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Gene Review

Csrp1  -  cysteine and glycine-rich protein 1

Rattus norvegicus

Synonyms: CRP, CRP1, Csrp, Cysteine and glycine-rich protein 1, Cysteine-rich protein 1
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Disease relevance of Csrp1

  • Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct [1].
  • These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease [1].
  • Levels of CRP reporter gene expression were increased 2-fold despite severe hyperinsulinemia compared with non-diabetic non-obese transgenic mice [2].
  • Although the role of CRP has been implicated in atherogenesis, its direct effects on vascular cells are poorly defined [3].
  • The basic mechanisms responsible for this association are not clear; CRP may merely be a marker of inflammation with no specific role in the pathogenesis of cardiac disease or may directly modulate the disease process [4].

High impact information on Csrp1

  • The proteins have several features common to the family of tyrosine kinase growth-factor receptors, including cysteine-rich external domains, a hydrophobic transmembrane region and a cytoplasmic tyrosine kinase domain [5].
  • The amino acid sequence deduced from the nucleotide sequences of the cDNAs indicated the presence of a cysteine-rich DNA-binding domain that is highly conserved in all steroid receptors [6].
  • The product of the Wnt-1 proto-oncogene is a cysteine-rich glycoprotein that plays a crucial role in the development of the vertebrate central nervous system [7].
  • Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by approximately 40% [1].
  • Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype) [8].

Chemical compound and disease context of Csrp1

  • In both age groups, ischemia resulted in a depletion of glucose, OAA, ATP AND CRP, a diminution of Pyr, Citr and alpha-Keto and an accumulation of FDP, Lact, Succ, ADP and AMP in brain cortex [9].
  • The second cysteine-rich (Cys-2) domain of rat brain PKC-gamma regulatory region C1 (92-173) was expressed in Escherichia coli cells and purified [10].
  • BACKGROUND: The aim of the present study was to evaluate the effects of systemic administration of low-dose doxycycline and a bisphosphonate, alendronate, on serum levels of interleukin-1beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis in rats [11].
  • Cadmium injection (less than 3 mg/kg body weight) in white rat was found to be associated with the appearance of CRP in liver cytosol after 8 hr and in serum after 18 hr of injection [12].
  • Interleukin-1 (IL-1) activity and the acute phase response, as measured by plasma CRP and iron, were used to determine if the standard disease modifying antirheumatic drugs (DMARDs), gold, chloroquine and D-penicillamine had a common profile of activity in the adjuvant arthritic (AA) rat [13].

Biological context of Csrp1


Anatomical context of Csrp1

  • Furthermore, by using an osteoblastic cell line (CRP 10/30) which is a powerful promoter of osteoclastic resorption in vitro, we obtained evidence that the inhibitory effect of bisphosphonates was the result of an action on osteoblasts rather than on osteoclasts [19].
  • CTGF is a 38 kDa cysteine-rich peptide whose synthesis and secretion are selectively induced by transforming growth factor beta (TGF-beta) in connective tissue cells [20].
  • We therefore conclude that CRP occurs as a membrane-associated protein constitutively expressed on liver macrophages functioning as a receptor mediating galactose-specific binding of particulate ligands [21].
  • The non-glycosylated rat CRP, however, was still able to bind to phosphorylcholine-Sepharose and to be secreted by hepatocytes [22].
  • This result was further confirmed by immunohistochemical staining of lung sections that showed the localization of CRP in alveolar macrophages [23].

Associations of Csrp1 with chemical compounds

  • The deduced extracellular parts of the AMIGOs contain six leucine-rich repeats (LRRs) flanked by cysteine-rich LRR NH2- and COOH-terminal domains and by one immunoglobulin domain close to the transmembrane region [24].
  • This domain comprises leucine and cysteine rich motifs, followed by two immunoglobulin like (Ig-like) domains [25].
  • Protein kinase C normally has a tandem repeat of a characteristic cysteine-rich sequence in C1, the conserved region of the regulatory domain [26].
  • These cationic arginine- and cysteine-rich peptides inhibit corticotropin (ACTH)-stimulated rat adrenal cell corticosterone production [27].
  • Studies using tunicamycin revealed that the N-linked oligosaccharide present in rat CRP was not required for formation of its dimeric component, oligomerization, ability to bind to phosphorylcholine, or secretion [22].

