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P50461 (CSRP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cysteine and glycine-rich protein 3
Alternative name(s):
Cardiac LIM protein
Cysteine-rich protein 3
Short name=CRP3
LIM domain protein, cardiac
Muscle LIM protein
Gene names
Name:CSRP3
Synonyms:CLP, MLP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length194 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Positive regulator of myogenesis. 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 By similarity.

Subunit structure

Interacts with LDHD By similarity. Interacts with GLRX3 (via C-terminus) By similarity.

Subcellular location

Nucleus Potential. Cytoplasm. Cytoplasmcytoskeleton Potential. CytoplasmmyofibrilsarcomereZ line By similarity. Note: Mainly cytoplasmic By similarity. In the nucleus it associates with the actin cytoskeleton Potential. In the Z line, found associated with GLRX3 By similarity. Ref.9

Tissue specificity

Cardiac and slow-twitch skeletal muscles.

Involvement in disease

Cardiomyopathy, dilated 1M (CMD1M) [MIM:607482]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9

Cardiomyopathy, familial hypertrophic 12 (CMH12) [MIM:612124]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9

Sequence similarities

Contains 2 LIM zinc-binding domains.

Ontologies

Keywords
   Biological processDifferentiation
Myogenesis
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   DiseaseCardiomyopathy
Disease mutation
   DomainLIM domain
Repeat
   LigandMetal-binding
Zinc
   Molecular functionDevelopmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle contraction

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

cardiac muscle hypertrophy

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

cardiac muscle tissue development

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac myofibril assembly

Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL

cellular calcium ion homeostasis

Inferred from sequence or structural similarity. Source: BHF-UCL

detection of muscle stretch

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

protein localization to organelle

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

regulation of the force of heart contraction

Inferred from sequence or structural similarity. Source: BHF-UCL

skeletal muscle tissue development

Traceable author statement PubMed 7954791. Source: ProtInc

   Cellular_componentZ disc

Inferred from direct assay Ref.7. Source: BHF-UCL

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionactinin binding

Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL

protein binding

Inferred from physical interaction PubMed 12127981. Source: UniProtKB

structural constituent of muscle

Inferred from mutant phenotype Ref.7. Source: BHF-UCL

telethonin binding

Inferred from direct assay Ref.7. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TCAPO152732EBI-5658719,EBI-954089

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 194194Cysteine and glycine-rich protein 3
PRO_0000075727

Regions

Domain10 – 6152LIM zinc-binding 1
Domain120 – 17152LIM zinc-binding 2
Motif64 – 696Nuclear localization signal Potential
Compositional bias63 – 7816Gly-rich
Compositional bias177 – 1859Gly-rich

Natural variations

Natural variant41W → R in CMD1M; there is a similar prevalence of this variant in controls, dilated cardiomyopathy (DCM) and hypetrophic cariomyopathy (HCM) patients, this variant may not be sufficient to cause cardiomyopathy but could act as a conditional modifier, which would explain the unusually low penetrance reported previously; may be a common polymorphism. Ref.7 Ref.9
Corresponds to variant rs45550635 [ dbSNP | Ensembl ].
VAR_015401
Natural variant441L → P in CMH12. Ref.8
VAR_045932
Natural variant54 – 552SE → RG in CMH12.
VAR_045933
Natural variant581C → G in CMH12. Ref.8 Ref.9
VAR_045934

Experimental info

Sequence conflict261N → H in AAF28868. Ref.4

Secondary structure

.................................... 194
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P50461 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: FDB6E4F8D258C35F

FASTA19420,969
        10         20         30         40         50         60 
MPNWGGGAKC GACEKTVYHA EEIQCNGRSF HKTCFHCMAC RKALDSTTVA AHESEIYCKV 

        70         80         90        100        110        120 
CYGRRYGPKG IGYGQGAGCL STDTGEHLGL QFQQSPKPAR SVTTSNPSKF TAKFGESEKC 

       130        140        150        160        170        180 
PRCGKSVYAA EKVMGGGKPW HKTCFRCAIC GKSLESTNVT DKDGELYCKV CYAKNFGPTG 

