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  7. Tyrosine-protein kinase JAK3

Tclin Tyrosine-protein kinase JAK3

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.

The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease). [provided by RefSeq, Jul 2008]

 Comments

Property Summary

Ligand Count 621
NCBI Gene PubMed Count 183
PubMed Score 453.65
PubTator Score 330.40

Knowledge Summary

Patent (132,317)

TINX Plot

  Disease (6)

Disease Target Count
Rheumatoid arthritis 1191
Disease Target Count Z-score Confidence
Cancer 2499 4.42 2.2
Polycythemia vera 27 3.41 1.7
Lactocele 3 3.001 1.5

Expression

  Differential Expression (15)

Disease log2 FC p
Atopic dermatitis 1.300 2.0e-03
ductal carcinoma in situ 1.100 2.3e-02
group 3 medulloblastoma -1.800 7.7e-07
head and neck cancer and chronic obstruc... 1.400 1.7e-03
interstitial cystitis 2.600 2.1e-04
lung adenocarcinoma 1.200 1.2e-04
medulloblastoma, large-cell -1.400 1.2e-04
oligodendroglioma -1.100 1.3e-02
osteosarcoma 1.283 1.0e-06
ovarian cancer 1.200 1.4e-04
periodontitis 1.100 2.7e-26
posterior fossa group B ependymoma -1.100 7.7e-06
primitive neuroectodermal tumor -1.500 3.9e-04
psoriasis 1.200 1.1e-04
ulcerative colitis 1.900 7.8e-05

Synonym

Accession P52333 Q13259 Q13260 Q13611 Q8N1E8 Q99699 Q9Y6S2
Symbols JAKL
LJAK
JAK-3
L-JAK
JAK3_HUMAN

Gene

JAK3

PDB

1YVJ   3LXK   3LXL   3PJC   3ZC6   3ZEP   4HVD   4HVG   4HVH   4HVI   4I6Q   4QPS   4QT1   4RIO   4V0G   4Z16   5LWM   5LWN   5TOZ   5TTS   5TTU   5TTV   5VO6   5W86   5WFJ  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (20)

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 GO Function (6)

 GO Component (4)

 GO Process (34)

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 Compartment GO Term (31)

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 MGI Phenotype (6)

 HCA RNA Cell Line (56)

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Pathway (72)

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Protein-protein Interaction (2)

IL2RG   PTK2B  

Drug (4)

Structure of tofacitinib

tofacitinib
pIC50 7.25

Structure of baricitinib

baricitinib
pIC50 7.60

Structure of ruxolitinib

ruxolitinib
pIC50 7.84

Structure of nintedanib

nintedanib
pKd 8.09

Ligand (616)

Structure of CHEMBL1630795

CHEMBL1630795
pIC50 7.54

Structure of CHEMBL3642404

CHEMBL3642404
pIC50 7.54

Structure of CHEMBL3670397

CHEMBL3670397
pKi 7.54

Structure of CHEMBL3335678

CHEMBL3335678
pIC50 7.54

Structure of CHEMBL3114774

CHEMBL3114774
pIC50 7.54

Structure of CHEMBL3359914

CHEMBL3359914
pIC50 7.55

Structure of CHEMBL1081190

CHEMBL1081190
pIC50 7.55

Structure of CHEMBL1081377

CHEMBL1081377
pIC50 7.55

Structure of CHEMBL3593590

CHEMBL3593590
pIC50 7.55

Structure of CHEMBL3642411

CHEMBL3642411
pIC50 7.56

Structure of CHEMBL218439

CHEMBL218439
pIC50 7.57

Structure of CHEMBL3357978

CHEMBL3357978
pIC50 7.57

Structure of CHEMBL3642262

CHEMBL3642262
pIC50 7.57

Structure of CHEMBL3593580

CHEMBL3593580
pIC50 7.57

Structure of CHEMBL1235315

CHEMBL1235315
pIC50 7.57

Structure of CHEMBL3764463

CHEMBL3764463
pIC50 7.57

Structure of CHEMBL323994

CHEMBL323994
pIC50 7.57

Structure of CHEMBL234718

CHEMBL234718
pIC50 7.57

Structure of CHEMBL3642340

CHEMBL3642340
pIC50 7.58

Structure of CHEMBL240429

CHEMBL240429
pIC50 7.59

Gene RIF (147)

AA Sequence 

MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSL      1 - 70
FALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGLRKDLASAILDLPVLEHLFAQ     71 - 140
HRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQRPGELLKTVSYKACLPPSLRDLIQGLSFVTR    141 - 210
RRIRRTVRRALRRVAACQADRHSLMAKYIMDLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIA    211 - 280
WTQGEQEVLQPFCDFPEIVDISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFR    281 - 350
LTTDSQHFFCKEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNP    351 - 420
LGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPKEKSNLIVVQR    421 - 490
GHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCRHEVVDGEARKTEVLLKVMDA    491 - 560
KHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQEFVHLGAIDMYLRKRGHLVPASWKLQVVKQ    561 - 630
LAYALNYLEDKGLPHGNVSARKVLLAREGADGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQ    631 - 700
TLSLEADKWGFGATVWEVFSGVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSF    701 - 770
RAVIRDLNSLISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCR    771 - 840
YDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRLVMEYLPSGCL    841 - 910
RDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDY    911 - 980
YVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKSCSPSAEFLRMMGCERDVPALCRL    981 - 1050
LELLEEGQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHS   1051 - 1120
LSFS                                                                     1121 - 1124
//

Text Mined References (189)

PMID Year Title