CPVL

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.

CPVL
Identifiers
AliasesCPVL, HVLP, carboxypeptidase, vitellogenic like, carboxypeptidase vitellogenic like
External IDsOMIM: 609780 MGI: 1918537 HomoloGene: 80235 GeneCards: CPVL
Gene location (Human)
Chr.Chromosome 7 (human)[1]
Band7p14.3Start28,995,235 bp[1]
End29,195,451 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
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_001276642
NP_001276643
NP_082025

Location (UCSC)Chr 7: 29 – 29.2 MbChr 6: 53.87 – 53.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 extraimmune 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.
  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.

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. 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.


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