CPVL
Vjerovatna serin-karboksipeptidaza CPVL je enzim koji je kod ljudi kodiran genom CPVL.[5][6] Gen "CPVL" eksprimira se uglavnom u monocitima i makrofagima,[5] i nalazi se u endoplazmatskom retikulumu i u endosomnom /lizosomnom odeljku. Raspodjela CPVL -a sugerira da enzim može biti uključen u obradu antigena i sekrecijski put.[7] Osim tkiva bogatih makrofagima, srce i bubrezi također eksprimiraju visoku razinu CPVL-ove iRNK. Enzim je sličan karboksipeptidazama CATHA i SCPEP1, ali do sada nije dobijena direktna potvrda enzimske aktivnosti.[8] Tačna funkcija ovog proteina, međutim, nije utvrđena.
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 476 aminokiselina, а molekulska težina Da. 54 164[9]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MVGAMWKVIV | SLVLLMPGPC | DGLFRSLYRS | VSMPPKGDSG | QPLFLTPYIE | ||||
| AGKIQKGREL | SLVGPFPGLN | MKSYAGFLTV | NKTYNSNLFF | WFFPAQIQPE | ||||
| DAPVVLWLQG | GPGGSSMFGL | FVEHGPYVVT | SNMTLRDRDF | PWTTTLSMLY | ||||
| IDNPVGTGFS | FTDDTHGYAV | NEDDVARDLY | SALIQFFQIF | PEYKNNDFYV | ||||
| TGESYAGKYV | PAIAHLIHSL | NPVREVKINL | NGIAIGDGYS | DPESIIGGYA | ||||
| EFLYQIGLLD | EKQKKYFQKQ | CHECIEHIRK | QNWFEAFEIL | DKLLDGDLTS | ||||
| DPSYFQNVTG | CSNYYNFLRC | TEPEDQLYYV | KFLSLPEVRQ | AIHVGNQTFN | ||||
| DGTIVEKYLR | EDTVQSVKPW | LTEIMNNYKV | LIYNGQLDII | VAAALTERSL | ||||
| MGMDWKGSQE | YKKAEKKVWK | IFKSDSEVAG | YIRQAGDFHQ | VIIRGGGHIL | ||||
| PYDQPLRAFD | MINRFIYGKG | WDPYVG |
C: Cistein
D: Aspartat
E: Glutamat
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
- W: Triptofan
Y: Tirozin
Struktura
[uredi | uredi izvor]Gen
[uredi | uredi izvor]Gen "CPVL" se nalazi na hromosomu 7, sekvenca p15.1, a sastoji se od 14 egzona. Uočena su najmanje dva alternativno prerađena transkripta koji kodiraju isti protein.[6]
Protein
[uredi | uredi izvor]Prava oznaka CPVL je serin-karboksipeptidaza. Iako primarna sekvenca prikazuje očekivano aktivno mjesto serin-karboksipeptidaze, ostaje dokazati enzimsku aktivnost. Primarna sekvenca CPVL-a sadrži pretpostavljenu signalnu sekvencu, četiri potencijalne N-povezanea mjesta glikozilacija i četiri mjesta miristoilacija, ali nema transmembranski domen, što ukazuje da može biti lumenska u organelama i /ili uključena u sekrecijski put.[7]
Funkcija
[uredi | uredi izvor]Iako primarna sekvenca CPVL -a nosi sva obilježja serin-karboksipeptidaze, enzimska funkcija CPVL -a nije potvrđena. Na temelju svoje lokalizacije, pretpostavlja se da CPVL ima ulogu u biosintezi sekretornih molekula ili u obradi i transportu peptida za učitavanje na molekulama MHC I ili u APK ovisnom o funkcijama MHC II.[7] Ekspresija CPVL-ove iRNK na visokom nivou u srcu i bubrezima implicira da CPVL može imati i ekstraimunske funkcije, poput regulacije kardiovaskularne homeostaze.[5]
Klinički značaj
[uredi | uredi izvor]Zabilježena je da je delecija ovog gena povezana s Wilmsovim tumorom.[10] GWAS-istraživanja pokazuju da su genetičke varijacije gena CPVL povezane s osjetljivošću na dijabetesku nefropatiju kod evropskih Amerikanaca, Japanaca i Kineza.[11][12][13] CPVL je također jedan od četiri podregulirana proteina povezana s težinom upala, a može biti i potencijalni biomarker za identifikaciju infekcije i predviđanje ishoda.[14]
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000106066 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000052955 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c Mahoney JA, Ntolosi B, DaSilva RP, Gordon S, McKnight AJ (mart 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.
- ^ a b "Entrez Gene: CPVL carboxypeptidase, vitellogenic-like".
- ^ a b c Harris J, Schwinn N, Mahoney JA, Lin HH, Shaw M, Howard CJ, da Silva RP, Gordon S (februar 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.
- ^ Pshezhetsky AV, Hinek A (januar 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.
- ^ "UniProt, Q9H3G5" (jezik: англ.). Pristupljeno 23. 9. 2021.CS1 održavanje: nepoznati jezik (link)
- ^ Grundy RG, Pritchard J, Scambler P, Cowell JK (juli 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.
- ^ 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.
- ^ Hu C, Zhang R, Yu W, Wang J, Wang C, Pang C, Ma X, Bao Y, Xiang K, Jia W (novembar 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.
- ^ Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, de Heer E, Freedman BI, Dekkers OM, Baelde HJ (mart 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.
- ^ 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.
Dopunska literatura
[uredi | uredi izvor]- Maruyama K, Sugano S (januar 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 (oktobar 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 (oktobar 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 (novembar 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 (novembar 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 (oktobar 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 (oktobar 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.
Vanjski linkovi
[uredi | uredi izvor]- Lokacija ljudskog genoma CPVL i stranica sa detaljima o genu CPVL u UCSC Genome Browseru.