       190 
IGFGGLTQQV EKKE 

« Hide

References

« Hide 'large scale' references
[1]"Mapping of a human LIM protein (CLP) to human chromosome 11p15.1 by fluorescence in situ hybridization."
Fung Y.W., Wang R.X., Heng H.H.Q., Liew C.C.
Genomics 28:602-603(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[2]"Cloning of the gene encoding the human muscle LIM protein, a regulator of myogenesis."
Medvedev A., Jetten A.M.
Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Muscle.
[3]"Cloning and characterization of the human muscle LIM protein gene."
Yasunaga S., Harada H., Kimura A.
Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]"A novel member of LIM gene family involved in cardiovascular diseases."
Chen K.H., Zhang J.F., Ma D.L., Tang J.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart and Skeletal muscle.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle and Testis.
[6]"Structure and dynamics of the human muscle LIM protein."
Schallus T., Feher K., Ulrich A.S., Stier G., Muhle-Goll C.
FEBS Lett. 583:1017-1022(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 7-66 AND 119-176.
[7]"The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy."
Knoell R., Hoshijima M., Hoffman H.M., Person V., Lorenzen-Schmidt I., Bang M.-L., Hayashi T., Shiga N., Yasukawa H., Schaper W., McKenna W., Yokoyama M., Schork N.J., Omens J.H., McCulloch A.D., Kimura A., Gregorio C.C., Poller W. expand/collapse author list , Schaper J., Schultheiss H.P., Chien K.R.
Cell 111:943-955(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD1M ARG-4.
[8]"Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy."
Geier C., Perrot A., Ozcelik C., Binner P., Counsell D., Hoffmann K., Pilz B., Martiniak Y., Gehmlich K., van der Ven P.F.M., Furst D.O., Vornwald A., von Hodenberg E., Nurnberg P., Scheffold T., Dietz R., Osterziel K.J.
Circulation 107:1390-1395(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMH12 PRO-44; 54-ARG-GLY-55 AND GLY-58.
[9]"Beyond the sarcomere: CSRP3 mutations cause hypertrophic cardiomyopathy."
Geier C., Gehmlich K., Ehler E., Hassfeld S., Perrot A., Hayess K., Cardim N., Wenzel K., Erdmann B., Krackhardt F., Posch M.G., Osterziel K.J., Bublak A., Nagele H., Scheffold T., Dietz R., Chien K.R., Spuler S. expand/collapse author list , Furst D.O., Nurnberg P., Ozcelik C.
Hum. Mol. Genet. 17:2753-2765(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CMD1M ARG-4, VARIANT CMH12 GLY-58, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U20324 mRNA. Translation: AAA91104.1.
U49837 mRNA. Translation: AAA92571.1.
U72898 expand/collapse EMBL AC list , U72894, U72895, U72896, U72897 Genomic DNA. Translation: AAD00189.1.
U72899 mRNA. Translation: AAD00183.1.
AF121260 mRNA. Translation: AAF28868.1.
BC005900 mRNA. Translation: AAH05900.1.
BC024010 mRNA. Translation: AAH24010.1.
BC057221 mRNA. Translation: AAH57221.1.
CCDSCCDS7848.1.
RefSeqNP_003467.1. NM_003476.4.
UniGeneHs.83577.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2O10NMR-A7-66[»]
2O13NMR-A119-176[»]
ProteinModelPortalP50461.
SMRP50461. Positions 1-178.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113736. 5 interactions.
IntActP50461. 3 interactions.
STRING9606.ENSP00000265968.

PTM databases

PhosphoSiteP50461.

Polymorphism databases

DMDM1705933.

Proteomic databases

MaxQBP50461.
PaxDbP50461.
PeptideAtlasP50461.
PRIDEP50461.

Protocols and materials databases

DNASU8048.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265968; ENSP00000265968; ENSG00000129170.
ENST00000533783; ENSP00000431813; ENSG00000129170.
GeneID8048.
KEGGhsa:8048.
UCSCuc001mpk.3. human.

Organism-specific databases

CTD8048.
GeneCardsGC11M019160.
GeneReviewsCSRP3.
HGNCHGNC:2472. CSRP3.
HPAHPA042581.
MIM600824. gene.
607482. phenotype.
612124. phenotype.
neXtProtNX_P50461.
Orphanet154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA26971.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG294681.
HOGENOMHOG000111233.
HOVERGENHBG051143.
InParanoidP50461.
KOK09377.
OMAQSPKQAR.
OrthoDBEOG7CK39M.
PhylomeDBP50461.
TreeFamTF313758.

Gene expression databases

ArrayExpressP50461.
BgeeP50461.
CleanExHS_CSRP3.
GenevestigatorP50461.

Family and domain databases

Gene3D2.10.110.10. 2 hits.
InterProIPR001781. Znf_LIM.
[Graphical view]
PfamPF00412. LIM. 2 hits.
[Graphical view]
SMARTSM00132. LIM. 2 hits.
[Graphical view]
PROSITEPS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP50461.
GeneWikiCSRP3.
GenomeRNAi8048.
NextBio30640.
PROP50461.
SOURCESearch...

Entry information

Entry nameCSRP3_HUMAN
AccessionPrimary (citable) accession number: P50461
Secondary accession number(s): Q9P131
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM