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Gene Review

CSRP1  -  cysteine and glycine-rich protein 1

Homo sapiens

Synonyms: CRP, CRP1, CSRP, CYRP, Cysteine and glycine-rich protein 1, ...
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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


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


Other interactions of CSRP1


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].


  1. Abundant cysteine-rich protein-1 is localized in the stromal compartment of the human prostate. Dubé, J.Y., Chapdelaine, P., Trahan, P.L., Deperthes, D., Frenette, G., Tremblay, R.R. Arch. Androl. (1998) [Pubmed]
  2. Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Wu, L.C., Wang, Z.W., Tsan, J.T., Spillman, M.A., Phung, A., Xu, X.L., Yang, M.C., Hwang, L.Y., Bowcock, A.M., Baer, R. Nat. Genet. (1996) [Pubmed]
  3. Chlamydia infections and heart disease linked through antigenic mimicry. Bachmaier, K., Neu, N., de la Maza, L.M., Pal, S., Hessel, A., Penninger, J.M. Science (1999) [Pubmed]
  4. Tat protein from human immunodeficiency virus forms a metal-linked dimer. Frankel, A.D., Bredt, D.S., Pabo, C.O. Science (1988) [Pubmed]
  5. Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor. Raychowdhury, R., Niles, J.L., McCluskey, R.T., Smith, J.A. Science (1989) [Pubmed]
  6. Intensive lifestyle intervention or metformin on inflammation and coagulation in participants with impaired glucose tolerance. Haffner, S., Temprosa, M., Crandall, J., Fowler, S., Goldberg, R., Horton, E., Marcovina, S., Mather, K., Orchard, T., Ratner, R., Barrett-Connor, E. Diabetes (2005) [Pubmed]
  7. A synthetic peptide corresponding to the phosphorylcholine (PC)-binding region of human C-reactive protein possesses the TEPC-15 myeloma PC-idiotype. Swanson, S.J., Lin, B.F., Mullenix, M.C., Mortensen, R.F. J. Immunol. (1991) [Pubmed]
  8. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. Meier-Ewert, H.K., Ridker, P.M., Rifai, N., Regan, M.M., Price, N.J., Dinges, D.F., Mullington, J.M. J. Am. Coll. Cardiol. (2004) [Pubmed]
  9. C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Strandberg, T.E., Tilvis, R.S. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  10. The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men. Yao, M., Tachibana, N., Okura, M., Ikeda, A., Tanigawa, T., Yamagishi, K., Sato, S., Shimamoto, T., Iso, H. Sleep. (2006) [Pubmed]
  11. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Hurvitz, J.R., Suwairi, W.M., Van Hul, W., El-Shanti, H., Superti-Furga, A., Roudier, J., Holderbaum, D., Pauli, R.M., Herd, J.K., Van Hul, E.V., Rezai-Delui, H., Legius, E., Le Merrer, M., Al-Alami, J., Bahabri, S.A., Warman, M.L. Nat. Genet. (1999) [Pubmed]
  12. Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase. Lin, H.Y., Wang, X.F., Ng-Eaton, E., Weinberg, R.A., Lodish, H.F. Cell (1992) [Pubmed]
  13. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Kanzaki, T., Olofsson, A., Morén, A., Wernstedt, C., Hellman, U., Miyazono, K., Claesson-Welsh, L., Heldin, C.H. Cell (1990) [Pubmed]
  14. Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Johnston, G.I., Cook, R.G., McEver, R.P. Cell (1989) [Pubmed]
  15. Structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin. Tamkun, J.W., DeSimone, D.W., Fonda, D., Patel, R.S., Buck, C., Horwitz, A.F., Hynes, R.O. Cell (1986) [Pubmed]
  16. Lymphocytes binding C-reactive protein during acute rheumatic fever. Williams, R.C., Kilpatrick, K.A., Kassaby, M., Abdin, Z.H. J. Clin. Invest. (1978) [Pubmed]
  17. Localization of human platelet autoantigens to the cysteine-rich region of glycoprotein IIIa. Kekomaki, R., Dawson, B., McFarland, J., Kunicki, T.J. J. Clin. Invest. (1991) [Pubmed]
  18. Progress towards development of a vaccine for amebiasis. Stanley, S.L. Clin. Microbiol. Rev. (1997) [Pubmed]
  19. A point mutation in the cysteine-rich domain of glycoprotein (GP) IIIa results in the expression of a GPIIb-IIIa (alphaIIbbeta3) integrin receptor locked in a high-affinity state and a Glanzmann thrombasthenia-like phenotype. Ruiz, C., Liu, C.Y., Sun, Q.H., Sigaud-Fiks, M., Fressinaud, E., Muller, J.Y., Nurden, P., Nurden, A.T., Newman, P.J., Valentin, N. Blood (2001) [Pubmed]
  20. 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. Santoso, S., Kiefel, V., Richter, I.G., Sachs, U.J., Rahman, A., Carl, B., Kroll, H. Blood (2002) [Pubmed]
