Q62120 (JAK2_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

Protein attributes

Sequence length	1129 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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. Ref.5 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.21
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 IL23R, SKB1 and STAM2 By similarity. Interacts with EPOR, LYN SIRPA, SH2B1 and TEC. Ref.5 Ref.6 Ref.9 Ref.13 Ref.14 Ref.17
Subcellular location	Endomembrane system; Peripheral membrane protein. Cytoplasm By similarity. Nucleus By similarity.
Tissue specificity	Ubiquitously expressed throughout most tissues.
Domain	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.
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. Ref.8 Ref.15 Ref.17 Ref.19 Ref.20 Ref.23
Disruption phenotype	Embryos are anemic and die around day 12.5 post-coitum (dpc). Primitive erythrocytes are found, but definitive erythropoiesis is absent. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fail to respond to erythropoietin (Epo), thrombopoietin (Thpo), interleukin-3 (Il3), or granulocyte and macrophage colony-stimulating factor 1 (Csf1 and Csf2). Fetal liver BFU-E and CFU-E colonies are completely absent. However, multilineage hematopoietic stem cells (CD34(low), c-kit(pos)) can be found, and B-lymphopoiesis appears intact. Ref.10 Ref.11
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL JAK-STAT cascade involved in growth hormone signaling pathway Inferred from mutant phenotype Ref.19. Source: UniProtKB STAT protein import into nucleus Inferred from direct assay PubMed 12147240. Source: MGI activation of JAK2 kinase activity Inferred from direct assay Ref.19. Source: UniProtKB activation of MAPKK activity Inferred from sequence or structural similarity. Source: BHF-UCL activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Inferred from direct assay PubMed 12426001. Source: BHF-UCL axon regeneration Inferred from sequence or structural similarity. Source: BHF-UCL elevation of cytosolic calcium ion concentration Inferred from sequence or structural similarity. Source: BHF-UCL erythrocyte differentiation Inferred from mutant phenotype Ref.10Ref.11. Source: UniProtKB hormone-mediated signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL interferon-gamma-mediated signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL interleukin-12-mediated signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL intrinsic apoptotic signaling pathway in response to oxidative stress Inferred from sequence or structural similarity. Source: BHF-UCL mammary gland epithelium development Inferred from mutant phenotype PubMed 12040017. Source: MGI mineralocorticoid receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of DNA binding Inferred from direct assay PubMed 12388746. Source: MGI negative regulation of cell proliferation Inferred from mutant phenotype PubMed 11821424. Source: MGI negative regulation of cell-cell adhesion Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of heart contraction Inferred from sequence or structural similarity. Source: BHF-UCL platelet-derived growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of apoptotic process Inferred from direct assay PubMed 12426001. Source: BHF-UCL positive regulation of cell activation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell migration Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell-substrate adhesion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of growth hormone receptor signaling pathway Inferred from mutant phenotype PubMed 17761766. Source: BHF-UCL positive regulation of inflammatory response Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of insulin secretion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-1 beta production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of nitric oxide biosynthetic process Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of nitric-oxide synthase biosynthetic process Inferred from direct assay PubMed 10600756PubMed 12426001. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype PubMed 7782332. Source: BHF-UCL positive regulation of phosphoprotein phosphatase activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein import into nucleus, translocation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of tumor necrosis factor production Inferred from direct assay PubMed 12426001. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay PubMed 15156153. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from direct assay PubMed 8923468. Source: BHF-UCL protein autophosphorylation Inferred from direct assay Ref.19. Source: UniProtKB response to antibiotic Inferred from sequence orthology PubMed 16280321. Source: MGI response to granulocyte macrophage colony-stimulating factor stimulus Non-traceable author statement PubMed 18424709. Source: BHF-UCL response to hydroperoxide Inferred from sequence or structural similarity. Source: BHF-UCL response to lipopolysaccharide Inferred from direct assay PubMed 11536325. Source: BHF-UCL tumor necrosis factor-mediated signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL tyrosine phosphorylation of Stat1 protein Inferred from sequence or structural similarity. Source: BHF-UCL tyrosine phosphorylation of Stat3 protein Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	caveola Inferred from direct assay PubMed 12388746. Source: MGI cytoskeleton Inferred from electronic annotation. Source: InterPro cytosol Traceable author statement. Source: Reactome endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear matrix Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW growth hormone receptor binding Inferred from sequence or structural similarity. Source: BHF-UCL 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 protein kinase binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDKN1B	P46527	7	EBI-646604,EBI-519280	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1129	1129	Tyrosine-protein kinase JAK2		PRO_0000088113
Regions
	Domain	37 – 380	344	FERM
	Domain	401 – 482	82	SH2; atypical
	Domain	545 – 809	265	Protein kinase 1
	Domain	849 – 1124	276	Protein kinase 2
	Nucleotide binding	855 – 863	9	ATP By similarity
	Region	1 – 239	239	Interaction with cytokine/interferon/growth hormone receptors
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 Ref.15
	Modified residue	372	1	Phosphotyrosine Ref.20
	Modified residue	373	1	Phosphotyrosine Ref.20
	Modified residue	523	1	Phosphoserine Ref.18
	Modified residue	570	1	Phosphotyrosine Ref.16
	Modified residue	813	1	Phosphotyrosine Ref.17 Ref.23
	Modified residue	868	1	Phosphotyrosine; by autocatalysis Ref.19
	Modified residue	966	1	Phosphotyrosine; by autocatalysis Ref.19
	Modified residue	972	1	Phosphotyrosine; by autocatalysis Ref.19
	Modified residue	1007	1	Phosphotyrosine; by autocatalysis
	Modified residue	1008	1	Phosphotyrosine; by autocatalysis Ref.19
Experimental info
	Mutagenesis	119	1	Y → E: Phosphorylation mimic mutant, leads to dissociation of JAK2 from the erythropoietin receptor complex. Ref.15
	Mutagenesis	119	1	Y → F: More stably associated with the erythropoietin receptor complex. Ref.15
	Mutagenesis	372	1	Y → F: About 60% loss of STAT1 phosphorylation by JAK2. Ref.20
	Mutagenesis	373	1	Y → F: Decreased the ability of JAK2 to autophosphorylate. Ref.20
	Mutagenesis	868	1	Y → F: Reduced activity in response to growth hormone. Ref.19
	Mutagenesis	966	1	Y → F: Reduced activity in response to growth hormone. Ref.19
	Mutagenesis	972	1	Y → F: Reduced activity in response to growth hormone. Ref.19
	Mutagenesis	1008	1	Y → F: Affects the phosphorylation pattern. Ref.19
	Sequence conflict	155	1	A → V in AAB41327. Ref.1
	Sequence conflict	468	1	K → N in AAB41327. Ref.1
	Sequence conflict	686	1	N → D in AAB41327. Ref.1
	Sequence conflict	1016	1	S → R in AAA40014. Ref.4
	Sequence conflict	1024	1	E → Q in AAB41327. Ref.1
	Sequence conflict	1042 – 1043	2	VV → IP in AAA40014. Ref.4
	Sequence conflict	1121 – 1129	9	LRVDQIIAA → FGWIKCGTV in AAB41327. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q62120 [UniParc]. Last modified May 20, 2008. Version 2. Checksum: DCB90FA000F99631	FASTA	1,129	130,235
	10 20 30 40 50 60 MGMACLTMTE MEATSTSPVH QNGDIPGSAN SVKQIEPVLQ VYLYHSLGQA EGEYLKFPSG 70 80 90 100 110 120 EYVAEEICVA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH DILYRIRFYF 130 140 150 160 170 180 PHWYCSGSSR TYRYGVSRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG 190 200 210 220 230 240 MAVLDMMRIA KEKDQTPLAV YNSVSYKTFL PKCVRAKIQD YHILTRKRIR YRFRRFIQQF 250 260 270 280 290 300 SQCKATARNL KLKYLINLET LQSAFYTEQF EVKESARGPS GEEIFATIII TGNGGIQWSR 310 320 330 340 350 360 GKHKESETLT EQDVQLYCDF PDIIDVSIKQ ANQECSNESR IVTVHKQDGK VLEIELSSLK 370 380 390 400 410 420 EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIHSNC HGPISMDFAI SKLKKAGNQT 430 440 450 460 470 480 GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENG EYNLSGTKRN FSNLKDLLNC 490 500 510 520 530 540 YQMETVRSDS IIFQFTKCCP PKPKDKSNLL VFRTNGISDV QISPTLQRHN NVNQMVFHKI 550 560 570 580 590 600 RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHKTEVLL KVLDKAHRNY SESFFEAASM 610 620 630 640 650 660 MSQLSHKHLV LNYGVCVCGE ENILVQEFVK FGSLDTYLKK NKNSINILWK LGVAKQLAWA 670 680 690 700 710 720 MHFLEEKSLI HGNVCAKNIL LIREENRRTG NPPFIKLSDP GISITVLPKD ILQERIPWVP 730 740 750 760 770 780 PECIENPKNL NLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDKH QLPAPKWTEL 790 800 810 820 830 840 ANLINNCMDY 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 LLKSNGRLPR PEGCPDEIYV IMTECWNNNV SQRPSFRDLS LRVDQIIAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of the murine Jak2 protein-tyrosine kinase and its role in interleukin 3 signal transduction." Silvennoinen O., Witthuhn B.A., Quelle F.W., Cleveland J.L., Yi T., Ihle J.N. Proc. Natl. Acad. Sci. U.S.A. 90:8429-8433(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[3]	"The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family." Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J. Gene 85:67-74(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 973-1043.
[4]	"Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction." Wilks A.F. Proc. Natl. Acad. Sci. U.S.A. 86:1603-1607(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 973-1043.
[5]	"JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin." Witthuhn B.A., Quelle F.W., Silvennoinen O., Yi T., Tang B., Miura O., Ihle J.N. Cell 74:227-236(1993) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EPOR.
[6]	"The amino-terminal portion of the JAK2 protein kinase is necessary for binding and phosphorylation of the granulocyte-macrophage colony-stimulating factor receptor beta c chain." Zhao Y., Wagner F., Frank S.J., Kraft A.S. J. Biol. Chem. 270:13814-13818(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CYTOKINE/INTERFERON/GROWTH HORMONE RECEPTORS.
[7]	"An epidermal growth factor receptor/Jak2 tyrosine kinase domain chimera induces tyrosine phosphorylation of Stat5 and transduces a growth signal in hematopoietic cells." Nakamura N., Chin H., Miyasaka N., Miura O. J. Biol. Chem. 271:19483-19488(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STAT5A AND STAT5B.
[8]	"Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription." Yamashita Y., Watanabe S., Miyazato A., Ohya K., Ikeda U., Shimada K., Komatsu N., Hatake K., Miura Y., Ozawa K., Mano H. Blood 91:1496-1507(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION BY TEC.
[9]	"Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway." Chin H., Arai A., Wakao H., Kamiyama R., Miyasaka N., Miura O. Blood 91:3734-3745(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LYN.
[10]	"Jak2 is essential for signaling through a variety of cytokine receptors." Parganas E., Wang D., Stravopodis D., Topham D.J., Marine J.C., Teglund S., Vanin E.F., Bodner S., Colamonici O.R., van Deursen J.M., Grosveld G., Ihle J.N. Cell 93:385-395(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[11]	"Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis." Neubauer H., Cumano A., Muller M., Wu H., Huffstadt U., Pfeffer K. Cell 93:397-409(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[12]	"The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure." Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M., Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M., Offermanns S., Pacaud P., Loirand G. Nat. Med. 16:183-190(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Negative regulation of growth hormone receptor/JAK2 signaling by signal regulatory protein alpha." Stofega M.R., Argetsinger L.S., Wang H., Ullrich A., Carter-Su C. J. Biol. Chem. 275:28222-28229(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIRPA.
[14]	"The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor." Huang L.J., Constantinescu S.N., Lodish H.F. Mol. Cell 8:1327-1338(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EPOR.
[15]	"Receptor specific downregulation of cytokine signaling by autophosphorylation in the FERM domain of Jak2." Funakoshi-Tago M., Pelletier S., Matsuda T., Parganas E., Ihle J.N. EMBO J. 25:4763-4772(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-119, MUTAGENESIS OF TYR-119.
[16]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-570, MASS SPECTROMETRY. Tissue: Mast cell.
[17]	"SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms." Li Z., Zhou Y., Carter-Su C., Myers M.G. Jr., Rui L. Mol. Endocrinol. 21:2270-2281(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SH2B1, PHOSPHORYLATION AT TYR-813.
[18]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523, MASS SPECTROMETRY. Tissue: Macrophage.
[19]	"Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity." Argetsinger L.S., Stuckey J.A., Robertson S.A., Koleva R.I., Cline J.M., Marto J.A., Myers M.G. Jr., Carter-Su C. Mol. Endocrinol. 24:1062-1076(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-868; TYR-966; TYR-972 AND TYR-1008, MUTAGENESIS OF TYR-868; TYR-966; TYR-972 AND TYR-1008.
[20]	"Phosphorylation of Y372 is critical for Jak2 tyrosine kinase activation." Sayyah J., Gnanasambandan K., Kamarajugudda S., Tsuda S., Caldwell-Busby J., Sayeski P.P. Cell. Signal. 23:1806-1815(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-372 AND TYR-373, MUTAGENESIS OF TYR-372 AND TYR-373.
[21]	"Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control." Jakel H., Weinl C., Hengst L. Oncogene 30:3502-3512(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CDKN1B.
[22]	"Jak2: normal function and role in hematopoietic disorders." Ihle J.N., Gilliland D.G. Curr. Opin. Genet. Dev. 17:8-14(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[23]	"Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS." Hu J., Hubbard S.R. J. Mol. Biol. 361:69-79(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 810-820 IN COMPLEX WITH SH2B1, PHOSPHORYLATION AT TYR-813.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L16956 mRNA. Translation: AAB41327.1.
BC054807 mRNA. Translation: AAH54807.1.
BC059834 mRNA. Translation: AAH59834.1.
M33423 mRNA. Translation: AAA40014.1.

IPI

IPI00122143.

PIR

A47511.
B39577.
JH0114.

RefSeq

NP_001041642.1. NM_001048177.1.
NP_032439.2. NM_008413.2.

UniGene

Mm.275839.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HDX	X-ray	2.35	G/H/I/J/K/L	810-820	[»]

ProteinModelPortal

Q62120.

SMR

Q62120. Positions 401-1126.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-320N.

IntAct

Q62120. 5 interactions.

MINT

MINT-188474.

PTM databases

PhosphoSite

Q62120.

Proteomic databases

PaxDb

Q62120.

PRIDE

Q62120.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

16452.

KEGG

mmu:16452.

UCSC

uc008hdb.1. mouse.

Organism-specific databases

CTD

3717.

MGI

MGI:96629. Jak2.

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000049158.

HOVERGEN

HBG006195.

InParanoid

Q62120.

KO

K04447.

OrthoDB

EOG4PZJ5W.

Enzyme and pathway databases

BRENDA

2.7.10.2. 3474.

Reactome

REACT_107772. Immune System.

Gene expression databases

CleanEx

MM_JAK2.

Genevestigator

Q62120.

GermOnline

ENSMUSG00000024789. Mus musculus.

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

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Other

ChEMBL

CHEMBL1649049.

EvolutionaryTrace

Q62120.

NextBio

289717.

SOURCE

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Entry information

Entry name

JAK2_MOUSE

Accession

Primary (citable) accession number: Q62120
Secondary accession number(s): Q62124, Q7TQD0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	May 20, 2008
Last modified:	May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program