Reviewed, UniProtKB/Swiss-Prot Q62120 (JAK2_MOUSE)

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1129 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Tyrosine kinase of the non-receptor type, involved in interleukin-3 and probably interleukin-23 signal transduction By similarity. Plays a role in leptin signaling and control of body weight.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with IL23R, SKB1 and STAM2 By similarity. Interacts with SIRPA and SH2B1.
Subcellular location	Endomembrane system; Peripheral membrane protein By similarity. Note: Wholly intracellular, possibly membrane associated By similarity.
Domain	Possesses two phosphotransferase domains. The second one probably contains the catalytic domain By similarity, while the presence of slight differences suggest a different role for domain 1.
Post-translational modification	Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. Contains 1 FERM domain. Contains 1 protein kinase domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Membrane
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	JAK-STAT cascade involved in growth hormone signaling pathway Inferred from direct assay. Source: UniProtKB STAT protein nuclear translocation Inferred from direct assay. Source: MGI apoptosis Inferred from direct assay. Source: MGI cytokine-mediated signaling pathway Traceable author statement. Source: MGI myeloid cell differentiation Inferred from mutant phenotype. Source: MGI negative regulation of DNA binding Inferred from direct assay. Source: MGI negative regulation of cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of growth hormone receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB positive regulation of phosphoinositide 3-kinase cascade Inferred from mutant phenotype. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from direct assay. Source: UniProtKB tyrosine phosphorylation of STAT protein Inferred from direct assay. Source: MGI
Cellular component	caveola Inferred from direct assay. Source: MGI cytoplasm Traceable author statement. Source: MGI cytoskeleton Inferred from electronic annotation. Source: InterPro extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW Janus kinase activity Inferred from direct assay. Source: MGI interleukin-12 receptor binding Inferred from physical interaction. Source: MGI non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Csf2rb	P26955	1	EBI-646604,EBI-1810026

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
Sites
	Active site	976	1	Proton acceptor By similarity
	Binding site	882	1	ATP By similarity
Amino acid modifications
	Modified residue	523	1	Phosphoserine Ref.9
	Modified residue	570	1	Phosphotyrosine Ref.6 Ref.8
	Modified residue	813	1	Phosphotyrosine Ref.7 Ref.10
	Modified residue	1007	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1008	1	Phosphotyrosine By similarity
Experimental info
	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 Ref.3
	Sequence conflict	1016	1	S → R Ref.4
	Sequence conflict	1024	1	E → Q in AAB41327. Ref.1
	Sequence conflict	1042 – 1043	2	VV → IP Ref.3
	Sequence conflict	1042 – 1043	2	VV → IP Ref.4
	Sequence conflict	1121 – 1129	9	LRVDQIIAA → FGWIKCGTV in AAB41327. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q62120-1 [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: 8378315] [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: 15489334] [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: 2482828] [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: 2466296] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 973-1043.
[5]	"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: 10842184] [Abstract] Cited for: INTERACTION WITH SIRPA.
[6]	"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: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-570, MASS SPECTROMETRY. Tissue: Mast cell.
[7]	"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: 17565041] [Abstract] Cited for: INTERACTION WITH SH2B1, PHOSPHORYLATION AT TYR-813.
[8]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-570, MASS SPECTROMETRY.
[9]	"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: 19144319] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523, MASS SPECTROMETRY. Tissue: Macrophage.
[10]	"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: 16824542] [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

EMBLGenBankDDBJ

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.
NP_032439.2.

UniGene

Mm.275839

3D structure databases

PDBPDBe

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

SMR

Q62120. Positions 840-1121.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q62120. 3 interactions.

STRING

Q62120.

PTM databases

PhosphoSite

Q62120.

Proteomic databases

PRIDE

Q62120.

Genome annotation databases

Ensembl

ENSMUST00000025705; ENSMUSP00000025705; ENSMUSG00000024789; Mus musculus. [Genome view]
ENSMUST00000065796; ENSMUSP00000064394; ENSMUSG00000024789; Mus musculus. [Genome view]

GeneID

16452.

KEGG

mmu:16452.

UCSC

uc008hdb.1. mouse.

Organism-specific databases

CTD

16452.

MGI

MGI:96629. Jak2.

Phylogenomic databases

HOVERGEN

Q62120.

Enzyme and pathway databases

BRENDA

2.7.10.2. 244.

Gene expression databases

ArrayExpress

Q62120.

Bgee

Q62120.

CleanEx

MM_JAK2.

Genevestigator

Q62120.

GermOnline

ENSMUSG00000024789. Mus musculus.

Family and domain databases

InterPro

IPR019749. Band_41_domain.
IPR019747. FERM_CS.
IPR000299. FERM_domain.
IPR009127. JAK.
IPR009129. JAK2.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR000980. SH2.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

Pfam

PF07714. Pkinase_Tyr. 2 hits.
PF00017. SH2. 1 hit.
[Graphical view]

PRINTS

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

ProDom

PD000001. Prot_kinase. 2 hits.
PD000093. SH2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]

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 Resources

NextBio

289717.

SOURCE

Search...

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:	October 13, 2009
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)