Probable serine carboxypeptidase CPVL is an enzyme that in humans is encoded by the CPVLgene.[1][2] The "CPVL" gene is expressed mainly in monocytes and macrophages,[1] and it is located in the endoplasmatic reticulum and in the endosomal/lysosomal compartment. The distribution of CPVL suggests that the enzyme may be involved in antigen processing and the secretory pathway.[3] Besides those macrophages-rich tissues, the heart and kidney also express high levels of CPVL mRNA.The enzyme is similar to the carboxypeptidasesCATHA and SCPEP1, but no direct confirmation of the enzymatic activity was obtained so far.[4] The exact function of this protein, however, has not been determined.
"CPVL" gene is located at chromosome 7p15.1, consisting of 14 exons.At least two alternatively spliced transcripts which encode the same protein have been observed.[2]
Protein
The designation of CPVL is a true serinecarboxypeptidase. Although the primary sequence displays the expected serine carboxypeptidase active site, the enzymatic activity remains to be demonstrated. The primary sequence of CPVL contains a putative signal sequence, four potential N-linked glycosylation sites and four myristoylation sites, but no transmembrane domain, suggesting that it may be luminal in an organelle and/or involved in the secretory pathway.[3]
Function
Although the primary sequence of CPVL bears every hallmarks of a serine carboxypeptidase, the enzymatic function of CPVL has not been confirmed. On the basis of its localization, CPVL is postulated to play a role in the biosynthesis of secretory molecules or in the processing and transport of peptides for loading onto MHC Ⅰ molecules, or in MHC Ⅱ-dependent APC functions.[3] The high-level expression of CPVL mRNA in heart and kidney implies that CPVL may also have extraimmune functions, such as regulation of cardiovascular homeostasis.[1]
Clinical significance
The deletion of this gene has been reported associated with Wilms tumor.[5]GWAS show that genetic variations of the CPVL gene are associated with susceptibility to diabetic nephropathy in European Americans, Japanese and Chinese.[6][7][8] CPVL is also reported to be one of the four down-regulated proteins which is related to severity of inflammation, and it may be a potential biomarker for identification of infection and prediction of outcome.[9]
References
↑ 1.01.11.2Mahoney JA, Ntolosi B, DaSilva RP, Gordon S, McKnight AJ (March 2001). "Cloning and characterization of CPVL, a novel serine carboxypeptidase, from human macrophages". Genomics. 72 (3): 243–51. doi:10.1006/geno.2000.6484. PMID11401439.
↑Pshezhetsky AV, Hinek A (January 2009). "Serine carboxypeptidases in regulation of vasoconstriction and elastogenesis". Trends in Cardiovascular Medicine. 19 (1): 11–7. doi:10.1016/j.tcm.2009.03.002. PMID19467448.
↑Grundy RG, Pritchard J, Scambler P, Cowell JK (July 1998). "Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour". Oncogene. 17 (3): 395–400. doi:10.1038/sj.onc.1201927. PMID9690521.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Striebich CC, Falta MT, Wang Y, Bill J, Kotzin BL (October 1998). "Selective accumulation of related CD4+ T cell clones in the synovial fluid of patients with rheumatoid arthritis". Journal of Immunology. 161 (8): 4428–36. PMID9780222.
Wang X, Stollar BD (November 1999). "Immunoglobulin VH gene expression in human aging". Clinical Immunology. 93 (2): 132–42. doi:10.1006/clim.1999.4781. PMID10527689.
Ignatovich O, Tomlinson IM, Popov AV, Brüggemann M, Winter G (November 1999). "Dominance of intrinsic genetic factors in shaping the human immunoglobulin Vlambda repertoire". Journal of Molecular Biology. 294 (2): 457–65. doi:10.1006/jmbi.1999.3243. PMID10610771.
Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID16303743.
Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC1847948. PMID17353931.
