EKS-HOS-00032

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00032

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Jak	344.2	2.9E-102	700	971	272

Status

Reviewed

Ensembl Protein

ENSP00000443103

UniProt Accession

O60674; O14636; O75297;

Protein Name

Tyrosine-protein kinase JAK2

Protein Synonyms/Alias

Janus kinase 2; JAK-2;

Gene Name

JAK2

Gene Synonyms/Alias

JAK2;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000096968	ENSP00000371067	ENST00000381652
ENSG00000096968	ENSP00000443103	ENST00000544510
ENSG00000096968	ENSP00000440387	ENST00000539801

Organism

Homo sapiens

Functional Description

Non-receptor tyrosine kinase involved in variousprocesses 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.

Protein Length

983

Protein Sequence
(FASTA)

MSYLFAQWRH DFVHGWIKVP VTHETQEECL GMAVLDMMRI AKENDQTPLA IYNSISYKTF 60

LPKCIRAKIQ DYHILTRKRI RYRFRRFIQQ FSQCKATARN LKLKYLINLE TLQSAFYTEK 120

FEVKEPGSGP SGEEIFATII ITGNGGIQWS RGKHKESETL TEQDLQLYCD FPNIIDVSIK 180

QANQEGSNES RVVTIHKQDG KNLEIELSSL REALSFVSLI DGYYRLTADA HHYLCKEVAP 240

PAVLENIQSN CHGPISMDFA ISKLKKAGNQ TGLYVLRCSP KDFNKYFLTF AVERENVIEY 300

KHCLITKNEN EEYNLSGTKK NFSSLKDLLN CYQMETVRSD NIIFQFTKCC PPKPKDKSNL 360

LVFRTNGVSD VPTSPTLQRP THMNQMVFHK IRNEDLIFNE SLGQGTFTKI FKGVRREVGD 420

YGQLHETEVL LKVLDKAHRN YSESFFEAAS MMSKLSHKHL VLNYGVCVCG DENILVQEFV 480

KFGSLDTYLK KNKNCINILW KLEVAKQLAW AMHFLEENTL IHGNVCAKNI LLIREEDRKT 540

GNPPFIKLSD PGISITVLPK DILQERIPWV PPECIENPKN LNLATDKWSF GTTLWEICSG 600

GDKPLSALDS QRKLQFYEDR HQLPAPKWAE LANLINNCMD YEPDFRPSFR AIIRDLNSLF 660

TPDYELLTEN DMLPNMRIGA LGFSGAFEDR DPTQFEERHL KFLQQLGKGN FGSVEMCRYD 720

PLQDNTGEVV AVKKLQHSTE EHLRDFEREI EILKSLQHDN IVKYKGVCYS AGRRNLKLIM 780

EYLPYGSLRD YLQKHKERID HIKLLQYTSQ ICKGMEYLGT KRYIHRDLAT RNILVENENR 840

VKIGDFGLTK VLPQDKEYYK VKEPGESPIF WYAPESLTES KFSVASDVWS FGVVLYELFT 900

YIEKSKSPPA EFMRMIGNDK QGQMIVFHLI ELLKNNGRLP RPDGCPDEIY MIMTECWNNN 960

VNQRPSFRDL ALRVDQIRDN MAG 983

Nucleotide Sequence
(FASTA)

