EKS-HOS-00030

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00030

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Jak	350.0	4.8E-104	822	1095	274

Status

Reviewed

Ensembl Protein

ENSP00000391676

UniProt Accession

P52333; Q13259; Q13260; Q13611; Q99699; Q9Y6S2;

Protein Name

Tyrosine-protein kinase JAK3

Protein Synonyms/Alias

Janus kinase 3; JAK-3; Leukocyte janus kinase; L-JAK;

Gene Name

JAK3

Gene Synonyms/Alias

JAK3;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000105639	ENSP00000432511	ENST00000527670
ENSG00000105639	ENSP00000391676	ENST00000458235
ENSG00000105639	ENSP00000436421	ENST00000534444

Organism

Homo sapiens

Functional Description

Non-receptor tyrosine kinase involved in variousprocesses such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. 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, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.

Protein Length

1124

Protein Sequence
(FASTA)

MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 60

SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 120

RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 180

PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 240

DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 300

ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 360

KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 420

LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 480

EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 540

HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 600

EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 660

DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 720

GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 780

ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 840

YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 900

VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 960

AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 1020

FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP 1080

SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS 1124

Nucleotide Sequence
(FASTA)

ATGGCACCTC CAAGTGAAGA GACGCCCCTG ATCCCTCAGC GTTCATGCAG CCTCTTGTCC 60

ACGGAGGCTG GTGCCCTGCA TGTGCTGCTG CCCGCTCGGG GCCCCGGGCC CCCCCAGCGC 120

CTATCTTTCT CCTTTGGGGA CCACTTGGCT GAGGACCTGT GCGTGCAGGC TGCCAAGGCC 180

AGCGGCATCC TGCCTGTGTA CCACTCCCTC TTTGCTCTGG CCACGGAGGA CCTGTCCTGC 240

TGGTTCCCCC CGAGCCACAT CTTCTCCGTG GAGGATGCCA GCACCCAAGT CCTGCTGTAC 300

AGGATTCGCT TTTACTTCCC CAATTGGTTT GGGCTGGAGA AGTGCCACCG CTTCGGGCTA 360

CGCAAGGATT TGGCCAGTGC TATCCTTGAC CTGCCAGTCC TGGAGCACCT CTTTGCCCAG 420

CACCGCAGTG ACCTGGTGAG TGGGCGCCTC CCCGTGGGCC TCAGTCTCAA GGAGCAGGGT 480

GAGTGTCTCA GCCTGGCCGT GTTGGACCTG GCCCGGATGG CGCGAGAGCA GGCCCAGCGG 540

CCGGGAGAGC TGCTGAAGAC TGTCAGCTAC AAGGCCTGCC TACCCCCAAG CCTGCGCGAC 600

CTGATCCAGG GCCTGAGCTT CGTGACGCGG AGGCGTATTC GGAGGACGGT GCGCAGAGCC 660

CTGCGCCGCG TGGCCGCCTG CCAGGCAGAC CGGCACTCGC TCATGGCCAA GTACATCATG 720

GACCTGGAGC GGCTGGATCC AGCCGGGGCC GCCGAGACCT TCCACGTGGG CCTCCCTGGG 780

GCCCTTGGTG GCCACGACGG GCTGGGGCTG CTCCGCGTGG CTGGTGACGG CGGCATCGCC 840

TGGACCCAGG GAGAACAGGA GGTCCTCCAG CCCTTCTGCG ACTTTCCAGA AATCGTAGAC 900

ATTAGCATCA AGCAGGCCCC GCGCGTTGGC CCGGCCGGAG AGCACCGCCT GGTCACTGTT 960

ACCAGGACAG ACAACCAGAT TTTAGAGGCC GAGTTCCCAG GGCTGCCCGA GGCTCTGTCG 1020

TTCGTGGCGC TCGTGGACGG CTACTTCCGG CTGACCACGG ACTCCCAGCA CTTCTTCTGC 1080

AAGGAGGTGG CACCGCCGAG GCTGCTGGAG GAAGTGGCCG AGCAGTGCCA CGGCCCCATC 1140

ACTCTGGACT TTGCCATCAA CAAGCTCAAG ACTGGGGGCT CACGTCCTGG CTCCTATGTT 1200

CTCCGCCGCA GCCCCCAGGA CTTTGACAGC TTCCTCCTCA CTGTCTGTGT CCAGAACCCC 1260

CTTGGTCCTG ATTATAAGGG CTGCCTCATC CGGCGCAGCC CCACAGGAAC CTTCCTTCTG 1320

GTTGGCCTCA GCCGACCCCA CAGCAGTCTT CGAGAGCTCC TGGCAACCTG CTGGGATGGG 1380

GGGCTGCACG TAGATGGGGT GGCAGTGACC CTCACTTCCT GCTGTATCCC CAGACCCAAA 1440

GAAAAGTCCA ACCTGATCGT GGTCCAGAGA GGTCACAGCC CACCCACATC ATCCTTGGTT 1500

CAGCCCCAAT CCCAATACCA GCTGAGTCAG ATGACATTTC ACAAGATCCC TGCTGACAGC 1560

CTGGAGTGGC ATGAGAACCT GGGCCATGGG TCCTTCACCA AGATTTACCG GGGCTGTCGC 1620

CATGAGGTGG TGGATGGGGA GGCCCGAAAG ACAGAGGTGC TGCTGAAGGT CATGGATGCC 1680

AAGCACAAGA ACTGCATGGA GTCATTCCTG GAAGCAGCGA GCTTGATGAG CCAAGTGTCG 1740

TACCGGCATC TCGTGCTGCT CCACGGCGTG TGCATGGCTG GAGACAGCAC CATGGTGCAG 1800

GAATTTGTAC ACCTGGGGGC CATAGACATG TATCTGCGAA AACGTGGCCA CCTGGTGCCA 1860

GCCAGCTGGA AGCTGCAGGT GGTCAAACAG CTGGCCTACG CCCTCAACTA TCTGGAGGAC 1920

AAAGGCCTGC CCCATGGCAA TGTCTCTGCC CGGAAGGTGC TCCTGGCTCG GGAGGGGGCT 1980

GATGGGAGCC CGCCCTTCAT CAAGCTGAGT GACCCTGGGG TCAGCCCCGC TGTGTTAAGC 2040

CTGGAGATGC TCACCGACAG GATCCCCTGG GTGGCCCCCG AGTGTCTCCG GGAGGCGCAG 2100

ACACTTAGCT TGGAAGCTGA CAAGTGGGGC TTCGGCGCCA CGGTCTGGGA AGTGTTTAGT 2160

GGCGTCACCA TGCCCATCAG TGCCCTGGAT CCTGCTAAGA AACTCCAATT TTATGAGGAC 2220

CGGCAGCAGC TGCCGGCCCC CAAGTGGACA GAGCTGGCCC TGCTGATTCA ACAGTGCATG 2280

GCCTATGAGC CGGTCCAGAG GCCCTCCTTC CGAGCCGTCA TTCGTGACCT CAATAGCCTC 2340

ATCTCTTCAG ACTATGAGCT CCTCTCAGAC CCCACACCTG GTGCCCTGGC ACCTCGTGAT 2400

GGGCTGTGGA ATGGTGCCCA GCTCTATGCC TGCCAAGACC CCACGATCTT CGAGGAGAGA 2460

CACCTCAAGT ACATCTCACA GCTGGGCAAG GGCAACTTTG GCAGCGTGGA GCTGTGCCGC 2520

TATGACCCGC TAGGCGACAA TACAGGTGCC CTGGTGGCCG TGAAACAGCT GCAGCACAGC 2580

GGGCCAGACC AGCAGAGGGA CTTTCAGCGG GAGATTCAGA TCCTCAAAGC ACTGCACAGT 2640

GATTTCATTG TCAAGTATCG TGGTGTCAGC TATGGCCCGG GCCGCCAGAG CCTGCGGCTG 2700

GTCATGGAGT ACCTGCCCAG CGGCTGCTTG CGCGACTTCC TGCAGCGGCA CCGCGCGCGC 2760

CTCGATGCCA GCCGCCTCCT TCTCTATTCC TCGCAGATCT GCAAGGGCAT GGAGTACCTG 2820

GGCTCCCGCC GCTGCGTGCA CCGCGACCTG GCCGCCCGAA ACATCCTCGT GGAGAGCGAG 2880

GCACACGTCA AGATCGCTGA CTTCGGCCTA GCTAAGCTGC TGCCGCTTGA CAAAGACTAC 2940

TACGTGGTCC GCGAGCCAGG CCAGAGCCCC ATTTTCTGGT ATGCCCCCGA ATCCCTCTCG 3000

GACAACATCT TCTCTCGCCA GTCAGACGTC TGGAGCTTCG GGGTCGTCCT GTACGAGCTC 3060

TTCACCTACT GCGACAAAAG CTGCAGCCCC TCGGCCGAGT TCCTGCGGAT GATGGGATGT 3120

GAGCGGGATG TCCCCGCCCT CTGCCGCCTC TTGGAACTGC TGGAGGAGGG CCAGAGGCTG 3180

CCGGCGCCTC CTGCCTGCCC TGCTGAGGTT CACGAGCTCA TGAAGCTGTG CTGGGCCCCT 3240

AGCCCACAGG ACCGGCCATC ATTCAGCGCC CTGGGCCCCC AGCTGGACAT GCTGTGGAGC 3300

GGAAGCCGGG GGTGTGAGAC TCATGCCTTC ACTGCTCACC CAGAGGGCAA ACACCACTCC 3360

CTGTCCTTTT CATAG 3375

Domain Profile

S: 1     lkqiesLgkgtftkvfevredaegdsteeevalkvLkesgedisrdfkreaeilsqlshe  60

         lk+i++Lgkg+f++v+++r+d+ gd+t++ va+k+L++sg+d++rdf+re++il++l+++

Q: 822   LKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSD  881

         799*********************************************************

S: 61    hivklkgvcvaegen..rlVmeyvesGsLdiyLrkkkealslsslldvakqlakameYLe  118

         +ivk++gv++ +g++  rlVmey++sG+L+++L++++++l++s+ll +++q++k+meYL+

Q: 882   FIVKYRGVSYGPGRQslRLVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKGMEYLG  941

         ************************************************************

S: 119   dkklvhrdvaarnvLveresnegtppfvklsdpglakavnqd.eYylvreerdsripwla  177

         ++++vhrd+aarn+Lve+e++      vk++d+glak+++ d +Yy+vre+++s+i+w+a

Q: 942   SRRCVHRDLAARNILVESEAH------VKIADFGLAKLLPLDkDYYVVREPGQSPIFWYA  995

         *********************......*********************************

S: 178   peclseaknlstasdvWsFgvtlyellt.cskgesp....lrsesle.......rklell  225

         pe+ls++  +s++sdvWsFgv+lyel+t c+k++sp    lr++++e       r+lell

Q: 996   PESLSDNI-FSRQSDVWSFGVVLYELFTyCDKSCSPsaefLRMMGCErdvpalcRLLELL  1054

         ********.***************************************************

S: 226   eekerlpkpk.cpaelaelmtnclsyepsqrpsFrailedl  265

         ee++rlp+p+ cpae++elm+ c++ +p++rpsF+a+  +l

Q: 1055  EEGQRLPAPPaCPAEVHELMKLCWAPSPQDRPSFSALGPQL  1095

         ***********************************998776

Domain Sequence
(FASTA)

LKYISQLGKG NFGSVELCRY DPLGDNTGAL VAVKQLQHSG PDQQRDFQRE IQILKALHSD 60

FIVKYRGVSY GPGRQSLRLV MEYLPSGCLR DFLQRHRARL DASRLLLYSS QICKGMEYLG 120

SRRCVHRDLA ARNILVESEA HVKIADFGLA KLLPLDKDYY VVREPGQSPI FWYAPESLSD 180

NIFSRQSDVW SFGVVLYELF TYCDKSCSPS AEFLRMMGCE RDVPALCRLL ELLEEGQRLP 240

APPACPAEVH ELMKLCWAPS PQDRPSFSAL GPQL 274

Keyword

3D-structure; Adaptive immunity; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Disease mutation; Immunity; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; SCID; SH2 domain; Transferase; Tyrosine-protein kinase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Felis catus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ornithorhynchus anatinus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Xenopus tropicalis"; ?>

Gene Ontology

GO:0005856	; C:cytoskeleton
GO:0005829	; C:cytosol
GO:0012505	; C:endomembrane system
GO:0016020	; C:membrane
GO:0005524	; F:ATP binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0004713	; F:protein tyrosine kinase activity
GO:0030183	; P:B cell differentiation
GO:0007204	; P:elevation of cytosolic calcium ion concentration
GO:0045087	; P:innate immune response
GO:0035771	; P:interleukin-4-mediated signaling pathway
GO:0060397	; P:JAK-STAT cascade involved in growth hormone signaling pathway
GO:0002731	; P:negative regulation of dendritic cell cytokine production
GO:0045221	; P:negative regulation of FasL biosynthetic process
GO:0032693	; P:negative regulation of interleukin-10 production
GO:0032695	; P:negative regulation of interleukin-12 production
GO:0045626	; P:negative regulation of T-helper 1 cell differentiation
GO:0070244	; P:negative regulation of thymocyte apoptotic process
GO:0042104	; P:positive regulation of activated T cell proliferation
GO:0051928	; P:positive regulation of calcium ion transport
GO:0050778	; P:positive regulation of immune response
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter
GO:0046777	; P:protein autophosphorylation
GO:0070672	; P:response to interleukin-15
GO:0070669	; P:response to interleukin-2
GO:0071104	; P:response to interleukin-9
GO:0007262	; P:STAT protein import into nucleus
GO:0043029	; P:T cell homeostasis
GO:0007260	; P:tyrosine phosphorylation of STAT protein
GO:0042506	; P:tyrosine phosphorylation of Stat5 protein

KEGG

hsa:3718

;

InterPros

IPR019749	; Band_41_domain.
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.
IPR020775	; Tyr_kinase_non-rcpt_Jak3.

Pfam

PF07714

; Pkinase_Tyr; 2.

SMARTs

SM00295	; B41; 1.
SM00252	; SH2; 1.
SM00219	; TyrKc; 2.

Prosites

PS00660	; FERM_1; FALSE_NEG.
PS00661	; FERM_2; FALSE_NEG.
PS50057	; FERM_3; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 2.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; FALSE_NEG.

Prints

PR01823	; JANUSKINASE.
PR01826	; JANUSKINASE3.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013