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P52333

- JAK3_HUMAN

UniProt

P52333 - JAK3_HUMAN

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Protein

Tyrosine-protein kinase JAK3

Gene
JAK3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei855 – 8551ATP By similarity
Active sitei949 – 9491Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi828 – 8369ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  3. protein binding Source: IntAct
  4. protein phosphatase binding Source: UniProtKB
  5. protein tyrosine kinase activity Source: BHF-UCL

GO - Biological processi

  1. B cell differentiation Source: BHF-UCL
  2. enzyme linked receptor protein signaling pathway Source: BHF-UCL
  3. innate immune response Source: UniProtKB-KW
  4. interleukin-4-mediated signaling pathway Source: BHF-UCL
  5. intracellular signal transduction Source: BHF-UCL
  6. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
  7. negative regulation of dendritic cell cytokine production Source: BHF-UCL
  8. negative regulation of FasL biosynthetic process Source: BHF-UCL
  9. negative regulation of interleukin-10 production Source: BHF-UCL
  10. negative regulation of interleukin-12 production Source: BHF-UCL
  11. negative regulation of T cell activation Source: BHF-UCL
  12. negative regulation of T-helper 1 cell differentiation Source: BHF-UCL
  13. negative regulation of thymocyte apoptotic process Source: BHF-UCL
  14. peptidyl-tyrosine phosphorylation Source: BHF-UCL
  15. positive regulation of dendritic cell apoptotic process Source: Ensembl
  16. positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  17. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  18. protein phosphorylation Source: ProtInc
  19. regulation of T cell apoptotic process Source: BHF-UCL
  20. response to interleukin-15 Source: BHF-UCL
  21. response to interleukin-2 Source: BHF-UCL
  22. response to interleukin-4 Source: BHF-UCL
  23. response to interleukin-9 Source: BHF-UCL
  24. STAT protein import into nucleus Source: UniProtKB
  25. T cell homeostasis Source: UniProtKB
  26. tyrosine phosphorylation of STAT protein Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiREACT_115529. Interleukin-7 signaling.
REACT_23891. Interleukin receptor SHC signaling.
REACT_27283. Interleukin-2 signaling.
SignaLinkiP52333.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:JAK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:6193. JAK3.

Subcellular locationi

GO - Cellular componenti

  1. cytoskeleton Source: InterPro
  2. cytosol Source: Reactome
  3. endomembrane system Source: UniProtKB-SubCell
  4. membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

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.10 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581Missing in T(-)B(+)NK(-) SCID. 1 Publication
VAR_019337
Natural varianti100 – 1001Y → C in T(-)B(+)NK(-) SCID. 1 Publication
VAR_006284
Natural varianti151 – 1511P → R in T(-)B(+)NK(-) SCID. 2 Publications
Corresponds to variant rs55778349 [ dbSNP | Ensembl ].
VAR_010492
Natural varianti169 – 1691D → E in T(-)B(+)NK(-) SCID. 1 Publication
VAR_019338
Natural varianti481 – 4811E → G in T(-)B(+)NK(-) SCID. 1 Publication
VAR_010493
Natural varianti582 – 5821R → W in T(-)B(+)NK(-) SCID. 1 Publication
VAR_010494
Natural varianti586 – 5927Missing in T(-)B(+)NK(-) SCID; lack of phosphorylation in response to cytokine stimulation.
VAR_010495
Natural varianti589 – 5891G → S in T(-)B(+)NK(-) SCID. 1 Publication
VAR_019339
Natural varianti759 – 7591C → R in T(-)B(+)NK(-) SCID; constitutive phosphorylation. 1 Publication
VAR_010497
Natural varianti910 – 9101L → S in T(-)B(+)NK(-) SCID. 1 Publication
VAR_010498

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi785 – 7851Y → F: Strong decrease of JAK3 phosphorylation. 1 Publication
Mutagenesisi855 – 8551K → A: More than 90% loss of STAT5a activation. 1 Publication
Mutagenesisi904 – 9041Y → F: About 40% loss of STAT5a activation. 1 Publication
Mutagenesisi939 – 9391Y → F: About 80% loss of STAT5a activation. 1 Publication

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

MIMi600802. phenotype.
Orphaneti35078. T-B+ severe combined immunodeficiency due to JAK3 deficiency.
PharmGKBiPA29990.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11241124Tyrosine-protein kinase JAK3PRO_0000088115Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei785 – 7851Phosphotyrosine; by autocatalysis1 Publication
Modified residuei904 – 9041Phosphotyrosine1 Publication
Modified residuei939 – 9391Phosphotyrosine1 Publication
Modified residuei980 – 9801Phosphotyrosine; by autocatalysis2 Publications
Modified residuei981 – 9811Phosphotyrosine; by autocatalysis2 Publications

Post-translational modificationi

Tyrosine phosphorylated in response to IL-2 and IL-4. Dephosphorylation of Tyr-980 and Tyr-981 by PTPN2 negatively regulates cytokine-mediated signaling Inferred.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP52333.
PaxDbiP52333.
PRIDEiP52333.

PTM databases

PhosphoSiteiP52333.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

ArrayExpressiP52333.
BgeeiP52333.
CleanExiHS_JAK3.
GenevestigatoriP52333.

Interactioni

Subunit structurei

Interacts with STAM2 and MYO18A By similarity. Interacts with SHB.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KHDRBS1Q076662EBI-518246,EBI-1364

Protein-protein interaction databases

BioGridi109921. 32 interactions.
DIPiDIP-274N.
IntActiP52333. 11 interactions.
MINTiMINT-1497014.
STRINGi9606.ENSP00000391676.

Structurei

Secondary structure

1
1124
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi816 – 8183
Helixi819 – 8213
Beta strandi822 – 83110
Beta strandi834 – 8418
Beta strandi845 – 8473
Beta strandi849 – 85911
Helixi862 – 87615
Beta strandi886 – 8916
Beta strandi893 – 8953
Beta strandi897 – 9037
Helixi910 – 9178
Helixi918 – 9203
Helixi923 – 94220
Helixi952 – 9543
Beta strandi955 – 9595
Beta strandi962 – 9654
Helixi968 – 9703
Beta strandi979 – 9824
Helixi991 – 9933
Helixi996 – 10016
Beta strandi1003 – 10053
Helixi1006 – 102116
Turni1022 – 10243
Helixi1026 – 10283
Helixi1030 – 10378
Beta strandi1041 – 10433
Helixi1046 – 105510
Helixi1068 – 107710
Helixi1082 – 10843
Helixi1088 – 109710

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP52333.
SMRiP52333. Positions 24-780, 787-1103.

Miscellaneous databases

EvolutionaryTraceiP52333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 356333FERMAdd
BLAST
Domaini375 – 475101SH2; atypicalAdd
BLAST
Domaini521 – 781261Protein kinase 1Add
BLAST
Domaini822 – 1111290Protein kinase 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 223223Interaction with cytokine/interferon/growth hormone receptors By similarityAdd
BLAST

Domaini

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 1.1 Publication

Sequence similaritiesi

Contains 1 FERM domain.
Contains 1 SH2 domain.

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiP52333.
KOiK11218.
OMAiNCMESFL.
OrthoDBiEOG7BW0HM.
PhylomeDBiP52333.
TreeFamiTF327041.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. 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]
PfamiPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 2 (identifier: P52333-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA     50
EDLCVQAAKA SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY 100
RIRFYFPNWF GLEKCHRFGL RKDLASAILD LPVLEHLFAQ HRSDLVSGRL 150
PVGLSLKEQG ECLSLAVLDL ARMAREQAQR PGELLKTVSY KACLPPSLRD 200
LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM DLERLDPAGA 250
AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 300
ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR 350
LTTDSQHFFC KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV 400
LRRSPQDFDS FLLTVCVQNP LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL 450
RELLATCWDG GLHVDGVAVT LTSCCIPRPK EKSNLIVVQR GHSPPTSSLV 500
QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR HEVVDGEARK 550
TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 600
EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA 650
RKVLLAREGA DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ 700
TLSLEADKWG FGATVWEVFS GVTMPISALD PAKKLQFYED RQQLPAPKWT 750
ELALLIQQCM AYEPVQRPSF RAVIRDLNSL ISSDYELLSD PTPGALAPRD 800
GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR YDPLGDNTGA 850
LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 900
VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL 950
AARNILVESE AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS 1000
DNIFSRQSDV WSFGVVLYEL FTYCDKSCSP SAEFLRMMGC ERDVPALCRL 1050
LELLEEGQRL PAPPACPAEV HELMKLCWAP SPQDRPSFSA LGPQLDMLWS 1100
GSRGCETHAF TAHPEGKHHS LSFS 1124
Length:1,124
Mass (Da):125,099
Last modified:July 19, 2004 - v2
Checksum:i895D8563439B2B7C
GO
Isoform 1 (identifier: P52333-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:1,094
Mass (Da):121,268
Checksum:iD491FADB3D772693
GO
Isoform 3 (identifier: P52333-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     597-619: TMVQEFVHLGAIDMYLRKRGHLV → ESPPPTHPTPASPKSRLFFPPLF
     620-1124: Missing.

Note: No experimental confirmation available.

Show »
Length:619
Mass (Da):68,279
Checksum:i2DA342038998636C
GO

Sequence cautioni

The sequence AAC50227.1 differs from that shown. Reason: Wrong choice of CDS. Was erroneously described as an isoform JAK3M while it is a fragmentary mRNA of INSL3.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121P → L.1 Publication
Corresponds to variant rs56061056 [ dbSNP | Ensembl ].
VAR_041722
Natural varianti40 – 401R → H.1 Publication
Corresponds to variant rs56384680 [ dbSNP | Ensembl ].
VAR_041723
Natural varianti58 – 581Missing in T(-)B(+)NK(-) SCID. 1 Publication
VAR_019337
Natural varianti100 – 1001Y → C in T(-)B(+)NK(-) SCID. 1 Publication
VAR_006284
Natural varianti132 – 1321P → T.2 Publications
Corresponds to variant rs3212723 [ dbSNP | Ensembl ].
VAR_019336
Natural varianti151 – 1511P → R in T(-)B(+)NK(-) SCID. 2 Publications
Corresponds to variant rs55778349 [ dbSNP | Ensembl ].
VAR_010492
Natural varianti169 – 1691D → E in T(-)B(+)NK(-) SCID. 1 Publication
VAR_019338
Natural varianti481 – 4811E → G in T(-)B(+)NK(-) SCID. 1 Publication
VAR_010493
Natural varianti521 – 5211L → V.1 Publication
Corresponds to variant rs55666418 [ dbSNP | Ensembl ].
VAR_041724
Natural varianti527 – 5271L → P in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
VAR_041725
Natural varianti582 – 5821R → W in T(-)B(+)NK(-) SCID. 1 Publication
VAR_010494
Natural varianti586 – 5927Missing in T(-)B(+)NK(-) SCID; lack of phosphorylation in response to cytokine stimulation.
VAR_010495
Natural varianti589 – 5891G → S in T(-)B(+)NK(-) SCID. 1 Publication
VAR_019339
Natural varianti688 – 6881I → F.1 Publication
Corresponds to variant rs35785705 [ dbSNP | Ensembl ].
VAR_041726
Natural varianti722 – 7221V → I.4 Publications
Corresponds to variant rs3213409 [ dbSNP | Ensembl ].
VAR_010496
Natural varianti759 – 7591C → R in T(-)B(+)NK(-) SCID; constitutive phosphorylation. 1 Publication
VAR_010497
Natural varianti910 – 9101L → S in T(-)B(+)NK(-) SCID. 1 Publication
VAR_010498

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei597 – 61923TMVQE…RGHLV → ESPPPTHPTPASPKSRLFFP PLF in isoform 3. VSP_054165Add
BLAST
Alternative sequencei620 – 1124505Missing in isoform 3. VSP_054166Add
BLAST
Alternative sequencei1071 – 112454HELMK…SLSFS → SAAGLASVSQSVDWAGVSGK PAGA in isoform 1. VSP_004989Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti34 – 341G → A in AAA19626. 1 Publication
Sequence conflicti45 – 451F → S in AAC50950. 1 Publication
Sequence conflicti103 – 1031R → RS in AAC50950. 1 Publication
Sequence conflicti147 – 1471Missing in AAC50542. 1 Publication
Sequence conflicti187 – 1871T → A in AAC50542. 1 Publication
Sequence conflicti212 – 2121R → A in AAA19626. 1 Publication
Sequence conflicti212 – 2121R → A in AAC50950. 1 Publication
Sequence conflicti222 – 2221R → P in AAA19626. 1 Publication
Sequence conflicti222 – 2221R → P in AAC50950. 1 Publication
Sequence conflicti271 – 2711L → F in AAC50950. 1 Publication
Sequence conflicti287 – 2871Missing in AAC50950. 1 Publication
Sequence conflicti610 – 6101M → I in AAC50226. 1 Publication
Sequence conflicti845 – 8462GD → AH in AAA19626. 1 Publication
Sequence conflicti895 – 8973RQS → EPE in AAC50950. 1 Publication
Sequence conflicti896 – 8972QS → PE in AAA19626. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS12366.1. [P52333-1]
PIRiA55747.
RefSeqiNP_000206.2. NM_000215.3. [P52333-1]
XP_006722808.1. XM_006722745.1. [P52333-1]
UniGeneiHs.515247.

Genome annotation databases

EnsembliENST00000458235; ENSP00000391676; ENSG00000105639. [P52333-1]
ENST00000527670; ENSP00000432511; ENSG00000105639. [P52333-1]
ENST00000534444; ENSP00000436421; ENSG00000105639. [P52333-2]
GeneIDi3718.
KEGGihsa:3718.
UCSCiuc002nhn.4. human. [P52333-1]
uc002nho.2. human. [P52333-2]
uc010xpx.1. human.

Polymorphism databases

DMDMi50403745.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
JAK3base

JAK3 mutation db

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS12366.1. [P52333-1 ]
PIRi A55747.
RefSeqi NP_000206.2. NM_000215.3. [P52333-1 ]
XP_006722808.1. XM_006722745.1. [P52333-1 ]
UniGenei Hs.515247.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1YVJ X-ray 2.55 A 814-1103 [» ]
3LXK X-ray 2.00 A 806-1124 [» ]
3LXL X-ray 1.74 A 806-1124 [» ]
3PJC X-ray 2.20 A 812-1124 [» ]
3ZC6 X-ray 2.42 A/B/C/D 813-1100 [» ]
3ZEP X-ray 2.35 A/B/C/D 813-1047 [» ]
A/B/C/D 813-1100 [» ]
4HVD X-ray 1.85 A 811-1124 [» ]
4HVG X-ray 2.75 A 811-1124 [» ]
4HVH X-ray 2.30 A 811-1124 [» ]
4HVI X-ray 2.40 A 811-1124 [» ]
4I6Q X-ray 1.85 A 811-1124 [» ]
ProteinModelPortali P52333.
SMRi P52333. Positions 24-780, 787-1103.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109921. 32 interactions.
DIPi DIP-274N.
IntActi P52333. 11 interactions.
MINTi MINT-1497014.
STRINGi 9606.ENSP00000391676.

Chemistry

BindingDBi P52333.
ChEMBLi CHEMBL2148.
GuidetoPHARMACOLOGYi 2049.

PTM databases

PhosphoSitei P52333.

Polymorphism databases

DMDMi 50403745.

Proteomic databases

MaxQBi P52333.
PaxDbi P52333.
PRIDEi P52333.

Protocols and materials databases

DNASUi 3718.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000458235 ; ENSP00000391676 ; ENSG00000105639 . [P52333-1 ]
ENST00000527670 ; ENSP00000432511 ; ENSG00000105639 . [P52333-1 ]
ENST00000534444 ; ENSP00000436421 ; ENSG00000105639 . [P52333-2 ]
GeneIDi 3718.
KEGGi hsa:3718.
UCSCi uc002nhn.4. human. [P52333-1 ]
uc002nho.2. human. [P52333-2 ]
uc010xpx.1. human.

Organism-specific databases

CTDi 3718.
GeneCardsi GC19M017935.
HGNCi HGNC:6193. JAK3.
MIMi 600173. gene.
600802. phenotype.
neXtProti NX_P52333.
Orphaneti 35078. T-B+ severe combined immunodeficiency due to JAK3 deficiency.
PharmGKBi PA29990.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000049158.
HOVERGENi HBG006195.
InParanoidi P52333.
KOi K11218.
OMAi NCMESFL.
OrthoDBi EOG7BW0HM.
PhylomeDBi P52333.
TreeFami TF327041.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 2681.
Reactomei REACT_115529. Interleukin-7 signaling.
REACT_23891. Interleukin receptor SHC signaling.
REACT_27283. Interleukin-2 signaling.
SignaLinki P52333.

Miscellaneous databases

EvolutionaryTracei P52333.
GeneWikii Janus_kinase_3.
GenomeRNAii 3718.
NextBioi 14571.
PROi P52333.
SOURCEi Search...

Gene expression databases

ArrayExpressi P52333.
Bgeei P52333.
CleanExi HS_JAK3.
Genevestigatori P52333.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR019749. 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 ]
Pfami PF07714. Pkinase_Tyr. 2 hits.
[Graphical view ]
PIRSFi PIRSF000636. TyrPK_Jak. 1 hit.
PRINTSi PR01823. JANUSKINASE.
PR01826. JANUSKINASE3.
PR00109. TYRKINASE.
SMARTi SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEi PS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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. Cited for: REVIEW ON FUNCTION.
  20. 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.
    , 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.

Entry informationi

Entry nameiJAK3_HUMAN
AccessioniPrimary (citable) accession number: P52333
Secondary accession number(s): Q13259
, Q13260, Q13611, Q8N1E8, Q99699, Q9Y6S2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 19, 2004
Last modified: September 3, 2014
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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