Disease relevance of CSRP1

• Prostatic cancer cells PC-3, DU-145, and LNCaP also expressed CRP1 mRNA but virtually no protein [1].
• The hereditary breast and ovarian cancer gene, BRCA1, encodes a large polypeptide that contains the cysteine-rich RING motif, a zinc-binding domain found in a variety of regulatory proteins [2].
• A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice [3].
• Tat, the transactivating protein from HIV, forms a metal-linked dimer with metal ions bridging cysteine-rich regions from each monomer [4].
• Autoantibodies from the kidneys of rats with Heymann nephritis reacted with a nonglycosylated segment of GP330 that contains cysteine-rich 40-amino acid repeats, which are also features of the LDL receptor [5].

Psychiatry related information on CSRP1

• In the lifestyle group weight loss rather than increased physical activity seems to account for most of the changes in CRP [6].
• The PC-binding peptide of CRP was recognized by two mAb specific for the T-15 Id [7].
• Two studies were undertaken to examine the effect of acute total and short-term partial sleep deprivation on concentrations of high-sensitivity CRP in healthy human subjects [8].
• CRP was not associated with diabetes or cardiovascular disease but was significantly (P=0.015) higher in persons with (n=70) than without (n=385) dementia [9].
• After adjustment for age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking status, alcohol consumption, and daily sleep duration, mean high-sensitivity CRP levels were 0.63, 0.65, and 0.96 mg/L for SDB severity levels of 3%ODI<5, 5 to 19.9, and >=20, respectively (p for trend=0.015) [10].

High impact information on CSRP1

• Members of the CCN (for CTGF, cyr61/cef10, nov) gene family encode cysteine-rich secreted proteins with roles in cell growth and differentiation [11].
• The predicted receptor structure includes a cysteine-rich extracellular domain, a single hydrophobic transmembrane domain, and a predicted cytoplasmic serine/threonine kinase domain [12].
• Most of the sequence of fibroblast TGF-beta 1-BP is made up of cysteine-rich repeats of two different kinds; there are 16 EGF-like repeats and three repeats with a distant resemblance to EGF, but of a distinct type hitherto not found in any other protein. beta-hydroxylated asparagine residues were identified in two of the EGF-like repeats [13].
• The cDNA-derived primary structure of GMP-140 predicts a cysteine-rich protein with multiple domains, including a "lectin" region, an "EGF" domain, nine tandem consensus repeats related to those in complement-binding proteins, a transmembrane domain, and a short cytoplasmic tail [14].
• The extracellular domain contains a threefold repeat of a novel 40 residue cysteine-rich segment, and the cytoplasmic domain contains a tyrosine residue that is a potential site for phosphorylation by tyrosine kinases [15].

Chemical compound and disease context of CSRP1

• A 12-15-h incubation of lymphocytes at 37 degrees C in 5% CO2-air showed persistence of CRP binding in substantial proportions of cells particularly in acute rheumatic fever [16].
• We conclude that the 50-kD cysteine-rich region of IIIa is a frequent target of autoantibodies in ITP, but that such antibodies may also be present in cases of thrombocytopenia that cannot be linked to an apparent autoimmune process [17].
• This approach has also led to the identification and structural characterization of three amebic antigens, the serine-rich Entamoeba histolytica protein (SREHP), the 170-kDa subunit of the Gal/GalNAc binding lectin, and the 29-kDa cysteine-rich protein, which all show promise as recombinant antigen-based vaccines to prevent amebiasis [18].
• This article reports a Glanzmann thrombasthenia (GT) patient, N.M., with a point mutation in the third cysteine-rich repeat of beta3-integrin or platelet glycoprotein (GP) IIIa, leading to the expression of a constitutively activated fibrinogen receptor [19].
• A functional platelet fibrinogen receptor with a deletion in the cysteine-rich repeat region of the beta(3) integrin: the Oe(a) alloantigen in neonatal alloimmune thrombocytopenia [20].

Biological context of CSRP1

• Assignment1 of CSRP1 encoding the LIM domain protein CRP1, to human chromosome 1q32 by fluorescence in situ hybridization [21].
• The dimerization ability of hCRP is mapped to the LIM domains, can be transferred to an unrelated protein by fusion of a single minimal LIM/double zinc-finger segment, occurs in the absence as well as the presence of DNA, and appears to depend on coordination of two zinc atoms in the finger doublet [22].
• The evolutionarily conserved structure of cysteine-rich protein, its structural similarity to a number of developmentally critical proteins, its distinctive tissue distribution, and its primary response to early events in the cell cycle suggest that crp plays an important role in cell function [23].
• Characterization of a human cDNA encoding a widely expressed and highly conserved cysteine-rich protein with an unusual zinc-finger motif [24].
• Using a panel of human x rodent somatic cell hybrids, the hCRP locus is assigned to chromosome 1 [25].