Other interactions of Csrp1


Analytical, diagnostic and therapeutic context of Csrp1

  • However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals [32].
  • Tissue TNF-alpha expression measured by Northern blot analysis and serum C-reactive protein (CRP) levels, a marker of inflammation, were significantly reduced in animals pretreated with rIL-6 [33].
  • A mAb specific for rat neo-CRP labels liver macrophages but not hepatocytes and reacts with the isolated protein in a Western blot assay [21].
  • Western blot analysis showed that CRP was present in the lung tissue, lung lavage, and alveolar macrophages [23].
  • In this study, the nature of the oligosaccharide chain of rat CRP was investigated by fast atom bombardment-mass spectrometry (FAB-MS), and general features of its biosynthetic pathway were also analyzed [22].


  1. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. Griselli, M., Herbert, J., Hutchinson, W.L., Taylor, K.M., Sohail, M., Krausz, T., Pepys, M.B. J. Exp. Med. (1999) [Pubmed]
  2. Phosphoenolpyruvate carboxykinase (GTP) gene transcription and hyperglycemia are regulated by glucocorticoids in genetically obese db/db transgenic mice. Friedman, J.E., Sun, Y., Ishizuka, T., Farrell, C.J., McCormack, S.E., Herron, L.M., Hakimi, P., Lechner, P., Yun, J.S. J. Biol. Chem. (1997) [Pubmed]
  3. Vascular smooth muscle cell activation by C-reactive protein. Hattori, Y., Matsumura, M., Kasai, K. Cardiovasc. Res. (2003) [Pubmed]
  4. C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes. Ikeda, U., Maeda, Y., Yamamoto, K., Shimada, K. Cardiovasc. Res. (2002) [Pubmed]
  5. A point mutation in the neu oncogene mimics ligand induction of receptor aggregation. Weiner, D.B., Liu, J., Cohen, J.A., Williams, W.V., Greene, M.I. Nature (1989) [Pubmed]
  6. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Chang, C.S., Kokontis, J., Liao, S.T. Science (1988) [Pubmed]
  7. Activity of Wnt-1 as a transmembrane protein. Parkin, N.T., Kitajewski, J., Varmus, H.E. Genes Dev. (1993) [Pubmed]
  8. Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. Weiser, J.N., Pan, N., McGowan, K.L., Musher, D., Martin, A., Richards, J. J. Exp. Med. (1998) [Pubmed]
  9. Ischemia and aging brain. Studies on glucose and energy metabolism in rat cerebral cortex. Hoyer, S., Krier, C. Neurobiol. Aging (1986) [Pubmed]
  10. Recombinant protein kinase C-gamma phorbol binding domain upon microinjection blocked insulin-induced maturation of Xenopus laevis oocytes. Pawelczyk, T., Matecki, A., Dettlaff, A. FEBS Lett. (1998) [Pubmed]
  11. Systemic low-dose doxycycline and alendronate administration and serum interleukin-1beta, osteocalcin, and C-reactive protein levels in rats. Buduneli, E., Buduneli, N., Vardar-Sengül, S., Kardeşler, L., Atilla, G., Lappin, D., Kinane, D.F. J. Periodontol. (2005) [Pubmed]
  12. Appearance of C-reactive protein (CRP) in serum and liver cytosol of cadmium-treated rats. Agrawal, A., Bhattacharya, S. Indian J. Exp. Biol. (1989) [Pubmed]
  13. Alteration of interleukin-1 activity and the acute phase response in adjuvant arthritic rats treated with disease modifying antirheumatic drugs. Connolly, K.M., Stecher, V.J., Danis, E., Pruden, D.J., LaBrie, T. Agents Actions (1988) [Pubmed]
  14. Isolation and developmental expression of a rat cDNA encoding a cysteine-rich zinc finger protein. McLaughlin, C.R., Tao, Q., Abood, M.E. Nucleic Acids Res. (1994) [Pubmed]
  15. 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]
