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Identification
HMDB Protein ID HMDBP01358
Secondary Accession Numbers
  • 6654
Name Tyrosine-protein kinase JAK3
Synonyms
  1. JAK-3
  2. Janus kinase 3
  3. L-JAK
  4. Leukocyte janus kinase
Gene Name JAK3
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Tyrosine kinase of the non-receptor type, involved in the interleukin-2 and interleukin-4 signaling pathway. Phosphorylates STAT6, IRS1, IRS2 and PI3K
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
cytoskeleton
organelle
non-membrane-bounded organelle
intracellular non-membrane-bounded organelle
Function
protein tyrosine kinase activity
non-membrane spanning protein tyrosine kinase activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
signaling process
signal transmission
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
signal transmission via phosphorylation event
intracellular protein kinase cascade
Cellular Location
  1. Endomembrane system
  2. Peripheral membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 19p13.1
SNPs JAK3
Gene Sequence
>3375 bp
ATGGCACCTCCAAGTGAAGAGACGCCCCTGATCCCTCAGCGTTCATGCAGCCTCTTGTCC
ACGGAGGCTGGTGCCCTGCATGTGCTGCTGCCCGCTCGGGCCCCGGGGCCCCCCCAGCGC
CTATCTTTCTCCTTTGGGGACCACTTGGCTGAGGACCTGTGCGTGCAGGCTGCCAAGGCC
AGCGGCATCCTGCCTGTGTACCACTCCCTCTTTGCTCTGGCCACGGAGGACCTGTCCTGC
TGGTTCCCCCCGAGCCACATCTTCTCCGTGGAGGATGCCAGCACCCAAGTCCTGCTGTAC
AGGATTCGCTTTTACTTCCCCAATTGGTTTGGGCTGGAGAAGTGCCACCGCTTCGGGCTA
CGCAAGGATTTGGCCAGTGCTATCCTTGACCTGCCAGTCCTGGAGCACCTCTTTGCCCAG
CACCGCAGTGACCTGGTGAGTGGGCGCCTCCCCGTGGGCCTCAGTCTCAAGGAGCAGGGT
GAGTGTCTCAGCCTGGCCGTGTTGGACCTGGCCCGGATGGCGCGAGAGCAGGCCCAGCGG
CCGGGAGAGCTGCTGAAGACTGTCAGCTACAAGGCCTGCCTACCCCCAAGCCTGCGCGAC
CTGATCCAGGGCCTGAGCTTCGTGACGCGGAGGGCTATTCGGAGGACGGTGCGCAGAGCC
CTGCCGCGCGTGGCCGCCTGCCAGGCAGACCGGCACTCGCTCATGGCCAAGTACATCATG
GACCTGGAGCGGCTGGATCCAGCCGGGGCCGCCGAGACCTTCCACGTGGGCCTCCCTGGG
GCCCTTGGTGGCCACGACGGGCTGGGGCTGCTCCGCGTGGCTGGTGACGGCGGCATCGCC
TGGACCCAGGGAGAACAGGAGGTCCTCCAGCCCTTCTGCGACTTTCCAGAAATCGTAGAC
ATTAGCATCAAGCAGGCCCCGCGCGTTGGCCCGGCCGGAGAGCACCGCCTGGTCACTGTT
ACCAGGACAGACAACCAGATTTTAGAGGCCGAGTTCCCAGGGCTGCCCGAGGCTCTGTCG
TTCGTGGCGCTCGTGGACGGCTACTTCCGGCTGACCACGGACTCCCAGCACTTCTTCTGC
AAGGAGGTGGCACCGCCGAGGCTGCTGGAGGAAGTGGCCGAGCAGTGCCACGGCCCCATC
ACTCTGGACTTTGCCATCAACAAGCTCAAGACTGGGGGCTCACGTCCTGGCTCCTATGTT
CTCCGCCGCAGCCCCCAGGACTTTGACAGCTTCCTCCTCACTGTCTGTGTCCAGAACCCC
CTTGGTCCTGATTATAAGGGCTGCCTCATCCGGCGCAGCCCCACAGGAACCTTCCTTCTG
GTTGGCCTCAGCCGACCCCACAGCAGTCTTCGAGAGCTCCTGGCAACCTGCTGGGATGGG
GGGCTGCACGTAGATGGGGTGGCAGTGACCCTCACTTCCTGCTGTATCCCCAGACCCAAA
GAAAAGTCCAACCTGATCGTGGTCCAGAGAGGTCACAGCCCACCCACATCATCCTTGGTT
CAGCCCCAATCCCAATACCAGCTGAGTCAGATGACATTTCACAAGATCCCTGCTGACAGC
CTGGAGTGGCATGAGAACCTGGGCCATGGGTCCTTCACCAAGATTTACCGGGGCTGTCGC
CATGAGGTGGTGGATGGGGAGGCCCGAAAGACAGAGGTGCTGCTGAAGGTCATGGATGCC
AAGCACAAGAACTGCATGGAGTCATTCCTGGAAGCAGCGAGCTTGATGAGCCAAGTGTCG
TACCGGCATCTCGTGCTGCTCCACGGCGTGTGCATGGCTGGAGACAGCACCATGGTGCAG
GAATTTGTACACCTGGGGGCCATAGACATGTATCTGCGAAAACGTGGCCACCTGGTGCCA
GCCAGCTGGAAGCTGCAGGTGGTCAAACAGCTGGCCTACGCCCTCAACTATCTGGAGGAC
AAAGGCCTGCCCCATGGCAATGTCTCTGCCCGGAAGGTGCTCCTGGCTCGGGAGGGGGCT
GATGGGAGCCCGCCCTTCATCAAGCTGAGTGACCCTGGGGTCAGCCCCGCTGTGTTAAGC
CTGGAGATGCTCACCGACAGGATCCCCTGGGTGGCCCCCGAGTGTCTCCGGGAGGCGCAG
ACACTTAGCTTGGAAGCTGACAAGTGGGGCTTCGGCGCCACGGTCTGGGAAGTGTTTAGT
GGCGTCACCATGCCCATCAGTGCCCTGGATCCTGCTAAGAAACTCCAATTTTATGAGGAC
CGGCAGCAGCTGCCGGCCCCCAAGTGGACAGAGCTGGCCCTGCTGATTCAACAGTGCATG
GCCTATGAGCCGGTCCAGAGGCCCTCCTTCCGAGCCGTCATTCGTGACCTCAATAGCCTC
ATCTCTTCAGACTATGAGCTCCTCTCAGACCCCACACCTGGTGCCCTGGCACCTCGTGAT
GGGCTGTGGAATGGTGCCCAGCTCTATGCCTGCCAAGACCCCACGATCTTCGAGGAGAGA
CACCTCAAGTACATCTCACAGCTGGGCAAGGGCAACTTTGGCAGCGTGGAGCTGTGCCGC
TATGACCCGCTAGCCCACAATACAGGTGCCCTGGTGGCCGTGAAACAGCTGCAGCACAGC
GGGCCAGACCAGCAGAGGGACTTTCAGCGGGAGATTCAGATCCTCAAAGCACTGCACAGT
GATTTCATTGTCAAGTATCGTGGTGTCAGCTATGGCCCGGGCCGGCCAGAGCTGCGGCTG
GTCATGGAGTACCTGCCCAGCGGCTGCTTGCGCGACTTCCTGCAGCGGCACCGCGCGCGC
CTCGATGCCAGCCGCCTCCTTCTCTATTCCTCGCAGATCTGCAAGGGCATGGAGTACCTG
GGCTCCCGCCGCTGCGTGCACCGCGACCTGGCCGCCCGAAACATCCTCGTGGAGAGCGAG
GCACACGTCAAGATCGCTGACTTCGGCCTAGCTAAGCTGCTGCCGCTTGACAAAGACTAC
TACGTGGTCCGCGAGCCAGGCCAGAGCCCCATTTTCTGGTATGCCCCCGAATCCCTCTCG
GACAACATCTTCTCTCGCCAGTCAGACGTCTGGAGCTTCGGGGTCGTCCTGTACGAGCTC
TTCACCTACTGCGACAAAAGCTGCAGCCCCTCGGCCGAGTTCCTGCGGATGATGGGATGT
GAGCGGGATGTCCCCGCCCTCTGCCGCCTCTTGGAACTGCTGGAGGAGGGCCAGAGGCTG
CCGGCGCCTCCTGCCTGCCCTGCTGAGGTTCACGAGCTCATGAAGCTGTGCTGGGCCCCT
AGCCCACAGGACCGGCCATCATTCAGCGCCCTGGGCCCCCAGCTGGACATGCTGTGGAGC
GGAAGCCGGGGGTGTGAGACTCATGCCTTCACTGCTCACCCAGAGGGCAAACACCACTCC
CTGTCCTTTTCATAG
Protein Properties
Number of Residues 1124
Molecular Weight 125097.6
Theoretical pI 7.18
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Tyrosine-protein kinase JAK3
MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLAEDLCVQAAKA
SGILPVYHSLFALATEDLSCWFPPSHIFSVEDASTQVLLYRIRFYFPNWFGLEKCHRFGL
RKDLASAILDLPVLEHLFAQHRSDLVSGRLPVGLSLKEQGECLSLAVLDLARMAREQAQR
PGELLKTVSYKACLPPSLRDLIQGLSFVTRRRIRRTVRRALRRVAACQADRHSLMAKYIM
DLERLDPAGAAETFHVGLPGALGGHDGLGLLRVAGDGGIAWTQGEQEVLQPFCDFPEIVD
ISIKQAPRVGPAGEHRLVTVTRTDNQILEAEFPGLPEALSFVALVDGYFRLTTDSQHFFC
KEVAPPRLLEEVAEQCHGPITLDFAINKLKTGGSRPGSYVLRRSPQDFDSFLLTVCVQNP
LGPDYKGCLIRRSPTGTFLLVGLSRPHSSLRELLATCWDGGLHVDGVAVTLTSCCIPRPK
EKSNLIVVQRGHSPPTSSLVQPQSQYQLSQMTFHKIPADSLEWHENLGHGSFTKIYRGCR
HEVVDGEARKTEVLLKVMDAKHKNCMESFLEAASLMSQVSYRHLVLLHGVCMAGDSTMVQ
EFVHLGAIDMYLRKRGHLVPASWKLQVVKQLAYALNYLEDKGLPHGNVSARKVLLAREGA
DGSPPFIKLSDPGVSPAVLSLEMLTDRIPWVAPECLREAQTLSLEADKWGFGATVWEVFS
GVTMPISALDPAKKLQFYEDRQQLPAPKWTELALLIQQCMAYEPVQRPSFRAVIRDLNSL
ISSDYELLSDPTPGALAPRDGLWNGAQLYACQDPTIFEERHLKYISQLGKGNFGSVELCR
YDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPGRQSLRL
VMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESE
AHVKIADFGLAKLLPLDKDYYVVREPGQSPIFWYAPESLSDNIFSRQSDVWSFGVVLYEL
FTYCDKSCSPSAEFLRMMGCERDVPALCRLLELLEEGQRLPAPPACPAEVHELMKLCWAP
SPQDRPSFSALGPQLDMLWSGSRGCETHAFTAHPEGKHHSLSFS
GenBank ID Protein 508731
UniProtKB/Swiss-Prot ID P52333
UniProtKB/Swiss-Prot Entry Name JAK3_HUMAN
PDB IDs Not Available
GenBank Gene ID U09607
GeneCard ID JAK3
GenAtlas ID JAK3
HGNC ID HGNC:6193
References
General References
  1. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [PubMed:15592455 ]
  2. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  3. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [PubMed:15057824 ]
  4. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, 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 DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  5. Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K: STAM2, a new member of the STAM family, binding to the Janus kinases. FEBS Lett. 2000 Jul 14;477(1-2):55-61. [PubMed:10899310 ]
  6. Lindholm CK: IL-2 receptor signaling through the Shb adapter protein in T and NK cells. Biochem Biophys Res Commun. 2002 Aug 30;296(4):929-36. [PubMed:12200137 ]
  7. Kawamura M, McVicar DW, Johnston JA, Blake TB, Chen YQ, Lal BK, Lloyd AR, Kelvin DJ, Staples JE, Ortaldo JR, et al.: Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6374-8. [PubMed:8022790 ]
  8. Lai KS, Jin Y, Graham DK, Witthuhn BA, Ihle JN, Liu ET: A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells. J Biol Chem. 1995 Oct 20;270(42):25028-36. [PubMed:7559633 ]
  9. Riedy MC, Dutra AS, Blake TB, Modi W, Lal BK, Davis J, Bosse A, O'Shea JJ, Johnston JA: Genomic sequence, organization, and chromosomal localization of human JAK3. Genomics. 1996 Oct 1;37(1):57-61. [PubMed:8921370 ]
  10. Verbsky JW, Bach EA, Fang YF, Yang L, Randolph DA, Fields LE: Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells. J Biol Chem. 1996 Jun 14;271(24):13976-80. [PubMed:8662778 ]
  11. Boggon TJ, Li Y, Manley PW, Eck MJ: Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog. Blood. 2005 Aug 1;106(3):996-1002. Epub 2005 Apr 14. [PubMed:15831699 ]
  12. Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ, et al.: Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. 1995 Sep 7;377(6544):65-8. [PubMed:7659163 ]
  13. Candotti F, Oakes SA, Johnston JA, Giliani S, Schumacher RF, Mella P, Fiorini M, Ugazio AG, Badolato R, Notarangelo LD, Bozzi F, Macchi P, Strina D, Vezzoni P, Blaese RM, O'Shea JJ, Villa A: Structural and functional basis for JAK3-deficient severe combined immunodeficiency. Blood. 1997 Nov 15;90(10):3996-4003. [PubMed:9354668 ]
  14. Bozzi F, Lefranc G, Villa A, Badolato R, Schumacher RF, Khalil G, Loiselet J, Bresciani S, O'Shea JJ, Vezzoni P, Notarangelo LD, Candotti F: Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment. Br J Haematol. 1998 Sep;102(5):1363-6. [PubMed:9753072 ]
  15. Schumacher RF, Mella P, Badolato R, Fiorini M, Savoldi G, Giliani S, Villa A, Candotti F, Tampalini A, O'Shea JJ, Notarangelo LD: Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism. Hum Genet. 2000 Jan;106(1):73-9. [PubMed:10982185 ]
  16. Roberts JL, Lengi A, Brown SM, Chen M, Zhou YJ, O'Shea JJ, Buckley RH: Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Blood. 2004 Mar 15;103(6):2009-18. Epub 2003 Nov 13. [PubMed:14615376 ]