Alternative titles; symbolsCYSTEINE-RICH PROTEIN 2; CRP2LIM DOMAIN ONLY, SMOOTH MUSCLELIM DOMAIN ONLY 5; LMO5HGNC Approved Gene Symbol: CSRP2Cytogenetic location...
Alternative titles; symbols
HGNC Approved Gene Symbol: CSRP2
Cytogenetic location: 12q21.2 Genomic coordinates (GRCh38): 12:76,858,708-76,879,018 (from NCBI)
CRSP2 is a member of the CRP family of LIM domain proteins (Weiskirchen et al., 1995). Members of this family are characterized by the presence of 2 tandemly arranged LIM domains linked to short glycine-rich regions. For background information on the LIM domain, see 605903.
▼ Cloning and Expression
Weiskirchen and Bister (1993) originally identified the CSRP2 gene in quail on the basis of its strong transcriptional suppression in avian fibroblasts transformed by retroviral oncogenes or chemical carcinogens. Weiskirchen et al. (1995) directly linked the suppression of CSRP2 gene expression to the transformed phenotype of fibroblasts in a conditional transformation system.
Jain et al. (1996) identified a member of the LIM family, which they termed SmLIM for 'smooth muscle LIM-containing protein,' by hybridization screening using the rat homolog as probe, and then cloned the gene from an aortic cDNA library. SmLIM encodes a polypeptide containing 2 LIM domains and a putative nuclear localization signal. Jain et al. (1996) used immunolocalization to determine that the protein is found in the nucleus of transfected cells. Northern blotting revealed that SmLIM is expressed in smooth muscle tissue, particularly the aorta. In situ hybridization showed that SmLIM is expressed preferentially in arterial smooth muscle cells. Jain et al. (1996) determined that SmLIM expression is downregulated in response to platelet-derived growth factor and arterial wall injury.
By screening a human fibroblast cDNA library with a human EST that shows significant sequence similarity to a quail CSRP2 cDNA, Weiskirchen et al. (1997) isolated CSRP2 cDNAs. The deduced 193-amino acid protein, which the authors called CRP2, is 96%, 79%, and 66% identical to the quail CSRP2, human CSRP1 (123876), and human CSRP3 (600824) proteins, respectively. Northern blot analysis of human skin fibroblast RNA detected an approximately 1.0-kb CSRP2 transcript.
By Northern blot analysis, Weiskirchen et al. (2001) found high expression of CSRP2 in human tumorigenic kidney and a fibroblast cell line. By in situ hybridization studies in rat liver, they found exclusive expression of CSRP2 in hepatic stellate cells (HSC).
▼ Gene Function
By yeast 2-hybrid analysis, Weiskirchen and Gressner (2000) identified human KAT14 (617501), which they called CRP2BP, as a binding partner or CRP2. They determined that CRP2BP interacted with the first LIM domain of CRP2.
Weiskirchen et al. (2001) studied the temporal expression of CSRP2 in the rat model of cholestatic liver fibrosis. Following ligation of the common bile duct, CSRP2 expression was initially upregulated in HSC but was subsequently lost following transdifferentiation of HSCs to myofibroblastic cells. Weiskirchen et al. (2001) also found that CSRP2 mRNA increased in cultured HSC following administration of platelet-derived growth factor (PDGF; 190040).
By a yeast 2-hybrid screen and coimmunoprecipitation experiments, Weiskirchen et al. (2001) found specific binding between the C-terminal LIM domain of CSRP2 and the protein inhibitor of activated STAT1 (PIAS1; 603566). They stated that CSRP2 is a potential factor in the JAK/STAT-signaling pathway and suggested that the suppression of CSRP2 might be a prerequisite for the myofibroblastic transition of hepatic stellate cells.
▼ Gene Structure
Weiskirchen et al. (1997) determined that the CSRP2 gene spans approximately 22 kb and contains 6 exons.
By fluorescence in situ hybridization (FISH), Weiskirchen et al. (1997) mapped the CSRP2 gene to 12q21.1.
Jain et al. (1996) used a somatic cell hybrid blot to localize SmLIM to human chromosome 3; however, in an erratum, the authors stated that they had actually mapped a pseudogene of SmLIM, called CSRP2P. Weiskirchen et al. (1997) localized the CSRP2P locus to 3q21.1 by physical linkage and FISH.