ITPK1

ITPK1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2Q7D, 2ODT, 2QB5
Identifikatori
Aliasi	ITPK1
Vanjski ID-jevi	OMIM: 601838 MGI: 2446159 HomoloGene: 8588 GeneCards: ITPK1
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	93,116,320 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	102,671,189 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • isomerase activity; • vezivanje iona metala; • kinase activity; • inositol-1,3,4,5,6-pentakisphosphate 1-phosphatase activity; • catalytic activity; • inositol-1,3,4,6-tetrakisphosphate 6-phosphatase activity; • inositol-1,3,4,6-tetrakisphosphate 1-phosphatase activity; • inositol-3,4,6-trisphosphate 1-kinase activity; • ATP binding; • hydrolase activity; • magnesium ion binding; • inositol-1,3,4-trisphosphate 6-kinase activity; • inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity; • inositol-1,3,4-trisphosphate 5-kinase activity; • inositol tetrakisphosphate 1-kinase activity; • inositol tetrakisphosphate 6-kinase activity;
Ćelijska komponenta	• citosol; • intracellular anatomical structure; • apical plasma membrane; • citoplazma;
Biološki proces	• Fosforilacija; • Koagulacija (krv); • inositol phosphate metabolic process; • inositol trisphosphate metabolic process; • neural tube development; • GO:0072468 Transdukcija signala; • GO:0098501, GO:0098502, GO:0006286 Defosforilacija; • GO:0060554, GO:0060555 necroptosis; • inositol phosphorylation;
	Izvori:Amigo / QuickGO
Ortolozi
	3705
	217837
	ENSG00000100605; ENSG00000274958
	ENSMUSG00000057963
	Q13572
	Q8BYN3
	NM_014216; NM_001142593; NM_001142594; NM_001363707
	NM_172584
	NP_001136065; NP_001136066; NP_055031; NP_001350636
	NP_766172
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Inozitol-tetrakisfosfat 1-kinaza je enzim koji je kod ljudi kodiran genom ITPK1.^[5]^[6]^[7]

Gross (2014) mapirao je je gen ITPK1 u hromosomskoj poziciji 14q32.12, na osnovu poravnvaanja sekvence ITPK1 (GenBank AF279372) sa genomskom sekvencom (GRCh38).^[8] Uključen je u signalne puteve inozitola, koji regulišu provodljivost kalcijem aktiviranih hloridnih kanala, i zato bi mogao biti relevantan u proučavanju cistaste fibroze.^[9]^[10]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 414 aminokiselina, a molekulska težina 45 621 Da.^[11].

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

10	20	30	40	50
MQTFLKGKRV	GYWLSEKKIK	KLNFQAFAEL	CRKRGMEVVQ	LNLSRPIEEQ
GPLDVIIHKL	TDVILEADQN	DSQSLELVHR	FQEYIDAHPE	TIVLDPLPAI
RTLLDRSKSY	ELIRKIEAYM	EDDRICSPPF	MELTSLCGDD	TMRLLEKNGL
TFPFICKTRV	AHGTNSHEMA	IVFNQEGLNA	IQPPCVVQNF	INHNAVLYKV
FVVGESYTVV	QRPSLKNFSA	GTSDRESIFF	NSHNVSKPES	SSVLTELDKI
EGVFERPSDE	VIRELSRALR	QALGVSLFGI	DIIINNQTGQ	HAVIDINAFP
GYEGVSEFFT	DLLNHIATVL	QGQSTAMAAT	GDVALLRHSK	LLAEPAGGLV
GERTCSASPG	CCGSMMGQDA	PWKAEADAGG	TAKLPHQRLG	CNAGVSPSFQ
QHCVASLATK	ASSQ

Kloniranje i ekspresija[uredi | uredi izvor]

Na osnovu sekvence goveđeg peptida, Wilson i Majerus (1996) pronašli su ljudski EST koji odgovara genu za inozitol 1,3,4-trisfosfat 5/6-kinazu (ITRPK1). Koristili su ovaj EST za kloniranje cDNK ITRPK1 iz biblioteke cDNK mozga ljudskog fetusa. Ova cDNK kodira polipeptid od 414 aminokiselina. Northern blot analiza otkrila je da je ITRPK1 eksprimiran kao poruka od 3,6 kb u svim testiranim tkivima, sa najvišim nivoima u mozgu. Ekspresija cDNK rezultirala je aktivnošću inozitol 1,3,4-trisfosfat 5/6-kinaze, pokazujući da pojedinačna kinaza fosforilira inozitol i u položaju D5 i D6.^[12]

Pretragom baze podataka pomoću sekvence ITPK1 za identifikaciju enzima sa aktivnošću 1-kinaze, Yang i Shears (2000) također su dobili cDNK koja kodira ITPK1, ali sa serinom koji zamjenjuje asparagin-356. Funkcionalna analiza pokazala je da varijanta, koju su nazvali protein tipa proteina, kao i protein sa asn356, koji su nazvali protein tip alfa, fosforilira ne samo 5- i 6-hidroksi grupe Ins (1,3,4 ) P3, nego tkođer i 1-hidroksi grupu Ins (3,4,5,6) P4, što sugerira da se dva inozitol fosfata nadmeću za fosforilaciju in vivo. Zaključili su da je ista kinaza zadužena za izvođenje konkurentskih aktivnosti koje istovremeno aktiviraju i deaktiviraju signalni put.^[13]

Reference[uredi | uredi izvor]

^ ^a ^b ^c ENSG00000274958 GRCh38: Ensembl release 89: ENSG00000100605, ENSG00000274958 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000057963 - 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.
^ Wilson MP, Majerus PW (Aug 1996). "Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme". J Biol Chem. 271 (20): 11904–10. doi:10.1074/jbc.271.20.11904. PMID 8662638.
^ Yang X, Shears SB (Jan 2001). "Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase". Biochem J. 351 (3): 551–5. doi:10.1042/0264-6021:3510551. PMC 1221393. PMID 11042108.
^ "Entrez Gene: ITPK1 inositol 1,3,4-triphosphate 5/6 kinase".
^ Gross, M. B. Personal Communication. Baltimore, Md. 7/25/2014.
^ Saiardi A, Cockcroft S (2008). "Human ITPK1: a reversible inositol phosphate kinase/phosphatase that links receptor-dependent phospholipase C to Ca2+-activated chloride channels". Sci Signal. 1 (4): pe5. doi:10.1126/stke.14pe5. PMID 18272466.
^ Chamberlain PP, Qian X, Stiles AR, Cho J, Jones DH, Lesley SA, Grabau EA, Shears SB, Spraggon G (septembar 2007). "Integration of inositol phosphate signaling pathways via human ITPK1". J. Biol. Chem. 282 (38): 28117–25. doi:10.1074/jbc.M703121200. PMC 2244811. PMID 17616525.
^ "UniProt, Q13572". Pristupljeno 26. 7. 2021.
^ Wilson, M. P., Majerus, P. W. Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning, and expression of the recombinant enzyme. J. Biol. Chem. 271: 11904-11910, 1996. PubMed: 8662638
^ Yang, X., Shears, S. B. Multitasking in signal transduction by a promiscuous human ins(3,4,5,6)P4 1-kinase/Ins(1,3,4)P3 5/6-kinase. Biochem. J. 351: 551-555, 2000. PubMed: 11042108

Dopunska literatura[uredi | uredi izvor]

Wilson MP, Sun Y, Cao L, Majerus PW (2001). "Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates the transcription factors c-Jun and ATF-2". J. Biol. Chem. 276 (44): 40998–1004. doi:10.1074/jbc.M106605200. PMID 11533064.
Ho MW, Yang X, Carew MA, et al. (2002). "Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase". Curr. Biol. 12 (6): 477–82. doi:10.1016/S0960-9822(02)00713-3. PMID 11909533.
Sun Y, Wilson MP, Majerus PW (2003). "Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1". J. Biol. Chem. 277 (48): 45759–64. doi:10.1074/jbc.M208709200. PMID 12324474.
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.
Sun Y, Mochizuki Y, Majerus PW (2003). "Inositol 1,3,4-trisphosphate 5/6-kinase inhibits tumor necrosis factor-induced apoptosis". J. Biol. Chem. 278 (44): 43645–53. doi:10.1074/jbc.M300674200. PMID 12925536.
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.
Qian X, Mitchell J, Wei SJ, et al. (2005). "The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein kinase". Biochem. J. 389 (Pt 2): 389–95. doi:10.1042/BJ20050297. PMC 1175116. PMID 15762844.
Miller GJ, Wilson MP, Majerus PW, Hurley JH (2005). "Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase". Mol. Cell. 18 (2): 201–12. doi:10.1016/j.molcel.2005.03.016. PMID 15837423.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.

Vanjski linkovi[uredi | uredi izvor]

[refGRCh38Ensembl-1] ENSG00000274958 GRCh38: Ensembl release 89: ENSG00000100605, ENSG00000274958 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000057963 - 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.

[pmid8662638-5] Wilson MP, Majerus PW (Aug 1996). "Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme". J Biol Chem. 271 (20): 11904–10. doi:10.1074/jbc.271.20.11904. PMID 8662638.

[pmid11042108-6] Yang X, Shears SB (Jan 2001). "Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase". Biochem J. 351 (3): 551–5. doi:10.1042/0264-6021:3510551. PMC 1221393. PMID 11042108.

[entrez-7] "Entrez Gene: ITPK1 inositol 1,3,4-triphosphate 5/6 kinase".

[8] Gross, M. B. Personal Communication. Baltimore, Md. 7/25/2014.

[pmid18272466-9] Saiardi A, Cockcroft S (2008). "Human ITPK1: a reversible inositol phosphate kinase/phosphatase that links receptor-dependent phospholipase C to Ca2+-activated chloride channels". Sci Signal. 1 (4): pe5. doi:10.1126/stke.14pe5. PMID 18272466.

[pmid17616525-10] Chamberlain PP, Qian X, Stiles AR, Cho J, Jones DH, Lesley SA, Grabau EA, Shears SB, Spraggon G (septembar 2007). "Integration of inositol phosphate signaling pathways via human ITPK1". J. Biol. Chem. 282 (38): 28117–25. doi:10.1074/jbc.M703121200. PMC 2244811. PMID 17616525.

[UniProt-11] "UniProt, Q13572". Pristupljeno 26. 7. 2021.

[12] Wilson, M. P., Majerus, P. W. Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning, and expression of the recombinant enzyme. J. Biol. Chem. 271: 11904-11910, 1996. PubMed: 8662638

[13] Yang, X., Shears, S. B. Multitasking in signal transduction by a promiscuous human ins(3,4,5,6)P4 1-kinase/Ins(1,3,4)P3 5/6-kinase. Biochem. J. 351: 551-555, 2000. PubMed: 11042108

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