P50462 (CSRP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Csrp3
Synonyms:	Clp, Mlp

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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. Ref.4 Ref.5
Subunit structure	Interacts with LDHD By similarity. Interacts with GLRX3. Ref.6
Subcellular location	Nucleus Potential. Cytoplasm. Cytoplasm › cytoskeleton Potential. Cytoplasm › myofibril › sarcomere › Z line. Note: Mainly cytoplasmic. In the nucleus it associates with the actin cytoskeleton Potential. In the Z line, found associated with GLRX3 (via C-terminus). Ref.6
Disruption phenotype	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 infaction. Ref.4 Ref.5
Sequence similarities	Contains 2 LIM zinc-binding domains.

Ontologies

Keywords
Biological process	Differentiation Myogenesis
Cellular component	Cytoplasm Cytoskeleton Nucleus
Domain	LIM domain Repeat
Ligand	Metal-binding Zinc
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle contraction Inferred from mutant phenotype PubMed 12507422. Source: BHF-UCL cardiac muscle hypertrophy Inferred from electronic annotation. Source: Compara cardiac myofibril assembly Inferred from mutant phenotype PubMed 12507422. Source: BHF-UCL cellular calcium ion homeostasis Inferred from genetic interaction PubMed 10555147. Source: MGI detection of muscle stretch Inferred from mutant phenotype PubMed 12507422. Source: BHF-UCL muscle organ development Inferred from electronic annotation. Source: UniProtKB-KW protein localization to organelle Inferred from mutant phenotype PubMed 12507422. Source: BHF-UCL regulation of the force of heart contraction Inferred from genetic interaction PubMed 10555147. Source: MGI
Cellular_component	Z disc Inferred from direct assay Ref.5. Source: MGI cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	actinin binding Inferred from direct assay PubMed 12507422. Source: BHF-UCL structural constituent of muscle Inferred from mutant phenotype PubMed 12507422. 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_0000075728
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
Experimental info
	Mutagenesis	4	1	W → 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. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P50462 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: E35CF30CA17CB227	FASTA	194	20,895
	10 20 30 40 50 60 MPNWGGGAKC GACEKTVYHA EEIQCNGRSF HKTCFHCMAC RKALDSTTVA AHESEIYCKV 70 80 90 100 110 120 CYGRRYGPKG IGFGQGAGCL STDTGEHLGL QFQQSPKPAR AATTSNPSKF SAKFGESEKC 130 140 150 160 170 180 PRCGKSVYAA EKVMGGGKPW HKTCFRCAIC GKSLESTNVT DKDGELYCKV CYAKNFGPTG 190 IGFGGLTQQV EKKE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Murine MLP: cloning and expression in the embryonic head." Harrod G.V., Kettunen P.J., Jowett A.K. J. Craniofac. Genet. Dev. Biol. 16:65-73(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: MF1. Tissue: Mandible.
[2]	Hashimoto N., Ogashiwa M. Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C3H.
[3]	"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: Liver.
[4]	"MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure." Arber S., Hunter J.J., Ross J. Jr., Hongo M., Sansig G., Borg J., Perriard J.C., Chien K.R., Caroni P. Cell 88:393-403(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE. Strain: 129/Sv.
[5]	"Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc." Heineke J., Ruetten H., Willenbockel C., Gross S.C., Naguib M., Schaefer A., Kempf T., Hilfiker-Kleiner D., Caroni P., Kraft T., Kaiser R.A., Molkentin J.D., Drexler H., Wollert K.C. Proc. Natl. Acad. Sci. U.S.A. 102:1655-1660(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"PICOT attenuates cardiac hypertrophy by disrupting calcineurin-NFAT signaling." Jeong D., Kim J.M., Cha H., Oh J.G., Park J., Yun S.H., Ju E.S., Jeon E.S., Hajjar R.J., Park W.J. Circ. Res. 102:711-719(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GLRX3, SUBCELLULAR LOCATION.
[7]	"A common MLP (muscle LIM protein) variant is associated with cardiomyopathy." Knoll R., Kostin S., Klede S., Savvatis K., Klinge L., Stehle I., Gunkel S., Kotter S., Babicz K., Sohns M., Miocic S., Didie M., Knoll G., Zimmermann W.H., Thelen P., Bickeboller H., Maier L.S., Schaper W. , Schaper J., Kraft T., Tschope C., Linke W.A., Chien K.R. Circ. Res. 106:695-704(2010) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TRP-4.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z49883 mRNA. Translation: CAA90039.1. D88791 mRNA. Translation: BAA13721.1. BC061131 mRNA. Translation: AAH61131.1.
IPI	IPI00118153.
PIR	S57472.
RefSeq	NP_001185770.1. NM_001198841.1. NP_038836.1. NM_013808.4.
UniGene	Mm.17235. Mm.488132.
3D structure databases
ProteinModelPortal	P50462.
SMR	P50462. Positions 1-178.
ModBase	Search...
Protein-protein interaction databases
IntAct	P50462. 1 interaction.
STRING	10090.ENSMUSP00000032658.
PTM databases
PhosphoSite	P50462.
Proteomic databases
PaxDb	P50462.
PRIDE	P50462.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032658; ENSMUSP00000032658; ENSMUSG00000030470. ENSMUST00000167786; ENSMUSP00000129378; ENSMUSG00000030470.
GeneID	13009.
KEGG	mmu:13009.
Organism-specific databases
CTD	8048.
MGI	MGI:1330824. Csrp3.
Phylogenomic databases
eggNOG	NOG294681.
HOGENOM	HOG000111233.
HOVERGEN	HBG051143.
InParanoid	P50462.
KO	K09377.
OMA	KYGPKGI.
OrthoDB	EOG470TJ6.
Gene expression databases
ArrayExpress	P50462.
Bgee	P50462.
CleanEx	MM_CSRP3.
Genevestigator	P50462.
GermOnline	ENSMUSG00000030470. Mus musculus.
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
NextBio	282844.
SOURCE	Search...

Entry information

Entry name

CSRP3_MOUSE

Accession

Primary (citable) accession number: P50462

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program