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Protein

Non-receptor tyrosine-protein kinase TYK2

Gene

Tyk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in intracellular signal transduction by amplifying type I and type II IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. Plays an essential role in promoting selective immune responses, including innate host defense mechanisms and specific antiviral activities.

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei923 – 9231ATPPROSITE-ProRule annotation
Active sitei1016 – 10161Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi896 – 9049ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. growth hormone receptor binding Source: MGI
  3. hormone receptor binding Source: GO_Central
  4. non-membrane spanning protein tyrosine kinase activity Source: GO_Central

GO - Biological processi

  1. cell differentiation Source: GO_Central
  2. cell migration Source: GO_Central
  3. innate immune response Source: GO_Central
  4. intracellular signal transduction Source: InterPro
  5. peptidyl-tyrosine autophosphorylation Source: GO_Central
  6. regulation of cell proliferation Source: GO_Central
  7. transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Non-receptor tyrosine-protein kinase TYK2 (EC:2.7.10.2)
Gene namesi
Name:Tyk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:1929470. Tyk2.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. cytoskeleton Source: InterPro
  3. extracellular vesicular exosome Source: MGI
  4. extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  5. nucleus Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11801180Non-receptor tyrosine-protein kinase TYK2PRO_0000088178Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei291 – 2911PhosphotyrosineBy similarity
Modified residuei600 – 6001Phosphotyrosine1 Publication
Modified residuei877 – 8771PhosphoserineBy similarity
Modified residuei1047 – 10471Phosphotyrosine; by autocatalysisBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9R117.
PaxDbiQ9R117.
PRIDEiQ9R117.

PTM databases

PhosphoSiteiQ9R117.

Expressioni

Gene expression databases

CleanExiMM_TYK2.
GenevestigatoriQ9R117.

Interactioni

Subunit structurei

Interacts with JAKMIP1.By similarity

Protein-protein interaction databases

MINTiMINT-1513145.

Structurei

Secondary structure

1
1180
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi887 – 8893Combined sources
Beta strandi890 – 8989Combined sources
Beta strandi900 – 90910Combined sources
Beta strandi913 – 9153Combined sources
Beta strandi918 – 9258Combined sources
Helixi931 – 94616Combined sources
Beta strandi955 – 9606Combined sources
Beta strandi967 – 9726Combined sources
Helixi979 – 9824Combined sources
Helixi983 – 9853Combined sources
Helixi990 – 100920Combined sources
Helixi1019 – 10213Combined sources
Beta strandi1022 – 10243Combined sources
Helixi1026 – 10283Combined sources
Beta strandi1030 – 10323Combined sources
Beta strandi1046 – 10494Combined sources
Beta strandi1054 – 10563Combined sources
Helixi1058 – 10603Combined sources
Helixi1063 – 10675Combined sources
Beta strandi1070 – 10723Combined sources
Helixi1073 – 108816Combined sources
Turni1089 – 10913Combined sources
Helixi1093 – 10953Combined sources
Helixi1097 – 11059Combined sources
Helixi1110 – 112314Combined sources
Helixi1135 – 114410Combined sources
Helixi1149 – 11513Combined sources
Helixi1155 – 116814Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4E1ZX-ray2.50A880-1170[»]
4E20X-ray2.60A881-1170[»]
ProteinModelPortaliQ9R117.
SMRiQ9R117. Positions 27-562, 573-863, 880-1170.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 426398FERMPROSITE-ProRule annotationAdd
BLAST
Domaini445 – 52581SH2; atypicalAdd
BLAST
Domaini585 – 862278Protein kinase 1PROSITE-ProRule annotationAdd
BLAST
Domaini890 – 1162273Protein kinase 2PROSITE-ProRule annotationAdd
BLAST

Domaini

The FERM domain mediates interaction with JAKMIP1.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.PROSITE-ProRule annotation
Contains 1 FERM domain.PROSITE-ProRule annotation
Contains 2 protein kinase domains.PROSITE-ProRule annotation
Contains 1 SH2 domain.Curated

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG006195.
InParanoidiQ9R117.

