CPVL

CPVL
Identifiers
Aliases	CPVL , HVLP, carboxypeptidase, vitellogenic like, carboxypeptidase vitellogenic like
External IDs	OMIM: 609780 MGI: 1918537 HomoloGene: 80235 GeneCards: CPVL
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p14.3 Start 28,995,235 bp [1] End 29,195,451 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6|6 B3 Start 53,850,264 bp [2] End 53,955,656 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte spleen renal medulla left lobe of thyroid gland right lobe of thyroid gland left ventricle blood gallbladder appendix lymph node Top expressed in spermatid secondary oocyte seminiferous tubule spermatocyte vastus lateralis muscle jejunum yolk sac ileum urinary bladder foregut More reference expression data BioGPS More reference expression data
Gene ontology Molecular function carboxypeptidase activity peptidase activity hydrolase activity serine-type carboxypeptidase activity Cellular component extracellular exosome Biological process proteolysis involved in cellular protein catabolic process proteolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54504 71287 Ensembl ENSG00000106066 ENSMUSG00000052955 UniProt Q9H3G5 Q9D3S9 RefSeq (mRNA) NM_019029 NM_031311 NM_001348052 NM_001348054 NM_001289713 NM_001289714 NM_027749 RefSeq (protein) NP_061902 NP_112601 NP_001334981 NP_001334983 NP_001358184 NP_001358185 NP_001358186 NP_001358187 NP_001358189 NP_001358190 NP_001358191 NP_001358192 NP_001358193 NP_001358194 NP_001358195 NP_001358196 NP_001358197 NP_001276642 NP_001276643 NP_082025 Location (UCSC) Chr 7: 29 – 29.2 Mb Chr 6: 53.85 – 53.96 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Probable serine carboxypeptidase CPVL is an enzyme that in humans is encoded by the CPVL gene. ^{[5] [6]} The "CPVL" gene is expressed mainly in monocytes and macrophages, ^[5] 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. ^[7] 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. ^[8] 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. ^[6]

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. ^[7]

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. ^[7] 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. ^[5]

Clinical significance

The deletion of this gene has been reported associated with Wilms tumor. ^[9] GWAS show that genetic variations of the CPVL gene are associated with susceptibility to diabetic nephropathy in European Americans, Japanese and Chinese. ^{[10] [11] [12]} 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. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000106066 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000052955 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Mahoney 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. PMID   11401439.
6. "Entrez Gene: CPVL carboxypeptidase, vitellogenic-like".
7. Harris J, Schwinn N, Mahoney JA, Lin HH, Shaw M, Howard CJ, da Silva RP, Gordon S (February 2006). "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. doi:10.1111/j.0959-9673.2006.00450.x. PMC   2517344 . PMID   16436111.
8. 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. PMID   19467448.
9. 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. PMID   9690521. S2CID   25548908.
10. 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 (August 2010). "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. doi:10.2337/db10-0067. PMC   2911071 . PMID   20460425.
11. Hu C, Zhang R, Yu W, Wang J, Wang C, Pang C, Ma X, Bao Y, Xiang K, Jia W (November 2011). "CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients". Diabetes. 60 (11): 3085–9. doi:10.2337/db11-0028. PMC   3198055 . PMID   21911749.
12. Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, de Heer E, Freedman BI, Dekkers OM, Baelde HJ (March 2011). "Genetic associations in diabetic nephropathy: a meta-analysis". Diabetologia. 54 (3): 544–53. doi:10.1007/s00125-010-1996-1. PMC   3034040 . PMID   21127830.
13. 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 (April 2016). "A Transcriptomic Biomarker to Quantify Systemic Inflammation in Sepsis - A Prospective Multicenter Phase II Diagnostic Study". eBioMedicine. 6: 114–25. doi:10.1016/j.ebiom.2016.03.006. PMC   4856796 . PMID   27211554.

External links

• Human CPVL genome location and CPVL gene details page in the UCSC Genome Browser .

Further reading

• 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. PMID   8125298.
• 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. PMID   9373149.
• 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. doi: 10.4049/jimmunol.161.8.4428 . PMID   9780222.
• 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. PMID   10527689.
• 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. PMID   10610771.
• 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 (October 2000). "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. doi:10.1101/gr.140200. PMC   310934 . PMID   11042152.
• 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 (October 2003). "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. doi:10.1101/gr.1293003. PMC   403697 . PMID   12975309.
• 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 . PMID   16303743.
• 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. PMC   1847948 . PMID   17353931.