Anatomical context of CSRP1

• At the mRNA level, the highest concentrations of CRP1 were found in the prostate and the colon followed by the brain and the testis [1].
• These results, along with previously reported data of colocalization of CRP1 with stress fibers and adhesion plaques, suggest that the main function of CRP1 may be structural [1].
• To test this concept, transgenic swine expressing the human CRP decay accelerating factor and CD59 were developed using a novel expression system involving transfer of the proteins from erythrocytes to endothelial cells [26].
• We report here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC) [27].
• These findings provide a possible biochemical explanation for binding of CRP to damaged but not intact cell membranes and might be relevant to its biological function [27].

Associations of CSRP1 with chemical compounds

• A site-directed mutagenesis analysis of the binding region has revealed the critical importance of a single lysine residue (lysine 65 in human CRP1) [28].
• CRP has a Ca2+-dependent binding specificity for phosphorylcholine, the polar head group of two widely distributed lipids, lecithin (phosphatidylcholine, PC) and sphingomyelin (SM) [27].
• WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich, heparin-binding, secreted proteins associated with the extracellular matrix, and can interact with cellular integrins [29].
• MAIN OUTCOME MEASURE: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100 [30].
• CONCLUSIONS: In this prospective trial, pravastatin reduced CRP levels at both 12 and 24 weeks in a largely LDL-C-independent manner [31].

Physical interactions of CSRP1

• A minireceptor containing the cluster of eight complement-type cysteine-rich repeats followed by four epidermal growth factor precursor homologous domains binds and internalizes 125I-labeled plasminogen activator-PAI-1 complexes [32].
• A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1 [33].
• It is concluded that domain III which is flanked by the two cysteine-rich domains is a major ligand-binding domain of the EGF-receptor [34].
• The data further indicate that the sixth repeat is required for binding of LDL, but not beta-migrating very low density lipoprotein, and that deletion of a single cysteine-rich repeat can alter the binding specificity of the LDL receptor [35].
• Dystrophin and its autosomal homologue utrophin interact with beta-dystroglycan via their highly conserved C-terminal cysteine-rich regions, comprising the WW domain (protein-protein interaction domain containing two conserved tryptophan residues), EF hand and ZZ domains [36].

Regulatory relationships of CSRP1

• CTGF is a cysteine-rich mitogenic peptide that has been involved in various fibrotic disorders and can be induced in fibroblasts by activation with TGF-beta [37].

Other interactions of CSRP1

• The multidomain structure includes a cysteine-rich motif resembling those of protein kinase C and n-chimaerin and a putative pleckstrin homology domain [38].
• The deduced amino acid sequence of edg-2 contains a putative nuclear translocation sequence, an N-terminal acidic domain and a cysteine-rich C-terminal domain containing a putative Zinc-finger structure [39].
• A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF [40].
• The TNF receptor contains four cysteine-rich subdomains in the extracellular portion [41].
• A third cysteine-rich domain conforms to the CXXC motif identified in DNA methyltransferase, human trithorax, and methyl-CpG binding domain protein 1 [42].

Analytical, diagnostic and therapeutic context of CSRP1

• Southern blot analyses indicate that this human cysteine-rich protein (hCRP) gene has been highly conserved over the span of evolution from yeast to man [24].
• Partial proteolysis and circular dichroism spectra suggest that metal binding has its primary effects in the cysteine-rich region and relatively little effect on the folding of other regions [4].
• Both overweight (body mass index [BMI], 25-29.9 kg/m2) and obese (BMI, > or =30 kg/m2) persons were more likely to have elevated CRP levels than their normal-weight counterparts (BMI, <25 kg/m2) [43].
• This effect was seen as early as 12 weeks (median reduction in CRP with pravastatin, 14.7%; P<.001) and was present among all prespecified subgroups according to sex, age, smoking status, body mass index, baseline lipid levels, presence of diabetes, and use of aspirin or hormone replacement therapy [31].
• Waist-to-hip ratio was positively associated with both elevated and clinically raised CRP levels, independent of BMI [43].

References