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Protein

Tyrosine-protein kinase JAK2

Gene

JAK2

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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.By similarity

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

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

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

ReactomeiR-SSC-1059683 Interleukin-6 signaling
R-SSC-110056 MAPK3 (ERK1) activation
R-SSC-112411 MAPK1 (ERK2) activation
R-SSC-1170546 Prolactin receptor signaling
R-SSC-1433557 Signaling by SCF-KIT
R-SSC-392451 G beta:gamma signalling through PI3Kgamma
R-SSC-512988 Interleukin-3, 5 and GM-CSF signaling
R-SSC-5673000 RAF activation
R-SSC-5673001 RAF/MAP kinase cascade
R-SSC-6785807 Interleukin-4 and 13 signaling
R-SSC-6788467 IL-6-type cytokine receptor ligand interactions
R-SSC-69231 Cyclin D associated events in G1
R-SSC-877300 Interferon gamma signaling
R-SSC-877312 Regulation of IFNG signaling
R-SSC-8854691 Interleukin-20 family signaling
R-SSC-8984722 Interleukin-35 Signalling
R-SSC-9020591 Interleukin-12 signaling
R-SSC-9020933 Interleukin-23 signaling
R-SSC-9020956 Interleukin-27 signaling
R-SSC-912526 Interleukin receptor SHC signaling
R-SSC-982772 Growth hormone receptor signaling
R-SSC-983231 Factors involved in megakaryocyte development and platelet production

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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003240931 – 1131Tyrosine-protein kinase JAK2Add BLAST1131

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei119Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei372PhosphotyrosineBy similarity1
Modified residuei373PhosphotyrosineBy similarity1
Modified residuei523PhosphoserineBy similarity1
Modified residuei570PhosphotyrosineBy similarity1
Modified residuei813PhosphotyrosineBy similarity1
Modified residuei868Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei966Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei972Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1007Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1008Phosphotyrosine; by autocatalysisBy similarity1

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

Phosphoprotein

Proteomic databases

PaxDbiO19064
PRIDEiO19064

Expressioni

Gene expression databases

ExpressionAtlasiO19064 baseline and differential

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 similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000005606

Structurei

3D structure databases

ProteinModelPortaliO19064
SMRiO19064
ModBaseiSearch...
MobiDBiSearch...

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 – 1126Protein kinase 2PROSITE-ProRule annotationAdd BLAST278

Region

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

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 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00900000140909
HOGENOMiHOG000049158
HOVERGENiHBG006195
InParanoidiO19064
KOiK04447

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, 1 hit
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.

O19064-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,131
Mass (Da):130,759
Last modified:January 1, 1998 - v1
Checksum:i6339C7417087EB2C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB006011 mRNA Translation: BAA21662.1
RefSeqiNP_999278.1, NM_214113.1
UniGeneiSsc.324

Genome annotation databases

EnsembliENSSSCT00000034678; ENSSSCP00000029236; ENSSSCG00000005215
GeneIDi397201
KEGGissc:397201

Similar proteinsi

Entry informationi

Entry nameiJAK2_PIG
AccessioniPrimary (citable) accession number: O19064
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: January 1, 1998
Last modified: May 23, 2018
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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