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O19064

- JAK2_PIG

UniProt

O19064 - JAK2_PIG

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Protein
Tyrosine-protein kinase JAK2
Gene
JAK2
Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5 - 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. 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.

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei882 – 8821ATP By similarity
Active sitei976 – 9761Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi855 – 8639ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. heme binding Source: UniProtKB
  3. histone binding Source: UniProtKB
  4. histone kinase activity (H3-Y41 specific) Source: UniProtKB
  5. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  6. protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  1. JAK-STAT cascade involved in growth hormone signaling pathway Source: UniProtKB
  2. activation of JAK2 kinase activity Source: UniProtKB
  3. cytokine-mediated signaling pathway Source: UniProtKB
  4. erythrocyte differentiation Source: UniProtKB
  5. histone H3-Y41 phosphorylation Source: UniProtKB
  6. innate immune response Source: UniProtKB-KW
  7. positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
  8. protein autophosphorylation Source: UniProtKB
  9. signal transduction Source: UniProtKB
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, 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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Unplaced

Subcellular locationi

Endomembrane system; Peripheral membrane protein By similarity. Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. cytoskeleton Source: InterPro
  3. endomembrane system Source: UniProtKB-SubCell
  4. membrane Source: UniProtKB-KW
  5. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11311131Tyrosine-protein kinase JAK2
PRO_0000324093Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei119 – 1191Phosphotyrosine; by autocatalysis By similarity
Modified residuei372 – 3721Phosphotyrosine By similarity
Modified residuei373 – 3731Phosphotyrosine By similarity
Modified residuei523 – 5231Phosphoserine By similarity
Modified residuei813 – 8131Phosphotyrosine By similarity
Modified residuei868 – 8681Phosphotyrosine; by autocatalysis By similarity
Modified residuei966 – 9661Phosphotyrosine; by autocatalysis By similarity
Modified residuei972 – 9721Phosphotyrosine; by autocatalysis By similarity
Modified residuei1007 – 10071Phosphotyrosine; by autocatalysis By similarity
Modified residuei1008 – 10081Phosphotyrosine; by autocatalysis By similarity

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.

Keywords - PTMi

Phosphoprotein

Interactioni

Subunit structurei

Interacts with EPOR, SIRPA and SH2B1. Interacts with IL23R, LYN, SKB1, STAM2 and TEC By similarity.

Structurei

3D structure databases

ProteinModelPortaliO19064.
SMRiO19064. Positions 840-1131.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini37 – 380344FERM
Add
BLAST
Domaini401 – 48282SH2; atypical
Add
BLAST
Domaini545 – 809265Protein kinase 1
Add
BLAST
Domaini849 – 1126278Protein kinase 2
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 239239Interaction with cytokine/interferon/growth hormone receptors By similarity
Add
BLAST

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.

Sequence similaritiesi

Contains 1 FERM domain.
Contains 1 SH2 domain.

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000049158.
HOVERGENiHBG006195.
KOiK04447.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
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.
SSF55550. SSF55550. 1 hit.
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.

O19064-1 [UniParc]FASTAAdd to Basket

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MGMACLTMTE MEGTSTSPVH QNGDIPGNAN SVKQIDPVLQ VYLYHSLGKA     50
EGDYLKFPAG EYVAEEICVA ASKACGITPV YHSMFALMNE TERIWYPPNH 100
VFHVDESTRH NVLYRIRFYF PYWYCNGSNR TYRHGISRGA EAPLLDDFVM 150
SYLFAQWRHD FLYGWVKIPV THETQEECLG MAVLDMMRIA KEKDQTPLDI 200
YSSVSYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIEQF SHCKATARNL 250
KLKYLINLET LQSAFYTEQF EVKEPGRGPS GEEIFATIII TGNGGIQWSR 300
GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQEGSNESR IVTIHKQDGK 350
SLEIELSSLR EALSFVSLID GYYRLTADAH HYLCKEVAPP MVLENIQSNC 400
HGPISMDFAI SKLKKAGNQT GLFVLRCSPK DFNKYFLTFA VERENVTEYK 450
HCLITKNENG EYNLSGTRKN FSNLKDLLNC YQMETVRSDS IIFQFTKCCP 500
PKPKDKSNLL VFRTNGISDV PTSPTLQRHN NVNQMVFHKI RNEDLIFNES 550
LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 600
MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK 650
LEVAKQLAWA MHFLEEKTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP 700
GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG 750
DKPLNALDSQ RKLQFYEDRH QLPAPKWTEL ANLINNCMDY EPDFRPSFRA 800
IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK 850
FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 900
ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH 950
KKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV 1000
LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY 1050
IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PDGCPDEIYI 1100
IMTECWNNNV NQRPSFRDLA LRVDQIRDSM A 1131
Length:1,131
Mass (Da):130,759
Last modified:January 1, 1998 - v1
Checksum:i6339C7417087EB2C
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB006011 mRNA. Translation: BAA21662.1.
RefSeqiNP_999278.1. NM_214113.1.
UniGeneiSsc.324.

Genome annotation databases

GeneIDi397201.
KEGGissc:397201.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB006011 mRNA. Translation: BAA21662.1 .
RefSeqi NP_999278.1. NM_214113.1.
UniGenei Ssc.324.

3D structure databases

ProteinModelPortali O19064.
SMRi O19064. Positions 840-1131.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 397201.
KEGGi ssc:397201.

Organism-specific databases

CTDi 3717.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000049158.
HOVERGENi HBG006195.
KOi K04447.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
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 ]
Pfami PF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view ]
PIRSFi PIRSF000636. TyrPK_Jak. 1 hit.
PRINTSi PR01823. JANUSKINASE.
PR01825. JANUSKINASE2.
PR00109. TYRKINASE.
SMARTi SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view ]
SUPFAMi SSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 2 hits.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Domestic pig mRNA for JAK2, complete cds."
    Ito Y., Mikawa S., Kobayashi E., Wada Y., Minezawa M.
    Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Muscle.

Entry informationi

Entry nameiJAK2_PIG
AccessioniPrimary (citable) accession number: O19064
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: January 1, 1998
Last modified: June 11, 2014
This is version 102 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

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