ENTPD5

ENTPD5
Identifikatori
Aliasi	ENTPD5
Vanjski ID-jevi	OMIM: 603162 MGI: 1321385 HomoloGene: 37457 GeneCards: ENTPD5
EC broj	3.6.1.42
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	74,019,399 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	84,455,803 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• guanosine-diphosphatase activity; • uridine-diphosphatase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • hydrolase activity; • nucleoside-diphosphatase activity;
Ćelijska komponenta	• Endoplazmatski retikulum; • extracellular region;
Biološki proces	• 'de novo' posttranslational protein folding; • ATP metabolic process; • GO:0033578, GO:0033577, GO:0033575, GO:0033576 protein glycosylation; • protein N-linked glycosylation; • Ćelijska proliferacija; • positive regulation of glycolytic process; • regulation of phosphatidylinositol 3-kinase signaling; • nucleobase-containing small molecule catabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	957
	12499
	ENSG00000187097
	ENSMUSG00000021236
	O75356
	Q9WUZ9
NM_001249; NM_001321984; NM_001321985; NM_001321986; NM_001321987;
	NM_001321988; NM_001330189; NM_001382256; NM_001382257; NM_001382258; NM_001382259; NM_001382260; NM_001382262; NM_001382263
	NM_001026214; NM_001286049; NM_001286058; NM_007647
NP_001240; NP_001308913; NP_001308914; NP_001308915; NP_001308916;
	NP_001308917; NP_001317118; NP_001369185; NP_001369186; NP_001369187; NP_001369188; NP_001369189; NP_001369191; NP_001369192
	NP_001021385; NP_001272978; NP_001272987; NP_031673
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Ektonukleozidna trifosfat-difosfohidrolaza 5 je enzim koji je kod ljudi kodiran genom ENTPD5.^[5]^[6]^[7]

Fluorescentnom in situ hibridizacijom i analizom veza, Chadwick et al. (1998) locirali su gen MNTPaze na mišjem hromosomu 12, u regiji koja pokazuje homologiju sinteze sa ljudskim hromozomom 14q. Analizom hibridnih ploča hibridnih i somatskih zračenih ćelija, Chadwick i Frischauf (1998) potvrdili su da se CD39L4 nalazi na ljudskom hromosomu 14, pozicija q24. Zaključili su da je CD39L4 ljudski homolog MNTPaze.^[8]

ENTPD5 je sličan nukleotidazama E-tipa (NTPaze)/ekto-ATPaza/apirazama. NTPaze, poput CD39, posreduju katabolizam vanćelijskih nukleotida. ENTPD5 sadrži četiri konzrrvirane regije apiraza, što je karakteristično za NTPaze.^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 428 aminokiselina, a molekulska težina 47.517 Da.^[9].

10	20	30	40	50
MATSWGTVFF	MLVVSCVCSA	VSHRNQQTWF	EGIFLSSMCP	INVSASTLYG
IMFDAGSTGT	RIHVYTFVQK	MPGQLPILEG	EVFDSVKPGL	SAFVDQPKQG
AETVQGLLEV	AKDSIPRSHW	KKTPVVLKAT	AGLRLLPEHK	AKALLFEVKE
IFRKSPFLVP	KGSVSIMDGS	DEGILAWVTV	NFLTGQLHGH	RQETVGTLDL
GGASTQITFL	PQFEKTLEQT	PRGYLTSFEM	FNSTYKLYTH	SYLGFGLKAA
RLATLGALET	EGTDGHTFRS	ACLPRWLEAE	WIFGGVKYQY	GGNQEGEVGF
EPCYAEVLRV	VRGKLHQPEE	VQRGSFYAFS	YYYDRAVDTD	MIDYEKGGIL
KVEDFERKAR	EVCDNLENFT	SGSPFLCMDL	SYITALLKDG	FGFADSTVLQ
LTKKVNNIET	GWALGATFHL	LQSLGISH

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
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

Kloniranje i ekspresija

Nukleozidne trifosfataze (NTPaze) su dvovalentni transmembranski glikoproteini koji zavise od kationa i hidroliziraju vanćelijske nukleozidne tri– i/ili difosfate. NTPaze karakterizira prisustvo četiri motiva poznata kao regije konzervirane apiraze (ACR). Chadwick et al. (1998) identificirali su cDNK koje kodiraju mišju NTPazu, simbolizirajući MNTPazu. Pretražujući EST bazu podataka za sekvence slične onim MNTPaze, Chadwick i Frischauf (1998) identificirali su cDNK koje odgovaraju dvama ljudskim genimaa, CD39L2 i CD39L4. Kodirajuće regije mišjeg i ljudskog gena CD39L4 dijele 88% identiteta nukleotidne sekvence. Predviđeni protein CD39L4 od 428 aminokiselina sadrži sva četiri ACR-a, jedan N-terminalni transmembranski segment i veliki vanćelijski C-terminalni domen. Northern blot analiza otkrila je da je CD39L4 eksprimiran kao iRNK od 4,8 kb u svim testiranim tkivima. Nekoliko manjih traka takođe je primijećeno u tkivima sa najjačom ekspresijom CD39L4.^[10]

Fang et al (2010) pokazali su da je Entpd5 označen fluorescencijom lokaliziran markerom endoplazmatskog retikuluma (ER) u mišjim embrionskim fibroblastima(MEF).

Funkcija gena

PCR analizom cDNK biblioteka, Mulero et al. (1999) otkrili su CD39L4 samo u makrofagima. Funkcionalnom i Western blot analizom utvrđeno je da je aktivnost ADPaze i nukleotid-difosfataze izlučenog proteina od 51 kD pojačana prisustvom dvovalentnih kationa. Liječenje glikozidazom ili tunikamicinom (Mulero et al., 2000) smanjilo je veličinu proteina na predviđenih 46 kD i smanjilo količinu sekrecije; za razliku od CD39L3, međutim, nije umanjio enzimsku aktivnost.^[11]^[12] Fang et al. (2010) pokazali su da in vitro translatirani ENTPD5 hidrolizira UDP i GDP, ali ne i druge nukleotide. Delecija Ptena u MEF rezultira aktivacijom puta PI3 kinaze / Akt, koji promovira rast i preživljavanje ćelija, uz istovremeno povećanje translacije proteina. Pokazali su da su ekspresija Entpd5 i hidroliza ATP značajno povišeni u Pten –/– MEF. Masenom spektrometrijskom analizom identificirani su ENTPD5, UMP/CMP kinaza-1 (CMPK1) i adenilat-kinaza-1 (AK1) kao komponente ciklusa hidrolize ATP u HeLa ćelijama. Unutar ovog ciklusa, ENTPD5 je pružio kritične UMP ili GMP kofaktore za hidrolizu ATP u AMP i nedostatak bilo kojeg od tri enzima koji su ugrozili hidrolizu ATP. Nokdaun Entpd5 u Pten –/– MEF povećao je ekspresiju markera ER stresa, smanjio N-glikozilaciju proteina i smanjio proizvodnju laktata. Western blot, imunohistokemijske i analize mikromreža pokazale su da je regulacija ENTPD5 korelirala s aktivacijom AKT-a u ljudskim ćelijskim linijama karcinoma prostate i primarnim uzorcima tumora prostate. Nokdaun ENTPD5 u LNCaP ćelijaa kamrcinoma prostate smanjio je rast tumora kod golih miševa. Zaključili su da ENTPD5 ima kritičnu ulogu u N-glikozilaciji i doprinosi Warburgovom efektu, tj. povišenoj proizvodnji laktata u aerobnim uvjetima, u ćelijama tumora.^[13]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000187097 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021236 - 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.
^ Chadwick BP, Frischauf AM (Oct 1997). "Cloning and mapping of a human and mouse gene with homology to ecto-ATPase genes". Mamm Genome. 8 (9): 668–72. doi:10.1007/s003359900534. PMID 9271669.
^ Chadwick BP, Frischauf AM (Oct 1998). "The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster". Genomics. 50 (3): 357–67. doi:10.1006/geno.1998.5317. PMID 9676430.
^ ^a ^b "Entrez Gene: ENTPD5 ectonucleoside triphosphate diphosphohydrolase 5".
^ Chadwick, B. P., Frischauf, A.-M. The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster. Genomics 50: 357-367, 1998. PubMed: 9676430
^ "UniProt, O75356". Pristupljeno 24. 7. 2021.
^ Chadwick, B. P., Williamson, J., Sheer, D., Frischauf, A.-M. cDNA cloning and chromosomal mapping of a mouse gene with homology to NTPases. Mammalian Genome 9: 162-164, 1998. PubMed: 9457681
^ Mulero, J. J., Yeung, G., Nelken, S. T., Bright, J. M., McGowan, D. W., Ford, J. E. Biochemical characterization of CD39L4. Biochemistry 39: 12924-12928, 2000. PubMed: 11041857
^ Mulero, J. J., Yeung, G., Nelken, S. T., Ford, J. E. CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates. J. Biol. Chem. 274: 20064-20067, 1999. PubMed: 10400613
^ Fang, M., Shen, Z., Huang, S., Zhao, L., Chen, S., Mak, T. W., Wang, X. The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143: 711-724, 2010. PubMed: 21074248

