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P52333 (JAK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase JAK3

EC=2.7.10.2
Alternative name(s):
Janus kinase 3
Short name=JAK-3
Leukocyte janus kinase
Short name=L-JAK
Gene names
Name:JAK3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1124 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.9 Ref.10 Ref.14 Ref.22

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Interacts with STAM2 and MYO18A By similarity. Interacts with SHB. Ref.12 Ref.13

Subcellular location

Endomembrane system; Peripheral membrane protein By similarity. Cytoplasm By similarity.

Tissue specificity

In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins. Ref.11

Domain

Possesses two phosphotransferase domains. The second one probably contains the catalytic domain By similarity, while the presence of slight differences suggest a different role for domain 1. Ref.15

Post-translational modification

Tyrosine phosphorylated in response to IL-2 and IL-4. Dephosphorylation of Tyr-980 and Tyr-981 by PTPN2 negatively regulates cytokine-mediated signaling Probable. Ref.14 Ref.16 Ref.18 Ref.23

Involvement in disease

Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-negative (T(-)B(+)NK(-) SCID) [MIM:600802]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.14 Ref.16 Ref.18 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

Contains 1 FERM domain.

Contains 2 protein kinase domains.

Contains 1 SH2 domain.

Sequence caution

The sequence AAC50227.1 differs from that shown. Reason: Wrong choice of CDS. Was erroneously described as an isoform JAK3Mwhile it is a fragmentary mRNA of INSL3.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Innate immunity
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
SCID
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

JAK-STAT cascade involved in growth hormone signaling pathway

Traceable author statement Ref.19. Source: UniProtKB

STAT protein import into nucleus

Traceable author statement Ref.19. Source: UniProtKB

T cell homeostasis

Traceable author statement Ref.19. Source: UniProtKB

enzyme linked receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

interleukin-4-mediated signaling pathway

Inferred from direct assay PubMed 7538655. Source: BHF-UCL

intracellular signal transduction

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of FasL biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of T cell activation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of T-helper 1 cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of dendritic cell cytokine production

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of interleukin-10 production

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of interleukin-12 production

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of thymocyte apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of dendritic cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of T cell apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

response to interleukin-15

Traceable author statement PubMed 7594533. Source: BHF-UCL

response to interleukin-2

Traceable author statement PubMed 9973401. Source: BHF-UCL

response to interleukin-4

Inferred from direct assay PubMed 7538655PubMed 7594533. Source: BHF-UCL

response to interleukin-9

Traceable author statement PubMed 7594533. Source: BHF-UCL

tyrosine phosphorylation of STAT protein

Traceable author statement Ref.19. Source: UniProtKB

   Cellular_componentcytoskeleton

Inferred from electronic annotation. Source: InterPro

cytosol

Traceable author statement. Source: Reactome

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein phosphatase binding

Inferred from physical interaction Ref.14. Source: UniProtKB

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KHDRBS1Q076662EBI-518246,EBI-1364

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P52333-1)

Also known as: JAK3S; Spleen-JAK3;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1 (identifier: P52333-2)

Also known as: JAK3B; Breast-JAK3;

The sequence of this isoform differs from the canonical sequence as follows:
     1071-1124: HELMKLCWAP...EGKHHSLSFS → SAAGLASVSQSVDWAGVSGKPAGA
Note: May be inactive as it lacks some part of the kinase domain.
Isoform 3 (identifier: P52333-4)

The sequence of this isoform differs from the canonical sequence as follows:
     597-619: TMVQEFVHLGAIDMYLRKRGHLV → ESPPPTHPTPASPKSRLFFPPLF
     620-1124: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11241124Tyrosine-protein kinase JAK3
PRO_0000088115

Regions

Domain24 – 356333FERM
Domain375 – 475101SH2; atypical
Domain521 – 781261Protein kinase 1
Domain822 – 1111290Protein kinase 2
Nucleotide binding828 – 8369ATP By similarity
Region1 – 223223Interaction with cytokine/interferon/growth hormone receptors By similarity

Sites

Active site9491Proton acceptor By similarity
Binding site8551ATP By similarity

Amino acid modifications

Modified residue7851Phosphotyrosine; by autocatalysis Ref.16
Modified residue9041Phosphotyrosine Ref.18
Modified residue9391Phosphotyrosine Ref.18
Modified residue9801Phosphotyrosine; by autocatalysis Ref.14 Ref.23
Modified residue9811Phosphotyrosine; by autocatalysis Ref.14 Ref.23

Natural variations

Alternative sequence597 – 61923TMVQE…RGHLV → ESPPPTHPTPASPKSRLFFP PLF in isoform 3.
VSP_054165
Alternative sequence620 – 1124505Missing in isoform 3.
VSP_054166
Alternative sequence1071 – 112454HELMK…SLSFS → SAAGLASVSQSVDWAGVSGK PAGA in isoform 1.
VSP_004989
Natural variant121P → L. Ref.29
Corresponds to variant rs56061056 [ dbSNP | Ensembl ].
VAR_041722
Natural variant401R → H. Ref.29
Corresponds to variant rs56384680 [ dbSNP | Ensembl ].
VAR_041723
Natural variant581Missing in T(-)B(+)NK(-) SCID. Ref.28
VAR_019337
Natural variant1001Y → C in T(-)B(+)NK(-) SCID. Ref.24
VAR_006284
Natural variant1321P → T. Ref.4 Ref.29
Corresponds to variant rs3212723 [ dbSNP | Ensembl ].
VAR_019336
Natural variant1511P → R in T(-)B(+)NK(-) SCID. Ref.27 Ref.29
Corresponds to variant rs55778349 [ dbSNP | Ensembl ].
VAR_010492
Natural variant1691D → E in T(-)B(+)NK(-) SCID. Ref.28
VAR_019338
Natural variant4811E → G in T(-)B(+)NK(-) SCID. Ref.25
VAR_010493
Natural variant5211L → V. Ref.29
Corresponds to variant rs55666418 [ dbSNP | Ensembl ].
VAR_041724
Natural variant5271L → P in a gastric adenocarcinoma sample; somatic mutation. Ref.29
VAR_041725
Natural variant5821R → W in T(-)B(+)NK(-) SCID. Ref.26
VAR_010494
Natural variant586 – 5927Missing in T(-)B(+)NK(-) SCID; lack of phosphorylation in response to cytokine stimulation.
VAR_010495
Natural variant5891G → S in T(-)B(+)NK(-) SCID. Ref.28
VAR_019339
Natural variant6881I → F. Ref.29
Corresponds to variant rs35785705 [ dbSNP | Ensembl ].
VAR_041726
Natural variant7221V → I. Ref.4 Ref.27 Ref.28 Ref.29
Corresponds to variant rs3213409 [ dbSNP | Ensembl ].
VAR_010496
Natural variant7591C → R in T(-)B(+)NK(-) SCID; constitutive phosphorylation. Ref.25
VAR_010497
Natural variant9101L → S in T(-)B(+)NK(-) SCID. Ref.27
VAR_010498

