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Protein

Cysteine and glycine-rich protein 3

Gene

Csrp3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Positive regulator of myogenesis. Acts as cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (PubMed:9039266, PubMed:15665106). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly. Proposed to contribute to the maintenance of muscle cell integerity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (By similarity). In vitro can inhibit PKC/PRKCA activity. Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (PubMed:27353086).By similarity3 Publications

GO - Molecular functioni

  • actinin binding Source: BHF-UCL
  • MRF binding Source: MGI
  • RNA polymerase II sequence-specific DNA binding transcription factor binding Source: MGI
  • structural constituent of muscle Source: BHF-UCL
  • telethonin binding Source: BHF-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cardiac muscle contraction Source: BHF-UCL
  • cardiac muscle hypertrophy Source: MGI
  • cardiac muscle tissue development Source: MGI
  • cardiac myofibril assembly Source: BHF-UCL
  • cellular calcium ion homeostasis Source: MGI
  • detection of muscle stretch Source: BHF-UCL
  • muscle organ development Source: UniProtKB-KW
  • negative regulation of actin filament severing Source: MGI
  • negative regulation of myoblast differentiation Source: MGI
  • positive regulation of actin filament severing Source: MGI
  • positive regulation of myoblast differentiation Source: MGI
  • positive regulation of myotube differentiation Source: MGI
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • protein localization to organelle Source: BHF-UCL
  • regulation of the force of heart contraction Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Myogenesis, Transcription, Transcription regulation

Keywords - Ligandi

Actin-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Cysteine and glycine-rich protein 3
Alternative name(s):
Cysteine-rich protein 3
Short name:
CRP3
LIM domain protein, cardiac
Muscle LIM protein
Gene namesi
Name:Csrp3
Synonyms:Clp, Mlp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1330824. Csrp3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytoskeleton Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • Z disc Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Ultrastructural analysis revealed a dramatic disruption of cardiomyocyte cytoarchitecture. At birth, these hearts are not hypertrophic, but already abnormally soft, with cell-autonomous and Csrp3-sensitive alterations in cytoarchitecture. The morphological, functional, and molecular features of the cardiac phenotype in mutant adult mice are undistinguishable from those seen in human heart failure resulting from dilated cardiomyopathy of various etiolologies, these mice can thus be used as model. Heterozygous mice display a more pronounced left ventricular dilation and systolic dysfunction and decreased survival after myocardial infarction.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4W → R: Mice develop an age- and gene dosage-dependent hypertrophic cardiomyopathy and heart failure phenotype, characterized by almost complete loss of contractile reserve under catecholamine induced stress. They display increased in septum wall thickness, fractional shortening, and wall thickness per diameter (h/r). There is also evidence for skeletal muscle pathology. In addition, homozygous mutants show increased left ventricle (LC) mass per body weight (BW) and significantly reduced body weight. An increased nuclear localization of Csrp3 is also observed. Decreases interaction with TCAP. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000757281 – 194Cysteine and glycine-rich protein 3Add BLAST194

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei95PhosphoserineCombined sources1
Modified residuei111PhosphoserineCombined sources1
Modified residuei153PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by PKC/PRKCA.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP50462.
PaxDbiP50462.
PeptideAtlasiP50462.
PRIDEiP50462.

PTM databases

iPTMnetiP50462.
PhosphoSitePlusiP50462.

Expressioni

Gene expression databases

BgeeiENSMUSG00000030470.
CleanExiMM_CSRP3.
ExpressionAtlasiP50462. baseline and differential.
GenevisibleiP50462. MM.

Interactioni

Subunit structurei

Self-associates. Oligomeric in the cytoplasm and monomeric in the nucleus. Homooligomers preferentially form along the actin cytoskeleton (By similarity). Interacts with TCAP (PubMed:20044516). Interacts with LDHD, MYOD1, MYOG, ACTN2, NRAP, MYF6 (By similarity). Interacts (via N-terminus)D with GLRX3 (via C-terminus) and PPP3CA; GLRX3 and calcineurin compete for interaction with CSRP3 (PubMed:18258855). Interacts with CFL2; the stoichiometry influences F-actin depolymerization and possibly two molecules of CFL2 can interact with one molecule of CSRP3 resulting in the highest functional impact; the interaction is stronger with phosphorylated CFL2 (By similarity).By similarity2 Publications

GO - Molecular functioni

  • actinin binding Source: BHF-UCL
  • MRF binding Source: MGI
  • RNA polymerase II sequence-specific DNA binding transcription factor binding Source: MGI
  • telethonin binding Source: BHF-UCL

Protein-protein interaction databases

IntActiP50462. 2 interactors.
MINTiMINT-4092342.
STRINGi10090.ENSMUSP00000032658.

