EKS-RAN-00032

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00032

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Jak	344.6	5.3E-103	849	1120	272

Status

Reviewed

Ensembl Protein

ENSRNOP00000021218

UniProt Accession

Q62689;

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
ENSRNOG00000015547	ENSRNOP00000021218	ENSRNOT00000021217

Organism

Rattus norvegicus

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 (By similarity).

Protein Length

1132

Protein Sequence
(FASTA)

MGMACLTMTE MEGTSTSPAH QNGDIPGNAN SVKQTEPVLQ VYLYHSLGQA EGDYLKFPNG 60

EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NILYRIRFYF 120

PHWYCSGSNR TYRYGVSRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG 180

MAVLDMMRIA KEKDQTPLAV YNSISYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF 240

SQCKATARNL KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR 300

GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQECSTESR VVTVHKQDGK VLEIELSSLK 360

EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC HGPISMDFAI SKLKKAGNQT 420

GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENG EYNLSGTKRN FSSLKDLLNC 480

YQMETVRSDS IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV QLSPTLQRHN NVNQMVFHKI 540

RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 600

MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK LGVAKQLAWA 660

MHFLEEKSLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP GISITVLPKD ILQERIPWVP 720

PECIENPKNL TLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL 780

ANLINTCMDY EPDFRPAFRA VIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD 840

PTQFEERHLK FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 900

ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH KKLLQYTSQI 960

CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV LPQDKEYYKV KEPGESPIFW 1020

YAPESLTESK FSVASDVWSF GVVLYELFTY IEKSKSPPVE FMRMIGNDKQ GQMIVFHLIE 1080

LLKNNGRLPR PEGCPDEIYV IMTECWNNNV NQRPSFRDLS LRVDQIRDSM AA 1132

Nucleotide Sequence
(FASTA)

ATGGGAATGG CTTGCCTTAC AATGACAGAA ATGGAGGGAA CCTCCACATC TCCTGCACAT 60

CAGAATGGTG ATATTCCTGG AAATGCTAAC TCTGTGAAGC AGACAGAGCC AGTCCTTCAA 120

GTGTACCTGT ACCATTCTCT TGGGCAAGCT GAAGGAGACT ATCTGAAGTT TCCAAATGGA 180

GAGTATGTTG CCGAAGAAAT TTGTGTGGCT GCTTCTAAAG CATGTGGTAT TACGCCTGTG 240

TATCATAATA TGTTTGCTTT AATGAGTGAA ACAGAAAGGA TCTGGTATCC ACCCAATCAT 300

GTCTTCCACA TAGATGAGTC AACCAGGCAT AATATACTCT ACAGAATAAG GTTTTACTTT 360

CCTCATTGGT ACTGCAGTGG CAGCAACAGA ACCTATAGGT ACGGAGTATC TCGTGGGGCT 420

GAAGCTCCTC TCCTTGACGA CTTTGTCATG TCTTACCTTT TTGCTCAGTG GCGGCATGAT 480

TTTGTTCATG GGTGGATAAA AGTACCTGTG ACTCACGAAA CTCAGGAAGA ATGTCTTGGC 540

ATGGCAGTGT TAGACATGAT GAGAATAGCT AAGGAGAAGG ACCAGACTCC CCTGGCTGTC 600

TATAACTCCA TCAGCTACAA GACGTTCTTA CCGAAGTGCG TGCGAGCGAA GATCCAGGAC 660

TATCACATTT TAACTCGGAA GCGGATAAGG TACAGATTCC GCAGGTTCAT TCAGCAGTTC 720

AGTCAGTGCA AAGCCACTGC CAGGAACCTA AAACTTAAGT ATCTCATAAA CCTGGAGACC 780

CTGCAGTCTG CCTTCTACAC AGAACAGTTT GAAGTAAAAG AATCTGCAAG AGGTCCTTCA 840

GGTGAGGAGA TTTTTGCAAC CATTATAATA ACTGGAAACG GTGGAATTCA GTGGTCAAGA 900

GGGAAACATA AGGAAAGTGA GACACTGACA GAACAGGATT TACAGTTGTA TTGTGATTTT 960

CCTGATATTA TTGATGTCAG TATTAAGCAA GCAAATCAGG AATGCTCAAC TGAAAGTAGA 1020

GTTGTGACCG TCCACAAGCA GGACGGGAAG GTCTTGGAAA TAGAACTTAG CTCATTAAAA 1080

GAAGCCTTGT CATTTGTGTC GTTAATTGAC GGGTATTACA GACTAACTGC GGATGCACAC 1140

CATTACCTCT GTAAAGAGGT GGCTCCTCCA GCCGTGCTTG AAAACATACA CAGCAACTGT 1200

CACGGCCCAA TTTCAATGGA TTTTGCCATC AGCAAACTAA AGAAGGCAGG AAACCAGACT 1260

GGACTGTATG TACTTCGATG TAGCCCTAAG GACTTCAACA AATACTTCCT GACCTTTGCC 1320

GTTGAGCGAG AAAATGTTAT TGAATATAAA CACTGTTTGA TTACAAAGAA TGAGAATGGA 1380

GAGTACAACC TCAGTGGGAC TAAGAGGAAC TTCAGTAGTC TTAAGGACCT TTTGAATTGC 1440

TACCAGATGG AAACTGTGCG CTCAGACAGT ATCATCTTCC AGTTCACCAA ATGCTGTCCT 1500

CCAAAGCCGA AAGATAAATC AAACCTTCTT GTCTTCAGAA CAAATGGTGT TTCTGATGTT 1560

CAGCTCTCAC CAACATTACA GAGGCATAAT AATGTGAATC AAATGGTGTT TCACAAAATC 1620

AGGAATGAAG ATTTGATATT TAATGAAAGC CTTGGCCAAG GCACTTTTAC AAAAATATTT 1680

AAAGGTGTAA GAAGAGAAGT TGGAGATTAT GGTCAGCTGC ACGAAACCGA AGTTCTTTTG 1740

AAAGTCCTAG ATAAAGCACA TAGAAACTAT TCAGAGTCTT TCTTTGAAGC AGCAAGCATG 1800

ATGAGTCAGC TTTCTCACAA GCATTTGGTT TTGAATTATG GAGTATGTGT CTGTGGAGAG 1860

GAGAACATTT TGGTTCAAGA GTTTGTAAAA TTTGGATCCC TGGATACATA CCTGAAAAAA 1920

AACAAAAATT CCATAAATAT ACTATGGAAA CTTGGAGTGG CCAAACAGTT GGCATGGGCC 1980

ATGCACTTCC TCGAAGAAAA ATCCCTTATT CATGGGAATG TGTGTGCCAA AAATATCCTG 2040

CTTATCAGAG AAGAAGACAG GAAAACAGGG AATCCACCTT TCATCAAACT TAGTGATCCT 2100

GGGATTAGCA TCACAGTTCT ACCAAAGGAC ATTCTTCAGG AGAGAATACC ATGGGTACCA 2160

CCTGAGTGCA TTGAAAACCC TAAAAATCTA ACTTTGGCAA CAGACAAGTG GAGCTTTGGC 2220

ACCACTCTGT GGGAGATCTG CAGTGGAGGA GACAAGCCTC TGAGTGCTCT GGACTCTCAA 2280

AGAAAGCTGC AGTTCTATGA AGATAAGCAC CAGCTCCCAG CACCCAAGTG GACAGAGTTG 2340

GCAAACCTTA TAAATACTTG CATGGATTAT GAGCCAGACT TCAGGCCTGC CTTCAGAGCT 2400

GTCATCCGTG ATCTGAACAG CCTGTTTACT CCAGATTATG AACTGCTGAC AGAAAATGAC 2460

ATGCTACCCA ACATGAGAAT AGGTGCCCTA GGATTTTCTG GTGCTTTTGA AGACAGGGAC 2520

CCTACACAGT TTGAAGAGAG ACACTTGAAA TTTCTACAGC AACTTGGCAA GGGTAACTTT 2580

GGGAGTGTGG AGATGTGCCG CTATGACCCG CTGCAGGACA ACACTGGAGA GGTGGTAGCT 2640

GTTAAGAAGC TCCAGCACAG CACGGAAGAG CATCTCCGAG ACTTTGAAAG GGAAATTGAA 2700

ATCCTGAAAT CCTTGCAGCA TGACAACATC GTGAAGTACA AGGGAGTGTG CTACAGTGCT 2760

GGTCGGCGCA ACCTAAGATT AATTATGGAA TATTTGCCGT ATGGAAGTTT ACGAGACTAT 2820

CTCCAAAAAC ATAAAGAACG GATAGATCAC AAAAAACTTC TGCAGTATAC ATCCCAGATA 2880

TGCAAGGGCA TGGAGTATCT TGGTACAAAA AGGTATATCC ACCGGGATCT GGCAACAAGG 2940

AATATATTGG TAGAAAATGA GAACAGAGTT AAAATAGGAG ATTTTGGATT AACCAAAGTC 3000

TTGCCACAGG ACAAAGAATA CTACAAAGTA AAGGAACCAG GTGAAAGTCC CATATTCTGG 3060

TATGCTCCCG AATCCTTGAC AGAGAGCAAG TTTTCTGTGG CCTCAGATGT GTGGAGCTTT 3120

GGTGTGGTTC TGTACGAACT TTTCACGTAT ATCGAGAAGA GCAAAAGCCC ACCTGTGGAA 3180

TTTATGCGAA TGATCGGCAA TGATAAACAA GGGCAGATGA TCGTATTCCA TTTGATAGAG 3240

CTACTGAAGA ACAACGGAAG ACTGCCGAGA CCAGAAGGGT GCCCAGACGA GATTTATGTG 3300

ATCATGACAG AATGCTGGAA CAACAATGTC AACCAACGTC CCTCTTTCAG GGACCTTTCC 3360

CTTCGGGTGG ATCAAATCCG GGACAGTATG GCTGCATGA 3399

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: 849   LKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHD  908

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

S: 61    hivklkgvcvaegen..rlVmeyvesGsLdiyLrkkkealslsslldvakqlakameYLe  118

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

Q: 909   NIVKYKGVCYSAGRRnlRLIMEYLPYGSLRDYLQKHKERIDHKKLLQYTSQICKGMEYLG  968

         **********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: 969   TKRYIHRDLATRNILVENENR------VKIGDFGLTKVLPQDkEYYKVKEPGESPIFWYA  1022

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

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

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

Q: 1023  PESLTESK-FSVASDVWSFGVVLYELFTyIEKSKSPpvefMRMIGNDkqgqmivfHLIEL  1081

         ********.****************************999999999899***********

S: 225   leekerlpkpk.cpaelaelmtnclsyepsqrpsFrail  262

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

Q: 1082  LKNNGRLPRPEgCPDEIYVIMTECWNNNVNQRPSFRDLS  1120

         ************************************985

Domain Sequence
(FASTA)

LKFLQQLGKG NFGSVEMCRY DPLQDNTGEV VAVKKLQHST EEHLRDFERE IEILKSLQHD 60

NIVKYKGVCY SAGRRNLRLI MEYLPYGSLR DYLQKHKERI DHKKLLQYTS QICKGMEYLG 120

TKRYIHRDLA TRNILVENEN RVKIGDFGLT KVLPQDKEYY KVKEPGESPI FWYAPESLTE 180

SKFSVASDVW SFGVVLYELF TYIEKSKSPP VEFMRMIGND KQGQMIVFHL IELLKNNGRL 240

PRPEGCPDEI YVIMTECWNN NVNQRPSFRD LS 272

Keyword

Adaptive immunity; ATP-binding; Chromatin regulator; Complete proteome; Cytoplasm; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; 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"; ?>Homo sapiens"; ?>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"; ?>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:0016363	; C:nuclear matrix
GO:0005524	; F:ATP binding
GO:0020037	; F:heme binding
GO:0042393	; F:histone binding
GO:0035401	; F:histone kinase activity (H3-Y41 specific)
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0042977	; P:activation of JAK2 kinase activity
GO:0000186	; P:activation of MAPKK activity
GO:0031103	; P:axon regeneration
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: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:0043524	; P:negative regulation of neuron apoptotic process
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: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: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:0042517	; P:positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0046777	; P:protein autophosphorylation
GO:0046677	; P:response to antibiotic
GO:0033194	; P:response to hydroperoxide
GO:0007262	; P:STAT protein import into nucleus
GO:0033209	; P:tumor necrosis factor-mediated signaling pathway
GO:0042508	; P:tyrosine phosphorylation of Stat1 protein
GO:0042503	; P:tyrosine phosphorylation of Stat3 protein
GO:0042506	; P:tyrosine phosphorylation of Stat5 protein

KEGG

rno:24514

;

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