  16. Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Ono, Y., Fujii, T., Ogita, K., Kikkawa, U., Igarashi, K., Nishizuka, Y. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  17. Molecular cloning and expression of a 90-kDa diacylglycerol kinase that predominantly localizes in neurons. Goto, K., Kondo, H. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  18. Molecular cloning of the large subunit of transforming growth factor type beta masking protein and expression of the mRNA in various rat tissues. Tsuji, T., Okada, F., Yamaguchi, K., Nakamura, T. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  19. Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. Sahni, M., Guenther, H.L., Fleisch, H., Collin, P., Martin, T.J. J. Clin. Invest. (1993) [Pubmed]
  20. Inhibition of TGF-beta-stimulated CTGF gene expression and anchorage-independent growth by cAMP identifies a CTGF-dependent restriction point in the cell cycle. Kothapalli, D., Hayashi, N., Grotendorst, G.R. FASEB J. (1998) [Pubmed]
  21. A membrane-associated form of C-reactive protein is the galactose-specific particle receptor on rat liver macrophages. Kempka, G., Roos, P.H., Kolb-Bachofen, V. J. Immunol. (1990) [Pubmed]
  22. Studies on the carbohydrate moiety and on the biosynthesis of rat C-reactive protein. Sambasivam, H., Rassouli, M., Murray, R.K., Nagpurkar, A., Mookerjea, S., Azadi, P., Dell, A., Morris, H.R. J. Biol. Chem. (1993) [Pubmed]
  23. Expression of C-reactive protein by alveolar macrophages. Dong, Q., Wright, J.R. J. Immunol. (1996) [Pubmed]
  24. AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats. Kuja-Panula, J., Kiiltomäki, M., Yamashiro, T., Rouhiainen, A., Rauvala, H. J. Cell Biol. (2003) [Pubmed]
  25. Immunoglobulin-like domains define the nerve growth factor binding site of the TrkA receptor. Holden, P.H., Asopa, V., Robertson, A.G., Clarke, A.R., Tyler, S., Bennett, G.S., Brain, S.D., Wilcock, G.K., Allen, S.J., Smith, S.K., Dawbarn, D. Nat. Biotechnol. (1997) [Pubmed]
  26. Phorbol ester binding to protein kinase C requires a cysteine-rich zinc-finger-like sequence. Ono, Y., Fujii, T., Igarashi, K., Kuno, T., Tanaka, C., Kikkawa, U., Nishizuka, Y. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  27. Isolation and structure of corticostatin peptides from rabbit fetal and adult lung. Zhu, Q.Z., Hu, J., Mulay, S., Esch, F., Shimasaki, S., Solomon, S. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  28. Characterization of elk, a brain-specific receptor tyrosine kinase. Lhoták, V., Greer, P., Letwin, K., Pawson, T. Mol. Cell. Biol. (1991) [Pubmed]
  29. Purification and antimicrobial properties of three defensins from rat neutrophils. Eisenhauer, P.B., Harwig, S.S., Szklarek, D., Ganz, T., Selsted, M.E., Lehrer, R.I. Infect. Immun. (1989) [Pubmed]
  30. Effect of metallothionein I on mitochondrial oxygen consumption. Simpkins, C.O., Zhao, H.L., Torrence, C.A. Life Sci. (1994) [Pubmed]
  31. A serine, threonine and proline-rich region near the carboxyl-terminus of a rat intestinal mucin peptide. Huan, L.J., Xu, G., Forstner, G., Forstner, J. Biochim. Biophys. Acta (1992) [Pubmed]
  32. Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins. Rowe, I.F., Soutar, A.K., Trayner, I.M., Baltz, M.L., de Beer, F.C., Walker, L., Bowyer, D., Herbert, J., Feinstein, A., Pepys, M.B. J. Exp. Med. (1984) [Pubmed]
  33. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Camargo, C.A., Madden, J.F., Gao, W., Selvan, R.S., Clavien, P.A. Hepatology (1997) [Pubmed]
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