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UniProtKB - Q62120 (JAK2_MOUSE)

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Protein

Tyrosine-protein kinase JAK2

Gene

Jak2

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, 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. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). 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.9 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

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 (PubMed:8343951, PubMed:20304997, PubMed:21726629). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (By similarity).By similarity1 Publication2 Publications

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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionChromatin regulator, Kinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity, Innate immunity
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase JAK2 (EC:2.7.10.22 Publications)
Alternative name(s):
Janus kinase 2
Short name:
JAK-2
Gene namesi
Name:Jak2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:96629 Jak2

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, 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). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206).By similarity8 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). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner. Interacts with STRA6 (By similarity).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi200857, 31 interactors
ComplexPortaliCPX-388 Interleukin-12-receptor complex
CPX-389 Interleukin-23-receptor complex
CORUMiQ62120
DIPiDIP-320N
IntActiQ62120, 24 interactors
MINTiQ62120
STRINGi10090.ENSMUSP00000025705

Chemistry databases

BindingDBiQ62120

Structurei

3D structure databases

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

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiQ62120
KOiK04447
PhylomeDBiQ62120

Family and domain databases

CDDicd13333 FERM_C_JAK2, 1 hit
cd05078 PTK_Jak2_rpt1, 1 hit
cd14205 PTKc_Jak2_rpt2, 1 hit
cd10379 SH2_Jak2, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR019749 Band_41_domain
IPR035963 FERM_2
IPR000299 FERM_domain
IPR037838 JAK2_FERM_C-lobe
IPR035860 JAK2_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR035588 PTK_Jak2_rpt1
IPR035589 PTKc_Jak2_rpt2
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
IPR020693 Tyr_kinase_non-rcpt_Jak2
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 2 hits
PF00017 SH2, 1 hit
PIRSFiPIRSF000636 TyrPK_Jak, 1 hit
PRINTSiPR01823 JANUSKINASE
PR01825 JANUSKINASE2
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00295 B41, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 2 hits
SUPFAMiSSF47031 SSF47031, 1 hit
SSF55550 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
PS50001 SH2, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiJAK2_MOUSE
AccessioniPrimary (citable) accession number: Q62120
Secondary accession number(s): Q62124, Q7TQD0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 20, 2008
Last modified: July 18, 2018
This is version 193 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

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

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