CSRP3_HUMAN
ID CSRP3_HUMAN Reviewed; 194 AA.
AC P50461; Q9P131; S4S7M7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Cysteine and glycine-rich protein 3;
DE AltName: Full=Cardiac LIM protein;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=7490106; DOI=10.1006/geno.1995.1200;
RA Fung Y.W., Wang R.X., Heng H.H.Q., Liew C.C.;
RT "Mapping of a human LIM protein (CLP) to human chromosome 11p15.1 by
RT fluorescence in situ hybridization.";
RL Genomics 28:602-603(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RA Medvedev A., Jetten A.M.;
RT "Cloning of the gene encoding the human muscle LIM protein, a regulator of
RT myogenesis.";
RL Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA Yasunaga S., Harada H., Kimura A.;
RT "Cloning and characterization of the human muscle LIM protein gene.";
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart, and Skeletal muscle;
RA Chen K.H., Zhang J.F., Ma D.L., Tang J.;
RT "A novel member of LIM gene family involved in cardiovascular diseases.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), SUBCELLULAR
RP LOCATION (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH MYOD1; MYOG;
RP TCAP AND ALPHA-ACTININ, AND SELF-ASSOCIATION.
RX PubMed=24860983; DOI=10.1111/febs.12859;
RA Vafiadaki E., Arvanitis D.A., Papalouka V., Terzis G., Roumeliotis T.I.,
RA Spengos K., Garbis S.D., Manta P., Kranias E.G., Sanoudou D.;
RT "Muscle lim protein isoform negatively regulates striated muscle actin
RT dynamics and differentiation.";
RL FEBS J. 281:3261-3279(2014).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle, and Testis;
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 [7]
RP INTERACTION WITH TCAP.
RX PubMed=15582318; DOI=10.1016/j.jacc.2004.08.058;
RA Hayashi T., Arimura T., Itoh-Satoh M., Ueda K., Hohda S., Inagaki N.,
RA Takahashi M., Hori H., Yasunami M., Nishi H., Koga Y., Nakamura H.,
RA Matsuzaki M., Choi B.Y., Bae S.W., You C.W., Han K.H., Park J.E.,
RA Knoell R., Hoshijima M., Chien K.R., Kimura A.;
RT "Tcap gene mutations in hypertrophic cardiomyopathy and dilated
RT cardiomyopathy.";
RL J. Am. Coll. Cardiol. 44:2192-2201(2004).
RN [8]
RP INTERACTION WITH NRAP AND ACTN2, AND CHARACTERIZATION OF VARIANT CMH12
RP GLY-58.
RX PubMed=15205937; DOI=10.1007/s00441-004-0873-y;
RA Gehmlich K., Geier C., Osterziel K.J., Van der Ven P.F., Fuerst D.O.;
RT "Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and
RT alpha-actinin and their implication for hypertrophic cardiomyopathy.";
RL Cell Tissue Res. 317:129-136(2004).
RN [9]
RP FUNCTION, AND INTERACTION WITH CFL2.
RX PubMed=19752190; DOI=10.1128/mcb.00654-09;
RA Papalouka V., Arvanitis D.A., Vafiadaki E., Mavroidis M., Papadodima S.A.,
RA Spiliopoulou C.A., Kremastinos D.T., Kranias E.G., Sanoudou D.;
RT "Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics
RT in cardiac and skeletal muscle.";
RL Mol. Cell. Biol. 29:6046-6058(2009).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, SELF-ASSOCIATION, AND LIM ZINC-BINDING
RP DOMAINS.
RX PubMed=24934443; DOI=10.1128/mcb.00651-14;
RA Hoffmann C., Moreau F., Moes M., Luthold C., Dieterle M., Goretti E.,
RA Neumann K., Steinmetz A., Thomas C.;
RT "Human muscle LIM protein dimerizes along the actin cytoskeleton and cross-
RT links actin filaments.";
RL Mol. Cell. Biol. 34:3053-3065(2014).
RN [11]
RP FUNCTION, PHOSPHORYLATION, CHARACTERIZATION OF VARIANTS CMH12 PRO-44;
RP 54-ARG-GLY-55 AND GLY-58, CHARACTERIZATION OF VARIANT ARG-72, AND
RP MUTAGENESIS OF LYS-69.
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).
RN [12]
RP STRUCTURE BY NMR OF 7-66 AND 119-176.