Experimental info

Mutagenesis7851Y → F: Strong decrease of JAK3 phosphorylation. Ref.16
Mutagenesis8551K → A: More than 90% loss of STAT5a activation. Ref.18
Mutagenesis9041Y → F: About 40% loss of STAT5a activation. Ref.18
Mutagenesis9391Y → F: About 80% loss of STAT5a activation. Ref.18
Sequence conflict341G → A in AAA19626. Ref.1
Sequence conflict451F → S in AAC50950. Ref.3
Sequence conflict1031R → RS in AAC50950. Ref.3
Sequence conflict1471Missing in AAC50542. Ref.8
Sequence conflict1871T → A in AAC50542. Ref.8
Sequence conflict2121R → A in AAA19626. Ref.1
Sequence conflict2121R → A in AAC50950. Ref.3
Sequence conflict2221R → P in AAA19626. Ref.1
Sequence conflict2221R → P in AAC50950. Ref.3
Sequence conflict2711L → F in AAC50950. Ref.3
Sequence conflict2871Missing in AAC50950. Ref.3
Sequence conflict6101M → I in AAC50226. Ref.2
Sequence conflict845 – 8462GD → AH in AAA19626. Ref.1
Sequence conflict895 – 8973RQS → EPE in AAC50950. Ref.3
Sequence conflict896 – 8972QS → PE in AAA19626. Ref.1

Secondary structure

....................................................... 1124
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (JAK3S) (Spleen-JAK3) [UniParc].

Last modified July 19, 2004. Version 2.
Checksum: 895D8563439B2B7C

FASTA1,124125,099
        10         20         30         40         50         60 
MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 

        70         80         90        100        110        120 
SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 

       130        140        150        160        170        180 
RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 

       190        200        210        220        230        240 
PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 

       250        260        270        280        290        300 
DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 

       310        320        330        340        350        360 
ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 

       370        380        390        400        410        420 
KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 

       430        440        450        460        470        480 
LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 

       490        500        510        520        530        540 
EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 

       550        560        570        580        590        600 
HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 

       610        620        630        640        650        660 
EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 

       670        680        690        700        710        720 
DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 

       730        740        750        760        770        780 
GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 

       790        800        810        820        830        840 
ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 

       850        860        870        880        890        900 
YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 

       910        920        930        940        950        960 
VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 

       970        980        990       1000       1010       1020 
AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 

      1030       1040       1050       1060       1070       1080 
FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP 

      1090       1100       1110       1120 
SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS 

« Hide

Isoform 1 (JAK3B) (Breast-JAK3) [UniParc].

Checksum: D491FADB3D772693
Show »

FASTA1,094121,268
Isoform 3 [UniParc].

Checksum: 2DA342038998636C
Show »

FASTA61968,279

References

« Hide 'large scale' references
[1]"Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes."
Kawamura M., McVicar D.W., Johnston J.A., Blake T.B., Chen Y.-Q., Lal B.K., Lloyd A.R., Kelvin D.J., Staples J.E., Ortaldo J.R., O'Shea J.J.
Proc. Natl. Acad. Sci. U.S.A. 91:6374-6378(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]"A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells."
Lai K.S., Jin Y., Graham D.K., Witthuhn B.A., Ihle J.N., Liu E.T.
J. Biol. Chem. 270:25028-25036(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 2).
[3]"Genomic sequence, organization, and chromosomal localization of human JAK3."
Riedy M.C., Dutra A.S., Blake T.B., Modi W., Lal B.K., Davis J., Bosse A., O'Shea J.J., Johnston J.A.
Genomics 37:57-61(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]SeattleSNPs variation discovery resource
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-132 AND ILE-722.
[5]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Blood.
[8]"Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells."
Verbsky J.W., Bach E.A., Fang Y.F., Yang L., Randolph D.A., Fields L.E.
J. Biol. Chem. 271:13976-13980(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-191.
[9]"Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2."
Johnston J.A., Kawamura M., Kirken R.A., Chen Y.Q., Blake T.B., Shibuya K., Ortaldo J.R., McVicar D.W., O'Shea J.J.
Nature 370:151-153(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IL2 SIGNALING PATHWAY.
[10]"JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinase."
Sharfe N., Dadi H.K., Roifman C.M.
Blood 86:2077-2085(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IL7 SIGNALING PATHWAY.
[11]"Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7."
Musso T., Johnston J.A., Linnekin D., Varesio L., Rowe T.K., O'Shea J.J., McVicar D.W.
J. Exp. Med. 181:1425-1431(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[12]"STAM2, a new member of the STAM family, binding to the Janus kinases."
Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., Yamada M., Chenb M., O'Shea J.J., Sugamura K.
FEBS Lett. 477:55-61(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STAM2.
Tissue: Fetal brain.
[13]"IL-2 receptor signaling through the Shb adapter protein in T and NK cells."
Lindholm C.K.
Biochem. Biophys. Res. Commun. 296:929-936(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHB.
[14]"The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3."
Simoncic P.D., Lee-Loy A., Barber D.L., Tremblay M.L., McGlade C.J.
Curr. Biol. 12:446-453(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CYTOKINE SIGNALING, PHOSPHORYLATION, DEPHOSPHORYLATION AT TYR-980 AND TYR-981 BY PTPN2.
[15]"The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction."
Saharinen P., Silvennoinen O.
J. Biol. Chem. 277:47954-47963(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[16]"Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation 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) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION AT TYR-785, MUTAGENESIS OF TYR-785.
[17]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
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) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity."
Cheng H., Ross J.A., Frost J.A., Kirken R.A.
Mol. Cell. Biol. 28:2271-2282(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-904 AND TYR-939, MUTAGENESIS OF LYS-855; TYR-904 AND TYR-939.
[19]"Janus kinases in immune cell signaling."
Ghoreschi K., Laurence A., O'Shea J.J.
Immunol. Rev. 228:273-287(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[20]"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) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[22]"IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis."
Malamut G., El Machhour R., Montcuquet N., Martin-Lanneree S., Dusanter-Fourt I., Verkarre V., Mention J.J., Rahmi G., Kiyono H., Butz E.A., Brousse N., Cellier C., Cerf-Bensussan N., Meresse B.
J. Clin. Invest. 120:2131-2143(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IL15 SIGNALING PATHWAY.
[23]"Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog."
Boggon T.J., Li Y., Manley P.W., Eck M.J.
Blood 106:996-1002(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 814-1103 IN COMPLEX WITH STAUROSPORINE ANALOG AFN941, PHOSPHORYLATION AT TYR-980 AND TYR-981.
[24]"Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)."
Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F., Ugazio A.G., Johnston J.A., Candotti F., O'Shea J.J., Vezzoni P., Notarangelo L.D.
Nature 377:65-68(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT T(-)B(+)NK(-) SCID CYS-100.
[25]"Structural and functional basis for JAK3-deficient severe combined immunodeficiency."
Candotti F., Oakes S.A., Johnston J.A., Giliani S., Schumacher R.F., Mella P., Fiorini M., Ugazio A.G., Badolato R., Notarangelo L.D., Bozzi F., Macchi P., Strina D., Vezzoni P., Blaese R.M., O'Shea J.J., Villa A.
Blood 90:3996-4003(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS T(-)B(+)NK(-) SCID GLY-481; 586-LEU--MET-592 DEL AND ARG-759.
[26]"Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment."
Bozzi F., Lefranc G., Villa A., Badolato R., Schumacher R.F., Khalil G., Loiselet J., Bresciani S., O'Shea J.J., Vezzoni P., Notarangelo L.D., Candotti F.
Br. J. Haematol. 102:1363-1366(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT T(-)B(+)NK(-) SCID TRP-582.
[27]"Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism."
Schumacher R.F., Mella P., Badolato R., Fiorini M., Savoldi G., Giliani S., Villa A., Candotti F., Tampalini A., O'Shea J.J., Notarangelo L.D.
Hum. Genet. 106:73-79(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS T(-)B(+)NK(-) SCID ARG-151 AND SER-910, VARIANT ILE-722.
[28]"Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation."
Roberts J.L., Lengi A., Brown S.M., Chen M., Zhou Y.-J., O'Shea J.J., Buckley R.H.
Blood 103:2009-2018(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS T(-)B(+)NK(-) SCID ALA-58 DEL; GLU-169 AND SER-589, VARIANT ILE-722.
[29]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-12; HIS-40; THR-132; ARG-151; VAL-521; PRO-527; PHE-688 AND ILE-722.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U09607 mRNA. Translation: AAA19626.1.
U31601 mRNA. Translation: AAC50226.1.
U31602 mRNA. Translation: AAC50227.1. Sequence problems.
U70065 Genomic DNA. Translation: AAC50950.1.
AF513860 Genomic DNA. Translation: AAM44860.1.
AC007201 Genomic DNA. Translation: AAD22741.1.
CH471106 Genomic DNA. Translation: EAW84639.1.
BC028068 mRNA. Translation: AAH28068.1.
U57096 mRNA. Translation: AAC50542.1.
PIRA55747.
RefSeqNP_000206.2. NM_000215.3.
UniGeneHs.515247.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YVJX-ray2.55A814-1103[»]
3LXKX-ray2.00A806-1124[»]
3LXLX-ray1.74A806-1124[»]
3PJCX-ray2.20A812-1124[»]
3ZC6X-ray2.42A/B/C/D813-1100[»]
3ZEPX-ray2.35A/B/C/D813-1047[»]
A/B/C/D813-1100[»]
4HVDX-ray1.85A811-1124[»]
4HVGX-ray2.75A811-1124[»]
4HVHX-ray2.30A811-1124[»]
4HVIX-ray2.40A811-1124[»]
4I6QX-ray1.85A811-1124[»]
ProteinModelPortalP52333.
SMRP52333. Positions 397-780, 787-1103.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109921. 30 interactions.
DIPDIP-274N.
IntActP52333. 11 interactions.
MINTMINT-1497014.
STRING9606.ENSP00000391676.

