Tyk2 tyrosine kinase 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tyk2provided by MGI
Official Full Name: tyrosine kinase 2provided by MGI
Primary source: MGI:MGI:1929470
See related: Ensembl:ENSMUSG00000032175 AllianceGenome:MGI:1929470
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: JTK1
Summary: Predicted to enable growth hormone receptor binding activity; protein tyrosine kinase activity; and type 1 angiotensin receptor binding activity. Predicted to be involved in intracellular signal transduction and protein phosphorylation. Predicted to act upstream of or within phosphorylation. Predicted to be located in cytoplasm and nucleus. Used to study obesity. Human ortholog(s) of this gene implicated in immunodeficiency 35. Orthologous to human TYK2 (tyrosine kinase 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in spleen adult (RPKM 21.7), mammary gland adult (RPKM 15.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 A3; 9 7.71 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (21015364..21042689, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (21104068..21131393, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.
Title: TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.
The study shows that poultry dust controls the induction of immune and inflammatory mediator expression via a cellular pathway involving oxidative stress-mediated STAT3 activation by TYK2 and EGFR tyrosine kinases.
Title: Organic dust induces inflammatory gene expression in lung epithelial cells via ROS-dependent STAT-3 activation.
our findings provide the first evidence, to our knowledge, for a key role of TYK2 in the host environment in promoting NK cell maturation and antitumor activity.
Title: NK Cells Require Cell-Extrinsic and -Intrinsic TYK2 for Full Functionality in Tumor Surveillance and Antibacterial Immunity.
TYK2(P) diminishes IL-12, IL-23, and IFN I signaling and that its protective effect is most likely manifest in the setting of autoimmune triggers that concurrently dysregulate at least two of these important signaling cascades.
Title: The TYK2-P1104A Autoimmune Protective Variant Limits Coordinate Signals Required to Generate Specialized T Cell Subsets.
TYK2 genetic variants are differentially associated with common autoimmune diseases
Title: Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.
Results show that loss of TYK2 does not affect disease severity of JAK2VF-induced murine myeloproliferative neoplasms (MPN) indicating that TYK2 has no cooperative effects with JAK2VF at the onset of MPN.
Title: Loss of Tyrosine Kinase 2 Does Not Affect the Severity of Jak2V617F-induced Murine Myeloproliferative Neoplasm.
mutated form which lacks tyrosine kinase activity restores differentiation of brown preadipocytes
Title: Kinase Inactive Tyrosine Kinase (Tyk2) Supports Differentiation of Brown Fat Cells.
Decreased Tyk2 expression in pancreatic beta cells due to mutation determines susceptibility to virus-induced diabetes mellitus.
Title: Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes.
Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3
Title: Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis.
A reduced survival fitness of the Th17 in the absence of Tyk-2 mediated by the up-regulation of SOCS3.
Title: Role of Tyk-2 in Th9 and Th17 cells in allergic asthma.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1) 1 citation
Targeted (9) 1 citation
Endonuclease-mediated (4)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D9Mit361 (e-PCR), detects polymorphism
- UniSTS:131927

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables growth hormone receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables growth hormone receptor binding	ISO Inferred from Sequence Orthology more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables non-membrane spanning protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables type 1 angiotensin receptor binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	ISO Inferred from Sequence Orthology more info
involved_in cytokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in growth hormone receptor signaling pathway via JAK-STAT	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in interleukin-12-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of NK T cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of NK T cell proliferation	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of T-helper 17 type immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of interleukin-17 production	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of natural killer cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to nucleus	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of receptor signaling pathway via JAK-STAT	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of type II interferon production	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in type I interferon-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in type II interferon-mediated signaling pathway	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
part_of interleukin-12 receptor complex	NAS Non-traceable Author Statement more info	PubMed
part_of interleukin-23 receptor complex	NAS Non-traceable Author Statement more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: non-receptor tyrosine-protein kinase TYK2

Names: tyrosine kinase TYK2

NP_001192241.1

EC 2.7.10.2

NP_001408188.1

EC 2.7.10.2

NP_061263.2

EC 2.7.10.2

XP_006510555.1

EC 2.7.10.2

XP_006510557.1

EC 2.7.10.2

XP_030100315.1

EC 2.7.10.2

XP_030100316.1

EC 2.7.10.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001205312.2 → NP_001192241.1 non-receptor tyrosine-protein kinase TYK2 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC163637

Consensus CDS

CCDS57656.1

UniProtKB/TrEMBL

E9QJS1, Q3U447

Related

ENSMUSP00000150354.2, ENSMUST00000216874.2

Conserved Domains (7) summary

smart00219
Location:917 → 1189

TyrKc; Tyrosine kinase, catalytic domain

smart00295
Location:45 → 299

B41; Band 4.1 homologues

cd05080
Location:912 → 1194

PTKc_Tyk2_rpt2; Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2

pfam07714
Location:612 → 886

Pkinase_Tyr; Protein tyrosine kinase

cl15255
Location:459 → 557

SH2; Src homology 2 (SH2) domain

cl17171
Location:296 → 459

PH-like; Pleckstrin homology-like domain

cl21453
Location:612 → 887

PKc_like; Protein Kinases, catalytic domain
NM_001421259.1 → NP_001408188.1 non-receptor tyrosine-protein kinase TYK2 isoform 2

Status: VALIDATED

Source sequence(s)

AC163637

UniProtKB/Swiss-Prot

O88431, Q3TXE3, Q52KQ2, Q8VE41, Q9R117
NM_018793.3 → NP_061263.2 non-receptor tyrosine-protein kinase TYK2 isoform 2

See identical proteins and their annotated locations for NP_061263.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AC163637

Consensus CDS

CCDS90510.1

UniProtKB/Swiss-Prot

O88431, Q3TXE3, Q52KQ2, Q8VE41, Q9R117

UniProtKB/TrEMBL

Q3TIS9

Related

ENSMUSP00000150214.2, ENSMUST00000214454.2

Conserved Domains (6) summary

cd05080
Location:889 → 1171

PTKc_Tyk2_rpt2; Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2

pfam17887
Location:288 → 431

Jak1_Phl; Jak1 pleckstrin homology-like domain

pfam18377
Location:146 → 269

FERM_F2; FERM F2 acyl-CoA binding protein-like domain

pfam18379
Location:33 → 128

FERM_F1; FERM F1 ubiquitin-like domain

cl15255
Location:436 → 534

SH2; Src homology 2 (SH2) domain

cl21453
Location:589 → 864

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

21015364..21042689 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030244455.1 → XP_030100315.1 non-receptor tyrosine-protein kinase TYK2 isoform X3

UniProtKB/TrEMBL

Q3TIS9

Conserved Domains (5) summary

cd05080
Location:726 → 1008

PTKc_Tyk2_rpt2; Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2

pfam17887
Location:125 → 268

Jak1_Phl; Jak1 pleckstrin homology-like domain

pfam18377
Location:2 → 106

FERM_F2; FERM F2 acyl-CoA binding protein-like domain

cl15255
Location:273 → 371

SH2; Src homology 2 (SH2) domain

cl21453
Location:426 → 701

PKc_like; Protein Kinases, catalytic domain
XM_006510492.4 → XP_006510555.1 non-receptor tyrosine-protein kinase TYK2 isoform X2

UniProtKB/TrEMBL

Q3TIS9

Conserved Domains (6) summary

cd05080
Location:785 → 1067

PTKc_Tyk2_rpt2; Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2

pfam17887
Location:184 → 327

Jak1_Phl; Jak1 pleckstrin homology-like domain

pfam18377
Location:104 → 165

FERM_F2; FERM F2 acyl-CoA binding protein-like domain

pfam18379
Location:33 → 110

FERM_F1; FERM F1 ubiquitin-like domain

cl15255
Location:332 → 430

SH2; Src homology 2 (SH2) domain

cl21453
Location:485 → 760

PKc_like; Protein Kinases, catalytic domain
XM_030244456.1 → XP_030100316.1 non-receptor tyrosine-protein kinase TYK2 isoform X4

Conserved Domains (4) summary

cd10381
Location:178 → 276

SH2_Jak_Tyk2; Src homology 2 (SH2) domain in Tyrosine Kinase 2 (Tyk2), a member of the Janus kinases (JAK)

cd05080
Location:631 → 913

PTKc_Tyk2_rpt2; Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2

pfam17887
Location:30 → 173

Jak1_Phl; Jak1 pleckstrin homology-like domain

cl21453
Location:331 → 606

PKc_like; Protein Kinases, catalytic domain
XM_006510494.2 → XP_006510557.1 non-receptor tyrosine-protein kinase TYK2 isoform X5

Conserved Domains (5) summary

pfam17887
Location:288 → 431

Jak1_Phl; Jak1 pleckstrin homology-like domain

pfam18377
Location:146 → 269

FERM_F2; FERM F2 acyl-CoA binding protein-like domain

pfam18379
Location:33 → 128

FERM_F1; FERM F1 ubiquitin-like domain

cl15255
Location:436 → 534

SH2; Src homology 2 (SH2) domain

cl21453
Location:589 → 722

PKc_like; Protein Kinases, catalytic domain