RX PubMed=19230835; DOI=10.1016/j.febslet.2009.02.021;
RA Schallus T., Feher K., Ulrich A.S., Stier G., Muhle-Goll C.;
RT "Structure and dynamics of the human muscle LIM protein.";
RL FEBS Lett. 583:1017-1022(2009).
RN [13]
RP VARIANT CMD1M ARG-4, INTERACTION WITH TCAP, AND CHARACTERIZATION OF VARIANT
RP CMD1M ARG-4.
RX PubMed=12507422; DOI=10.1016/s0092-8674(02)01226-6;
RA Knoell R., Hoshijima M., Hoffman H.M., Person V., Lorenzen-Schmidt I.,
RA Bang M.-L., Hayashi T., Shiga N., Yasukawa H., Schaper W., McKenna W.,
RA Yokoyama M., Schork N.J., Omens J.H., McCulloch A.D., Kimura A.,
RA Gregorio C.C., Poller W., Schaper J., Schultheiss H.P., Chien K.R.;
RT "The cardiac mechanical stretch sensor machinery involves a Z disc complex
RT that is defective in a subset of human dilated cardiomyopathy.";
RL Cell 111:943-955(2002).
RN [14]
RP VARIANTS CMH12 PRO-44; 54-ARG-GLY-55 AND GLY-58.
RX PubMed=12642359; DOI=10.1161/01.cir.0000056522.82563.5f;
RA Geier C., Perrot A., Ozcelik C., Binner P., Counsell D., Hoffmann K.,
RA Pilz B., Martiniak Y., Gehmlich K., van der Ven P.F.M., Furst D.O.,
RA Vornwald A., von Hodenberg E., Nurnberg P., Scheffold T., Dietz R.,
RA Osterziel K.J.;
RT "Mutations in the human muscle LIM protein gene in families with
RT hypertrophic cardiomyopathy.";
RL Circulation 107:1390-1395(2003).
RN [15]
RP VARIANT CMD1M ARG-72.
RX PubMed=19412328; DOI=10.1111/j.1752-8062.2008.00017.x;
RA Hershberger R.E., Parks S.B., Kushner J.D., Li D., Ludwigsen S., Jakobs P.,
RA Nauman D., Burgess D., Partain J., Litt M.;
RT "Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3,
RT and TCAP from 313 patients with familial or idiopathic dilated
RT cardiomyopathy.";
RL Clin. Transl. Sci. 1:21-26(2008).
RN [16]
RP CHARACTERIZATION OF VARIANT CMD1M ARG-4, VARIANT CMH12 GLY-58, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18505755; DOI=10.1093/hmg/ddn160;
RA Geier C., Gehmlich K., Ehler E., Hassfeld S., Perrot A., Hayess K.,
RA Cardim N., Wenzel K., Erdmann B., Krackhardt F., Posch M.G.,
RA Osterziel K.J., Bublak A., Nagele H., Scheffold T., Dietz R., Chien K.R.,
RA Spuler S., Furst D.O., Nurnberg P., Ozcelik C.;
RT "Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy.";
RL Hum. Mol. Genet. 17:2753-2765(2008).
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 (By similarity). The role in regulation of cytoskeleton
CC dynamics by association with CFL2 is reported conflictingly: Shown to
CC enhance CFL2-mediated F-actin depolymerization dependent on the
CC CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of
CC CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190,
CC PubMed:24934443). Proposed to contribute to the maintenance of muscle
CC cell integrity through an actin-based mechanism. Can directly bind to
CC actin filaments, cross-link actin filaments into bundles without
CC polarity selectivity and protect them from dilution- and cofilin-
CC mediated depolymerization; the function seems to involve its self-
CC association (PubMed:24934443). In vitro can inhibit PKC/PRKCA activity
CC (PubMed:27353086). Proposed to be involved in cardiac stress signaling
CC by down-regulating excessive PKC/PRKCA signaling (By similarity).
CC {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463,
CC ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24934443,
CC ECO:0000269|PubMed:27353086}.
CC -!- FUNCTION: [Isoform 2]: May play a role in early sarcomere organization.
CC Overexpression in myotubes negatively regulates myotube
CC differentiation. By association with isoform 1 and thus changing the
CC CSRP3 isoform 1:CFL2 stoichiometry is proposed to down-regulate CFL2-
CC mediated F-actin depolymerization. {ECO:0000269|PubMed:24860983}.
CC -!- SUBUNIT: Self-associates. Oligomeric in the cytoplasm and monomeric in
CC the nucleus (By similarity). Homooligomers preferentially form along
CC the actin cytoskeleton. Isoform 2 interacts with isoform 1
CC (PubMed:24934443, PubMed:24860983). Isoform 1 but not isoform 2
CC interacts with MYOD1 and MYOG. Isoform 1 interacts with TCAP, ACTN2 and
CC NRAP. Isoform 2 interacts with TCAP and alpha-actinin (PubMed:24860983,
CC PubMed:15582318, PubMed:15205937, PubMed:12507422). Interacts with
CC LDHD. Interacts (via N-terminus)with GLRX3 (via C-terminus) and PPP3CA;
CC GLRX3 and calcineurin compete for interaction with CSRP3. Interacts
CC with MYF6 (By similarity). Interacts with CFL2; the stoichiometry
CC influences F-actin depolymerization and possibly two molecules of CFL2
CC can interact with one molecule of CSRP3 resulting in the highest
CC functional impact; the interaction is stronger with phosphorylated CFL2
CC (PubMed:19752190). {ECO:0000250|UniProtKB:P50462,
CC ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:12507422,
CC ECO:0000269|PubMed:15205937, ECO:0000269|PubMed:15582318,
CC ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24860983,
CC ECO:0000269|PubMed:24934443}.
CC -!- INTERACTION:
CC P50461; P35609: ACTN2; NbExp=4; IntAct=EBI-5658719, EBI-77797;
CC P50461; Q9Y281: CFL2; NbExp=2; IntAct=EBI-5658719, EBI-351218;
CC P50461; P50461: CSRP3; NbExp=2; IntAct=EBI-5658719, EBI-5658719;
CC P50461; P42858: HTT; NbExp=3; IntAct=EBI-5658719, EBI-466029;
CC P50461; Q86VF7: NRAP; NbExp=2; IntAct=EBI-5658719, EBI-5660292;
CC P50461; O15273: TCAP; NbExp=3; IntAct=EBI-5658719, EBI-954089;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P50463}. Cytoplasm
CC {ECO:0000269|PubMed:18505755}. Cytoplasm, cytoskeleton {ECO:0000305}.
CC Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:24860983}.
CC Cytoplasm, myofibril, sarcomere {ECO:0000269|PubMed:24934443}.
CC Note=Nucleocytoplasmic shuttling protein. Mainly cytoplasmic. In the Z
CC line, found associated with GLRX3 (By similarity).
CC {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, myofibril, sarcomere, Z
CC line {ECO:0000269|PubMed:24860983}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=MLP-a;
CC IsoId=P50461-1; Sequence=Displayed;
CC Name=2; Synonyms=MLP-b;
CC IsoId=P50461-2; Sequence=VSP_058575, VSP_058576;
CC -!- TISSUE SPECIFICITY: Cardiac and slow-twitch skeletal muscles. Isoform 2
CC is expressed in striated muscle. Isoform 2 is specifically expressed at
CC higher levels in patients with neuromuscular diseases, such as limb-
CC girdle muscular dystrophy 2A (LGMD2A), Duchenne muscular dystrophy
CC (DMD) and dermatomyositis (PubMed:24860983).
CC {ECO:0000269|PubMed:24860983}.
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 (PubMed:24934443). LIM zinc-binding
CC domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates
CC binding to SPTB (By similarity). {ECO:0000250|UniProtKB:P50463,
CC ECO:0000269|PubMed:24934443}.
CC -!- PTM: Phosphorylated by PKC/PRKCA. {ECO:0000305|PubMed:27353086}.
CC -!- DISEASE: Cardiomyopathy, dilated 1M (CMD1M) [MIM:607482]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:12507422,
CC ECO:0000269|PubMed:18505755, ECO:0000269|PubMed:19412328}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 12 (CMH12) [MIM:612124]:
CC A hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:12642359, ECO:0000269|PubMed:15205937,
CC ECO:0000269|PubMed:18505755, ECO:0000269|PubMed:27353086}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; U20324; AAA91104.1; -; mRNA.
DR EMBL; U49837; AAA92571.1; -; mRNA.
DR EMBL; U72898; AAD00189.1; -; Genomic_DNA.
DR EMBL; U72894; AAD00189.1; JOINED; Genomic_DNA.
DR EMBL; U72895; AAD00189.1; JOINED; Genomic_DNA.
DR EMBL; U72896; AAD00189.1; JOINED; Genomic_DNA.
DR EMBL; U72897; AAD00189.1; JOINED; Genomic_DNA.
DR EMBL; U72899; AAD00183.1; -; mRNA.
DR EMBL; AF121260; AAF28868.1; -; mRNA.
DR EMBL; JN898958; AFH66949.1; -; mRNA.
DR EMBL; BC005900; AAH05900.1; -; mRNA.
DR EMBL; BC024010; AAH24010.1; -; mRNA.
DR EMBL; BC057221; AAH57221.1; -; mRNA.
DR CCDS; CCDS7848.1; -. [P50461-1]
DR RefSeq; NP_003467.1; NM_003476.4. [P50461-1]
DR PDB; 2O10; NMR; -; A=7-66.
DR PDB; 2O13; NMR; -; A=119-176.
DR PDBsum; 2O10; -.
DR PDBsum; 2O13; -.
DR AlphaFoldDB; P50461; -.
DR BMRB; P50461; -.
DR SMR; P50461; -.
DR BioGRID; 113736; 15.
DR IntAct; P50461; 10.
DR MINT; P50461; -.
DR STRING; 9606.ENSP00000431813; -.
DR iPTMnet; P50461; -.
DR PhosphoSitePlus; P50461; -.
DR BioMuta; CSRP3; -.
DR DMDM; 1705933; -.
DR EPD; P50461; -.
DR jPOST; P50461; -.
DR MassIVE; P50461; -.
DR MaxQB; P50461; -.
DR PaxDb; P50461; -.
DR PeptideAtlas; P50461; -.
DR PRIDE; P50461; -.
DR ProteomicsDB; 56231; -.
DR Antibodypedia; 12424; 316 antibodies from 35 providers.
DR DNASU; 8048; -.
DR Ensembl; ENST00000265968.9; ENSP00000265968.3; ENSG00000129170.10. [P50461-1]
DR Ensembl; ENST00000533783.2; ENSP00000431813.1; ENSG00000129170.10. [P50461-1]
DR Ensembl; ENST00000649235.1; ENSP00000497388.1; ENSG00000129170.10. [P50461-1]
DR GeneID; 8048; -.
DR KEGG; hsa:8048; -.
DR MANE-Select; ENST00000265968.9; ENSP00000265968.3; NM_003476.5; NP_003467.1.
DR UCSC; uc001mpk.4; human. [P50461-1]
DR CTD; 8048; -.
DR DisGeNET; 8048; -.
DR GeneCards; CSRP3; -.
DR GeneReviews; CSRP3; -.
DR HGNC; HGNC:2472; CSRP3.
DR HPA; ENSG00000129170; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR MalaCards; CSRP3; -.
DR MIM; 600824; gene.
DR MIM; 607482; phenotype.
DR MIM; 612124; phenotype.
DR neXtProt; NX_P50461; -.
DR OpenTargets; ENSG00000129170; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA26971; -.
DR VEuPathDB; HostDB:ENSG00000129170; -.
DR eggNOG; KOG1700; Eukaryota.
DR GeneTree; ENSGT00940000159533; -.
DR HOGENOM; CLU_054591_1_1_1; -.
DR InParanoid; P50461; -.
DR OMA; TCYGRRY; -.
DR PhylomeDB; P50461; -.
DR TreeFam; TF313758; -.
DR PathwayCommons; P50461; -.
DR SignaLink; P50461; -.
DR SIGNOR; P50461; -.
DR BioGRID-ORCS; 8048; 16 hits in 1072 CRISPR screens.
DR ChiTaRS; CSRP3; human.
DR EvolutionaryTrace; P50461; -.
DR GeneWiki; CSRP3; -.
DR GenomeRNAi; 8048; -.
DR Pharos; P50461; Tbio.
DR PRO; PR:P50461; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P50461; protein.
DR Bgee; ENSG00000129170; Expressed in skeletal muscle tissue of rectus abdominis and 109 other tissues.
DR ExpressionAtlas; P50461; baseline and differential.
DR Genevisible; P50461; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008307; F:structural constituent of muscle; IMP:BHF-UCL.
DR GO; GO:0031433; F:telethonin binding; IDA: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; IMP:BHF-UCL.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISS:BHF-UCL.
DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:BHF-UCL.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:BHF-UCL.
DR GO; GO:0035995; P:detection of muscle stretch; IMP:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:0060537; P:muscle tissue development; IBA:GO_Central.
DR GO; GO:1903919; P:negative regulation of actin filament severing; IDA:MGI.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:MGI.
DR GO; GO:1903920; P:positive regulation of actin filament severing; IDA:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0070528; P:protein kinase C signaling; IEA:Ensembl.
DR GO; GO:0033365; P:protein localization to organelle; IMP:BHF-UCL.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISS:BHF-UCL.
DR GO; GO:0045214; P:sarcomere organization; IBA:GO_Central.
DR GO; GO:0007519; P:skeletal muscle tissue development; TAS:ProtInc.
DR GO; GO:0033292; P:T-tubule organization; IEA:Ensembl.
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 3D-structure; Actin-binding; Alternative splicing; Cardiomyopathy;
KW Cytoplasm; Cytoskeleton; Developmental protein; Differentiation;
KW Disease variant; 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_0000075727"
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:0000269|PubMed:12507422"
FT REGION 94..105
FT /note="Interaction with CLF2 and isoform 2"
FT /evidence="ECO:0000269|PubMed:19752190,
FT ECO:0000269|PubMed:24860983"
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:0000250|UniProtKB:P50462"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50463"
FT VAR_SEQ 38..59
FT /note="MACRKALDSTTVAAHESEIYCK -> TLAQDLFPLCHLWEESGVHKC (in
FT isoform 2)"
FT /id="VSP_058575"
FT VAR_SEQ 60..194
FT /note="Missing (in isoform 2)"
FT /id="VSP_058576"
FT VARIANT 4
FT /note="W -> R (in CMD1M; unknown pathological significance;
FT decreases interaction with TCAP; dbSNP:rs45550635)"
FT /evidence="ECO:0000269|PubMed:12507422,
FT ECO:0000269|PubMed:18505755"
FT /id="VAR_015401"
FT VARIANT 44
FT /note="L -> P (in CMH12; decreases PKC/PRKCA activity;
FT dbSNP:rs104894205)"
FT /evidence="ECO:0000269|PubMed:12642359,
FT ECO:0000269|PubMed:27353086"
FT /id="VAR_045932"
FT VARIANT 54..55
FT /note="SE -> RG (in CMH12; decreases PKC/PRKCA activity;
FT dbSNP:rs281865416)"
FT /evidence="ECO:0000269|PubMed:27353086"
FT /id="VAR_045933"
FT VARIANT 58
FT /note="C -> G (in CMH12; decreases interaction with NRAP
FT and ACTN2, decreases zinc-binding and impairs protein
FT stability, decreases PKC/PRKCA activity;
FT dbSNP:rs104894204)"
FT /evidence="ECO:0000269|PubMed:12642359,
FT ECO:0000269|PubMed:15205937, ECO:0000269|PubMed:18505755"
FT /id="VAR_045934"
FT VARIANT 72
FT /note="G -> R (in CMD1M; unknown pathological significance;
FT increases PKC/PRKCA activity; dbSNP:rs45552933)"
FT /evidence="ECO:0000269|PubMed:19412328,
FT ECO:0000269|PubMed:27353086"
FT /id="VAR_076805"
FT MUTAGEN 69
FT /note="K->R: Increases PKC/PRKCA activity."
FT /evidence="ECO:0000269|PubMed:27353086"
FT CONFLICT 26
FT /note="N -> H (in Ref. 4; AAF28868)"
FT /evidence="ECO:0000305"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:2O10"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:2O10"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:2O10"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:2O10"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:2O10"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:2O10"
FT TURN 46..48
FT /evidence="ECO:0007829|PDB:2O10"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:2O10"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:2O10"
FT HELIX 59..65
FT /evidence="ECO:0007829|PDB:2O10"
FT TURN 121..124
FT /evidence="ECO:0007829|PDB:2O13"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:2O13"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:2O13"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:2O13"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:2O13"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2O13"
FT TURN 148..151
FT /evidence="ECO:0007829|PDB:2O13"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:2O13"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:2O13"
FT HELIX 169..175
FT /evidence="ECO:0007829|PDB:2O13"
SQ SEQUENCE 194 AA; 20969 MW; FDB6E4F8D258C35F CRC64;
MPNWGGGAKC GACEKTVYHA EEIQCNGRSF HKTCFHCMAC RKALDSTTVA AHESEIYCKV
CYGRRYGPKG IGYGQGAGCL STDTGEHLGL QFQQSPKPAR SVTTSNPSKF TAKFGESEKC
PRCGKSVYAA EKVMGGGKPW HKTCFRCAIC GKSLESTNVT DKDGELYCKV CYAKNFGPTG
IGFGGLTQQV EKKE
