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JAK1 (Janus kinase 1)

Written2009-09Laurent Knoops, Tekla Hornakova, Jean-Christophe Renauld
Hematology unit, Cliniques Universitaires Saint-Luc (LK); Ludwig Institute for Cancer Research de Duve Institute, Université Catholique de Louvain, Avenue Hippocrate 74, B-1200 Brussels, Belgium (LK, TH, JCR)

(Note : for Links provided by Atlas : click)

Identity

Other aliasEC 2.7.10.2
JAK-1
JAK1A
JAK1B
JTK3
LocusID (NCBI) 3716
Atlas_Id 41031
Location 1p31.3  [Link to chromosome band 1p31]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
JAK1 (1p31.3) / ATF3 (1q32.3)JAK1 (1p31.3) / HSD11B1 (1q32.2)JAK1 (1p31.3) / JAK1 (1p31.3)
NSRP1 (17q11.2) / JAK1 (1p31.3)PA2G4 (12q13.2) / JAK1 (1p31.3)PDE4B (1p31.3) / JAK1 (1p31.3)
SCARB2 (4q21.1) / JAK1 (1p31.3)SH3BGRL (Xq21.1) / JAK1 (1p31.3)SMOC1 (14q24.2) / JAK1 (1p31.3)

DNA/RNA

Description 25 exons spanning roughly 135 kb of genomic DNA.
Transcription 5053 bp pre-mRNA; 1 transcript described.

Protein

Description 1154 amino acids; 133,3 kDa; JAK1 contains a N-terminal FERM domain, responsible of the binding to the receptor, a central Src homology 2 (SH2) domain, and two C-terminal domains: a tyrosine kinase domain JH1 and a pseudokinase domain JH2.
Expression Ubiquitous.
Localisation Intracellular, associated to cytokine receptors.
Function JAK1 is a non-receptor tyrosine kinase that associates to cytokine receptors without intrinsic kinase activity to mediate cytokine-induced signal transduction; JAK1 associates with numerous cytokine receptors chains and is involved in signaling by the majority of cytokines: the gamma-C family (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21), the gp130 family (IL-6, OSM, LIF, ...), interferons, ...
Homology JAK1 belongs to the janus kinase subfamily; four mammalian JAKs have been identified (JAK1, JAK2, JAK3 and TYK2); human JAK1 is > 90% identical to the mouse and the rat JAK1 homologs.

Implicated in

Note
  
Entity Acute lymphoblastic leukemia T cell type (T-ALL) and Acute lymphoblastic leukemia B cell type (B-ALL)
Prognosis JAK1 mutations are associated with advanced age, poor response to therapy and overall prognosis (Flex et al., 2008).
Oncogenesis Somatic JAK1 mutations occur in T cell acute lymphoblastic leukemia (ALL). These mutations seem to be more frequent among adult T-ALL patients, but the frequency varies between studies: 8/38 (21.0%; adult; Flex et al., 2008), 1/49 (2.0%; children; Flex et al., 2008), 2/11 (27.3%; adult; Jeong et al., 2008), 4/108 (3.7%; adult; Asnafi et al., 2009). These mutations represent gain of function mutations that participate in the leukemogenic process by inducing the constitutive activation of the JAK-STAT pathway.
Table 1: Somatic mutations in JAK1 found in T-ALL patients.
Amino acid substitutionProof of hyperactivitydomainreference
S512L SH2Flex et al., 2008
A634DYesPseudokinaseFlex et al., 2008
Y652H PseudokinaseAsnafi et al., 2009
V658FYesPseudokinaseJeong et al., 2008
R724HYesPseudokinaseFlex et al., 2008
R724Q PseudokinaseAsnafi et al., 2009
T782M PseudokinaseJeong et al., 2008
L783F PseudokinaseJeong et al., 2008
R879S KinaseFlex et al., 2008
R879CYesKinaseFlex et al., 2008
R879H KinaseeFlex et al., 2008

JAK1 mutations were found in 3 B-cell ALL samples after the resequencing of 173 B-ALL (Flex et al., 2008) and in 3 samples after the resequencing of 187 high risk childhood B-ALL (Mullighan et al., 2009). No mutations were found after the resequencing of 69 B-ALL (Jeong et al., 2008).
Table 2: Somatic mutations in JAK1 found in B-ALL patients.

Amino acid substitutionProof of hyperactivitydomainreference
K204M FERMFlex et al., 2008
L624_R629>WYesPseudokinaseMullighan et al., 2009
A634DYesPseudokinaseFlex et al., 2008
S646FYesPseudokinaseMullighan et al., 2009
L653F PseudokinaseFlex et al., 2008
V658FYesPseudokinaseMullighan et al., 2009
R724HYesPseudokinaseFlex et al., 2008

JAK1 mutants induce the activation of different cytokine-receptor complexes like the IL-9 receptor or the IL-2 receptor, that will induce the constitutive activation of the JAK-STAT pathway.

  
  
Entity Acute myeloid leukemia (AML)
Oncogenesis JAK1 mutations were found in two AML samples after the resequencing of 94 AML (Xiang et al., 2008) and in one AML sample after the resequencing of 105 AML.
Table 3: Somatic mutations in JAK1 found in AML samples.
Amino acid substitutionProof of hyperactivitydomainreference
T478S SH2Xiang et al., 2008
V623A PseudokinaseXiang et al., 2008
V658FYesPseudokinaseJeong et al., 2008

  
  
Entity Hepatocellular carcinoma
Oncogenesis JAK1 mutations were found in one hepatocellular carcinoma sample after the screening of 84 hepatocellular carcinoma.
Table 4: Somatic mutations in JAK1 found in hepatocellular carcinomas.
Amino acid substitutionProof of hyperactivitydomainreference
Q644H;V645F PseudokinaseXie et al., 2009

  
  
Entity Breast cancer
Oncogenesis JAK1 mutation was found in a breast cancer sample after the resequencing of 90 breast cancers.
Table 5: Somatic mutations in JAK1 found in breast cancer samples.
Amino acid substitutionProof of hyperactivitydomainreference
H647Y PseudokinaseJeong et al., 2008

  
  
Entity Non-small cell lung cancer
Oncogenesis JAK1 mutation was found in a non-small cell lung cancer sample after the resequencing of 47 non-small cell lung cancer samples.
Table 6: Somatic mutations in JAK1 found in non-small cell lung cancer samples.
Amino acid substitutionProof of hyperactivitydomainreference
P782M PseudokinaseJeong et al., 2008

  

Bibliography

JAK1 mutations are not frequent events in adult T-ALL: a GRAALL study.
Asnafi V, Le Noir S, Lhermitte L, Gardin C, Legrand F, Vallantin X, Malfuson JV, Ifrah N, Dombret H, Macintyre E.
Br J Haematol. 2009 Sep 18. [Epub ahead of print]
PMID 19764985
 
Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia.
Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, Ariola C, Fodale V, Clappier E, Paoloni F, Martinelli S, Fragale A, Sanchez M, Tavolaro S, Messina M, Cazzaniga G, Camera A, Pizzolo G, Tornesello A, Vignetti M, Battistini A, Cave H, Gelb BD, Renauld JC, Biondi A, Constantinescu SN, Foa R, Tartaglia M.
J Exp Med. 2008 Apr 14;205(4):751-8. Epub 2008 Mar 24.
PMID 18362173
 
Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor alpha homodimers.
Hornakova T, Staerk J, Royer Y, Flex E, Tartaglia M, Constantinescu SN, Knoops L, Renauld JC.
J Biol Chem. 2009 Mar 13;284(11):6773-81. Epub 2009 Jan 12.
PMID 19139102
 
Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers.
Jeong EG, Kim MS, Nam HK, Min CK, Lee S, Chung YJ, Yoo NJ, Lee SH.
Clin Cancer Res. 2008 Jun 15;14(12):3716-21.
PMID 18559588
 
JAK kinases overexpression promotes in vitro cell transformation.
Knoops L, Hornakova T, Royer Y, Constantinescu SN, Renauld JC.
Oncogene. 2008 Mar 6;27(11):1511-9. Epub 2007 Sep 17.
PMID 17873904
 
JAK mutations in high-risk childhood acute lymphoblastic leukemia.
Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, Tasian SK, Loh ML, Su X, Liu W, Devidas M, Atlas SR, Chen IM, Clifford RJ, Gerhard DS, Carroll WL, Reaman GH, Smith M, Downing JR, Hunger SP, Willman CL.
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9414-8. Epub 2009 May 22.
PMID 19470474
 
Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia.
Tomasson MH, Xiang Z, Walgren R, Zhao Y, Kasai Y, Miner T, Ries RE, Lubman O, Fremont DH, McLellan MD, Payton JE, Westervelt P, DiPersio JF, Link DC, Walter MJ, Graubert TA, Watson M, Baty J, Heath S, Shannon WD, Nagarajan R, Bloomfield CD, Mardis ER, Wilson RK, Ley TJ.
Blood. 2008 May 1;111(9):4797-808. Epub 2008 Feb 12.
PMID 18270328
 
Identification of somatic JAK1 mutations in patients with acute myeloid leukemia.
Xiang Z, Zhao Y, Mitaksov V, Fremont DH, Kasai Y, Molitoris A, Ries RE, Miner TL, McLellan MD, DiPersio JF, Link DC, Payton JE, Graubert TA, Watson M, Shannon W, Heath SE, Nagarajan R, Mardis ER, Wilson RK, Ley TJ, Tomasson MH.
Blood. 2008 May 1;111(9):4809-12. Epub 2007 Dec 26.
PMID 18160671
 
Mutational analysis of JAK1 gene in human hepatocellular carcinoma.
Xie HJ, Bae HJ, Noh JH, Eun JW, Kim JK, Jung KH, Ryu JC, Ahn YM, Kim SY, Lee SH, Yoo NJ, Lee JY, Park WS, Nam SW.
Neoplasma. 2009;56(2):136-40.
PMID 19239328
 

Citation

This paper should be referenced as such :
Knoops, L ; Hornakova, T ; Renauld, JC
JAK1 (Janus kinase 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(8):717-719.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/JAK1ID41031ch1p31.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
  Pediatric T-Cell Acute Lymphoblastic Leukemia
Anaplastic large cell lymphoma, ALK-negative
del(X)(p22p22) P2RY8/CRLF2::del(Y)(p11p11) P2RY8/CRLF2
Early T-cell precursor acute lymphoblastic leukemia
Acute lymphoblastic leukemia in Down syndrome
Myeloid proliferations in Down syndrome


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  PDE4B/JAK1 (1p31)
t(1;1)(p31;q32) JAK1/HSD11B1


External links

Nomenclature
Cards
AtlasJAK1ID41031ch1p31.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)3716
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:40:21 CEST 2018

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