P50461 (CSRP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	194 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Cytoplasm › cytoskeleton Potential. Cytoplasm › myofibril › sarcomere › Z 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 process	Differentiation Myogenesis
Cellular component	Cytoplasm Cytoskeleton Nucleus
Disease	Cardiomyopathy Disease mutation
Domain	LIM domain Repeat
Ligand	Metal-binding Zinc
Molecular function	Developmental protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle contraction Inferred from mutant phenotype Ref.7. Source: BHF-UCL cardiac muscle hypertrophy Inferred from mutant phenotype Ref.7. 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_component	Z 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_function	actinin binding Inferred from sequence or structural similarity Ref.7. Source: BHF-UCL 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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 194

194

Cysteine and glycine-rich protein 3

PRO_0000075727

Regions

Domain

10 – 61

52

LIM zinc-binding 1

Domain

120 – 171

52

LIM zinc-binding 2

Motif

64 – 69

6

Nuclear localization signal Potential

Compositional bias

63 – 78

16

Gly-rich

Compositional bias

177 – 185

9

Gly-rich

Natural variations

Natural variant

4

1

W → 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 variant

44

1

L → P in CMH12. Ref.8

VAR_045932

Natural variant

54 – 55

2

SE → RG in CMH12.

VAR_045933

Natural variant

58

1

C → G in CMH12. Ref.8 Ref.9

VAR_045934

Experimental info

Sequence conflict

26

1

N → H in AAF28868. Ref.4

Secondary structure

1

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194

Helix Strand Turn

Details...

Beta strand

14 – 17

4

Helix

19 – 21

3

Beta strand

22 – 25

4

Beta strand

28 – 31

4

Turn

32 – 34

3

Beta strand

38 – 40

3

Turn

46 – 48

3

Beta strand

50 – 52

3

Beta strand

55 – 57

3

Helix

59 – 65

7

Turn

121 – 124

4

Turn

129 – 131

3

Beta strand

133 – 135

3

Beta strand

138 – 140

3

Turn

142 – 144

3

Beta strand

145 – 147

3

Turn

148 – 151

4

Beta strand

159 – 162

4

Beta strand

165 – 168

4

Helix

169 – 175

7

Sequences

	Sequence		Length	Mass (Da)
	P50461 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: FDB6E4F8D258C35F	FASTA	194	20,969
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U20324 mRNA. Translation: AAA91104.1.
U49837 mRNA. Translation: AAA92571.1.
U72898 , 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.

IPI

IPI00032164.

RefSeq

NP_003467.1. NM_003476.4.

UniGene

Hs.83577.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2O10	NMR	-	A	7-66	[»]
2O13	NMR	-	A	119-176	[»]

ProteinModelPortal

P50461.

ModBase

Search...

Protein-protein interaction databases

IntAct

P50461. 2 interactions.

STRING

9606.ENSP00000265968.

PTM databases

PhosphoSite

P50461.

Polymorphism databases

DMDM

1705933.

Proteomic databases

PaxDb

P50461.

PeptideAtlas

P50461.

PRIDE

P50461.

Protocols and materials databases

DNASU

8048.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265968; ENSP00000265968; ENSG00000129170.
ENST00000533783; ENSP00000431813; ENSG00000129170.

GeneID

8048.

KEGG

hsa:8048.

UCSC

uc001mpk.2. human.

Organism-specific databases

CTD

8048.

GeneCards

GC11M019160.

HGNC

HGNC:2472. CSRP3.

HPA

HPA042581.

MIM

600824. gene.
607482. phenotype.
612124. phenotype.

neXtProt

NX_P50461.

Orphanet

154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.

PharmGKB

PA26971.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG294681.

HOGENOM

HOG000111233.

HOVERGEN

HBG051143.

InParanoid

P50461.

KO

K09377.

OMA

KYGPKGI.

OrthoDB

EOG470TJ6.

PhylomeDB

P50461.

Gene expression databases

ArrayExpress

P50461.

Bgee

P50461.

CleanEx

HS_CSRP3.

Genevestigator

P50461.

GermOnline

ENSG00000129170. Homo sapiens.

Family and domain databases

Gene3D

2.10.110.10. 2 hits.

InterPro

IPR001781. Znf_LIM.
[Graphical view]

Pfam

PF00412. LIM. 2 hits.
[Graphical view]

SMART

SM00132. LIM. 2 hits.
[Graphical view]

PROSITE

PS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P50461.

GenomeRNAi

8048.

NextBio

30640.

SOURCE

Search...

Entry information

Entry name

CSRP3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.