Dopunska literatura

Mulero JJ, Yeung G, Nelken ST, Ford JE (1999). "CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates". J. Biol. Chem. 274 (29): 20064–7. doi:10.1074/jbc.274.29.20064. PMID 10400613.
Recio JA, Zambrano N, Peña L, et al. (2000). "The human PCPH proto-oncogene: cDNA identification, primary structure, chromosomal mapping, and expression in normal and tumor cells". Mol. Carcinog. 27 (3): 229–36. doi:10.1002/(SICI)1098-2744(200003)27:3<229::AID-MC10>3.0.CO;2-Z. PMID 10708485.
Mulero JJ, Yeung G, Nelken ST, et al. (2000). "Biochemical characterization of CD39L4". Biochemistry. 39 (42): 12924–8. doi:10.1021/bi000960y. PMID 11041857.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Blánquez MJ, Regadera J, Mariño J, et al. (2003). "Gradual deregulation and loss of PCPH expression in the progression of human laryngeal neoplasia". Mol. Carcinog. 35 (4): 186–95. doi:10.1002/mc.10091. PMID 12489110.
Murphy-Piedmonte DM, Crawford PA, Kirley TL (2005). "Bacterial expression, folding, purification and characterization of soluble NTPDase5 (CD39L4) ecto-nucleotidase". Biochim. Biophys. Acta. 1747 (2): 251–9. doi:10.1016/j.bbapap.2004.11.017. PMID 15698960.
Liu T, Qian WJ, Gritsenko MA, et al. (2006). "Human Plasma N-Glycoproteome Analysis by Immunoaffinity Subtraction, Hydrazide Chemistry, and Mass Spectrometry". J. Proteome Res. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.
Regadera J, Blánquez MJ, González-Peramato P, et al. (2006). "PCPH expression is an early event in the development of testicular germ cell tumors". Int. J. Oncol. 28 (3): 595–604. doi:10.3892/ijo.28.3.595. PMID 16465363.
Villar J, Arenas MI, MacCarthy CM, et al. (2007). "PCPH/ENTPD5 expression enhances the invasiveness of human prostate cancer cells by a protein kinase C delta-dependent mechanism". Cancer Res. 67 (22): 10859–68. doi:10.1158/0008-5472.CAN-07-2041. PMID 18006831.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000187097 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021236 - Ensembl, maj 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.

[pmid9271669-5] Chadwick BP, Frischauf AM (Oct 1997). "Cloning and mapping of a human and mouse gene with homology to ecto-ATPase genes". Mamm Genome. 8 (9): 668–72. doi:10.1007/s003359900534. PMID 9271669.

[pmid9676430-6] Chadwick BP, Frischauf AM (Oct 1998). "The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster". Genomics. 50 (3): 357–67. doi:10.1006/geno.1998.5317. PMID 9676430.

[entrez-7] "Entrez Gene: ENTPD5 ectonucleoside triphosphate diphosphohydrolase 5".

[8] Chadwick, B. P., Frischauf, A.-M. The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster. Genomics 50: 357-367, 1998. PubMed: 9676430

[UniProt-9] "UniProt, O75356". Pristupljeno 24. 7. 2021.

[10] Chadwick, B. P., Williamson, J., Sheer, D., Frischauf, A.-M. cDNA cloning and chromosomal mapping of a mouse gene with homology to NTPases. Mammalian Genome 9: 162-164, 1998. PubMed: 9457681

[11] Mulero, J. J., Yeung, G., Nelken, S. T., Bright, J. M., McGowan, D. W., Ford, J. E. Biochemical characterization of CD39L4. Biochemistry 39: 12924-12928, 2000. PubMed: 11041857

[12] Mulero, J. J., Yeung, G., Nelken, S. T., Ford, J. E. CD39-L4 is a secreted human apyrase, specific for the hydrolysis of nucleoside diphosphates. J. Biol. Chem. 274: 20064-20067, 1999. PubMed: 10400613

[13] Fang, M., Shen, Z., Huang, S., Zhao, L., Chen, S., Mak, T. W., Wang, X. The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143: 711-724, 2010. PubMed: 21074248

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