ATGTCTTACC TCTTTGCTCA GTGGCGGCAT GATTTTGTGC ACGGATGGAT AAAAGTACCT 60

GTGACTCATG AAACACAGGA AGAATGTCTT GGGATGGCAG TGTTAGATAT GATGAGAATA 120

GCCAAAGAAA ACGATCAAAC CCCACTGGCC ATCTATAACT CTATCAGCTA CAAGACATTC 180

TTACCAAAAT GTATTCGAGC AAAGATCCAA GACTATCATA TTTTGACAAG GAAGCGAATA 240

AGGTACAGAT TTCGCAGATT TATTCAGCAA TTCAGCCAAT GCAAAGCCAC TGCCAGAAAC 300

TTGAAACTTA AGTATCTTAT AAATCTGGAA ACTCTGCAGT CTGCCTTCTA CACAGAGAAA 360

TTTGAAGTAA AAGAACCTGG AAGTGGTCCT TCAGGTGAGG AGATTTTTGC AACCATTATA 420

ATAACTGGAA ACGGTGGAAT TCAGTGGTCA AGAGGGAAAC ATAAAGAAAG TGAGACACTG 480

ACAGAACAGG ATTTACAGTT ATATTGCGAT TTTCCTAATA TTATTGATGT CAGTATTAAG 540

CAAGCAAACC AAGAGGGTTC AAATGAAAGC CGAGTTGTAA CTATCCATAA GCAAGATGGT 600

AAAAATCTGG AAATTGAACT TAGCTCATTA AGGGAAGCTT TGTCTTTCGT GTCATTAATT 660

GATGGATATT ATAGATTAAC TGCAGATGCA CATCATTACC TCTGTAAAGA AGTAGCACCT 720

CCAGCCGTGC TTGAAAATAT ACAAAGCAAC TGTCATGGCC CAATTTCGAT GGATTTTGCC 780

ATTAGTAAAC TGAAGAAAGC AGGTAATCAG ACTGGACTGT ATGTACTTCG ATGCAGTCCT 840

AAGGACTTTA ATAAATATTT TTTGACTTTT GCTGTCGAGC GAGAAAATGT CATTGAATAT 900

AAACACTGTT TGATTACAAA AAATGAGAAT GAAGAGTACA ACCTCAGTGG GACAAAGAAG 960

AACTTCAGCA GTCTTAAAGA TCTTTTGAAT TGTTACCAGA TGGAAACTGT TCGCTCAGAC 1020

AATATAATTT TCCAGTTTAC TAAATGCTGT CCCCCAAAGC CAAAAGATAA ATCAAACCTT 1080

CTAGTCTTCA GAACGAATGG TGTTTCTGAT GTACCAACCT CACCAACATT ACAGAGGCCT 1140

ACTCATATGA ACCAAATGGT GTTTCACAAA ATCAGAAATG AAGATTTGAT ATTTAATGAA 1200

AGCCTTGGCC AAGGCACTTT TACAAAGATT TTTAAAGGCG TACGAAGAGA AGTAGGAGAC 1260

TACGGTCAAC TGCATGAAAC AGAAGTTCTT TTAAAAGTTC TGGATAAAGC ACACAGAAAC 1320

TATTCAGAGT CTTTCTTTGA AGCAGCAAGT ATGATGAGCA AGCTTTCTCA CAAGCATTTG 1380

GTTTTAAATT ATGGAGTATG TGTCTGTGGA GACGAGAATA TTCTGGTTCA GGAGTTTGTA 1440

AAATTTGGAT CACTAGATAC ATATCTGAAA AAGAATAAAA ATTGTATAAA TATATTATGG 1500

AAACTTGAAG TTGCTAAACA GTTGGCATGG GCCATGCATT TTCTAGAAGA AAACACCCTT 1560

ATTCATGGGA ATGTATGTGC CAAAAATATT CTGCTTATCA GAGAAGAAGA CAGGAAGACA 1620

GGAAATCCTC CTTTCATCAA ACTTAGTGAT CCTGGCATTA GTATTACAGT TTTGCCAAAG 1680

GACATTCTTC AGGAGAGAAT ACCATGGGTA CCACCTGAAT GCATTGAAAA TCCTAAAAAT 1740

TTAAATTTGG CAACAGACAA ATGGAGTTTT GGTACCACTT TGTGGGAAAT CTGCAGTGGA 1800

GGAGATAAAC CTCTAAGTGC TCTGGATTCT CAAAGAAAGC TACAATTTTA TGAAGATAGG 1860

CATCAGCTTC CTGCACCAAA GTGGGCAGAA TTAGCAAACC TTATAAATAA TTGTATGGAT 1920

TATGAACCAG ATTTCAGGCC TTCTTTCAGA GCCATCATAC GAGATCTTAA CAGTTTGTTT 1980

ACTCCAGATT ATGAACTATT AACAGAAAAT GACATGTTAC CAAATATGAG GATAGGTGCC 2040

CTGGGGTTTT CTGGTGCCTT TGAAGACCGG GATCCTACAC AGTTTGAAGA GAGACATTTG 2100

AAATTTCTAC AGCAACTTGG CAAGGGTAAT TTTGGGAGTG TGGAGATGTG CCGGTATGAC 2160

CCTCTACAGG ACAACACTGG GGAGGTGGTC GCTGTAAAAA AGCTTCAGCA TAGTACTGAA 2220

GAGCACCTAA GAGACTTTGA AAGGGAAATT GAAATCCTGA AATCCCTACA GCATGACAAC 2280

ATTGTAAAGT ACAAGGGAGT GTGCTACAGT GCTGGTCGGC GTAATCTAAA ATTAATTATG 2340

GAATATTTAC CATATGGAAG TTTACGAGAC TATCTTCAAA AACATAAAGA ACGGATAGAT 2400

CACATAAAAC TTCTGCAGTA CACATCTCAG ATATGCAAGG GTATGGAGTA TCTTGGTACA 2460

AAAAGGTATA TCCACAGGGA TCTGGCAACG AGAAATATAT TGGTGGAGAA CGAGAACAGA 2520

GTTAAAATTG GAGATTTTGG GTTAACCAAA GTCTTGCCAC AAGACAAAGA ATACTATAAA 2580

GTAAAAGAAC CTGGTGAAAG TCCCATATTC TGGTATGCTC CAGAATCACT GACAGAGAGC 2640

AAGTTTTCTG TGGCCTCAGA TGTTTGGAGC TTTGGAGTGG TTCTGTATGA ACTTTTCACA 2700

TACATTGAGA AGAGTAAAAG TCCACCAGCG GAATTTATGC GTATGATTGG CAATGACAAA 2760

CAAGGACAGA TGATCGTGTT CCATTTGATA GAACTTTTGA AGAATAATGG AAGATTACCA 2820

AGACCAGATG GATGCCCAGA TGAGATCTAT ATGATCATGA CAGAATGCTG GAACAATAAT 2880

GTAAATCAAC GCCCCTCCTT TAGGGATCTA GCTCTTCGAG TGGATCAAAT AAGGGATAAC 2940

ATGGCTGGAT GA 2952

Domain Profile

S: 1     lkqiesLgkgtftkvfevredaegdsteeevalkvLkesgedisrdfkreaeilsqlshe  60

         lk++++Lgkg+f++v+++r+d+ +d+t+e va+k L++s+e++ rdf+re+eil++l+h+

Q: 700   LKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHD  759

         6899********************************************************

S: 61    hivklkgvcvaegen..rlVmeyvesGsLdiyLrkkkealslsslldvakqlakameYLe  118

         +ivk+kgvc++ g++  +l+mey+++GsL++yL+k+ke++++ +ll++++q++k+meYL+

Q: 760   NIVKYKGVCYSAGRRnlKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLG  819

         **********999888********************************************

S: 119   dkklvhrdvaarnvLveresnegtppfvklsdpglakavnqd.eYylvreerdsripwla  177

         +k+++hrd+a+rn+Lve+e++      vk++d+gl+k+++qd eYy v+e+++s+i+w+a

Q: 820   TKRYIHRDLATRNILVENENR------VKIGDFGLTKVLPQDkEYYKVKEPGESPIFWYA  873

         *********************......*********************************

S: 178   peclseaknlstasdvWsFgvtlyellt.cskgesp....lrsesle........rklel  224

         pe+l+e+k +s+asdvWsFgv+lyel+t ++k++sp    +r+++++        +++el

Q: 874   PESLTESK-FSVASDVWSFGVVLYELFTyIEKSKSPpaefMRMIGNDkqgqmivfHLIEL  932

         ********.*******************************999999999***********

S: 225   leekerlpkpk.cpaelaelmtnclsyepsqrpsFrail  262

         l+++ rlp+p+ cp+e++++mt+c++++ +qrpsFr+++

Q: 933   LKNNGRLPRPDgCPDEIYMIMTECWNNNVNQRPSFRDLA  971

         ************************************995

Domain Sequence
(FASTA)

LKFLQQLGKG NFGSVEMCRY DPLQDNTGEV VAVKKLQHST EEHLRDFERE IEILKSLQHD 60

NIVKYKGVCY SAGRRNLKLI MEYLPYGSLR DYLQKHKERI DHIKLLQYTS QICKGMEYLG 120

TKRYIHRDLA TRNILVENEN RVKIGDFGLT KVLPQDKEYY KVKEPGESPI FWYAPESLTE 180

SKFSVASDVW SFGVVLYELF TYIEKSKSPP AEFMRMIGND KQGQMIVFHL IELLKNNGRL 240

PRPDGCPDEI YMIMTECWNN NVNQRPSFRD LA 272

Keyword

3D-structure; Adaptive immunity; ATP-binding; Chromatin regulator; Chromosomal rearrangement; Complete proteome; Cytoplasm; Disease mutation; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Repeat; SH2 domain; Transferase; Tyrosine-protein kinase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005901	; C:caveola
GO:0005856	; C:cytoskeleton
GO:0005829	; C:cytosol
GO:0012505	; C:endomembrane system
GO:0031904	; C:endosome lumen
GO:0016363	; C:nuclear matrix
GO:0005634	; C:nucleus
GO:0005524	; F:ATP binding
GO:0005131	; F:growth hormone receptor binding
GO:0020037	; F:heme binding
GO:0042393	; F:histone binding
GO:0035401	; F:histone kinase activity (H3-Y41 specific)
GO:0005143	; F:interleukin-12 receptor binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0019901	; F:protein kinase binding
GO:0030041	; P:actin filament polymerization
GO:0006919	; P:activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0097296	; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:0042977	; P:activation of JAK2 kinase activity
GO:0000186	; P:activation of MAPKK activity
GO:0031103	; P:axon regeneration
GO:0007596	; P:blood coagulation
GO:0006928	; P:cellular component movement
GO:0007204	; P:elevation of cytosolic calcium ion concentration
GO:0030218	; P:erythrocyte differentiation
GO:0007186	; P:G-protein coupled receptor signaling pathway
GO:0009755	; P:hormone-mediated signaling pathway
GO:0060333	; P:interferon-gamma-mediated signaling pathway
GO:0035722	; P:interleukin-12-mediated signaling pathway
GO:0008631	; P:intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0060397	; P:JAK-STAT cascade involved in growth hormone signaling pathway
GO:0061180	; P:mammary gland epithelium development
GO:0007498	; P:mesoderm development
GO:0031959	; P:mineralocorticoid receptor signaling pathway
GO:0008285	; P:negative regulation of cell proliferation
GO:0022408	; P:negative regulation of cell-cell adhesion
GO:0043392	; P:negative regulation of DNA binding
GO:0045822	; P:negative regulation of heart contraction
GO:0048008	; P:platelet-derived growth factor receptor signaling pathway
GO:0043065	; P:positive regulation of apoptotic process
GO:0050867	; P:positive regulation of cell activation
GO:0045597	; P:positive regulation of cell differentiation
GO:0030335	; P:positive regulation of cell migration
GO:0008284	; P:positive regulation of cell proliferation
GO:0010811	; P:positive regulation of cell-substrate adhesion
GO:0043388	; P:positive regulation of DNA binding
GO:0060399	; P:positive regulation of growth hormone receptor signaling pathway
GO:0050729	; P:positive regulation of inflammatory response
GO:0032024	; P:positive regulation of insulin secretion
GO:0032731	; P:positive regulation of interleukin-1 beta production
GO:0045429	; P:positive regulation of nitric oxide biosynthetic process
GO:0051770	; P:positive regulation of nitric-oxide synthase biosynthetic process
GO:0014068	; P:positive regulation of phosphatidylinositol 3-kinase cascade
GO:0032516	; P:positive regulation of phosphoprotein phosphatase activity
GO:0033160	; P:positive regulation of protein import into nucleus, translocation
GO:0051091	; P:positive regulation of sequence-specific DNA binding transcription factor activity
GO:0032760	; P:positive regulation of tumor necrosis factor production
GO:0042517	; P:positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042523	; P:positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0046777	; P:protein autophosphorylation
GO:0050727	; P:regulation of inflammatory response
GO:0060334	; P:regulation of interferon-gamma-mediated signaling pathway
GO:0046677	; P:response to antibiotic
GO:0033194	; P:response to hydroperoxide
GO:0032496	; P:response to lipopolysaccharide
GO:0007262	; P:STAT protein import into nucleus
GO:0033209	; P:tumor necrosis factor-mediated signaling pathway
GO:0007260	; P:tyrosine phosphorylation of STAT protein
GO:0042508	; P:tyrosine phosphorylation of Stat1 protein
GO:0042503	; P:tyrosine phosphorylation of Stat3 protein

KEGG

hsa:3717

;

InterPros

IPR019749	; Band_41_domain.
IPR019748	; FERM_central.
IPR000299	; FERM_domain.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_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.

Pfam

PF07714	; Pkinase_Tyr; 2.
PF00017	; SH2; 1.

SMARTs

SM00295	; B41; 1.
SM00252	; SH2; 1.
SM00219	; TyrKc; 2.

Prosites

PS00660	; FERM_1; FALSE_NEG.
PS00661	; FERM_2; FALSE_NEG.
PS50057	; FERM_3; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 2.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; 1.

Prints

PR01823	; JANUSKINASE.
PR01825	; JANUSKINASE2.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013