Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein kinase JAK3

Gene

Jak3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei851ATPPROSITE-ProRule annotation1
Active sitei945Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi824 – 832ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • B cell differentiation Source: BHF-UCL
  • cell migration Source: GO_Central
  • cellular response to cytokine stimulus Source: MGI
  • cytokine-mediated signaling pathway Source: MGI
  • enzyme linked receptor protein signaling pathway Source: MGI
  • erythrocyte differentiation Source: GO_Central
  • inflammatory response Source: GO_Central
  • innate immune response Source: GO_Central
  • interleukin-4-mediated signaling pathway Source: MGI
  • intracellular signal transduction Source: MGI
  • lymph node development Source: MGI
  • negative regulation of dendritic cell cytokine production Source: BHF-UCL
  • negative regulation of FasL biosynthetic process Source: BHF-UCL
  • negative regulation of interleukin-10 production Source: BHF-UCL
  • negative regulation of interleukin-12 production Source: BHF-UCL
  • negative regulation of T cell activation Source: BHF-UCL
  • negative regulation of T-helper 1 cell differentiation Source: BHF-UCL
  • negative regulation of thymocyte apoptotic process Source: BHF-UCL
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of activated T cell proliferation Source: BHF-UCL
  • positive regulation of calcium ion transport Source: BHF-UCL
  • positive regulation of cytosolic calcium ion concentration Source: BHF-UCL
  • positive regulation of dendritic cell apoptotic process Source: BHF-UCL
  • positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • positive regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • regulation of T cell apoptotic process Source: BHF-UCL
  • response to interleukin-15 Source: BHF-UCL
  • response to interleukin-2 Source: BHF-UCL
  • response to interleukin-4 Source: BHF-UCL
  • response to interleukin-9 Source: BHF-UCL
  • T cell homeostasis Source: BHF-UCL
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
  • tyrosine phosphorylation of STAT protein Source: GO_Central

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474

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
Gene namesi
Name:Jak3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:99928 Jak3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show a severe block in B-cell development at the pre-B stage in the bone marrow. Additionally, they possesses small thymuses revealing a defect in T-cell development. The distribution of developmental subsets is relatively normal, suggesting a block in the expansion of early T-cell progenitors. Peripheral T-cells are present at normal or increased numbers but are functionally incompetent.3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi853L → R: Loss of activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5250

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881161 – 1100Tyrosine-protein kinase JAK3Add BLAST1100

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei17PhosphoserineCombined sources1
Modified residuei781Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei900PhosphotyrosineBy similarity1
Modified residuei935PhosphotyrosineBy similarity1
Modified residuei976Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei977Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated, leading to regulate its activity. IL2 promotes phosphorylation on tyrosine residues, including autophosphorylation on Tyr-781 (By similarity). Dephosphorylation of Tyr-976 and Tyr-977 by PTPN2 negatively regulates cytokine-mediated signaling (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ62137
PaxDbiQ62137
PRIDEiQ62137

PTM databases

iPTMnetiQ62137
PhosphoSitePlusiQ62137

Expressioni

Tissue specificityi

In contrast with the ubiquitous expression of the other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.1 Publication

Gene expression databases

CleanExiMM_JAK3

Interactioni

Subunit structurei

Interacts with STAM2 and MYO18A. Interacts with SHB (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200858, 5 interactors
IntActiQ62137, 2 interactors
MINTiQ62137
STRINGi10090.ENSMUSP00000060073

Chemistry databases

BindingDBiQ62137

Structurei

3D structure databases

ProteinModelPortaliQ62137
SMRiQ62137
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 353FERMPROSITE-ProRule annotationAdd BLAST330
Domaini372 – 472SH2; atypicalAdd BLAST101
Domaini517 – 777Protein kinase 1PROSITE-ProRule annotationAdd BLAST261
Domaini818 – 1100Protein kinase 2PROSITE-ProRule annotationAdd BLAST283

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 223Interaction with cytokine/interferon/growth hormone receptorsBy similarityAdd BLAST223

Domaini

Possesses two phosphotransferase domains. The second one contains the catalytic domain, while the presence of a pseudokinase domain is required for suppression of basal activity of JAK3.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
HOVERGENiHBG006195
InParanoidiQ62137
KOiK11218
PhylomeDBiQ62137
TreeFamiTF327041

Family and domain databases

Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR000299 FERM_domain
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016251 Tyr_kinase_non-rcpt_Jak/Tyk2
IPR020775 Tyr_kinase_non-rcpt_Jak3
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 2 hits
PIRSFiPIRSF000636 TyrPK_Jak, 1 hit
PRINTSiPR01823 JANUSKINASE
PR01826 JANUSKINASE3
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 2 hits
SUPFAMiSSF55550 SSF55550, 2 hits
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS50057 FERM_3, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 2 hits
PS00109 PROTEIN_KINASE_TYR, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q62137-1) [UniParc]FASTAAdd to basket

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

        10         20         30         40         50
MAPPSEETPL IPQRSCSLSS SEAGALHVLL PPRGPGPPQR LSFSFGDYLA
60 70 80 90 100
EDLCVRAAKA CGILPVYHSL FALATEDFSC WFPPSHIFCI EDVDTQVLVY
110 120 130 140 150
RLRFYFPDWF GLETCHRFGL RKDLTSAILD LHVLEHLFAQ HRSDLVSGRL
160 170 180 190 200
PVGLSMKEQG EFLSLAVLDL AQMAREQAQR PGELLKTVSY KACLPPSLRD
210 220 230 240 250
VIQGQNFVTR RRIRRTVVLA LRRVVACQAD RYALMAKYIL DLERLHPAAT
260 270 280 290 300
TETFRVGLPG AQEEPGLLRV AGDNGISWSS GDQELFQTFC DFPEIVDVSI
310 320 330 340 350
KQAPRVGPAG EHRLVTVTRM DGHILEAEFP GLPEALSFVA LVDGYFRLIC
360 370 380 390 400
DSRHYFCKEV APPRLLEEEA ELCHGPITLD FAIHKLKAAG SLPGTYILRR
410 420 430 440 450
SPQDYDSFLL TACVQTPLGP DYKGCLIRQD PSGAFSLVGL SQPHRSLREL
460 470 480 490 500
LAACWNSGLR VDGAALNLTS CCAPRPKEKS NLIVVRRGCT PAPAPGCSPS
510 520 530 540 550
CCALTQLSFH TIPTDSLEWH ENLGHGSFTK IFRGRRREVV DGETHDSEVL
560 570 580 590 600
LKVMDSRHRN CMESFLEAAS LMSQVSYPHL VLLHGVCMAG DSIMVQEFVY
610 620 630 640 650
LGAIDMYLRK RGHLVSASWK LQVTKQLAYA LNYLEDKGLP HGNVSARKVL
660 670 680 690 700
LAREGGDGNP PFIKLSDPGV SPTVLSLEML TDRIPWVAPE CLQEAQTLCL
710 720 730 740 750
EADKWGFGAT TWEVFSGGPA HITSLEPAKK LKFYEDQGQL PALKWTELAG
760 770 780 790 800
LITQCMAYDP GRRPSFRAIL RDLNGLITSD YELLSDPTPG IPSPRDELCG
810 820 830 840 850
GAQLYACQDP AIFEERHLKY ISLLGKGNFG SVELCRYDPL GDNTGPLVAV
860 870 880 890 900
KQLQHSGPDQ QRDFQREIQI LKALHSDFIV KYRGVSYGPG RQSLRLVMEY
910 920 930 940 950
LPSGCLRDFL QRHRARLHTD RLLLFAWQIC KGMEYLGARR CVHRDLAARN
960 970 980 990 1000
ILVESEAHVK IADFGLAKLL PLGKDYYVVR EPGQSPIFWY APESLSDNIF
1010 1020 1030 1040 1050
SRQSDVWSFG VVLYELFTYC DKSCSPSAEF LRMMGPEREG PPLCRLLELL
1060 1070 1080 1090 1100
AEGRRLPPPP TCPTEVQELM QLCWAPSPHD RPAFGTLSPQ LDALWRGRPG
Length:1,100
Mass (Da):122,641
Last modified:August 21, 2007 - v2
Checksum:i979A120861ED37C1
GO
Isoform 2 (identifier: Q62137-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     284-284: E → EVLGLGLRSG...RRYCLSFLPQ
     379-379: L → LGASWGQQWGWGWAARTVLGWTWLLSWPRL

Note: No experimental confirmation available.
Show »
Length:1,319
Mass (Da):146,899
Checksum:iCC2DDD3C6F824439
GO

Sequence cautioni

The sequence AAA21415 differs from that shown. Reason: Frameshift at several positions.Curated
The sequence AAA21565 differs from that shown. Reason: Frameshift at positions 222 and 232.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti62G → A in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti62G → A in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti277S → P in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti281 – 283GDQ → ND in AAA21565 (PubMed:8605329).Curated3
Sequence conflicti301K → N in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti362P → A in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti371 – 372EL → DV in AAA21565 (PubMed:8605329).Curated2
Sequence conflicti390G → A in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti454Missing in BAC40305 (PubMed:16141072).Curated1
Sequence conflicti467N → Y in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti490T → N in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti518 – 519EW → G in AAA21415 (PubMed:7518579).Curated2
Sequence conflicti535R → S in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti699C → G in BAC40305 (PubMed:16141072).Curated1
Sequence conflicti699C → G in BAC29956 (PubMed:16141072).Curated1
Sequence conflicti699C → G in BAE24964 (PubMed:16141072).Curated1
Sequence conflicti699C → G in BAE33790 (PubMed:16141072).Curated1
Sequence conflicti699C → G in BAE37819 (PubMed:16141072).Curated1
Sequence conflicti716 – 717SG → QR in AAA21565 (PubMed:8605329).Curated2
Sequence conflicti800G → VA in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti826K → N in AAI31647 (PubMed:15489334).Curated1
Sequence conflicti841Missing in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti857G → V in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti909F → L in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti915 – 916AR → G in AAA21565 (PubMed:8605329).Curated2
Sequence conflicti916R → A in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti1032R → S in BAC40305 (PubMed:16141072).Curated1
Sequence conflicti1032R → S in BAC29956 (PubMed:16141072).Curated1
Sequence conflicti1032R → S in BAE24964 (PubMed:16141072).Curated1
Sequence conflicti1032R → S in BAE33790 (PubMed:16141072).Curated1
Sequence conflicti1032R → S in BAE37819 (PubMed:16141072).Curated1
Sequence conflicti1074W → V in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti1077S → E in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti1085G → A in AAA21565 (PubMed:8605329).Curated1
Sequence conflicti1093A → G in AAA21415 (PubMed:7518579).Curated1
Sequence conflicti1093A → P in AAA21565 (PubMed:8605329).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_027575284E → EVLGLGLRSGVRGEAWRLVK KPVRTIRKVASPGRADCTTG QGGGVNLKVGPGMELPQGLT WGVTRRVRLDRGRGRTEGDS MDWISGHDPTRPVFSPLTSS PPPHKWRWEGGRRGGCAGSR SVIPWLLSLFLFFFFNGFAR QGFSYSSGCPGTHFVRPGWP RTQKSACLCLSSAVIKGRVP LRRYCLSFLPQ in isoform 2. 1 Publication1
Alternative sequenceiVSP_027576379L → LGASWGQQWGWGWAARTVLG WTWLLSWPRL in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33768 mRNA Translation: AAA21415.1 Frameshift.
L40172 mRNA Translation: AAC42085.1
L32955 mRNA Translation: AAA21565.1 Frameshift.
AK038268 mRNA Translation: BAC29956.1
AK142178 mRNA Translation: BAE24964.1
AK156646 mRNA Translation: BAE33790.1
AK164520 mRNA Translation: BAE37819.1
AK088365 mRNA Translation: BAC40305.1
BC105577 mRNA Translation: AAI05578.1
BC131646 mRNA Translation: AAI31647.1
BC131647 mRNA Translation: AAI31648.1
CCDSiCCDS22403.1 [Q62137-1]
PIRiI58401
S48053
RefSeqiNP_001177759.1, NM_001190830.1
NP_034719.2, NM_010589.6
UniGeneiMm.249645
Mm.476857

Genome annotation databases

GeneIDi16453
KEGGimmu:16453
UCSCiuc009mel.2 mouse [Q62137-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiJAK3_MOUSE
AccessioniPrimary (citable) accession number: Q62137
Secondary accession number(s): A2RRI3
, Q0D2M8, Q61746, Q61747, Q8BTY6, Q8BYU2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 21, 2007
Last modified: May 23, 2018
This is version 183 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health