Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Tyrosine-protein kinase JAK3  

UniProtKB / Swiss-Prot ID :  JAK3_HUMAN

Gene Name (Synonyms) : 
JAK3  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Endomembrane system; Peripheral membrane protein (By similarity). Cytoplasm (By similarity). 

Protein Function :  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. 

Protein Sequence MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKASGILPVYHSL...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCCCCCCCEEEEEECCCCCCCCCCEEECCCCHHHHHHHHHHHHHHCCCCHHHHH...
Protein Variant
LocationDescription
12P -> L (in dbSNP:rs56061056). VAR_041722
40R -> H (in dbSNP:rs56384680). VAR_041723
58Missing (in T(-)B(+)NK(-) SCID). VAR_019337
100Y -> C (in T(-)B(+)NK(-) SCID). VAR_006284
132P -> T (in dbSNP:rs3212723). VAR_019336
151P -> R (in T(-)B(+)NK(-) SCID;dbSNP:rs55778349).
169D -> E (in T(-)B(+)NK(-) SCID). VAR_019338
481E -> G (in T(-)B(+)NK(-) SCID). VAR_010493
521L -> V (in dbSNP:rs55666418). VAR_041724
527L -> P (in a gastric adenocarcinomasample; somatic mutation).
582R -> W (in T(-)B(+)NK(-) SCID). VAR_010494
586Missing (in T(-)B(+)NK(-) SCID; lack ofphosphorylation in response to cytokine
589G -> S (in T(-)B(+)NK(-) SCID). VAR_019339
688I -> F (in dbSNP:rs35785705). VAR_041726
722V -> I (in dbSNP:rs3213409). VAR_010496
759C -> R (in T(-)B(+)NK(-) SCID;constitutive phosphorylation).
910L -> S (in T(-)B(+)NK(-) SCID). VAR_010498
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
361Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)HFFCKEVAP
CCCCCCCCC
50.49Phosphositeplus
Link-
783Phosphoserine.SLISSDYEL
HHHCCCCHH
36.90UniProtKB
Link-
785PhosphotyrosineISSDYELLS
HCCCCHHHH
15.49Phosphositeplus
Link-
785Phosphotyrosine (JAK3)ISSDYELLS
HCCCCHHHH
15.49HPRD
Link-
785Phosphotyrosine (JAK3)ISSDYELLS
HCCCCHHHH
15.49PhosphoELM
Link-
785Phosphotyrosine; by autocatalysis.ISSDYELLS
HCCCCHHHH
15.49UniProtKB
Link-
823Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)ERHLKYISQ
CCCEEEEEE
34.12Phosphositeplus
Link
904PhosphotyrosineLVMEYLPSG
EEEEECCCC
13.05Phosphositeplus
Link
904Phosphotyrosine.LVMEYLPSG
EEEEECCCC
13.05UniProtKB
Link
939PhosphotyrosineKGMEYLGSR
HHHHHHHHC
13.89Phosphositeplus
Link
939Phosphotyrosine.KGMEYLGSR
HHHHHHHHC
13.89UniProtKB
Link
972Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FGLAKLLPL
CCEEEECCC
56.45Phosphositeplus
Link
980PhosphotyrosineLDKDYYVVR
CCCCEEEEC
12.14Phosphositeplus
Link
980Phosphotyrosine (JAK3)LDKDYYVVR
CCCCEEEEC
12.14HPRD
Link
980Phosphotyrosine (JAK3)LDKDYYVVR
CCCCEEEEC
12.14PhosphoELM
Link
980Phosphotyrosine; by autocatalysis.LDKDYYVVR
CCCCEEEEC
12.14UniProtKB
Link
981PhosphotyrosineDKDYYVVRE
CCCEEEECC
11.55Phosphositeplus
Link
981Phosphotyrosine (JAK3)DKDYYVVRE
CCCEEEECC
11.55HPRD
Link
981Phosphotyrosine (JAK3)DKDYYVVRE
CCCEEEECC
11.55PhosphoELM
Link
981Phosphotyrosine; by autocatalysis.DKDYYVVRE
CCCEEEECC
11.55UniProtKB
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
ERBB3_HUMANphysical interactionMINT-74564MINT16273093
IL2RG_HUMANphysical interactionDIP:1060EDIP7973658
STAT3_HUMANin vivoHPRD:02547HPRD10037026
ALK_HUMANin vivoHPRD:02547HPRD11850821
IL2RB_HUMANin vitro
in vivo
HPRD:02547HPRD10825200
7973659
9553136
IRS1_HUMANin vivoHPRD:02547HPRD7499365
JAK2_HUMANin vivoHPRD:02547HPRD11585385
IL4RA_HUMANin vivoHPRD:02547HPRD7538655
JAK1_HUMANin vitro
in vivo
HPRD:02547HPRD9553136
12559972
CXCR4_HUMANin vivoHPRD:02547HPRD10506573
CD45_HUMANin vitroHPRD:02547HPRD11994288
LCK_HUMANin vitro
in vivo
HPRD:02547HPRD11278738
CD3Z_HUMANin vitro
in vivo
HPRD:02547HPRD11349123
IL2RG_HUMANin vivoHPRD:02547HPRD7973658
JAK3_HUMANin vitroHPRD:02547HPRD9391116
15121872
P85A_HUMANin vivoHPRD:02547HPRD7662955
SOCS3_HUMANin vitroHPRD:02547HPRD10373548
SHIP1_HUMANin vivoHPRD:02547HPRD10875931
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Disease Reference
Kegg disease
H00091 T-B+Severe combined immunodeficiencies (SCIDs), including the following eight diseases: X-linked SCI
OMIM disease
600802Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID)
Drug Reference
Kegg drug
D09783 Tofacitinib citrate (JAN/USAN); Tasocitinib citrate; Xeljanz (TN)
D09970 Tofacitinib (USAN); Tasocitinib
DrugBank
DB08895Tofacitinib
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Tyrosine 813 is a site of JAK2 autophosphorylation critical foractivation of JAK2 by SH2-B beta.";
Kurzer J.H., Argetsinger L.S., Zhou Y.J., Kouadio J.L., O'Shea J.J.,Carter-Su C.;
Mol. Cell. Biol. 24:4557-4570(2004).
Cited for: AUTOPHOSPHORYLATION AT TYR-785, AND MUTAGENESIS OF TYR-785.
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.;
Nat. Biotechnol. 23:94-101(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-785, AND MASSSPECTROMETRY.
"Phosphorylation of human Jak3 at tyrosines 904 and 939 positivelyregulates its activity.";
Cheng H., Ross J.A., Frost J.A., Kirken R.A.;
Mol. Cell. Biol. 28:2271-2282(2008).
Cited for: PHOSPHORYLATION AT TYR-904 AND TYR-939, AND MUTAGENESIS OF LYS-855;TYR-904 AND TYR-939.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783 AND TYR-785, ANDMASS SPECTROMETRY.
"Crystal structure of the Jak3 kinase domain in complex with astaurosporine analog.";
Boggon T.J., Li Y., Manley P.W., Eck M.J.;
Blood 106:996-1002(2005).
Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 814-1103 IN COMPLEX WITHSTAUROSPORINE ANALOG AFN941, AND PHOSPHORYLATION AT TYR-980 ANDTYR-981.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures