TYK2

Protein identityUniProt · HPA

UniProt accession

P29597

Gene

TYK2

Ensembl

ENSG00000105397

Chromosome

19

Canonical length

1187 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with Immunodeficiency 35. [provided by RefSeq, Sep 2020]

Canonical amino-acid sequenceUniProt

1187 residues, UniProt reviewed canonical sequence.

>P29597|TYK2
     1  MPLRHWGMAR GSKPVGDGAQ PMAAMGGLKV LLHWAGPGGG EPWVTFSESS LTAEEVCIHI
    61  AHKVGITPPC FNLFALFDAQ AQVWLPPNHI LEIPRDASLM LYFRIRFYFR NWHGMNPREP
   121  AVYRCGPPGT EASSDQTAQG MQLLDPASFE YLFEQGKHEF VNDVASLWEL STEEEIHHFK
   181  NESLGMAFLH LCHLALRHGI PLEEVAKKTS FKDCIPRSFR RHIRQHSALT RLRLRNVFRR
   241  FLRDFQPGRL SQQMVMVKYL ATLERLAPRF GTERVPVCHL RLLAQAEGEP CYIRDSGVAP
   301  TDPGPESAAG PPTHEVLVTG TGGIQWWPVE EEVNKEEGSS GSSGRNPQAS LFGKKAKAHK
   361  AVGQPADRPR EPLWAYFCDF RDITHVVLKE HCVSIHRQDN KCLELSLPSR AAALSFVSLV
   421  DGYFRLTADS SHYLCHEVAP PRLVMSIRDG IHGPLLEPFV QAKLRPEDGL YLIHWSTSHP
   481  YRLILTVAQR SQAPDGMQSL RLRKFPIEQQ DGAFVLEGWG RSFPSVRELG AALQGCLLRA
   541  GDDCFSLRRC CLPQPGETSN LIIMRGARAS PRTLNLSQLS FHRVDQKEIT QLSHLGQGTR
   601  TNVYEGRLRV EGSGDPEEGK MDDEDPLVPG RDRGQELRVV LKVLDPSHHD IALAFYETAS
   661  LMSQVSHTHL AFVHGVCVRG PENIMVTEYV EHGPLDVWLR RERGHVPMAW KMVVAQQLAS
   721  ALSYLENKNL VHGNVCGRNI LLARLGLAEG TSPFIKLSDP GVGLGALSRE ERVERIPWLA
   781  PECLPGGANS LSTAMDKWGF GATLLEICFD GEAPLQSRSP SEKEHFYQRQ HRLPEPSCPQ
   841  LATLTSQCLT YEPTQRPSFR TILRDLTRLQ PHNLADVLTV NPDSPASDPT VFHKRYLKKI
   901  RDLGEGHFGK VSLYCYDPTN DGTGEMVAVK ALKADCGPQH RSGWKQEIDI LRTLYHEHII
   961  KYKGCCEDQG EKSLQLVMEY VPLGSLRDYL PRHSIGLAQL LLFAQQICEG MAYLHAQHYI
  1021  HRDLAARNVL LDNDRLVKIG DFGLAKAVPE GHEYYRVRED GDSPVFWYAP ECLKEYKFYY
  1081  ASDVWSFGVT LYELLTHCDS SQSPPTKFLE LIGIAQGQMT VLRLTELLER GERLPRPDKC
  1141  PCEVYHLMKN CWETEASFRP TFENLIPILK TVHEKYQGQA PSVFSVC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TYK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

101 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TYK2.

Disease | AllUniProt

Conditions TYK2 is implicated in, by any mechanism.

• Immunodeficiency 35 (IMD35) MIM:611521

Disease | GeneticClinVar

46 pathogenic / likely-pathogenic of 1,126 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency 35

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0

gnomAD missense Z

1.59

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell differentiation
• cell population proliferation
• cell surface receptor signaling pathway via JAK-STAT
• cellular response to virus
• cytokine-mediated signaling pathway
• growth hormone receptor signaling pathway via JAK-STAT
• immune response
• interleukin-10-mediated signaling pathway
• interleukin-12-mediated signaling pathway
• interleukin-23-mediated signaling pathway
• intracellular signal transduction
• positive regulation of interleukin-17 production
• positive regulation of natural killer cell proliferation
• positive regulation of NK T cell proliferation
• positive regulation of protein localization to nucleus
• positive regulation of receptor signaling pathway via JAK-STAT
• positive regulation of T cell proliferation
• positive regulation of T-helper 17 type immune response
• positive regulation of type II interferon production
• protein phosphorylation
• type I interferon-mediated signaling pathway
• type II interferon-mediated signaling pathway
• type III interferon-mediated signaling pathway

Molecular functions

• ATP binding
• growth hormone receptor binding
• non-membrane spanning protein tyrosine kinase activity
• protein tyrosine kinase activity

Cellular components

• cytoplasm
• cytoplasmic side of plasma membrane
• cytosol
• extracellular exosome
• extrinsic component of cytoplasmic side of plasma membrane
• extrinsic component of plasma membrane
• interleukin-12 receptor complex
• interleukin-23 receptor complex
• nucleus
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• FERM domain
• Protein kinase domain
• SH2 domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• Tyrosine-protein kinase, non-receptor Jak/Tyk2
• Protein kinase, ATP binding site
• Band 4.1 domain
• Tyrosine-protein kinase, catalytic domain
• FERM superfamily, second domain
• SH2 domain superfamily
• JAK, FERM F2 lobe domain
• FERM F1 lobe ubiquitin-like domain
• JAK1-3/TYK2, pleckstrin homology-like domain
• Janus Kinase (JAK)
• Protein tyrosine and serine/threonine kinase
• Jak1 pleckstrin homology-like domain
• FERM F2 acyl-CoA binding protein-like domain
• FERM F1 ubiquitin-like domain
• SH2 domain
• Tyrosine-protein kinase, non-receptor, TYK2, N-terminal

KeywordsUniProt

• ATP-binding
• Kinase
• Nucleotide-binding
• Phosphoprotein
• Repeat
• SH2 domain
• Transferase
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of TYK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PIK3R1
• IFNAR1
• JAKMIP1
• MPL
• HNRNPK