Q62689 (JAK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase JAK2
EC=2.7.10.2

Alternative name(s):
Janus kinase 2
Short name=JAK-2

Gene names

Name:

Jak2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1132 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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 activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	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.
Subunit structure	Interacts with EPOR, SIRPA and SH2B1. Interacts with IL23R, LYN, SKB1, STAM2 and TEC By similarity.
Subcellular location	Endomembrane system; Peripheral membrane protein By similarity. Cytoplasm By similarity. Nucleus By similarity.
Tissue specificity	Ubiquitously expressed throughout most tissues. Ref.1
Domain	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.
Post-translational modification	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.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. Contains 1 FERM domain. Contains 2 protein kinase domains. Contains 1 SH2 domain.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Innate immunity
Cellular component	Cytoplasm Membrane Nucleus
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chromatin regulator Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from mutant phenotype PubMed 17021051. Source: RGD JAK-STAT cascade involved in growth hormone signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB STAT protein import into nucleus Inferred from electronic annotation. Source: Compara activation of JAK2 kinase activity Inferred from sequence or structural similarity. Source: UniProtKB activation of MAPKK activity Inferred from mutant phenotype PubMed 16567515. Source: RGD axon regeneration Inferred from mutant phenotype PubMed 15716400. Source: RGD elevation of cytosolic calcium ion concentration Inferred from mutant phenotype PubMed 16597920. Source: RGD erythrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB hormone-mediated signaling pathway Inferred from direct assay PubMed 11064147. Source: RGD interferon-gamma-mediated signaling pathway Inferred from direct assay PubMed 11536325. Source: BHF-UCL interleukin-12-mediated signaling pathway Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway in response to oxidative stress Inferred from mutant phenotype PubMed 15659221. Source: RGD mammary gland epithelium development Inferred from electronic annotation. Source: Compara mineralocorticoid receptor signaling pathway Inferred from mutant phenotype PubMed 15932931. Source: RGD negative regulation of DNA binding Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of cell-cell adhesion Inferred from mutant phenotype PubMed 15530849. Source: RGD negative regulation of heart contraction Inferred from mutant phenotype PubMed 12595539. Source: RGD negative regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 12244045. Source: RGD platelet-derived growth factor receptor signaling pathway Inferred from mutant phenotype PubMed 15948243. Source: RGD positive regulation of DNA binding Inferred from mutant phenotype PubMed 15322111. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype PubMed 16269269. Source: RGD positive regulation of cell activation Inferred from mutant phenotype PubMed 15256805. Source: RGD positive regulation of cell differentiation Inferred from mutant phenotype PubMed 16514419. Source: RGD positive regulation of cell migration Inferred from mutant phenotype PubMed 15530849. Source: RGD positive regulation of cell proliferation Inferred from mutant phenotype PubMed 16567515. Source: RGD positive regulation of cell-substrate adhesion Inferred from electronic annotation. Source: Compara positive regulation of inflammatory response Inferred from mutant phenotype PubMed 16934228. Source: RGD positive regulation of insulin secretion Inferred from mutant phenotype PubMed 16597920. Source: RGD positive regulation of interleukin-1 beta production Inferred from mutant phenotype PubMed 16934228. Source: RGD positive regulation of nitric oxide biosynthetic process Inferred from mutant phenotype PubMed 12595539. Source: RGD positive regulation of nitric-oxide synthase biosynthetic process Inferred from direct assay PubMed 11536325. Source: BHF-UCL positive regulation of phosphoprotein phosphatase activity Inferred from mutant phenotype PubMed 17021051. Source: RGD positive regulation of protein import into nucleus, translocation Inferred from mutant phenotype PubMed 15530849. Source: RGD positive regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 15322111. Source: RGD positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB response to antibiotic Inferred from electronic annotation. Source: Compara response to hydroperoxide Inferred from mutant phenotype PubMed 15659221. Source: RGD tumor necrosis factor-mediated signaling pathway Inferred from electronic annotation. Source: Compara tyrosine phosphorylation of Stat1 protein Inferred from mutant phenotype PubMed 15659221. Source: RGD tyrosine phosphorylation of Stat3 protein Inferred from mutant phenotype PubMed 15659221PubMed 17920330. Source: RGD tyrosine phosphorylation of Stat5 protein Inferred from mutant phenotype PubMed 17920330. Source: RGD
Cellular_component	caveola Inferred from electronic annotation. Source: Compara cytoskeleton Inferred from electronic annotation. Source: InterPro cytosol Inferred from direct assay PubMed 16972141. Source: RGD endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear matrix Inferred from direct assay PubMed 8756581. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW heme binding Inferred from sequence or structural similarity. Source: UniProtKB histone binding Inferred from sequence or structural similarity. Source: UniProtKB histone kinase activity (H3-Y41 specific) Inferred from sequence or structural similarity. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1132	1132	Tyrosine-protein kinase JAK2		PRO_0000088114
Regions
	Domain	37 – 380	344	FERM
	Domain	401 – 482	82	SH2; atypical
	Domain	545 – 809	265	Protein kinase 1
	Domain	849 – 1126	278	Protein kinase 2
	Nucleotide binding	855 – 863	9	ATP By similarity
	Region	1 – 239	239	Interaction with cytokine/interferon/growth hormone receptors By similarity
Sites
	Active site	976	1	Proton acceptor By similarity
	Binding site	882	1	ATP By similarity
Amino acid modifications
	Modified residue	119	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	372	1	Phosphotyrosine By similarity
	Modified residue	373	1	Phosphotyrosine By similarity
	Modified residue	523	1	Phosphoserine By similarity
	Modified residue	570	1	Phosphotyrosine By similarity
	Modified residue	813	1	Phosphotyrosine By similarity
	Modified residue	868	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	966	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	972	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1007	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1008	1	Phosphotyrosine; by autocatalysis By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q62689 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: C3AEDF2FECE8B95A	FASTA	1,132	130,585
	10 20 30 40 50 60 MGMACLTMTE MEGTSTSPAH QNGDIPGNAN SVKQTEPVLQ VYLYHSLGQA EGDYLKFPNG 70 80 90 100 110 120 EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NILYRIRFYF 130 140 150 160 170 180 PHWYCSGSNR TYRYGVSRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG 190 200 210 220 230 240 MAVLDMMRIA KEKDQTPLAV YNSISYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF 250 260 270 280 290 300 SQCKATARNL KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR 310 320 330 340 350 360 GKHKESETLT EQDLQLYCDF PDIIDVSIKQ ANQECSTESR VVTVHKQDGK VLEIELSSLK 370 380 390 400 410 420 EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC HGPISMDFAI SKLKKAGNQT 430 440 450 460 470 480 GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENG EYNLSGTKRN FSSLKDLLNC 490 500 510 520 530 540 YQMETVRSDS IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV QLSPTLQRHN NVNQMVFHKI 550 560 570 580 590 600 RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM 610 620 630 640 650 660 MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK LGVAKQLAWA 670 680 690 700 710 720 MHFLEEKSLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP GISITVLPKD ILQERIPWVP 730 740 750 760 770 780 PECIENPKNL TLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL 790 800 810 820 830 840 ANLINTCMDY EPDFRPAFRA VIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD 850 860 870 880 890 900 PTQFEERHLK FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE 910 920 930 940 950 960 ILKSLQHDNI VKYKGVCYSA GRRNLRLIME YLPYGSLRDY LQKHKERIDH KKLLQYTSQI 970 980 990 1000 1010 1020 CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV LPQDKEYYKV KEPGESPIFW 1030 1040 1050 1060 1070 1080 YAPESLTESK FSVASDVWSF GVVLYELFTY IEKSKSPPVE FMRMIGNDKQ GQMIVFHLIE 1090 1100 1110 1120 1130 LLKNNGRLPR PEGCPDEIYV IMTECWNNNV NQRPSFRDLS LRVDQIRDSM AA

References

[1]	"Cloning of the gene encoding rat JAK2, a protein tyrosine kinase." Duhe R.J., Rui H., Greenwood J.D., Garvey K., Farrar W.L. Gene 158:281-285(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U13396 mRNA. Translation: AAA79911.1.
IPI	IPI00207182.
PIR	JC4127.
RefSeq	NP_113702.1. NM_031514.1.
UniGene	Rn.18909.
3D structure databases
ProteinModelPortal	Q62689.
SMR	Q62689. Positions 840-1132.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-491N.
PTM databases
PhosphoSite	Q62689.
Proteomic databases
PRIDE	Q62689.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000021217; ENSRNOP00000021218; ENSRNOG00000015547.
GeneID	24514.
KEGG	rno:24514.
UCSC	RGD:2939. rat.
Organism-specific databases
CTD	3717.
RGD	2939. Jak2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00630000089536.
HOGENOM	HOG000049158.
HOVERGEN	HBG006195.
InParanoid	Q62689.
KO	K04447.
OrthoDB	EOG4PZJ5W.
Enzyme and pathway databases
BRENDA	2.7.10.2. 5301.
Reactome	REACT_109781. Immune System. REACT_111984. Signal Transduction.
Gene expression databases
ArrayExpress	Q62689.
Genevestigator	Q62689.
GermOnline	ENSRNOG00000015547. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	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. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 2 hits. PF00017. SH2. 1 hit. [Graphical view]
PIRSF	PIRSF000636. TyrPK_Jak. 1 hit.
PRINTS	PR01823. JANUSKINASE. PR01825. JANUSKINASE2. PR00109. TYRKINASE.
SMART	SM00295. B41. 1 hit. SM00252. SH2. 1 hit. SM00219. TyrKc. 2 hits. [Graphical view]
SUPFAM	SSF47031. FERM_3-hlx. 1 hit. SSF56112. Kinase_like. 2 hits.
PROSITE	PS00660. FERM_1. False negative. PS00661. FERM_2. False negative. 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]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1075225.
NextBio	603541.

Entry information

Entry name

JAK2_RAT

Accession

Primary (citable) accession number: Q62689

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program