JAK1
Janus-kinaza 1 jest enzim koji je kod ljudi kodiran genom JAK1 sa hromosoma 1.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.154 aminokiseline, a molekulska težina 133.277 Da.[5]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MQYLNIKEDC | NAMAFCAKMR | SSKKTEVNLE | APEPGVEVIF | YLSDREPLRL | ||||
GSGEYTAEEL | CIRAAQACRI | SPLCHNLFAL | YDENTKLWYA | PNRTITVDDK | ||||
MSLRLHYRMR | FYFTNWHGTN | DNEQSVWRHS | PKKQKNGYEK | KKIPDATPLL | ||||
DASSLEYLFA | QGQYDLVKCL | APIRDPKTEQ | DGHDIENECL | GMAVLAISHY | ||||
AMMKKMQLPE | LPKDISYKRY | IPETLNKSIR | QRNLLTRMRI | NNVFKDFLKE | ||||
FNNKTICDSS | VSTHDLKVKY | LATLETLTKH | YGAEIFETSM | LLISSENEMN | ||||
WFHSNDGGNV | LYYEVMVTGN | LGIQWRHKPN | VVSVEKEKNK | LKRKKLENKH | ||||
KKDEEKNKIR | EEWNNFSYFP | EITHIVIKES | VVSINKQDNK | KMELKLSSHE | ||||
EALSFVSLVD | GYFRLTADAH | HYLCTDVAPP | LIVHNIQNGC | HGPICTEYAI | ||||
NKLRQEGSEE | GMYVLRWSCT | DFDNILMTVT | CFEKSEQVQG | AQKQFKNFQI | ||||
EVQKGRYSLH | GSDRSFPSLG | DLMSHLKKQI | LRTDNISFML | KRCCQPKPRE | ||||
ISNLLVATKK | AQEWQPVYPM | SQLSFDRILK | KDLVQGEHLG | RGTRTHIYSG | ||||
TLMDYKDDEG | TSEEKKIKVI | LKVLDPSHRD | ISLAFFEAAS | MMRQVSHKHI | ||||
VYLYGVCVRD | VENIMVEEFV | EGGPLDLFMH | RKSDVLTTPW | KFKVAKQLAS | ||||
ALSYLEDKDL | VHGNVCTKNL | LLAREGIDSE | CGPFIKLSDP | GIPITVLSRQ | ||||
ECIERIPWIA | PECVEDSKNL | SVAADKWSFG | TTLWEICYNG | EIPLKDKTLI | ||||
EKERFYESRC | RPVTPSCKEL | ADLMTRCMNY | DPNQRPFFRA | IMRDINKLEE | ||||
QNPDIVSEKK | PATEVDPTHF | EKRFLKRIRD | LGEGHFGKVE | LCRYDPEGDN | ||||
TGEQVAVKSL | KPESGGNHIA | DLKKEIEILR | NLYHENIVKY | KGICTEDGGN | ||||
GIKLIMEFLP | SGSLKEYLPK | NKNKINLKQQ | LKYAVQICKG | MDYLGSRQYV | ||||
HRDLAARNVL | VESEHQVKIG | DFGLTKAIET | DKEYYTVKDD | RDSPVFWYAP | ||||
ECLMQSKFYI | ASDVWSFGVT | LHELLTYCDS | DSSPMALFLK | MIGPTHGQMT | ||||
VTRLVNTLKE | GKRLPCPPNC | PDEVYQLMRK | CWEFQPSNRT | SFQNLIEGFE | ||||
ALLK |
Funkcija
urediJanus-kinaza je ljudska tirozin-kinaza, protein neophodan za signalizaciju određenih tipova I i tipa II citokina. Stupa u interakciju sa zajedničkim gama lancem (γc) citokinskog receptora tipa I, da izazove signale iz porodice IL-2 receptora (npr. IL -2R, IL-7R, IL-9R i IL-15R), IL-4 porodica receptora (npr. IL-4R i IL-13R), porodica gp130 receptora (npr. IL-6R , IL-11R, LIF-R, OSM-R, kardiotrofin-1 receptor (CT-1R), cilijarni neurotrofni faktor receptor (CNTF-R), neurotrofin-1 receptor (NNT-1R) i leptin-R). Također je važan za transdukciju signala po tipu I (IFN-α/β) i tipu II (IFN-γ) interferona, i članovima porodice IL-10 preko citokinskih receptora tipa II.[6] Jak1 ima ključnu ulogu u pokretanju odgovora na višestruke velike porodice citokinskih receptora. Gubitak Jak1 je smrtonosan kod neonatusih miševa, vjerovatno zbog poteškoća u sisanju.[7] Ekspresija gena JAK1 u ćelijama raka omogućava pojedinačnim ćelijama da se kontrahuju, potencijalno im omogućavajući da pobegnu od tumora i metastaziraju u druge dijelove tijela.[8]
Interakcije
urediPokazalo se da je Janus-kinaza 1 u interakciji sa:
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000162434 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028530 - 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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- ^ Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (decembar 1995). "Involvement of Janus kinases in the insulin signaling pathway". Eur. J. Biochem. 234 (2): 656–60. doi:10.1111/j.1432-1033.1995.656_b.x. PMID 8536716.
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- ^ Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN (novembar 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science. 266 (5187): 1045–7. Bibcode:1994Sci...266.1045M. doi:10.1126/science.7973659. PMID 7973659.
- ^ Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (novembar 1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science. 266 (5187): 1042–5. Bibcode:1994Sci...266.1042R. doi:10.1126/science.7973658. PMID 7973658.
- ^ Zhu MH, Berry JA, Russell SM, Leonard WJ (april 1998). "Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta". J. Biol. Chem. 273 (17): 10719–25. doi:10.1074/jbc.273.17.10719. PMID 9553136.
- ^ Migone TS, Rodig S, Cacalano NA, Berg M, Schreiber RD, Leonard WJ (novembar 1998). "Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation". Mol. Cell. Biol. 18 (11): 6416–22. doi:10.1128/mcb.18.11.6416. PMC 109227. PMID 9774657.
- ^ Gual P, Baron V, Lequoy V, Van Obberghen E (mart 1998). "Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor". Endocrinology. 139 (3): 884–93. doi:10.1210/endo.139.3.5829. PMID 9492017.
- ^ Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, Pierce JH, O'Shea JJ (decembar 1995). "Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases". J. Biol. Chem. 270 (48): 28527–30. doi:10.1074/jbc.270.48.28527. PMID 7499365.
- ^ Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, Colamonici OR (decembar 2002). "Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation". J. Biol. Chem. 277 (50): 48220–6. doi:10.1074/jbc.M205757200. PMID 12374810.
- ^ Yin T, Shen R, Feng GS, Yang YC (januar 1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. 272 (2): 1032–7. doi:10.1074/jbc.272.2.1032. PMID 8995399.
- ^ Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F (januar 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. doi:10.1074/jbc.M210552200. PMID 12403768.
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- ^ Ueda T, Bruchovsky N, Sadar MD (mart 2002). "Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways". J. Biol. Chem. 277 (9): 7076–85. doi:10.1074/jbc.M108255200. PMID 11751884.
- ^ Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F (august 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia". Eur. J. Haematol. 67 (2): 63–71. doi:10.1034/j.1600-0609.2001.t01-1-00385.x. PMID 11722592. S2CID 38074766.
- ^ a b Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T (februar 1997). "An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT". Oncogene. 14 (7): 751–61. doi:10.1038/sj.onc.1200907. PMID 9047382.
- ^ Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (mart 1998). "Induction of Jak/STAT signaling by activation of the type 1 TNF receptor". J. Immunol. 160 (6): 2742–50. PMID 9510175.
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Dopunska literatura
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- Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (1996). "Involvement of Janus kinases in the insulin signaling pathway". Eur. J. Biochem. 234 (2): 656–60. doi:10.1111/j.1432-1033.1995.656_b.x. PMID 8536716.
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- Yin T, Shen R, Feng GS, Yang YC (1997). "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. 272 (2): 1032–7. doi:10.1074/jbc.272.2.1032. PMID 8995399.
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Vanjski linkovi
uredi- Janus Kinase 1 na US National Library of Medicine Medical Subject Headings (MeSH)