Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:P29597 TYK2

Class:IdReferenceGeneProduct:66635
_chainChangeLogchain:1-1187 added on Fri February 6 2015
_displayNameUniProt:P29597 TYK2
_timestamp2025-02-21 20:05:06
chainchain:1-1187
checksumF76C25D6A919EDBC
commentFUNCTION Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862).CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION The protein kinase 1 domain (also termed pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain.SUBUNIT Interacts (via FERM domain) with JAKMIP1 (PubMed:15277531, PubMed:20478313). Interacts with PIK3R1; this interaction is important for cell migration (PubMed:10995743). Interacts with MPL/TPOR (PubMed:15899890).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus protein LMP1; this interaction inhibits TYK2-mediated interferon signaling.SUBUNIT (Microbial infection) Interacts with papillomavirus-18 protein E6; this interaction impairs JAK-STAT activation by interferon-alpha.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction participates in the inhibition of type I IFN signaling by the virus.INTERACTION Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines.PTM Phosphorylated (PubMed:7638186). Phosphorylation by JAK1 at Tyr-1054 and Tyr-1055 induces kinase activation (PubMed:8232552, PubMed:8702790).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.ONLINE INFORMATION tyrosine kinase 2
descriptionrecommendedName: Non-receptor tyrosine-protein kinase TYK2 ecNumber evidence="7 21"2.7.10.2
geneNameTYK2
identifierP29597
isSequenceChangedFALSE
keyword3D-structure
ATP-binding
Kinase
Nucleotide-binding
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
SH2 domain
Transferase
Tyrosine-protein kinase
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameTYK2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8999835] ENSEMBL:ENSG00000105397 TYK2 [Homo sapiens]
secondaryIdentifierTYK2_HUMAN
Q6QB10
Q96CH0
sequenceLength1187
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:877348] TYK2 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:909682] p-Y1054,Y1055-TYK2 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:1112598] p-Y1054-TYK2 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:6784366] p-Y-TYK2 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:8950424] p-TYK2 [cytosol] [Homo sapiens]
(referenceSequence)[ModifiedResidue:909677] O4'-phospho-L-tyrosine at 1054
[ModifiedResidue:909679] O4'-phospho-L-tyrosine at 1055
[ModifiedResidue:6784321] O4'-phospho-L-tyrosine at unknown position
[ModifiedResidue:8950281] phosphorylated residue at unknown position
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:P29597 TYK2 (66635)