PI4KA

PI4KA
Identifikatori
Aliasi	PI4KA
Vanjski ID-jevi	OMIM: 600286 MGI: 2448506 HomoloGene: 11171 GeneCards: PI4KA
Lokacija gena (čovjek)
Hrom.	Hromosom 22 (čovjek)
Kraj	20,859,417 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	17,224,178 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • GO:0001948, GO:0016582 vezivanje za proteine; • ATP binding; • 1-phosphatidylinositol 4-kinase activity; • kinase activity; • cadherin binding;
Ćelijska komponenta	• citoplazma; • Golgi-associated vesicle membrane; • citosol; • Egzosom; • membrana; • focal adhesion; • ćelijska membrana;
Biološki proces	• phosphatidylinositol biosynthetic process; • phosphatidylinositol phosphate biosynthetic process; • GO:0072468 Transdukcija signala; • viral RNA genome replication; • Fosforilacija; • actin cytoskeleton organization; • phosphatidylinositol-mediated signaling;
	Izvori:Amigo / QuickGO
Ortolozi
	5297
	224020
	ENSG00000241973
	ENSMUSG00000041720
	P42356
	E9Q3L2
	NM_002650; NM_058004; NM_001362862; NM_001362863
	NM_001001983; NM_001373955
	NP_477352; NP_001349791; NP_001349792
	NP_001001983
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Fosfatidilinozitol 4-kinaza alfa jest enzim koji je kod ljudi kodiran genom PI4KA sa hromosoma 22.^[5]^[6]^[7]

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 2.102 aminokiseline, a molekulska težina 236 830 Da.^[7]

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

10	20	30	40	50
MAAAPARGGG	GGGGGGGGCS	GSGSSASRGF	YFNTVLSLAR	SLAVQRPASL
EKVQKLLCMC	PVDFHGIFQL	DERRRDAVIA	LGIFLIESDL	QHKDCVVPYL
LRLLKGLPKV	YWVEESTARK	GRGALPVAES	FSFCLVTLLS	DVAYRDPSLR
DEILEVLLQV	LHVLLGMCQA	LEIQDKEYLC	KYAIPCLIGI	SRAFGRYSNM
EESLLSKLFP	KIPPHSLRVL	EELEGVRRRS	FNDFRSILPS	NLLTVCQEGT
LKRKTSSVSS	ISQVSPERGM	PPPSSPGGSA	FHYFEASCLP	DGTALEPEYY
FSTISSSFSV	SPLFNGVTYK	EFNIPLEMLR	ELLNLVKKIV	EEAVLKSLDA
IVASVMEANP	SADLYYTSFS	DPLYLTMFKM	LRDTLYYMKD	LPTSFVKEIH
DFVLEQFNTS	QGELQKILHD	ADRIHNELSP	LKLRCQANAA	CVDLMVWAVK
DEQGAENLCI	KLSEKLQSKT	SSKVIIAHLP	LLICCLQGLG	RLCERFPVVV
HSVTPSLRDF	LVIPSPVLVK	LYKYHSQYHT	VAGNDIKISV	TNEHSESTLN
VMSGKKSQPS	MYEQLRDIAI	DNICRCLKAG	LTVDPVIVEA	FLASLSNRLY
ISQESDKDAH	LIPDHTIRAL	GHIAVALRDT	PKVMEPILQI	LQQKFCQPPS
PLDVLIIDQL	GCLVITGNQY	IYQEVWNLFQ	QISVKASSVV	YSATKDYKDH
GYRHCSLAVI	NALANIAANI	QDEHLVDELL	MNLLELFVQL	GLEGKRASER
ASEKGPALKA	SSSAGNLGVL	IPVIAVLTRR	LPPIKEAKPR	LQKLFRDFWL
YSVLMGFAVE	GSGLWPEEWY	EGVCEIATKS	PLLTFPSKEP	LRSVLQYNSA
MKNDTVTPAE	LSELRSTIIN	LLDPPPEVSA	LINKLDFAMS	TYLLSVYRLE
YMRVLRSTDP	DRFQVMFCYF	EDKAIQKDKS	GMMQCVIAVA	DKVFDAFLNM
MADKAKTKEN	EEELERHAQF	LLVNFNHIHK	RIRRVADKYL	SGLVDKFPHL
LWSGTVLKTM	LDILQTLSLS	LSADIHKDQP	YYDIPDAPYR	ITVPDTYEAR
ESIVKDFAAR	CGMILQEAMK	WAPTVTKSHL	QEYLNKHQNW	VSGLSQHTGL
AMATESILHF	AGYNKQNTTL	GATQLSERPA	CVKKDYSNFM	ASLNLRNRYA
GEVYGMIRFS	GTTGQMSDLN	KMMVQDLHSA	LDRSHPQHYT	QAMFKLTAML
ISSKDCDPQL	LHHLCWGPLR	MFNEHGMETA	LACWEWLLAG	KDGVEVPFMR
EMAGAWHMTV	EQKFGLFSAE	IKEADPLAAS	EASQPKPCPP	EVTPHYIWID
FLVQRFEIAK	YCSSDQVEIF	SSLLQRSMSL	NIGGAKGSMN	RHVAAIGPRF
KLLTLGLSLL	HADVVPNATI	RNVLREKIYS	TAFDYFSCPP	KFPTQGEKRL
REDISIMIKF	WTAMFSDKKY	LTASQLVPPD	NQDTRSNLDI	TVGSRQQATQ
GWINTYPLSS	GMSTISKKSG	MSKKTNRGSQ	LHKYYMKRRT	LLLSLLATEI
ERLITWYNPL	SAPELELDQA	GENSVANWRS	KYISLSEKQW	KDNVNLAWSI
SPYLAVQLPA	RFKNTEAIGN	EVTRLVRLDP	GAVSDVPEAI	KFLVTWHTID
ADAPELSHVL	CWAPTDPPTG	LSYFSSMYPP	HPLTAQYGVK	VLRSFPPDAI
LFYIPQIVQA	LRYDKMGYVR	EYILWAASKS	QLLAHQFIWN	MKTNIYLDEE
GHQKDPDIGD	LLDQLVEEIT	GSLSGPAKDF	YQREFDFFNK	ITNVSAIIKP
YPKGDERKKA	CLSALSEVKV	QPGCYLPSNP	EAIVLDIDYK	SGTPMQSAAK
APYLAKFKVK	RCGVSELEKE	GLRCRSDSED	ECSTQEADGQ	KISWQAAIFK
VGDDCRQDML	ALQIIDLFKN	IFQLVGLDLF	VFPYRVVATA	PGCGVIECIP
DCTSRDQLGR	QTDFGMYDYF	TRQYGDESTL	AFQQARYNFI	RSMAAYSLLL
FLLQIKDRHN	GNIMLDKKGH	IIHIDFGFMF	ESSPGGNLGW	EPDIKLTDEM
VMIMGGKMEA	TPFKWFMEMC	VRGYLAVRPY	MDAVVSLVTL	MLDTGLPCFR
GQTIKLLKHR	FSPNMTEREA	ANFIMKVIQS	CFLSNRSRTY	DMIQYYQNDI
PY

Funkcija uredi

Ovaj gen kodira 1-fosfatidilinozitol 4-kinazu koja katalizira prvi posvećeni korak u biosintezi fosfatidilinozitol 4,5-bisfosfata. PI 4-kinaze kod sisara klasifikovane su u dva tipa, II i III, na osnovu njihove molekulske mase i modulacije deterdžentnim i adenozinom. Za ovaj gen su opisane dvije varijante transkripta koje kodiraju različite izoforme.^[7]

Klinički značaj uredi

Alfa izoforma PI4KIII ima ulogu u replikaciji virusa hepatitisa C (HCV).^[8] Zatim, PI4KA lipidna kinaza utiče na replikaciju HCV mijenjajući fosforilaciju HCV-ovog proteina NS5A.^[9]

Reference uredi

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000241973 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000041720 - 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.
^ Wong K, Cantley LC (Dec 1994). "Cloning and characterization of a human phosphatidylinositol 4-kinase". J Biol Chem. 269 (46): 28878–84. doi:10.1016/S0021-9258(19)61989-7. PMID 7961848.
^ Nakagawa T, Goto K, Kondo H (Aug 1996). "Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase". J Biol Chem. 271 (20): 12088–94. doi:10.1074/jbc.271.20.12088. PMID 8662589.
^ ^a ^b ^c "Entrez Gene: PIK4CA phosphatidylinositol 4-kinase, catalytic, alpha polypeptide".
^ Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R (January 2011). "Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment". Cell Host Microbe. 9 (1): 32–45. doi:10.1016/j.chom.2010.12.002. PMC 3433060. PMID 21238945.
^ Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V (May 2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLOS Pathog. 9 (5): e1003359. doi:10.1371/journal.ppat.1003359. PMC 3649985. PMID 23675303.

Dopunska literatura uredi

Gehrmann T, Heilmeyer LM (1998). "Phosphatidylinositol 4-kinases". Eur. J. Biochem. 253 (2): 357–70. doi:10.1046/j.1432-1327.1998.2530357.x. PMID 9654085.
Graziani A, Ling LE, Endemann G, et al. (1992). "Purification and characterization of human erythrocyte phosphatidylinositol 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate 4-kinase are distinct enzymes". Biochem. J. 284 (Pt 1): 39–45. doi:10.1042/bj2840039. PMC 1132694. PMID 1318025.
Kauffmann-Zeh A, Thomas GM, Ball A, et al. (1995). "Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling". Science. 268 (5214): 1188–90. doi:10.1126/science.7761838. PMID 7761838.
Prasad KV, Kapeller R, Janssen O, et al. (1994). "Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". Mol. Cell. Biol. 13 (12): 7708–17. doi:10.1128/mcb.13.12.7708. PMC 364842. PMID 8246987.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Berditchevski F, Chang S, Bodorova J, Hemler ME (1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". J. Biol. Chem. 272 (46): 29174–80. doi:10.1074/jbc.272.46.29174. PMID 9360995.
Gehrmann T, Gülkan H, Suer S, et al. (1999). "Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230". Biochim. Biophys. Acta. 1437 (3): 341–56. doi:10.1016/s1388-1981(99)00029-3. PMID 10101268.
Huang C, Handlogten ME, Miller RT (2002). "Parallel activation of phosphatidylinositol 4-kinase and phospholipase C by the extracellular calcium-sensing receptor". J. Biol. Chem. 277 (23): 20293–300. doi:10.1074/jbc.M200831200. PMID 11907035.
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.
Subrahmanyam G, Rudd CE, Schneider H (2003). "Association of T cell antigen CD7 with type II phosphatidylinositol-4 kinase, a key component in pathways of inositol phosphate turnover". Eur. J. Immunol. 33 (1): 46–52. doi:10.1002/immu.200390006. PMID 12594831. S2CID 26388891.
Carloni V, Mazzocca A, Ravichandran KS (2004). "Tetraspanin CD81 is linked to ERK/MAPKinase signaling by Shc in liver tumor cells". Oncogene. 23 (8): 1566–74. doi:10.1038/sj.onc.1207287. PMID 14676841.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ahn J, Chung KS, Kim DU, et al. (2005). "Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus". J. Biochem. Mol. Biol. 37 (6): 741–8. doi:10.5483/bmbrep.2004.37.6.741. PMID 15607035.
Weixel KM, Blumental-Perry A, Watkins SC, et al. (2005). "Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases". J. Biol. Chem. 280 (11): 10501–8. doi:10.1074/jbc.M414304200. PMID 15634669.
Israels SJ, McMillan-Ward EM (2005). "CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen". Thromb. Haemost. 93 (2): 311–8. doi:10.1160/TH04-08-0503. PMID 15711748.
Waugh MG, Minogue S, Chotai D, et al. (2006). "Lipid and peptide control of phosphatidylinositol 4-kinase IIalpha activity on Golgi-endosomal Rafts". J. Biol. Chem. 281 (7): 3757–63. doi:10.1074/jbc.M506527200. PMID 16249177.
Israels SJ, McMillan-Ward EM (2005). "CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen". Thromb. Haemost. 93 (2): 311–8. doi:10.1160/TH04-08-0503. PMID 15711748.
Reiss S, et al. (2011). "Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment". Cell Host Microbe. 9 (1): 32–45. doi:10.1016/j.chom.2010.12.002. PMC 3433060. PMID 21238945.
Reiss S, et al. (2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLOS Pathog. 9 (5): e1003359. doi:10.1371/journal.ppat.1003359. PMC 3649985. PMID 23675303.

Vanjski linkovi uredi

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000241973 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000041720 - 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.

[pmid7961848-5] Wong K, Cantley LC (Dec 1994). "Cloning and characterization of a human phosphatidylinositol 4-kinase". J Biol Chem. 269 (46): 28878–84. doi:10.1016/S0021-9258(19)61989-7. PMID 7961848.

[pmid8662589-6] Nakagawa T, Goto K, Kondo H (Aug 1996). "Cloning, expression, and localization of 230-kDa phosphatidylinositol 4-kinase". J Biol Chem. 271 (20): 12088–94. doi:10.1074/jbc.271.20.12088. PMID 8662589.

[entrez-7] "Entrez Gene: PIK4CA phosphatidylinositol 4-kinase, catalytic, alpha polypeptide".

[pmid21238945-8] Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R (January 2011). "Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment". Cell Host Microbe. 9 (1): 32–45. doi:10.1016/j.chom.2010.12.002. PMC 3433060. PMID 21238945.

[pmid23675303-9] Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V (May 2013). "The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A". PLOS Pathog. 9 (5): e1003359. doi:10.1371/journal.ppat.1003359. PMC 3649985. PMID 23675303.

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