Reviewed, UniProtKB/Swiss-Prot P23458 (JAK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase JAK1
    EC=2.7.10.2
Alternative name(s):
    Janus kinase 1
      Short name=JAK-1

Gene names

Name:	JAK1
Synonyms:	JAK1A, JAK1B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1154 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 the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with IL31RA, JAKMIP1 and SHB.
Subcellular location	Intracytoplasmic membrane; Peripheral membrane protein. Note= Wholly intracellular, possibly membrane associated.
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. The FERM domain mediates interaction with JAKMIP1.
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.
Sequence caution	The sequence AAA36527.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAA36527.1 differs from that shown. Reason: Frameshift at positions 858 and 862.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Gene Ontology (GO)
Cellular component	cytoskeleton Inferred from electronic annotation. Source: InterPro endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro Janus kinase activity Inferred from electronic annotation. Source: InterPro non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1154	1154	Tyrosine-protein kinase JAK1		PRO_0000088108
Regions
	Domain	34 – 420	387	FERM
	Domain	439 – 544	106	SH2
	Domain	583 – 855	273	Protein kinase 1
	Domain	875 – 1153	279	Protein kinase 2
	Nucleotide binding	881 – 889	9	ATP By similarity
Sites
	Active site	1003	1	Proton acceptor By similarity
	Binding site	908	1	ATP By similarity
Amino acid modifications
	Modified residue	1034	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1035	1	Phosphotyrosine
Natural variations
	Natural variant	973	1	N → K		VAR_041715
Experimental info
	Sequence conflict	350	1	H → D in M64174. Ref.1
	Sequence conflict	368	1	Y → F in M64174. Ref.1
	Sequence conflict	898	1	Missing in M64174. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P23458-1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: A2C4BE27851ACABB	FASTA	1,154	133,277
	10 20 30 40 50 60 MQYLNIKEDC NAMAFCAKMR SSKKTEVNLE APEPGVEVIF YLSDREPLRL GSGEYTAEEL 70 80 90 100 110 120 CIRAAQACRI SPLCHNLFAL YDENTKLWYA PNRTITVDDK MSLRLHYRMR FYFTNWHGTN 130 140 150 160 170 180 DNEQSVWRHS PKKQKNGYEK KKIPDATPLL DASSLEYLFA QGQYDLVKCL APIRDPKTEQ 190 200 210 220 230 240 DGHDIENECL GMAVLAISHY AMMKKMQLPE LPKDISYKRY IPETLNKSIR QRNLLTRMRI 250 260 270 280 290 300 NNVFKDFLKE FNNKTICDSS VSTHDLKVKY LATLETLTKH YGAEIFETSM LLISSENEMN 310 320 330 340 350 360 WFHSNDGGNV LYYEVMVTGN LGIQWRHKPN VVSVEKEKNK LKRKKLENKH KKDEEKNKIR 370 380 390 400 410 420 EEWNNFSYFP EITHIVIKES VVSINKQDNK KMELKLSSHE EALSFVSLVD GYFRLTADAH 430 440 450 460 470 480 HYLCTDVAPP LIVHNIQNGC HGPICTEYAI NKLRQEGSEE GMYVLRWSCT DFDNILMTVT 490 500 510 520 530 540 CFEKSEQVQG AQKQFKNFQI EVQKGRYSLH GSDRSFPSLG DLMSHLKKQI LRTDNISFML 550 560 570 580 590 600 KRCCQPKPRE ISNLLVATKK AQEWQPVYPM SQLSFDRILK KDLVQGEHLG RGTRTHIYSG 610 620 630 640 650 660 TLMDYKDDEG TSEEKKIKVI LKVLDPSHRD ISLAFFEAAS MMRQVSHKHI VYLYGVCVRD 670 680 690 700 710 720 VENIMVEEFV EGGPLDLFMH RKSDVLTTPW KFKVAKQLAS ALSYLEDKDL VHGNVCTKNL 730 740 750 760 770 780 LLAREGIDSE CGPFIKLSDP GIPITVLSRQ ECIERIPWIA PECVEDSKNL SVAADKWSFG 790 800 810 820 830 840 TTLWEICYNG EIPLKDKTLI EKERFYESRC RPVTPSCKEL ADLMTRCMNY DPNQRPFFRA 850 860 870 880 890 900 IMRDINKLEE QNPDIVSEKK PATEVDPTHF EKRFLKRIRD LGEGHFGKVE LCRYDPEGDN 910 920 930 940 950 960 TGEQVAVKSL KPESGGNHIA DLKKEIEILR NLYHENIVKY KGICTEDGGN GIKLIMEFLP 970 980 990 1000 1010 1020 SGSLKEYLPK NKNKINLKQQ LKYAVQICKG MDYLGSRQYV HRDLAARNVL VESEHQVKIG 1030 1040 1050 1060 1070 1080 DFGLTKAIET DKEYYTVKDD RDSPVFWYAP ECLMQSKFYI ASDVWSFGVT LHELLTYCDS 1090 1100 1110 1120 1130 1140 DSSPMALFLK MIGPTHGQMT VTRLVNTLKE GKRLPCPPNC PDEVYQLMRK CWEFQPSNRT 1150 SFQNLIEGFE ALLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase." Wilks A.F., Harpur A.G., Kurban R.R., Ralph S.J., Zuercher G., Ziemiecki A. Mol. Cell. Biol. 11:2057-2065(1991) [PubMed: 1848670] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Brain.
[6]	"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes." Lee S.-T., Strunk K.M., Spritz R.A. Oncogene 8:3403-3410(1993) [PubMed: 8247543] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1005-1062.
[7]	"IL-2 receptor signaling through the Shb adapter protein in T and NK cells." Lindholm C.K. Biochem. Biophys. Res. Commun. 296:929-936(2002) [PubMed: 12200137] [Abstract] Cited for: INTERACTION WITH SHB.
[8]	"Characterization of the signaling capacities of the novel gp130-like cytokine receptor." Dreuw A., Radtke S., Pflanz S., Lippok B.E., Heinrich P.C., Hermanns H.M. J. Biol. Chem. 279:36112-36120(2004) [PubMed: 15194700] [Abstract] Cited for: INTERACTION WITH IL31RA.
[9]	"Jamip1 (marlin-1) defines a family of proteins interacting with Janus kinases and microtubules." Steindler C., Li Z., Algarte M., Alcover A., Libri V., Ragimbeau J., Pellegrini S. J. Biol. Chem. 279:43168-43177(2004) [PubMed: 15277531] [Abstract] Cited for: INTERACTION WITH JAKMIP1.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1034 AND TYR-1035, MASS SPECTROMETRY.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-973.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M64174 mRNA. Translation: AAA36527.1. Sequence problems. AB209057 mRNA. Translation: BAD92294.1. AC093427 Genomic DNA. No translation available. CH471059 Genomic DNA. Translation: EAX06547.1. BC132729 mRNA. Translation: AAI32730.1.
PIR	A39577.
UniGene	Hs.207538
3D structure databases
HSSP	HSSP built from PDB template 1JQH based on UniProtKB P08069.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:133N.
PTM databases
PhosphoSite	P23458.
Genome annotation databases
Ensembl	ENSG00000162434. Homo sapiens. [Contig view]
KEGG	hsa:3716.
Organism-specific databases
HGNC	HGNC:6190. JAK1.
HPA	CAB013088.
MIM	147795. gene.
PharmGKB	PA29988.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P23458.
Gene expression databases
ArrayExpress	P23458.
CleanEx	HS_JAK1.
GermOnline	ENSG00000162434. Homo sapiens.
Family and domain databases
InterPro	IPR000299. Band_4.1_N. IPR009127. JAK. IPR009128. JAK1. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR000980. SH2. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. IPR016251. TyrPK_Jak. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 2 hits. [Graphical view]
PIRSF	PIRSF000636. TyrPK_Jak. 1 hit.
PRINTS	PR01823. JANUSKINASE. PR01824. JANUSKINASE1. 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
SOURCE	Search...

Entry information

Entry name

JAK1_HUMAN

Accession

Primary (citable) accession number: P23458
Secondary accession number(s): Q59GQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	November 25, 2008
Last modified:	November 25, 2008
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)