JAK1

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JAK1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

3EYG, 3EYH, 4E4L, 4E4N, 4E5W, 4EHZ, 4EI4, 4FK6, 4I5C, 4IVB, 4IVC, 4IVD, 4K6Z, 4K77, 4L00, 4L01, 5E1E, 5HX8, 5IXD, 5IXI

Identifikatori
AliasiJAK1
Vanjski ID-jeviOMIM: 147795 MGI: 96628 HomoloGene: 1678 GeneCards: JAK1
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za JAK1
Genomska lokacija za JAK1
Bend1p31.3Početak64,833,229 bp[1]
Kraj65,067,754 bp[1]
Lokacija gena (miš)
Hromosom 4 (miš)
Hrom.Hromosom 4 (miš)[2]
Hromosom 4 (miš)
Genomska lokacija za JAK1
Genomska lokacija za JAK1
Bend4 C6|4 46.19 cMPočetak101,152,367 bp[2]
Kraj101,265,282 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• aktivnost sa transferazom
• nucleotide binding
• protein kinase activity
• CCR5 chemokine receptor binding
• growth hormone receptor binding
• vezivanje iona metala
• kinase activity
• GO:0001948, GO:0016582 vezivanje za proteine
• protein tyrosine kinase activity
• protein phosphatase binding
• signaling receptor binding
• ATP binding
• ubiquitin protein ligase binding
• non-membrane spanning protein tyrosine kinase activity
Ćelijska komponenta• citoplazma
• citosol
• membrana
• focal adhesion
• extrinsic component of cytoplasmic side of plasma membrane
• citoskelet
• Endomembranski sistem
• jedro
• endozom
Biološki proces• Ćelijska diferencijacija
• GO:0007243 intracellular signal transduction
• Fosforilacija
• transmembrane receptor protein tyrosine kinase signaling pathway
• interferon-gamma-mediated signaling pathway
• GO:1904576 response to antibiotic
• MAPK cascade
• positive regulation of sprouting angiogenesis
• protein phosphorylation
• regulation of type I interferon-mediated signaling pathway
• regulation of interferon-gamma-mediated signaling pathway
• regulation of cell population proliferation
• type I interferon signaling pathway
• interleukin-2-mediated signaling pathway
• peptidyl-tyrosine autophosphorylation
• protein autophosphorylation
• Ćelijska migracija
• Urođeni imunski sistem
• interleukin-12-mediated signaling pathway
• interleukin-7-mediated signaling pathway
• interleukin-15-mediated signaling pathway
• interleukin-9-mediated signaling pathway
• regulation of molecular function
• peptidyl-tyrosine phosphorylation
• cytokine-mediated signaling pathway
• interleukin-21-mediated signaling pathway
• interleukin-6-mediated signaling pathway
• interleukin-27-mediated signaling pathway
• interleukin-35-mediated signaling pathway
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

3716

16451

Ensembl

ENSG00000162434

ENSMUSG00000028530

UniProt

P23458

P52332

RefSeq (mRNK)
NM_002227
NM_001320923
NM_001321852
NM_001321853
NM_001321854

NM_001321855
NM_001321856
NM_001321857

NM_146145
NM_013567

RefSeq (bjelančevina)
NP_001307852
NP_001308781
NP_001308782
NP_001308783
NP_001308784

NP_001308785
NP_001308786
NP_002218

n/a

Lokacija (UCSC)Chr 1: 64.83 – 65.07 MbChr 4: 101.15 – 101.27 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Janus-kinaza 1 jest enzim koji je kod ljudi kodiran genom JAK1 sa hromosoma 1.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 1.154 aminokiseline, a molekulska težina 133.277 Da.[5]

1020304050
MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRL
GSGEYTAEELCIRAAQACRISPLCHNLFALYDENTKLWYAPNRTITVDDK
MSLRLHYRMRFYFTNWHGTNDNEQSVWRHSPKKQKNGYEKKKIPDATPLL
DASSLEYLFAQGQYDLVKCLAPIRDPKTEQDGHDIENECLGMAVLAISHY
AMMKKMQLPELPKDISYKRYIPETLNKSIRQRNLLTRMRINNVFKDFLKE
FNNKTICDSSVSTHDLKVKYLATLETLTKHYGAEIFETSMLLISSENEMN
WFHSNDGGNVLYYEVMVTGNLGIQWRHKPNVVSVEKEKNKLKRKKLENKH
KKDEEKNKIREEWNNFSYFPEITHIVIKESVVSINKQDNKKMELKLSSHE
EALSFVSLVDGYFRLTADAHHYLCTDVAPPLIVHNIQNGCHGPICTEYAI
NKLRQEGSEEGMYVLRWSCTDFDNILMTVTCFEKSEQVQGAQKQFKNFQI
EVQKGRYSLHGSDRSFPSLGDLMSHLKKQILRTDNISFMLKRCCQPKPRE
ISNLLVATKKAQEWQPVYPMSQLSFDRILKKDLVQGEHLGRGTRTHIYSG
TLMDYKDDEGTSEEKKIKVILKVLDPSHRDISLAFFEAASMMRQVSHKHI
VYLYGVCVRDVENIMVEEFVEGGPLDLFMHRKSDVLTTPWKFKVAKQLAS
ALSYLEDKDLVHGNVCTKNLLLAREGIDSECGPFIKLSDPGIPITVLSRQ
ECIERIPWIAPECVEDSKNLSVAADKWSFGTTLWEICYNGEIPLKDKTLI
EKERFYESRCRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEE
QNPDIVSEKKPATEVDPTHFEKRFLKRIRDLGEGHFGKVELCRYDPEGDN
TGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGN
GIKLIMEFLPSGSLKEYLPKNKNKINLKQQLKYAVQICKGMDYLGSRQYV
HRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVKDDRDSPVFWYAP
ECLMQSKFYIASDVWSFGVTLHELLTYCDSDSSPMALFLKMIGPTHGQMT
VTRLVNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFE
ALLK

Funkcija[uredi | uredi izvor]

Janus-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[uredi | uredi izvor]

Pokazalo se da je Janus-kinaza 1 u interakciji sa:

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162434 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028530 - 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.
  5. ^ "UniProt, P23458" (jezik: eng.). Pristupljeno 29. 11. 2021.CS1 održavanje: nepoznati jezik (link)
  6. ^ Gadina M, Hilton D, Johnston JA, Morinobu A, Lighvani A, Zhou YJ, Visconti R, O'Shea JJ (2001). "Signaling by type I and II cytokine receptors: ten years after". Curr. Opin. Immunol. 13 (3): 363–73. doi:10.1016/S0952-7915(00)00228-4. PMID 11406370.
  7. ^ Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KC, Yin L, Pennica D, Johnson EM, Schreiber RD (1998). "Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses". Cell. 93 (3): 373–83. doi:10.1016/S0092-8674(00)81166-6. PMID 9590172. S2CID 18684846.
  8. ^ Christian Nordqvist. "Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out Of A Tumor". Medical News Today.
  9. ^ Collum RG, Brutsaert S, Lee G, Schindler C (august 2000). "A Stat3-interacting protein (StIP1) regulates cytokine signal transduction". Proc. Natl. Acad. Sci. U.S.A. 97 (18): 10120–5. Bibcode:2000PNAS...9710120C. doi:10.1073/pnas.170192197. PMC 27739. PMID 10954736.
  10. ^ Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici OR (septembar 2003). "The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex". J. Immunol. 171 (6): 2989–94. doi:10.4049/jimmunol.171.6.2989. PMID 12960323.
  11. ^ Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, Grötzinger J, Behrmann I (oktobar 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. 276 (40): 37451–8. doi:10.1074/jbc.M106135200. PMID 11468294.
  12. ^ Kim H, Baumann H (decembar 1997). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. 272 (49): 30741–7. doi:10.1074/jbc.272.49.30741. PMID 9388212.
  13. ^ Haan C, Heinrich PC, Behrmann I (januar 2002). "Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation". Biochem. J. 361 (Pt 1): 105–11. doi:10.1042/0264-6021:3610105. PMC 1222284. PMID 11742534.
  14. ^ Kim H, Lee YH, Won J, Yun Y (septembar 2001). "Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers". Biochem. Biophys. Res. Commun. 286 (5): 886–94. doi:10.1006/bbrc.2001.5496. PMID 11527382.
  15. ^ 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.
  16. ^ a b Usacheva A, Kotenko S, Witte MM, Colamonici OR (august 2002). "Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors". J. Immunol. 169 (3): 1302–8. doi:10.4049/jimmunol.169.3.1302. PMID 12133952.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, Mann M, Lodish HF (decembar 2000). "Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways". J. Biol. Chem. 275 (49): 38633–9. doi:10.1074/jbc.M007849200. PMID 10993906.
  27. ^ Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K (juli 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Lett. 477 (1–2): 55–61. doi:10.1016/s0014-5793(00)01760-9. PMID 10899310.
  28. ^ 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.
  29. ^ 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.
  30. ^ 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.
  31. ^ 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.
  32. ^ Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, Garaci F, Zauli G, Bonvini E, Di Baldassarre A (januar 2002). "Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells". Cell Growth Differ. 13 (1): 13–8. PMID 11801527.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]


Šablon:Modulator citokinskih receptora

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