UniProtKB - O19064 (JAK2_PIG)
Protein
Tyrosine-protein kinase JAK2
Gene
JAK2
Organism
Sus scrofa (Pig)
Status
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.By similarity
Catalytic activityi
- EC:2.7.10.2PROSITE-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
Activity 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
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 882 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 976 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 855 – 863 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- growth hormone receptor binding Source: GO_Central
- heme binding Source: UniProtKB
- histone binding Source: UniProtKB
- histone kinase activity (H3-Y41 specific) Source: UniProtKB
- identical protein binding Source: Ensembl
- metal ion binding Source: UniProtKB-KW
- protein kinase binding Source: Ensembl
- protein tyrosine kinase activity Source: UniProtKB
- SH2 domain binding Source: Ensembl
GO - Biological processi
- activation of Janus kinase activity Source: UniProtKB
- adaptive immune response Source: UniProtKB-KW
- cytokine-mediated signaling pathway Source: UniProtKB
- erythrocyte differentiation Source: UniProtKB
- growth hormone receptor signaling pathway via JAK-STAT Source: UniProtKB
- histone H3-Y41 phosphorylation Source: UniProtKB
- innate immune response Source: UniProtKB-KW
- interleukin-12-mediated signaling pathway Source: Ensembl
- intracellular signal transduction Source: InterPro
- positive regulation of cell-substrate adhesion Source: Ensembl
- positive regulation of SMAD protein signal transduction Source: Ensembl
- positive regulation of tyrosine phosphorylation of STAT protein Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- regulation of apoptotic process Source: GO_Central
- regulation of inflammatory response Source: Ensembl
- response to antibiotic Source: Ensembl
- signal transduction Source: UniProtKB
- tumor necrosis factor-mediated signaling pathway Source: Ensembl
- tyrosine phosphorylation of STAT protein Source: GO_Central
Keywordsi
Molecular function | Chromatin regulator, Kinase, Transferase, Tyrosine-protein kinase |
Biological process | Adaptive immunity, Immunity, Innate immunity |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
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 |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:89271, JAK2 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Endomembrane system By similarity; Peripheral membrane protein By similarity
- Cytoplasm By similarity
Cytoskeleton
- cytoskeleton Source: InterPro
Nucleus
- nucleoplasm Source: Ensembl
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: Ensembl
Other locations
- cytoplasm Source: UniProtKB-SubCell
- endomembrane system Source: UniProtKB-SubCell
- focal adhesion Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000324093 | 1 – 1131 | Tyrosine-protein kinase JAK2Add BLAST | 1131 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 119 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 372 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 373 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 523 | PhosphoserineBy similarity | 1 | |
Modified residuei | 570 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 813 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 868 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 966 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 972 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 1007 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 1008 | Phosphotyrosine; by autocatalysisBy similarity | 1 |
Post-translational modificationi
Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813. Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity. Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity. Also phosphorylated by TEC (By similarity). Phosphorylated on tyrosine residues in response to interferon gamma signaling. Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (By similarity).By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | O19064 |
PRIDEi | O19064 |
Interactioni
Subunit structurei
Interacts with IL23R, SKB1 and STAM2 (By similarity).
Interacts with EPOR.
Interacts with LYN.
Interacts with SIRPA.
Interacts with SH2B1.
Interacts with TEC (By similarity).
Interacts with IFNGR2 (via intracellular domain) (By similarity).
Interacts with LEPR (Isoform B) (By similarity).
Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner.
Interacts with STRA6 (By similarity).
By similarityGO - Molecular functioni
- growth hormone receptor binding Source: GO_Central
- histone binding Source: UniProtKB
- identical protein binding Source: Ensembl
- protein kinase binding Source: Ensembl
- SH2 domain binding Source: Ensembl
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000005606 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 37 – 380 | FERMPROSITE-ProRule annotationAdd BLAST | 344 | |
Domaini | 401 – 482 | SH2; atypicalPROSITE-ProRule annotationAdd BLAST | 82 | |
Domaini | 545 – 809 | Protein kinase 1PROSITE-ProRule annotationAdd BLAST | 265 | |
Domaini | 849 – 1126 | Protein kinase 2PROSITE-ProRule annotationAdd BLAST | 278 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 239 | Interaction with cytokine/interferon/growth hormone receptorsBy similarityAdd BLAST | 239 |
Domaini
The N-terminal domain of JAKs mediates their interaction with cytokine/interferon/growth hormone receptors. 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 (By similarity).By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation
Keywords - Domaini
Repeat, SH2 domainPhylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000155640 |
InParanoidi | O19064 |
OMAi | HIFHVDE |
OrthoDBi | 58906at2759 |
Family and domain databases
CDDi | cd13333, FERM_C_JAK2, 1 hit cd05078, PTK_Jak2_rpt1, 1 hit cd14205, PTKc_Jak2_rpt2, 1 hit cd10379, SH2_Jak2, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR019749, Band_41_domain IPR035963, FERM_2 IPR000299, FERM_domain IPR041155, FERM_F1 IPR041046, FERM_F2 IPR041381, Jak1_PHL_dom 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 |
Pfami | View protein in Pfam PF18379, FERM_F1, 1 hit PF18377, FERM_F2, 1 hit PF17887, Jak1_Phl, 1 hit PF07714, PK_Tyr_Ser-Thr, 2 hits PF00017, SH2, 1 hit |
PIRSFi | PIRSF000636, TyrPK_Jak, 1 hit |
PRINTSi | PR01823, JANUSKINASE PR01825, JANUSKINASE2 PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00295, B41, 1 hit SM00252, SH2, 1 hit SM00219, TyrKc, 2 hits |
SUPFAMi | SSF47031, SSF47031, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 2 hits |
PROSITEi | View 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 |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
O19064-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGMACLTMTE MEGTSTSPVH QNGDIPGNAN SVKQIDPVLQ VYLYHSLGKA
60 70 80 90 100
EGDYLKFPAG EYVAEEICVA ASKACGITPV YHSMFALMNE TERIWYPPNH
110 120 130 140 150
VFHVDESTRH NVLYRIRFYF PYWYCNGSNR TYRHGISRGA EAPLLDDFVM
160 170 180 190 200
SYLFAQWRHD FLYGWVKIPV THETQEECLG MAVLDMMRIA KEKDQTPLDI
210 220 230 240 250
YSSVSYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIEQF SHCKATARNL
260 270 280 290 300
KLKYLINLET LQSAFYTEQF EVKEPGRGPS GEEIFATIII TGNGGIQWSR
310 320 330 340 350
GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQEGSNESR IVTIHKQDGK
360 370 380 390 400
SLEIELSSLR EALSFVSLID GYYRLTADAH HYLCKEVAPP MVLENIQSNC
410 420 430 440 450
HGPISMDFAI SKLKKAGNQT GLFVLRCSPK DFNKYFLTFA VERENVTEYK
460 470 480 490 500
HCLITKNENG EYNLSGTRKN FSNLKDLLNC YQMETVRSDS IIFQFTKCCP
510 520 530 540 550
PKPKDKSNLL VFRTNGISDV PTSPTLQRHN NVNQMVFHKI RNEDLIFNES
560 570 580 590 600
LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM
610 620 630 640 650
MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK
660 670 680 690 700
LEVAKQLAWA MHFLEEKTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP
710 720 730 740 750
GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG
760 770 780 790 800
DKPLNALDSQ RKLQFYEDRH QLPAPKWTEL ANLINNCMDY EPDFRPSFRA
810 820 830 840 850
IIRDLNSLFT 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
IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PDGCPDEIYI
1110 1120 1130
IMTECWNNNV NQRPSFRDLA LRVDQIRDSM A
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ9JIK9 | J9JIK9_PIG | Tyrosine-protein kinase | JAK2 | 1,095 | Annotation score: | ||
A0A5G2R6U0 | A0A5G2R6U0_PIG | Tyrosine-protein kinase | JAK2 | 1,068 | Annotation score: | ||
Q9TTJ0 | Q9TTJ0_PIG | Tyrosine-protein kinase | JAK2 | 861 | Annotation score: | ||
A0A5G2QGG0 | A0A5G2QGG0_PIG | Tyrosine-protein kinase | JAK2 | 864 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB006011 mRNA Translation: BAA21662.1 |
RefSeqi | NP_999278.1, NM_214113.1 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB006011 mRNA Translation: BAA21662.1 |
RefSeqi | NP_999278.1, NM_214113.1 |
3D structure databases
SMRi | O19064 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000005606 |
Proteomic databases
PaxDbi | O19064 |
PRIDEi | O19064 |
Genome annotation databases
Organism-specific databases
CTDi | 3717 |
VGNCi | VGNC:89271, JAK2 |
Phylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000155640 |
InParanoidi | O19064 |
OMAi | HIFHVDE |
OrthoDBi | 58906at2759 |
Miscellaneous databases
ChiTaRSi | JAK2, pig |
Gene expression databases
ExpressionAtlasi | O19064, baseline and differential |
Family and domain databases
CDDi | cd13333, FERM_C_JAK2, 1 hit cd05078, PTK_Jak2_rpt1, 1 hit cd14205, PTKc_Jak2_rpt2, 1 hit cd10379, SH2_Jak2, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR019749, Band_41_domain IPR035963, FERM_2 IPR000299, FERM_domain IPR041155, FERM_F1 IPR041046, FERM_F2 IPR041381, Jak1_PHL_dom 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 |
Pfami | View protein in Pfam PF18379, FERM_F1, 1 hit PF18377, FERM_F2, 1 hit PF17887, Jak1_Phl, 1 hit PF07714, PK_Tyr_Ser-Thr, 2 hits PF00017, SH2, 1 hit |
PIRSFi | PIRSF000636, TyrPK_Jak, 1 hit |
PRINTSi | PR01823, JANUSKINASE PR01825, JANUSKINASE2 PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00295, B41, 1 hit SM00252, SH2, 1 hit SM00219, TyrKc, 2 hits |
SUPFAMi | SSF47031, SSF47031, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 2 hits |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | JAK2_PIG | |
Accessioni | O19064Primary (citable) accession number: O19064 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | January 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 144 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families