Structurei

3D structure databases

ProteinModelPortaliP50462.
SMRiP50462.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 61LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST52
Domaini120 – 171LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST52

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 5Interaction with TCAPBy similarity5
Regioni94 – 105Interaction with CLF2By similarityAdd BLAST12

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi64 – 69Nuclear localization signalSequence analysisBy similarity6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi63 – 78Gly-richAdd BLAST16
Compositional biasi177 – 185Gly-rich9

Domaini

LIM zinc-binding domain 1 is required for self-association. LIM zinc-binding domain 1 and LIM zinc-binding domain 2 both are required for optimal actin-bundling activity. LIM zinc-binding domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates binding to SPTB.By similarity

Sequence similaritiesi

Contains 2 LIM zinc-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

LIM domain, Repeat

Phylogenomic databases

eggNOGiENOG410ITI8. Eukaryota.
ENOG410Z840. LUCA.
GeneTreeiENSGT00550000074548.
HOGENOMiHOG000111233.
HOVERGENiHBG051143.
InParanoidiP50462.
KOiK09377.
OMAiQSPKQAR.
OrthoDBiEOG091G11RX.
PhylomeDBiP50462.
TreeFamiTF313758.

Family and domain databases

Gene3Di2.10.110.10. 2 hits.
InterProiIPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 2 hits.
[Graphical view]
SMARTiSM00132. LIM. 2 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P50462-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPNWGGGAKC GACEKTVYHA EEIQCNGRSF HKTCFHCMAC RKALDSTTVA
60 70 80 90 100
AHESEIYCKV CYGRRYGPKG IGFGQGAGCL STDTGEHLGL QFQQSPKPAR
110 120 130 140 150
AATTSNPSKF SAKFGESEKC PRCGKSVYAA EKVMGGGKPW HKTCFRCAIC
160 170 180 190
GKSLESTNVT DKDGELYCKV CYAKNFGPTG IGFGGLTQQV EKKE
Length:194
Mass (Da):20,895
Last modified:October 1, 1996 - v1
Checksum:iE35CF30CA17CB227
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49883 mRNA. Translation: CAA90039.1.
D88791 mRNA. Translation: BAA13721.1.
BC061131 mRNA. Translation: AAH61131.1.
CCDSiCCDS21305.1.
PIRiS57472.
RefSeqiNP_001185770.1. NM_001198841.1.
NP_038836.1. NM_013808.4.
UniGeneiMm.17235.
Mm.488132.

Genome annotation databases

EnsembliENSMUST00000032658; ENSMUSP00000032658; ENSMUSG00000030470.
ENSMUST00000167786; ENSMUSP00000129378; ENSMUSG00000030470.
GeneIDi13009.
KEGGimmu:13009.
UCSCiuc009hax.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z49883 mRNA. Translation: CAA90039.1.
D88791 mRNA. Translation: BAA13721.1.
BC061131 mRNA. Translation: AAH61131.1.
CCDSiCCDS21305.1.
PIRiS57472.
RefSeqiNP_001185770.1. NM_001198841.1.
NP_038836.1. NM_013808.4.
UniGeneiMm.17235.
Mm.488132.

3D structure databases

ProteinModelPortaliP50462.
SMRiP50462.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP50462. 2 interactors.
MINTiMINT-4092342.
STRINGi10090.ENSMUSP00000032658.

PTM databases

iPTMnetiP50462.
PhosphoSitePlusiP50462.

Proteomic databases

EPDiP50462.
PaxDbiP50462.
PeptideAtlasiP50462.
PRIDEiP50462.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032658; ENSMUSP00000032658; ENSMUSG00000030470.
ENSMUST00000167786; ENSMUSP00000129378; ENSMUSG00000030470.
GeneIDi13009.
KEGGimmu:13009.
UCSCiuc009hax.2. mouse.

Organism-specific databases

CTDi8048.
MGIiMGI:1330824. Csrp3.

Phylogenomic databases

eggNOGiENOG410ITI8. Eukaryota.
ENOG410Z840. LUCA.
GeneTreeiENSGT00550000074548.
HOGENOMiHOG000111233.
HOVERGENiHBG051143.
InParanoidiP50462.
KOiK09377.
OMAiQSPKQAR.
OrthoDBiEOG091G11RX.
PhylomeDBiP50462.
TreeFamiTF313758.

Miscellaneous databases

PROiP50462.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030470.
CleanExiMM_CSRP3.
ExpressionAtlasiP50462. baseline and differential.
GenevisibleiP50462. MM.

Family and domain databases

Gene3Di2.10.110.10. 2 hits.
InterProiIPR001781. Znf_LIM.
[Graphical view]
PfamiPF00412. LIM. 2 hits.
[Graphical view]
SMARTiSM00132. LIM. 2 hits.
[Graphical view]
PROSITEiPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCSRP3_MOUSE
AccessioniPrimary (citable) accession number: P50462
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.