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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]
JAK3 (Janus Kinase 3) is a Protein Coding gene. Diseases associated with JAK3 include Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Negative and Severe Combined Immunodeficiency. Among its related pathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and RET signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is JAK2.
JAKs (or Janus kinases) are a family of tyrosine kinases that are associated with cytokine receptors. Upon receptor activation JAKs phosphorylate the transcription factors known as STATs and initiate the JAK-STAT signaling pathway. Four JAK family members have been identified.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | ISS,TAS | -- |
GO:0004715 | non-membrane spanning protein tyrosine kinase activity | IEA | -- |
GO:0005515 | protein binding | IPI | 9045636 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IEA | -- |
GO:0005768 | endosome | TAS | -- |
GO:0005829 | cytosol | TAS | -- |
GO:0005856 | cytoskeleton | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Common Cytokine Receptor Gamma-Chain Family Signaling Pathways |
Immune response IL-9 signaling pathway
.42
IL-9 Pathway
.36
|
|
3 | Th17 cell differentiation |
Immune response IL-22 signaling pathway
.36
|
|
4 | IL-2 Pathway |
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
|
IL-4 Pathway
.34
|
5 | G beta-gamma signalling through PI3Kgamma |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0002250 | adaptive immune response | IEA | -- |
GO:0002376 | immune system process | IEA | -- |
GO:0002731 | negative regulation of dendritic cell cytokine production | ISS | -- |
GO:0006468 | protein phosphorylation | TAS | 8022790 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Tofacitinib | Approved, Investigational | Pharma | Target, inhibitor | 168 | ||
Baricitinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Zanubrutinib | Approved, Investigational | Pharma | Target, inhibitor | 33 | ||
Fedratinib | Approved, Investigational | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
AT9283 | Aurora kinase/JAK inhibitor | 896466-04-9 |
AZ 960 | JAKs inhibitor | 905586-69-8 |
Bardoxolone methyl | IKK inhibitor, potent antioxidant inflammation modulator | 218600-53-4 |
Cercosporamide | Mnk2 and JAK3 inhibitor | 131436-22-1 |
Cerdulatinib | Syk/JAK inhibitor | 1198300-79-6 |
Decernotinib(VX-509) | Selective and orally active JAK3 inhibitor | 944842-54-0 |
GLPG0634 | JAK1 inhibitor | 1206161-97-8 |
GSK-3 Inhibitor IX (BIO) | 667463-62-9 | |
JANEX-1 | JAK3 inhibitor | 202475-60-3 |
NVP-BSK805 | ATP-competitive JAK2 inhibitor | 1092499-93-8 |
Peficitinb (ASP015K, JNJ-54781532) | JAK inhibitor | 944118-01-8 |
Pyridone 6 | Pan-JAK inhibitor | 457081-03-7 |
Ruxolitinib (INCB018424) | JAK inhibitor | 941678-49-5 |
S-Ruxolitinib (INCB018424) | JAK1/2 inhibitor,potent and selective | 941685-37-6 |
TCS 21311 | JAK3 inhibitor | 1260181-14-3 |
TG101209 | JAK2/3 inhibitor | 936091-14-4 |
Tofacitinib (CP-690550) Citrate | Potent JAK inhibitor | 540737-29-9 |
Tofacitinib (CP-690550,Tasocitinib) | Janus kinase inhibitor | 477600-75-2 |
WHI-P154 | JAK3 inhibitor | 211555-04-3 |
WHI-P180 | EGFR/Janus Kinase 3 inhibitor | 211555-08-7 |
WHI-P97 | Janus kinase (JAK)-3 inhibitor | 211555-05-4 |
ZM 39923 HCl | JAK3 inhibitor,potent and selective | 1021868-92-7 |
ZM 449829 | JAK3 inhibitor | 4452-06-6 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | ^ | 11 | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 | ^ | 16 | ^ | 17 | ^ | 18 | ^ | 19a | · | 19b | ^ | 20 | ^ | 21a | · | 21b | ^ | 22a | · | 22b | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: |
ExUns: | 23a | · | 23b | ^ | 24a | · | 24b | · | 24c | ^ | 25 | ^ | 26a | · | 26b | · | 26c |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | |||||||||||||||||
SP2: | |||||||||||||||||
SP3: | |||||||||||||||||
SP4: | - | ||||||||||||||||
SP5: | |||||||||||||||||
SP6: | - | - | |||||||||||||||
SP7: | - |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | JAK3 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | JAK3 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | JAK3 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Jak3 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Jak3 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | JAK3 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | JAK3 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | JAK3 30 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | jak3 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | jak3 30 31 |
|
OneToOne | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 19 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
636398 | Uncertain Significance: not provided | 17,840,332(-) | A/T | MISSENSE_VARIANT | |
636504 | Uncertain Significance: not provided | 17,832,696(-) | T/A | MISSENSE_VARIANT | |
638620 | Pathogenic: NK-cell enteropathy | 17,837,936(-) | ATGCAGTTCT/A | INFRAME_DELETION | |
639139 | Uncertain Significance: Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-negative | 17,832,539(-) | C/T | MISSENSE_VARIANT | |
639318 | Uncertain Significance: Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-negative | 17,841,458(-) | A/C | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
severe combined immunodeficiency, autosomal recessive, t cell-negative, b cell-positive, nk cell-negative |
|
|
severe combined immunodeficiency |
|
|
nk-cell enteropathy |
|
|
adenoid cystic carcinoma |
|
|
janus kinase-3 deficiency |
|
|