Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P29597 (TYK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-receptor tyrosine-protein kinase TYK2

EC=2.7.10.2
Gene names
Name:TYK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1187 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. Ref.7

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Interacts with JAKMIP1. Ref.8

Tissue specificity

Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines. Ref.5

Domain

The FERM domain mediates interaction with JAKMIP1.

Involvement in disease

Protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:611521]: Consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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
   Coding sequence diversityPolymorphism
   DomainRepeat
SH2 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

peptidyl-tyrosine phosphorylation

Traceable author statement Ref.1. Source: GOC

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of type I interferon-mediated signaling pathway

Traceable author statement. Source: Reactome

type I interferon signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10502458. Source: BHF-UCL

cytoskeleton

Inferred from electronic annotation. Source: InterPro

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

membrane

Inferred from electronic annotation. Source: InterPro

nucleus

Inferred from direct assay PubMed 10502458. Source: BHF-UCL

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

growth hormone receptor binding

Inferred from physical interaction PubMed 10502458. Source: BHF-UCL

non-membrane spanning protein tyrosine kinase activity

Traceable author statement Ref.1. Source: ProtInc

protein tyrosine kinase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HSP90AB1P082382EBI-1383454,EBI-352572

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11871187Non-receptor tyrosine-protein kinase TYK2
PRO_0000088177

Regions

Domain26 – 431406FERM
Domain450 – 52980SH2; atypical
Domain589 – 875287Protein kinase 1
Domain897 – 1176280Protein kinase 2
Nucleotide binding903 – 9119ATP By similarity

Sites

Active site10231Proton acceptor By similarity
Binding site9301ATP By similarity

Amino acid modifications

Modified residue2921Phosphotyrosine Ref.10 Ref.11
Modified residue6041Phosphotyrosine By similarity
Modified residue8841Phosphoserine Ref.10 Ref.11
Modified residue10541Phosphotyrosine; by autocatalysis Ref.12

Natural variations

Natural variant41R → C.
Corresponds to variant rs35163004 [ dbSNP | Ensembl ].
VAR_037796
Natural variant41R → H. Ref.2
Corresponds to variant rs12720343 [ dbSNP | Ensembl ].
VAR_020597
Natural variant811A → V.
Corresponds to variant rs1049619 [ dbSNP | Ensembl ].
VAR_037797
Natural variant1971R → H. Ref.2
Corresponds to variant rs12720263 [ dbSNP | Ensembl ].
VAR_020598
Natural variant3621V → F. Ref.1 Ref.2 Ref.13
Corresponds to variant rs2304256 [ dbSNP | Ensembl ].
VAR_020599
Natural variant3631G → S. Ref.2 Ref.13
Corresponds to variant rs2304255 [ dbSNP | Ensembl ].
VAR_020600
Natural variant3861V → M. Ref.13
Corresponds to variant rs55956017 [ dbSNP | Ensembl ].
VAR_041870
Natural variant4421R → Q.
Corresponds to variant rs2304254 [ dbSNP | Ensembl ].
VAR_037798
Natural variant6841I → S. Ref.1 Ref.2 Ref.13
Corresponds to variant rs12720356 [ dbSNP | Ensembl ].
VAR_020286
Natural variant7031R → W. Ref.13
Corresponds to variant rs55882956 [ dbSNP | Ensembl ].
VAR_041871
Natural variant7321H → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.13
VAR_041872
Natural variant8201P → H.
Corresponds to variant rs34046749 [ dbSNP | Ensembl ].
VAR_037799
Natural variant9281A → V. Ref.13
Corresponds to variant rs35018800 [ dbSNP | Ensembl ].
VAR_041873
Natural variant11041P → A. Ref.13
Corresponds to variant rs34536443 [ dbSNP | Ensembl ].
VAR_041874
Natural variant11631E → G. Ref.13
Corresponds to variant rs55886939 [ dbSNP | Ensembl ].
VAR_041875

Experimental info

Sequence conflict8691L → V in CAA38449. Ref.1
Sequence conflict8821P → R in CAA38449. Ref.1
Sequence conflict887 – 8882SD → VG in CAA38449. Ref.1
Sequence conflict8911V → T in CAA38449. Ref.1
Sequence conflict10161A → S in AAH14243. Ref.3
Sequence conflict1017 – 10182QH → HD in CAA38449. Ref.1

Secondary structure

............................................................................................. 1187
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P29597 [UniParc].

Last modified December 7, 2004. Version 3.
Checksum: F76C25D6A919EDBC

FASTA1,187133,650
        10         20         30         40         50         60 
MPLRHWGMAR GSKPVGDGAQ PMAAMGGLKV LLHWAGPGGG EPWVTFSESS LTAEEVCIHI 

        70         80         90        100        110        120 
AHKVGITPPC FNLFALFDAQ AQVWLPPNHI LEIPRDASLM LYFRIRFYFR NWHGMNPREP 

       130        140        150        160        170        180 
AVYRCGPPGT EASSDQTAQG MQLLDPASFE YLFEQGKHEF VNDVASLWEL STEEEIHHFK 

       190        200        210        220        230        240 
NESLGMAFLH LCHLALRHGI PLEEVAKKTS FKDCIPRSFR RHIRQHSALT RLRLRNVFRR 

       250        260        270        280        290        300 
FLRDFQPGRL SQQMVMVKYL ATLERLAPRF GTERVPVCHL RLLAQAEGEP CYIRDSGVAP 

       310        320        330        340        350        360 
TDPGPESAAG PPTHEVLVTG TGGIQWWPVE EEVNKEEGSS GSSGRNPQAS LFGKKAKAHK 

       370        380        390        400        410        420 
AVGQPADRPR EPLWAYFCDF RDITHVVLKE HCVSIHRQDN KCLELSLPSR AAALSFVSLV 

       430        440        450        460        470        480 
DGYFRLTADS SHYLCHEVAP PRLVMSIRDG IHGPLLEPFV QAKLRPEDGL YLIHWSTSHP 

       490        500        510        520        530        540 
YRLILTVAQR SQAPDGMQSL RLRKFPIEQQ DGAFVLEGWG RSFPSVRELG AALQGCLLRA 

       550        560        570        580        590        600 
GDDCFSLRRC CLPQPGETSN LIIMRGARAS PRTLNLSQLS FHRVDQKEIT QLSHLGQGTR 

       610        620        630        640        650        660 
TNVYEGRLRV EGSGDPEEGK MDDEDPLVPG RDRGQELRVV LKVLDPSHHD IALAFYETAS 

       670        680        690        700        710        720 
LMSQVSHTHL AFVHGVCVRG PENIMVTEYV EHGPLDVWLR RERGHVPMAW KMVVAQQLAS 

       730        740        750        760        770        780 
ALSYLENKNL VHGNVCGRNI LLARLGLAEG TSPFIKLSDP GVGLGALSRE ERVERIPWLA 

       790        800        810        820        830        840 
PECLPGGANS LSTAMDKWGF GATLLEICFD GEAPLQSRSP SEKEHFYQRQ HRLPEPSCPQ 

       850        860        870        880        890        900 
LATLTSQCLT YEPTQRPSFR TILRDLTRLQ PHNLADVLTV NPDSPASDPT VFHKRYLKKI 

       910        920        930        940        950        960 
RDLGEGHFGK VSLYCYDPTN DGTGEMVAVK ALKADCGPQH RSGWKQEIDI LRTLYHEHII 

       970        980        990       1000       1010       1020 
KYKGCCEDQG EKSLQLVMEY VPLGSLRDYL PRHSIGLAQL LLFAQQICEG MAYLHAQHYI 

      1030       1040       1050       1060       1070       1080 
HRDLAARNVL LDNDRLVKIG DFGLAKAVPE GHEYYRVRED GDSPVFWYAP ECLKEYKFYY 

      1090       1100       1110       1120       1130       1140 
ASDVWSFGVT LYELLTHCDS SQSPPTKFLE LIGIAQGQMT VLRLTELLER GERLPRPDKC 

      1150       1160       1170       1180 
PCEVYHLMKN CWETEASFRP TFENLIPILK TVHEKYQGQA PSVFSVC 

« Hide

References

« Hide 'large scale' references
[1]"TYK2, prototype of a novel class of non-receptor tyrosine kinase genes."
Firmbach-Kraft I., Byers M., Shows T., Dalla-Favera R., Krolewski J.J.
Oncogene 5:1329-1336(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PHE-362 AND SER-684.
[2]SeattleSNPs variation discovery resource
Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-4; HIS-197; PHE-362; SER-363 AND SER-684.
[3]"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].
Tissue: Kidney.
[4]"A protein tyrosine kinase in the interferon alpha/beta signaling pathway."
Velazquez L., Fellous M., Stark G.R., Pellegrini S.
Cell 70:313-322(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-1187.
[5]"Identification and chromosomal mapping of new human tyrosine kinase genes."
Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R.
Oncogene 5:277-282(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1007-1162, TISSUE SPECIFICITY.
[6]"Putative tyrosine kinases expressed in K-562 human leukemia cells."
Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.
Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1025-1082.
[7]"Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase."
Colamonici O., Yan H., Domanski P., Handa R., Smalley D., Mullersman J., Witte M., Krishnan K., Krolewski J.
Mol. Cell. Biol. 14:8133-8142(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF IFNAR1.
[8]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JAKMIP1.
[9]"Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity."
Minegishi Y., Saito M., Morio T., Watanabe K., Agematsu K., Tsuchiya S., Takada H., Hara T., Kawamura N., Ariga T., Kaneko H., Kondo N., Tsuge I., Yachie A., Sakiyama Y., Iwata T., Bessho F., Ohishi T. expand/collapse author list , Joh K., Imai K., Kogawa K., Shinohara M., Fujieda M., Wakiguchi H., Pasic S., Abinun M., Ochs H.D., Renner E.D., Jansson A., Belohradsky B.H., Metin A., Shimizu N., Mizutani S., Miyawaki T., Nonoyama S., Karasuyama H.
Immunity 25:745-755(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN TYK2 DEFICIENCY.
[10]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-884, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-884, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6."
Chrencik J.E., Patny A., Leung I.K., Korniski B., Emmons T.L., Hall T., Weinberg R.A., Gormley J.A., Williams J.M., Day J.E., Hirsch J.L., Kiefer J.R., Leone J.W., Fischer H.D., Sommers C.D., Huang H.C., Jacobsen E.J., Tenbrink R.E., Tomasselli A.G., Benson T.E.
J. Mol. Biol. 400:413-433(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 888-1182 IN COMPLEX WITH INHIBITOR, PHOSPHORYLATION AT TYR-1054.
[13]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-362; SER-363; MET-386; SER-684; TRP-703; ARG-732; VAL-928; ALA-1104 AND GLY-1163.
+Additional computationally mapped references.

Web resources

TYK2base

TYK2 mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54637 mRNA. Translation: CAA38449.1.
AY549314 Genomic DNA. Translation: AAS37680.1.
BC014243 mRNA. Translation: AAH14243.1.
PIRTVHUY2. S12127.
RefSeqNP_003322.3. NM_003331.4.
UniGeneHs.75516.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3LXNX-ray2.50A888-1182[»]
3LXPX-ray1.65A888-1182[»]
3NYXX-ray2.50A885-1176[»]
3NZ0X-ray2.00A885-1176[»]
3ZONX-ray2.15A541-873[»]
4GFOX-ray2.30A884-1176[»]
4GIHX-ray2.00A884-1176[»]
4GIIX-ray2.31A885-1176[»]
4GJ2X-ray2.40A885-1176[»]
4GJ3X-ray2.50A885-1176[»]
4GVJX-ray2.03A885-1176[»]
ProteinModelPortalP29597.
SMRP29597. Positions 448-1177.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113148. 32 interactions.
DIPDIP-1062N.
IntActP29597. 11 interactions.
MINTMINT-107878.
STRING9606.ENSP00000264818.

Chemistry

BindingDBP29597.
ChEMBLCHEMBL2363062.
GuidetoPHARMACOLOGY2269.

PTM databases

PhosphoSiteP29597.

Polymorphism databases

DMDM56405328.

Proteomic databases

PaxDbP29597.
PRIDEP29597.

Protocols and materials databases

DNASU7297.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264818; ENSP00000264818; ENSG00000105397.
ENST00000525621; ENSP00000431885; ENSG00000105397.
GeneID7297.
KEGGhsa:7297.
UCSCuc002moc.4. human.

Organism-specific databases

CTD7297.
GeneCardsGC19M010461.
H-InvDBHIX0202831.
HGNCHGNC:12440. TYK2.
HPAHPA005157.
MIM176941. gene.
611521. phenotype.
neXtProtNX_P29597.
Orphanet331226. Autosomal recessive hyper-IgE syndrome due to TYK2 deficiency.
85408. Juvenile rheumatoid factor-negative polyarthritis.
85410. Oligoarticular juvenile arthritis.
PharmGKBPA37094.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000049158.
HOVERGENHBG006195.
InParanoidP29597.
KOK11219.
OMAFCDFQDI.
PhylomeDBP29597.
TreeFamTF327041.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_6900. Immune System.
SignaLinkP29597.

Gene expression databases

ArrayExpressP29597.
BgeeP29597.
CleanExHS_TYK2.
GenevestigatorP29597.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
IPR016045. Tyr_kinase_non-rcpt_TYK2_N.
[Graphical view]
PfamPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSPR01823. JANUSKINASE.
PR00109. TYRKINASE.
PR01827. YKINASETYK2.
SMARTSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTYK2. human.
EvolutionaryTraceP29597.
GeneWikiTyrosine_kinase_2.
GenomeRNAi7297.
NextBio28539.
PROP29597.
SOURCESearch...

Entry information

Entry nameTYK2_HUMAN
AccessionPrimary (citable) accession number: P29597
Secondary accession number(s): Q6QB10, Q96CH0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM