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Protein

Tyrosine-protein kinase JAK2

Gene

Jak2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. 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, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.8 Publications

Catalytic activityi

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

Cofactori

Mg2+CuratedNote: Mn2+ was used in the in vitro kinase assay but Mg2+ is likely to be the in vivo cofactor.Curated

Enzyme regulationi

Regulated by autophosphorylation, can both activate or decrease activity. Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei882ATPPROSITE-ProRule annotation1
Active sitei976Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi855 – 863ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-982772. Growth hormone receptor signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK2 (EC:2.7.10.2)
Alternative name(s):
Janus kinase 2
Short name:
JAK-2
Gene namesi
Name:Jak2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:96629. Jak2.

Subcellular locationi

GO - Cellular componenti

  • caveola Source: MGI
  • cytoplasm Source: BHF-UCL
  • cytoskeleton Source: InterPro
  • cytosol Source: Reactome
  • endomembrane system Source: UniProtKB-SubCell
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • membrane raft Source: MGI
  • nuclear matrix Source: BHF-UCL
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryos are anemic and die around day 12.5 post-coitum (dpc). Primitive erythrocytes are found, but definitive erythropoiesis is absent. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fail to respond to erythropoietin (Epo), thrombopoietin (Thpo), interleukin-3 (Il3), or granulocyte and macrophage colony-stimulating factor 1 (Csf1 and Csf2). Fetal liver BFU-E and CFU-E colonies are completely absent. However, multilineage hematopoietic stem cells (CD34(low), c-kit(pos)) can be found, and B-lymphopoiesis appears intact.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi119Y → E: Phosphorylation mimic mutant, leads to dissociation of JAK2 from the erythropoietin receptor complex. 1 Publication1
Mutagenesisi119Y → F: More stably associated with the erythropoietin receptor complex. 1 Publication1
Mutagenesisi372Y → F: About 60% loss of STAT1 phosphorylation by JAK2. 1 Publication1
Mutagenesisi373Y → F: Decreased the ability of JAK2 to autophosphorylate. 1 Publication1
Mutagenesisi868Y → F: Reduced activity in response to growth hormone. 1 Publication1
Mutagenesisi966Y → F: Reduced activity in response to growth hormone. 1 Publication1
Mutagenesisi972Y → F: Reduced activity in response to growth hormone. 1 Publication1
Mutagenesisi1008Y → F: Affects the phosphorylation pattern. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1649049.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881131 – 1129Tyrosine-protein kinase JAK2Add BLAST1129

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei119Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei372Phosphotyrosine1 Publication1
Modified residuei373Phosphotyrosine1 Publication1
Modified residuei523PhosphoserineCombined sources1
Modified residuei570PhosphotyrosineBy similarity1
Modified residuei813Phosphotyrosine2 Publications1
Modified residuei868Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei966Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei972Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1007Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1008Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (PubMed:16824542, PubMed:17565041). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (PubMed:17024180). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (PubMed:20304997). Also phosphorylated by TEC (PubMed:9473212). Phosphorylated on tyrosine residues in response to interferon gamma signaling (By similarity).By similarity6 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ62120.
PaxDbiQ62120.
PRIDEiQ62120.

PTM databases

iPTMnetiQ62120.
PhosphoSitePlusiQ62120.

Expressioni

Tissue specificityi

Ubiquitously expressed throughout most tissues.

Gene expression databases

CleanExiMM_JAK2.

Interactioni

Subunit structurei

Interacts with IL23R, SKB1 and STAM2 (By similarity). Interacts with EPOR (PubMed:8343951, PubMed:11779507). Interacts with LYN (PubMed:9573010). Interacts with SIRPA (PubMed:10842184). Interacts with SH2B1 (PubMed:17565041, PubMed:16824542). Interacts with TEC (PubMed:9473212). Interacts with IFNGR2 (via intracellular domain) (By similarity). Interacts with LEPR (Isoform B) (PubMed:11923481).By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDKN1BP465277EBI-646604,EBI-519280From a different organism.
EporP147534EBI-646604,EBI-617901
Fcer1gP204912EBI-646604,EBI-9306159
IL23RQ5VWK52EBI-646604,EBI-10248005From a different organism.
Plcg1P106863EBI-646604,EBI-520788From a different organism.
Sh2b1Q91ZM23EBI-646604,EBI-7178606
SHC1P293532EBI-646604,EBI-78835From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200857. 31 interactors.
DIPiDIP-320N.
IntActiQ62120. 18 interactors.
MINTiMINT-188474.
STRINGi10090.ENSMUSP00000025705.

Chemistry databases

BindingDBiQ62120.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HDXX-ray2.35G/H/I/J/K/L810-820[»]
4GL9X-ray3.90A/B/C/D836-1129[»]
ProteinModelPortaliQ62120.
SMRiQ62120.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62120.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini37 – 380FERMPROSITE-ProRule annotationAdd BLAST344
Domaini401 – 482SH2; atypicalPROSITE-ProRule annotationAdd BLAST82
Domaini545 – 809Protein kinase 1PROSITE-ProRule annotationAdd BLAST265
Domaini849 – 1124Protein kinase 2PROSITE-ProRule annotationAdd BLAST276

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 239Interaction with cytokine/interferon/growth hormone receptorsAdd BLAST239

Domaini

Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation
Contains 1 FERM domain.PROSITE-ProRule annotation
Contains 2 protein kinase domains.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiQ62120.
KOiK04447.
PhylomeDBiQ62120.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
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.
IPR020693. Tyr_kinase_non-rcpt_Jak2.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. 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.
PS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q62120-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGMACLTMTE MEATSTSPVH QNGDIPGSAN SVKQIEPVLQ VYLYHSLGQA
60 70 80 90 100
EGEYLKFPSG EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH
110 120 130 140 150
VFHIDESTRH DILYRIRFYF PHWYCSGSSR TYRYGVSRGA EAPLLDDFVM
160 170 180 190 200
SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KEKDQTPLAV
210 220 230 240 250
YNSVSYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL
260 270 280 290 300
KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR
310 320 330 340 350
GKHKESETLT EQDVQLYCDF PDIIDVSIKQ ANQECSNESR IVTVHKQDGK
360 370 380 390 400
VLEIELSSLK EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC
410 420 430 440 450
HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK
460 470 480 490 500
HCLITKNENG EYNLSGTKRN FSNLKDLLNC YQMETVRSDS IIFQFTKCCP
510 520 530 540 550
PKPKDKSNLL VFRTNGISDV QISPTLQRHN NVNQMVFHKI RNEDLIFNES
560 570 580 590 600
LGQGTFTKIF KGVRREVGDY GQLHKTEVLL KVLDKAHRNY SESFFEAASM
610 620 630 640 650
MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK
660 670 680 690 700
LGVAKQLAWA MHFLEEKSLI HGNVCAKNIL LIREENRRTG NPPFIKLSDP
710 720 730 740 750
GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG
760 770 780 790 800
DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL ANLINNCMDY EPDFRPAFRA
810 820 830 840 850
VIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK
860 870 880 890 900
FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE
910 920 930 940 950
ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH
960 970 980 990 1000
KKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV
1010 1020 1030 1040 1050
LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY
1060 1070 1080 1090 1100
IEKSKSPPVE FMRMIGNDKQ GQMIVFHLIE LLKSNGRLPR PEGCPDEIYV
1110 1120
IMTECWNNNV SQRPSFRDLS LRVDQIIAA
Length:1,129
Mass (Da):130,235
Last modified:May 20, 2008 - v2
Checksum:iDCB90FA000F99631
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti155A → V in AAB41327 (PubMed:8378315).Curated1
Sequence conflicti468K → N in AAB41327 (PubMed:8378315).Curated1
Sequence conflicti686N → D in AAB41327 (PubMed:8378315).Curated1
Sequence conflicti1016S → R in AAA40014 (PubMed:2466296).Curated1
Sequence conflicti1024E → Q in AAB41327 (PubMed:8378315).Curated1
Sequence conflicti1042 – 1043VV → IP in AAA40014 (PubMed:2466296).Curated2
Sequence conflicti1121 – 1129LRVDQIIAA → FGWIKCGTV in AAB41327 (PubMed:8378315).Curated9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L16956 mRNA. Translation: AAB41327.1.
BC054807 mRNA. Translation: AAH54807.1.
BC059834 mRNA. Translation: AAH59834.1.
M33423 mRNA. Translation: AAA40014.1.
PIRiA47511.
B39577.
JH0114.
RefSeqiNP_001041642.1. NM_001048177.2.
NP_032439.2. NM_008413.3.
UniGeneiMm.275839.

Genome annotation databases

GeneIDi16452.
KEGGimmu:16452.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L16956 mRNA. Translation: AAB41327.1.
BC054807 mRNA. Translation: AAH54807.1.
BC059834 mRNA. Translation: AAH59834.1.
M33423 mRNA. Translation: AAA40014.1.
PIRiA47511.
B39577.
JH0114.
RefSeqiNP_001041642.1. NM_001048177.2.
NP_032439.2. NM_008413.3.
UniGeneiMm.275839.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HDXX-ray2.35G/H/I/J/K/L810-820[»]
4GL9X-ray3.90A/B/C/D836-1129[»]
ProteinModelPortaliQ62120.
SMRiQ62120.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200857. 31 interactors.
DIPiDIP-320N.
IntActiQ62120. 18 interactors.
MINTiMINT-188474.
STRINGi10090.ENSMUSP00000025705.

Chemistry databases

BindingDBiQ62120.
ChEMBLiCHEMBL1649049.

PTM databases

iPTMnetiQ62120.
PhosphoSitePlusiQ62120.

Proteomic databases

MaxQBiQ62120.
PaxDbiQ62120.
PRIDEiQ62120.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi16452.
KEGGimmu:16452.

Organism-specific databases

CTDi3717.
MGIiMGI:96629. Jak2.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
InParanoidiQ62120.
KOiK04447.
PhylomeDBiQ62120.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-982772. Growth hormone receptor signaling.

Miscellaneous databases

ChiTaRSiJak2. mouse.
EvolutionaryTraceiQ62120.
PROiQ62120.
SOURCEiSearch...

Gene expression databases

CleanExiMM_JAK2.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
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.
IPR020693. Tyr_kinase_non-rcpt_Jak2.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. 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.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiJAK2_MOUSE
AccessioniPrimary (citable) accession number: Q62120
Secondary accession number(s): Q62124, Q7TQD0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 20, 2008
Last modified: November 2, 2016
This is version 176 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.