Fosfatidilinozitol 4-kinaza 2-alfa je enzim koji je kod ljudi kodiran genom PI4K2A .[ 5] [ 6] [ 7]
Dužina polipeptidnog lanca je 479 aminokiselina , а molekulska težina 54.022 Da .[ 8]
10 20 30 40 50
MDETSPLVSP ERAQPPDYTF PSGSGAHFPQ VPGGAVRVAA AAGSGPSPPG
SPGHDRERQP LLDRARGAAA QGQTQTVAAQ AQALAAQAAA AAHAAQAHRE
RNEFPEDPEF EAVVRQAELA IERCIFPERI YQGSSGSYFV KDPQGRIIAV
FKPKNEEPYG HLNPKWTKWL QKLCCPCCFG RDCLVLNQGY LSEAGASLVD
QKLELNIVPR TKVVYLASET FNYSAIDRVK SRGKRLALEK VPKVGQRFNR
IGLPPKVGSF QLFVEGYKDA DYWLRRFEAE PLPENTNRQL LLQFERLVVL
DYIIRNTDRG NDNWLIKYDC PMDSSSSRDT DWVVVKEPVI KVAAIDNGLA
FPLKHPDSWR AYPFYWAWLP QAKVPFSQEI KDLILPKISD PNFVKDLEED
LYELFKKDPG FDRGQFHKQI AVMRGQILNL TQALKDNKSP LHLVQMPPVI
VETARSHQRS SSESYTQSFQ SRKPFFSWW
Ovaj gen kodira fosfatidilinozitol 4-kinazu koja katalizira fosforilaciju fosfatidilinositola na položaju D-4, dajući fosfatidilinositol 4-fosfat (PI4P). Osim činjenice da PI4P služi kao prekursor za druge važne fosfoinozitide, poput fosfatidilinositol 4,5-bisfosfata , PI4P , neophodns je molekula u ćelijskoj signalizaciji i prometu posebno u Golgijevom aparatu i trans Golgijevoj mreži.
Fosfatidilinozitol 4-kinaze evolucijski su konzervirane među eukariotima i uključuju četiri ljudske izoforme
Fosfatidilinositol 4-kinaza 2-alfa (PI4K2A) je najzastupljenija fosfatidilinozitol 4-kinaza u ljudskim ćelijama i odgovorna je za sintezu približno 50% ukupni PI4P unutar ćelije. PI4K2A je uglavnom povezan s membranama trans Golgijeve mreže i ranim i kasnim endosomima ;[ 9] njegova membranska povezanost postiže se teškom palmitoilacijom unutar specifičnog motiva bogatog cisteinom .[ 10] Osim sinteze fosfatidilinositol 4,5-bisfosfata , PI4K2A je uključen u različite ćelijske procese, uključujući promjenu membrana, regulaciju endosomskog sortiranja, promovirajući regrutovanje ciljnih proteina u endosomima ili trans Golgijevoj mreži ili transdukciju signala . Posebno regulira npr. ciljanje kompleksa klatrinskog adaptera na Golgijev aparat ,[ 11] signalni EGFR signaling,[ 12] ili Wnt-signalni put .[ 13]
Disfunkcija PI4K2A može doprinijeti rastu tumora ,[ 14] spazamskoj paraplegiji ,[ 15] Gaucherovoj ,[ 16] ili Alzhemerovoj bolesti .[ 17]
Kinazni domen fosfatidilinositol 4-kinaze 2-alfa . N-režanj je obojen zlatno, C-režanj u akvamarinu, ATP na aktivnom mjestu između režnjeva u reprezentaciji štapića. PDB kod: 4PLA.[ 18]
PI4K2A se sastoji od prolinom bogate N -terminalne regije i kinaznog domena koji se nalazi C -terminalno . Prolin -bogato N -terminalno područje sadrži fiziološki važna mjesta vezivanja za ubikvitin -ligazu Svrab [ 19] i klatrinski adapterski kompleks 3,[ 20] ali je vjerojatno poremećen i nepotreban za aktivnost kinaze.[ 21] Domen kinaza može se podijeliti na N -terminalne i C -završne režnjeve sa ATP veznim žljebom i navodnim fosfatidilinositolskim veznim džepom između . C -režanj domena kinaza sadrži dodatni bočni hidrofobni džep bez još dodijeljene posebne funkcije.[ 18] [ 22]
^ a b c GRCh38: Ensembl release 89: ENSG00000155252 - Ensembl , maj 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025178 - 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 .
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^ "Entrez Gene: PI4KII phosphatidylinositol 4-kinase type II" .
^ "UniProt, Q9BTU6" . Pristupljeno 3. 9. 2021 .
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^ Pan, W; Choi, SC; Wang, H; Qin, Y; Volpicelli-Daley, L; Swan, L; Lucast, L; Khoo, C; Zhang, X; Li, L; Abrams, CS; Sokol, SY; Wu, D (5. 9. 2008). "Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation" . Science . 321 (5894): 1350–3. doi :10.1126/science.1160741 . PMC 2532521 . PMID 18772438 .
^ Li, J; Lu, Y; Zhang, J; Kang, H; Qin, Z; Chen, C (29. 4. 2010). "PI4KIIalpha is a novel regulator of tumor growth by its action on angiogenesis and HIF-1alpha regulation" . Oncogene . 29 (17): 2550–9. doi :10.1038/onc.2010.14 . PMID 20154717 .
^ Simons, JP; Al-Shawi, R; Minogue, S; Waugh, MG; Wiedemann, C; Evangelou, S; Loesch, A; Sihra, TS; King, R; Warner, TT; Hsuan, JJ (14. 7. 2009). "Loss of phosphatidylinositol 4-kinase 2alpha activity causes late onset degeneration of spinal cord axons" . Proceedings of the National Academy of Sciences of the United States of America . 106 (28): 11535–9. doi :10.1073/pnas.0903011106 . PMC 2710652 . PMID 19581584 .
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^ a b Baumlova, A.; Chalupska, D.; Rozycki, B.; Jovic, M.; Wisniewski, E.; Klima, M.; Dubankova, A.; Kloer, D. P.; Nencka, R.; Balla, T.; Boura, E. (28. 8. 2014). "The crystal structure of the phosphatidylinositol 4-kinase II" . EMBO Reports . 15 (10): 1085–1092. doi :10.15252/embr.201438841 . PMC 4253849 . PMID 25168678 .
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^ Craige, B.; Salazar, G.; Faundez, V. (1. 4. 2008). "Phosphatidylinositol-4-Kinase Type II Alpha Contains an AP-3-sorting Motif and a Kinase Domain That Are Both Required for Endosome Traffic" . Molecular Biology of the Cell . 19 (4): 1415–1426. doi :10.1091/mbc.E07-12-1239 . PMC 2291421 . PMID 18256276 .
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