JAK3

Protein identityUniProt · HPA

UniProt accession

P52333

Gene

JAK3

Ensembl

ENSG00000105639

Chromosome

19

Canonical length

1124 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins

Subcellular location

Plasma membrane,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1124 residues, UniProt reviewed canonical sequence.

>P52333|JAK3
     1  MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA
    61  SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL
   121  RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR
   181  PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM
   241  DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD
   301  ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC
   361  KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP
   421  LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK
   481  EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR
   541  HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ
   601  EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA
   661  DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS
   721  GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL
   781  ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR
   841  YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL
   901  VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE
   961  AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL
  1021  FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP
  1081  SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against JAK3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

53 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about JAK3.

Disease | AllUniProt

Conditions JAK3 is implicated in, by any mechanism.

• Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) MIM:600802

Disease | GeneticClinVar

137 pathogenic / likely-pathogenic of 1,400 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• T-B+ severe combined immunodeficiency due to JAK3 deficiency
• Severe combined immunodeficiency disease
• Thyroid cancer, nonmedullary, 1
• JAK3-related disorder
• Adenoid cystic carcinoma

Disease | ImmuneIEDB

Conditions an epitope on JAK3 was assayed in.

• ankylosing spondylitis T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.53

gnomAD pLI

0

gnomAD missense Z

2.81

DepMap mean gene effect

-0.1

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• B cell differentiation
• cell differentiation
• cell surface receptor signaling pathway via JAK-STAT
• cytokine-mediated signaling pathway
• enzyme-linked receptor protein signaling pathway
• growth hormone receptor signaling pathway via JAK-STAT
• innate immune response
• interleukin-15-mediated signaling pathway
• interleukin-2-mediated signaling pathway
• interleukin-4-mediated signaling pathway
• interleukin-7-mediated signaling pathway
• interleukin-9-mediated signaling pathway
• intracellular signal transduction
• negative regulation of glycoprotein biosynthetic process
• negative regulation of interleukin-10 production
• negative regulation of interleukin-12 production
• negative regulation of T cell activation
• negative regulation of T-helper 1 cell differentiation
• negative regulation of T-helper 17 cell lineage commitment
• negative regulation of thymocyte apoptotic process
• regulation of apoptotic process
• regulation of receptor signaling pathway via JAK-STAT
• regulation of T cell apoptotic process
• response to interleukin-15
• response to interleukin-2
• response to interleukin-4
• response to interleukin-9
• T cell homeostasis
• tyrosine phosphorylation of STAT protein
• negative regulation of dendritic cell cytokine production

Molecular functions

• ATP binding
• growth hormone receptor binding
• non-membrane spanning protein tyrosine kinase activity
• protein phosphatase binding
• protein tyrosine kinase activity

Cellular components

• cytoplasmic side of plasma membrane
• cytosol
• endosome
• extrinsic component of cytoplasmic side of plasma membrane
• extrinsic component of plasma membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• FERM domain
• Protein kinase domain
• SH2 domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• PH-like domain superfamily
• Tyrosine-protein kinase, non-receptor Jak/Tyk2
• Protein kinase, ATP binding site
• Band 4.1 domain
• Tyrosine-protein kinase, catalytic domain
• SH2 domain superfamily
• JAK, FERM F2 lobe domain
• FERM F1 lobe ubiquitin-like domain
• JAK1-3/TYK2, pleckstrin homology-like domain
• Janus Kinase (JAK)
• Protein tyrosine and serine/threonine kinase
• Jak1 pleckstrin homology-like domain
• FERM F2 acyl-CoA binding protein-like domain
• FERM F1 ubiquitin-like domain
• SH2 domain
• Tyrosine-protein kinase, non-receptor Jak3

KeywordsUniProt

• Adaptive immunity
• ATP-binding
• Cytoplasm
• Immunity
• Innate immunity
• Kinase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Repeat
• SCID
• SH2 domain
• Transferase
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of JAK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD69
• MYO18A
• SHB
• STAM2
• KHDRBS1
• IL4R
• MAGED2
• NAP1L1