Chemistry

BindingDBP52333.
ChEMBLCHEMBL2148.
GuidetoPHARMACOLOGY2049.

PTM databases

PhosphoSiteP52333.

Polymorphism databases

DMDM50403745.

Proteomic databases

PaxDbP52333.
PRIDEP52333.

Protocols and materials databases

DNASU3718.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000458235; ENSP00000391676; ENSG00000105639. [P52333-1]
ENST00000527670; ENSP00000432511; ENSG00000105639. [P52333-1]
ENST00000534444; ENSP00000436421; ENSG00000105639. [P52333-2]
GeneID3718.
KEGGhsa:3718.
UCSCuc002nhn.4. human. [P52333-1]
uc002nho.2. human. [P52333-2]

Organism-specific databases

CTD3718.
GeneCardsGC19M017935.
HGNCHGNC:6193. JAK3.
MIM600173. gene.
600802. phenotype.
neXtProtNX_P52333.
Orphanet35078. T-B+ severe combined immunodeficiency due to JAK3 deficiency.
PharmGKBPA29990.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000049158.
HOVERGENHBG006195.
InParanoidP52333.
KOK11218.
OMANCMESFL.
OrthoDBEOG7BW0HM.
PhylomeDBP52333.
TreeFamTF327041.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_6900. Immune System.
SignaLinkP52333.

Gene expression databases

ArrayExpressP52333.
BgeeP52333.
CleanExHS_JAK3.
GenevestigatorP52333.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR019749. Band_41_domain.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016251. Tyr_kinase_non-rcpt_Jak/Tyk2.
IPR020775. Tyr_kinase_non-rcpt_Jak3.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSPR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.
SMARTSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMSSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP52333.
GeneWikiJanus_kinase_3.
GenomeRNAi3718.
NextBio14571.
PROP52333.
SOURCESearch...

Entry information

Entry nameJAK3_HUMAN
AccessionPrimary (citable) accession number: P52333
Secondary accession number(s): Q13259 expand/collapse secondary AC list , Q13260, Q13611, Q8N1E8, Q99699, Q9Y6S2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 19, 2004
Last modified: April 16, 2014
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM