CSRP3_RAT
ID CSRP3_RAT Reviewed; 194 AA.
AC P50463;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 136.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=Lewis; TISSUE=Skeletal muscle;
RX PubMed=7954791; DOI=10.1016/0092-8674(94)90192-9;
RA Arber S., Halder G., Caroni P.;
RT "Muscle LIM protein, a novel essential regulator of myogenesis, promotes
RT myogenic differentiation.";
RL Cell 79:221-231(1994).
RN [2]
RP FUNCTION, INTERACTION WITH MYOD1; MYOG AND MYF6, AND SUBCELLULAR LOCATION.
RX PubMed=9234731; DOI=10.1128/mcb.17.8.4750;
RA Kong Y., Flick M.J., Kudla A.J., Konieczny S.F.;
RT "Muscle LIM protein promotes myogenesis by enhancing the activity of
RT MyoD.";
RL Mol. Cell. Biol. 17:4750-4760(1997).
RN [3]
RP INTERACTION WITH SPTB.
RX PubMed=10751147; DOI=10.1242/jcs.113.9.1553;
RA Flick M.J., Konieczny S.F.;
RT "The muscle regulatory and structural protein MLP is a cytoskeletal binding
RT partner of betaI-spectrin.";
RL J. Cell Sci. 113:1553-1564(2000).
RN [4]
RP INTERACTION WITH LDHD.
RX PubMed=12127981; DOI=10.1016/s0006-291x(02)00768-4;
RA Flick M.J., Konieczny S.F.;
RT "Identification of putative mammalian D-lactate dehydrogenase enzymes.";
RL Biochem. Biophys. Res. Commun. 295:910-916(2002).
RN [5]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=16963613; DOI=10.1152/ajpheart.00766.2006;
RA Boateng S.Y., Belin R.J., Geenen D.L., Margulies K.B., Martin J.L.,
RA Hoshijima M., de Tombe P.P., Russell B.;
RT "Cardiac dysfunction and heart failure are associated with abnormalities in
RT the subcellular distribution and amounts of oligomeric muscle LIM
RT protein.";
RL Am. J. Physiol. 292:H259-269(2007).
RN [6]
RP INTERACTION WITH GLRX3.
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 SUBCELLULAR LOCATION.
RX PubMed=19376126; DOI=10.1016/j.yjmcc.2009.04.006;
RA Boateng S.Y., Senyo S.E., Qi L., Goldspink P.H., Russell B.;
RT "Myocyte remodeling in response to hypertrophic stimuli requires
RT nucleocytoplasmic shuttling of muscle LIM protein.";
RL J. Mol. Cell. Cardiol. 47:426-435(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (PubMed:7954791,
CC PubMed:9234731). Plays a crucial and specific role in the organization
CC of cytosolic structures in cardiomyocytes. Could play a role in
CC mechanical stretch sensing. May be a scaffold protein that promotes the
CC assembly of interacting proteins at Z-line structures. It is essential
CC for calcineurin anchorage to the Z line. Required for stress-induced
CC calcineurin-NFAT activation. The role in regulation of cytoskeleton
CC dynamics by association with CFL2 is reported conflictingly. Proposed
CC to contribute to the maintenance of muscle cell integrity through an
CC actin-based mechanism. Can directly bind to actin filaments, cross-link
CC actin filaments into bundles without polarity selectivity and protect
CC them from dilution- and cofilin-mediated depolymerization; the function
CC seems to involve its self-association. In vitro can inhibit PKC/PRKCA
CC activity. Proposed to be involved in cardiac stress signaling by down-
CC regulating excessive PKC/PRKCA signaling (By similarity).
CC {ECO:0000250|UniProtKB:P50461, ECO:0000250|UniProtKB:P50462,
CC ECO:0000269|PubMed:7954791, ECO:0000269|PubMed:9234731}.
CC -!- SUBUNIT: Self-associates. Oligomeric in the cytoplasm and monomeric in
CC the nucleus (PubMed:16963613). Homooligomers preferentially form along
CC the actin cytoskeleton (By similarity). Interacts with TCAP, ACTN2 and
CC NRAP (By similarity). Interacts with LDHD, SPTB, MYOD1, MYOG, MYF6.
CC Interacts with GLRX3 (via C-terminus); GLRX3 and calcineurin compete
CC for interaction with CSRP3 (PubMed:9234731, PubMed:10751147,
CC PubMed:12127981, PubMed:18258855). Interacts with CFL2; the
CC stoichiometry influences F-actin depolymerization and possibly two
CC molecules of CFL2 can interact with one molecule of CSRP3 resulting in
CC the highest functional impact; the interaction is stronger with
CC phosphorylated CFL2 (By similarity). {ECO:0000250|UniProtKB:P50461,
CC ECO:0000269|PubMed:10751147, ECO:0000269|PubMed:12127981,
CC ECO:0000269|PubMed:16963613, ECO:0000269|PubMed:18258855,
CC ECO:0000269|PubMed:9234731}.
CC -!- INTERACTION:
CC P50463; P10085: Myod1; Xeno; NbExp=3; IntAct=EBI-12502290, EBI-4405734;
CC P50463; P11277: SPTB; Xeno; NbExp=6; IntAct=EBI-12502290, EBI-514908;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16963613,
CC ECO:0000269|PubMed:19376126, ECO:0000269|PubMed:9234731}. Cytoplasm
CC {ECO:0000269|PubMed:16963613, ECO:0000269|PubMed:19376126,
CC ECO:0000269|PubMed:9234731}. Cytoplasm, cytoskeleton. Cytoplasm,
CC myofibril, sarcomere, Z line {ECO:0000250|UniProtKB:P50462}. Cytoplasm,
CC myofibril, sarcomere {ECO:0000250|UniProtKB:P50461}.
CC Note=Nucleocytoplasmic shuttling protein (PubMed:19376126). Mainly
CC cytoplasmic. In the Z line, found associated with GLRX3 (By
CC similarity). {ECO:0000250|UniProtKB:P50462,
CC ECO:0000269|PubMed:19376126}.
CC -!- TISSUE SPECIFICITY: High in striated muscle and adult heart.
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 (By similarity). LIM zinc-binding
CC domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates
CC binding to SPTB (PubMed:9234731, PubMed:10751147).
CC {ECO:0000250|UniProtKB:P50461, ECO:0000269|PubMed:10751147,
CC ECO:0000269|PubMed:9234731}.
CC -!- PTM: Phosphorylated by PKC/PRKCA. {ECO:0000250|UniProtKB:P50461}.
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DR EMBL; X81193; CAA57065.1; -; mRNA.
DR PIR; A55099; A55099.
DR RefSeq; NP_476485.1; NM_057144.1.
DR AlphaFoldDB; P50463; -.
DR SMR; P50463; -.
DR IntAct; P50463; 5.
DR STRING; 10116.ENSRNOP00000019310; -.
DR iPTMnet; P50463; -.
DR PhosphoSitePlus; P50463; -.
DR PaxDb; P50463; -.
DR PRIDE; P50463; -.
DR GeneID; 117505; -.
DR KEGG; rno:117505; -.
DR UCSC; RGD:71092; rat.
DR CTD; 8048; -.
DR RGD; 71092; Csrp3.
DR eggNOG; KOG1700; Eukaryota.
DR InParanoid; P50463; -.
DR OrthoDB; 1214165at2759; -.
DR PhylomeDB; P50463; -.
DR PRO; PR:P50463; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0042805; F:actinin binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043426; F:MRF binding; IDA:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:MGI.
DR GO; GO:0008307; F:structural constituent of muscle; ISO:RGD.
DR GO; GO:0031433; F:telethonin binding; ISO:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0001974; P:blood vessel remodeling; IEP:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISO:RGD.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0035995; P:detection of muscle stretch; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
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:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0070528; P:protein kinase C signaling; ISO:RGD.
DR GO; GO:0033365; P:protein localization to organelle; ISO:RGD.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:RGD.
DR GO; GO:0045214; P:sarcomere organization; IBA:GO_Central.
DR GO; GO:0033292; P:T-tubule organization; ISO:RGD.
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_0000075729"
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:0000255, ECO:0000305|PubMed:19376126"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50462"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50462"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 194 AA; 20803 MW; 2D6848C271BA7EAB CRC64;
MPNWGGGAKC GACDKTVYHA EEIQCNGRSF HKTCFHCMAC RKALDSTTVA AHESEIYCKV
CYGRKYGPKG IGFGQGAGCL STDTGEHLGL QFQQSPKPAR AATTSNPSKF SAKFGESEKC
PRCGKSVYAA EKVMGGGKPW HKTCFPCAIC GKSLESTNVT DKDGELYCKV CYAKNFGPTG
IGFGGLTHQV EKKE
