CPVL explained

Probable serine carboxypeptidase CPVL is an enzyme that in humans is encoded by the CPVL gene.^{[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 carboxypeptidases CATHA 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.

Structure

Gene

"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.

Protein

The designation of CPVL is a true serine carboxypeptidase. 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 extra immune 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]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Striebich CC, Falta MT, Wang Y, Bill J, Kotzin BL . Selective accumulation of related CD4+ T cell clones in the synovial fluid of patients with rheumatoid arthritis . Journal of Immunology . 161 . 8 . 4428–36 . October 1998 . 10.4049/jimmunol.161.8.4428 . 9780222 . free .
• Wang X, Stollar BD . Immunoglobulin VH gene expression in human aging . Clinical Immunology . 93 . 2 . 132–42 . November 1999 . 10527689 . 10.1006/clim.1999.4781 .
• Ignatovich O, Tomlinson IM, Popov AV, Brüggemann M, Winter G . Dominance of intrinsic genetic factors in shaping the human immunoglobulin Vlambda repertoire . Journal of Molecular Biology . 294 . 2 . 457–65 . November 1999 . 10610771 . 10.1006/jmbi.1999.3243 .
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z . Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells . Genome Research . 10 . 10 . 1546–60 . October 2000 . 11042152 . 310934 . 10.1101/gr.140200 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–70 . October 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• 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 . 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 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . free .
• 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 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Mahoney JA, Ntolosi B, DaSilva RP, Gordon S, McKnight AJ . Cloning and characterization of CPVL, a novel serine carboxypeptidase, from human macrophages . Genomics . 72 . 3 . 243–51 . March 2001 . 11401439 . 10.1006/geno.2000.6484 .
2. Web site: Entrez Gene: CPVL carboxypeptidase, vitellogenic-like.
3. Harris J, Schwinn N, Mahoney JA, Lin HH, Shaw M, Howard CJ, da Silva RP, Gordon S . A vitellogenic-like carboxypeptidase expressed by human macrophages is localized in endoplasmic reticulum and membrane ruffles . International Journal of Experimental Pathology . 87 . 1 . 29–39 . February 2006 . 16436111 . 10.1111/j.0959-9673.2006.00450.x . 2517344.
4. Pshezhetsky AV, Hinek A . Serine carboxypeptidases in regulation of vasoconstriction and elastogenesis . Trends in Cardiovascular Medicine . 19 . 1 . 11–7 . January 2009 . 19467448 . 10.1016/j.tcm.2009.03.002 .
5. Grundy RG, Pritchard J, Scambler P, Cowell JK . Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour . Oncogene . 17 . 3 . 395–400 . July 1998 . 9690521 . 10.1038/sj.onc.1201927 . 25548908 .
6. Maeda S, Araki S, Babazono T, Toyoda M, Umezono T, Kawai K, Imanishi M, Uzu T, Watada H, Suzuki D, Kashiwagi A, Iwamoto Y, Kaku K, Kawamori R, Nakamura Y . Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes . Diabetes . 59 . 8 . 2075–9 . August 2010 . 20460425 . 10.2337/db10-0067 . 2911071.
7. Hu C, Zhang R, Yu W, Wang J, Wang C, Pang C, Ma X, Bao Y, Xiang K, Jia W . CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients . Diabetes . 60 . 11 . 3085–9 . November 2011 . 21911749 . 10.2337/db11-0028 . 3198055.
8. Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, de Heer E, Freedman BI, Dekkers OM, Baelde HJ . Genetic associations in diabetic nephropathy: a meta-analysis . Diabetologia . 54 . 3 . 544–53 . March 2011 . 21127830 . 10.1007/s00125-010-1996-1 . 3034040.
9. Bauer M, Giamarellos-Bourboulis EJ, Kortgen A, Möller E, Felsmann K, Cavaillon JM, Guntinas-Lichius O, Rutschmann O, Ruryk A, Kohl M, Wlotzka B, Rußwurm S, Marshall JC, Reinhart K . A Transcriptomic Biomarker to Quantify Systemic Inflammation in Sepsis - A Prospective Multicenter Phase II Diagnostic Study . eBioMedicine . 6 . 114–25 . April 2016 . 27211554 . 10.1016/j.ebiom.2016.03.006 . 4856796.