  21. Assignment1 of CSRP1 encoding the LIM domain protein CRP1, to human chromosome 1q32 by fluorescence in situ hybridization. Erdel, M., Weiskirchen, R. Cytogenet. Cell Genet. (1998) [Pubmed]
  22. The LIM/double zinc-finger motif functions as a protein dimerization domain. Feuerstein, R., Wang, X., Song, D., Cooke, N.E., Liebhaber, S.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  23. Human cysteine-rich protein. A member of the LIM/double-finger family displaying coordinate serum induction with c-myc. Wang, X., Lee, G., Liebhaber, S.A., Cooke, N.E. J. Biol. Chem. (1992) [Pubmed]
  24. Characterization of a human cDNA encoding a widely expressed and highly conserved cysteine-rich protein with an unusual zinc-finger motif. Liebhaber, S.A., Emery, J.G., Urbanek, M., Wang, X.K., Cooke, N.E. Nucleic Acids Res. (1990) [Pubmed]
  25. Analysis of the human cysteine-rich protein gene (CSRP), assignment to chromosome 1q24-1q32, and identification of an associated MspI polymorphism. Wang, X., Ray, K., Szpirer, J., Levan, G., Liebhaber, S.A., Cooke, N.E. Genomics (1992) [Pubmed]
  26. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. McCurry, K.R., Kooyman, D.L., Alvarado, C.G., Cotterell, A.H., Martin, M.J., Logan, J.S., Platt, J.L. Nat. Med. (1995) [Pubmed]
  27. Interaction of C-reactive protein with artificial phosphatidylcholine bilayers. Volanakis, J.E., Wirtz, K.W. Nature (1979) [Pubmed]
  28. Fine mapping of the alpha-actinin binding site within cysteine-rich protein. Harper, B.D., Beckerle, M.C., Pomiès, P. Biochem. J. (2000) [Pubmed]
  29. WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. Su, F., Overholtzer, M., Besser, D., Levine, A.J. Genes Dev. (2002) [Pubmed]
  30. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. Ridker, P.M., Stampfer, M.J., Rifai, N. JAMA (2001) [Pubmed]
  31. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. Albert, M.A., Danielson, E., Rifai, N., Ridker, P.M. JAMA (2001) [Pubmed]
  32. Molecular dissection of ligand binding sites on the low density lipoprotein receptor-related protein. Willnow, T.E., Orth, K., Herz, J. J. Biol. Chem. (1994) [Pubmed]
  33. A dynactin subunit with a highly conserved cysteine-rich motif interacts directly with Arp1. Karki, S., Tokito, M.K., Holzbaur, E.L. J. Biol. Chem. (2000) [Pubmed]
  34. Functional analysis of the ligand binding site of EGF-receptor utilizing chimeric chicken/human receptor molecules. Lax, I., Bellot, F., Howk, R., Ullrich, A., Givol, D., Schlessinger, J. EMBO J. (1989) [Pubmed]
  35. Deletion of exon encoding cysteine-rich repeat of low density lipoprotein receptor alters its binding specificity in a subject with familial hypercholesterolemia. Hobbs, H.H., Brown, M.S., Goldstein, J.L., Russell, D.W. J. Biol. Chem. (1986) [Pubmed]
  36. ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan interaction site. Hnia, K., Zouiten, D., Cantel, S., Chazalette, D., Hugon, G., Fehrentz, J.A., Masmoudi, A., Diment, A., Bramham, J., Mornet, D., Winder, S.J. Biochem. J. (2007) [Pubmed]
  37. Effect of small interfering RNA on the expression of connective tissue growth factor and type I and III collagen in skin fibroblasts of patients with systemic sclerosis. Xiao, R., Liu, F.Y., Luo, J.Y., Yang, X.J., Wen, H.Q., Su, Y.W., Yan, K.L., Li, Y.P., Liang, Y.S. Br. J. Dermatol. (2006) [Pubmed]
  38. Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization. Leung, T., Chen, X.Q., Tan, I., Manser, E., Lim, L. Mol. Cell. Biol. (1998) [Pubmed]
  39. Characterization of edg-2, a human homologue of the Xenopus maternal transcript G10 from endothelial cells. Hla, T., Jackson, A.Q., Appleby, S.B., Maciag, T. Biochim. Biophys. Acta (1995) [Pubmed]
  40. Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor. Lantz, M., Gullberg, U., Nilsson, E., Olsson, I. J. Clin. Invest. (1990) [Pubmed]
  41. Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein. Gray, P.W., Barrett, K., Chantry, D., Turner, M., Feldmann, M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  42. Cloning of a mammalian transcriptional activator that binds unmethylated CpG motifs and shares a CXXC domain with DNA methyltransferase, human trithorax, and methyl-CpG binding domain protein 1. Voo, K.S., Carlone, D.L., Jacobsen, B.M., Flodin, A., Skalnik, D.G. Mol. Cell. Biol. (2000) [Pubmed]
  43. Elevated C-reactive protein levels in overweight and obese adults. Visser, M., Bouter, L.M., McQuillan, G.M., Wener, M.H., Harris, T.B. JAMA (1999) [Pubmed]
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