of cardiomyocyte cytoarchitecture. At
CC birth, these hearts are not hypertrophic, but already abnormally soft,
CC with cell-autonomous and Csrp3-sensitive alterations in
CC cytoarchitecture. The morphological, functional, and molecular features
CC of the cardiac phenotype in mutant adult mice are undistinguishable
CC from those seen in human heart failure resulting from dilated
CC cardiomyopathy of various etiolologies, these mice can thus be used as
CC model. Heterozygous mice display a more pronounced left ventricular
CC dilation and systolic dysfunction and decreased survival after
CC myocardial infarction. {ECO:0000269|PubMed:15665106,
CC ECO:0000269|PubMed:9039266}.
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DR EMBL; Z49883; CAA90039.1; -; mRNA.
DR EMBL; D88791; BAA13721.1; -; mRNA.
DR EMBL; BC061131; AAH61131.1; -; mRNA.
DR CCDS; CCDS21305.1; -.
DR PIR; S57472; S57472.
DR RefSeq; NP_001185770.1; NM_001198841.1.
DR RefSeq; NP_038836.1; NM_013808.4.
DR AlphaFoldDB; P50462; -.
DR BMRB; P50462; -.
DR SMR; P50462; -.
DR BioGRID; 198954; 5.
DR IntAct; P50462; 3.
DR STRING; 10090.ENSMUSP00000129378; -.
DR iPTMnet; P50462; -.
DR PhosphoSitePlus; P50462; -.
DR EPD; P50462; -.
DR jPOST; P50462; -.
DR PaxDb; P50462; -.
DR PeptideAtlas; P50462; -.
DR PRIDE; P50462; -.
DR ProteomicsDB; 285379; -.
DR Antibodypedia; 12424; 316 antibodies from 35 providers.
DR DNASU; 13009; -.
DR Ensembl; ENSMUST00000032658; ENSMUSP00000032658; ENSMUSG00000030470.
DR Ensembl; ENSMUST00000167786; ENSMUSP00000129378; ENSMUSG00000030470.
DR GeneID; 13009; -.
DR KEGG; mmu:13009; -.
DR UCSC; uc009hax.2; mouse.
DR CTD; 8048; -.
DR MGI; MGI:1330824; Csrp3.
DR VEuPathDB; HostDB:ENSMUSG00000030470; -.
DR eggNOG; KOG1700; Eukaryota.
DR GeneTree; ENSGT00940000159533; -.
DR HOGENOM; CLU_054591_1_1_1; -.
DR InParanoid; P50462; -.
DR OMA; TCYGRRY; -.
DR OrthoDB; 1214165at2759; -.
DR PhylomeDB; P50462; -.
DR TreeFam; TF313758; -.
DR BioGRID-ORCS; 13009; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Marcksl1; mouse.
DR PRO; PR:P50462; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P50462; protein.
DR Bgee; ENSMUSG00000030470; Expressed in atrioventricular valve and 133 other tissues.
DR ExpressionAtlas; P50462; baseline and differential.
DR Genevisible; P50462; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0042805; F:actinin binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043426; F:MRF binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0008307; F:structural constituent of muscle; IMP:BHF-UCL.
DR GO; GO:0031433; F:telethonin binding; IPI:BHF-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; ISO:MGI.
DR GO; GO:0048738; P:cardiac muscle tissue development; IGI:MGI.
DR GO; GO:0055003; P:cardiac myofibril assembly; IMP:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IGI:MGI.
DR GO; GO:0035995; P:detection of muscle stretch; IMP:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:MGI.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0060537; P:muscle tissue development; IBA:GO_Central.
DR GO; GO:1903919; P:negative regulation of actin filament severing; ISO:MGI.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:MGI.
DR GO; GO:1903920; P:positive regulation of actin filament severing; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISO:MGI.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0070528; P:protein kinase C signaling; IGI:MGI.
DR GO; GO:0033365; P:protein localization to organelle; IMP:BHF-UCL.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IMP:MGI.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IGI:MGI.
DR GO; GO:0045214; P:sarcomere organization; IBA:GO_Central.
DR GO; GO:0033292; P:T-tubule organization; IGI:MGI.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00412; LIM; 2.
DR SMART; SM00132; LIM; 2.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Actin-binding; Cytoplasm; Cytoskeleton; Developmental protein;
KW Differentiation; LIM domain; Metal-binding; Myogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..194
FT /note="Cysteine and glycine-rich protein 3"
FT /id="PRO_0000075728"
FT DOMAIN 10..61
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 120..171
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT REGION 1..5
FT /note="Interaction with TCAP"
FT /evidence="ECO:0000250|UniProtKB:P50461"
FT REGION 94..105
FT /note="Interaction with CLF2"
FT /evidence="ECO:0000250|UniProtKB:P50461"
FT MOTIF 64..69
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P50463, ECO:0000255"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50463"
FT MUTAGEN 4
FT /note="W->R: Mice develop an age- and gene dosage-dependent
FT hypertrophic cardiomyopathy and heart failure phenotype,
FT characterized by almost complete loss of contractile
FT reserve under catecholamine induced stress. They display
FT increased in septum wall thickness, fractional shortening,
FT and wall thickness per diameter (h/r). There is also
FT evidence for skeletal muscle pathology. In addition,
FT homozygous mutants show increased left ventricle (LC) mass
FT per body weight (BW) and significantly reduced body weight.
FT An increased nuclear localization of Csrp3 is also
FT observed. Decreases interaction with TCAP."
FT /evidence="ECO:0000269|PubMed:20044516"
SQ SEQUENCE 194 AA; 20895 MW; E35CF30CA17CB227 CRC64;
MPNWGGGAKC GACEKTVYHA EEIQCNGRSF HKTCFHCMAC RKALDSTTVA AHESEIYCKV
CYGRRYGPKG IGFGQGAGCL STDTGEHLGL QFQQSPKPAR AATTSNPSKF SAKFGESEKC
PRCGKSVYAA EKVMGGGKPW HKTCFRCAIC GKSLESTNVT DKDGELYCKV CYAKNFGPTG
IGFGGLTQQV EKKE