Family and domain databases

InterProiIPR019749. 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]
PfamiPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR00109. TYRKINASE.
PR01827. YKINASETYK2.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9R117-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPLCGRRAIL EDSKADGTEA QPLVPTGCLM VLLHWPGPEG GEPWVTFSQT
60 70 80 90 100
SLTAEEVCIH IAHKVGITPP CLNLFALYNA QAKVWLPPNH ILDTSQDMNL
110 120 130 140 150
YFRMRFYFRN WHGMNPQEPA VYRCGFPGAE TSSDRAEQGV QLLDSASFEY
160 170 180 190 200
LFEQGKHEFM NDVVSLRDLS SEEEIHHFKN ESLGMAFLHL CHLALSRGVP
210 220 230 240 250
LEEMAREISF KNCIPHSFRQ HIRQHNVLTR LRLHRVFRRF LRAFRPGHLS
260 270 280 290 300
QQVVMVKYLA TLERLAPRFG SERIPVCHLE VLAQPERDPC YIQNSGQTAG
310 320 330 340 350
DPGPELPSGP PTHEVLVTGT GGIQWHPLQT QESERGNSRG NPHGSRSGKK
360 370 380 390 400
PKAPKAGEHL TESPQEPPWT YFCDFQDISH VVLKERRVHI HLQDNKCLLL
410 420 430 440 450
CLCSQAEALS FVALVDGYFR LTADSSHYLC HEVAPPRLVT SIQNGIHGPL
460 470 480 490 500
MDPFVQAKLW PEDGLYLIQW STSHLHRLIL TVAHRNPAXS NGPRGLRLRK
510 520 530 540 550
FPITQQPGAF VLDGWGRSFA SLGDLRLALQ GCSLRAGDDC FPLHXCCLPR
560 570 580 590 600
PREISNLVIM RGSRAHTRPL NLSQLSFHRV HQDEITQLSH LGQGTRTNVY
610 620 630 640 650
EGLLRVGGPD EGKVDNGCPP EPGGTSGQQL RVVLKVLDPS HHDIALAFYE
660 670 680 690 700
XASLMSQVSH MHLAFLHGVC VRGSENIIVT EFVEHGPLDV WLRRQRGQVP
710 720 730 740 750
MTWKMVVAQQ LASALSYLED KNLVHGNVCG RNILLARLGL EEGTNPFIKL
760 770 780 790 800
SDPGVGQGAL SREERVERIP WTAPECLSGG TSSLGTATDM WGFGATLLEI
810 820 830 840 850
CFDGEAPLQG RGPSEKERFY TKKHQLPEPS CPELATLTRQ CLTYEPAQRP
860 870 880 890 900
SFRTILRDLT RLQPQNLVGT SAVNSDSPAS DPTVFHKRYL KKIRDLGEGH
910 920 930 940 950
FGKVSLYCYD PTNDGTGEMV AVKALKEGCG PQLRSGWQRE IEILRTLYHE
960 970 980 990 1000
HIVKYKGCCE DQGEKSVQLV MEYVPLGSLR DYLPRHCVGL AQLLLFAQQI
1010 1020 1030 1040 1050
CEGMAYLHAQ HYIHRDLAAR NVLLDNDRLV KIGDFGLAKA VPEGHEYYRV
1060 1070 1080 1090 1100
REDGDSPVFW YAPECLKECK FYYASDVWSF GVTLYELLTY CDSNQSPHTK
1110 1120 1130 1140 1150
FTELIGHTQG QMTVLRLTEL LERGERLPRP DRCPCEIYHL MKNCWETEAS
1160 1170 1180
FRPTFQNLVP ILQTAQEKYQ GQVPSVFSVC
Length:1,180
Mass (Da):132,861
Last modified:August 15, 2003 - v2
Checksum:i65E060079F08B1C9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti191 – 1911C → F in AAC34580. (PubMed:11070173)Curated
Sequence conflicti234 – 2341H → R in AAC34580. (PubMed:11070173)Curated
Sequence conflicti355 – 3551K → E in AAC34580. (PubMed:11070173)Curated
Sequence conflicti831 – 8311C → S in AAD49423. (PubMed:11070173)Curated
Sequence conflicti1099 – 10991T → M in AAD49423. (PubMed:11070173)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF173032 mRNA. Translation: AAD49423.1.
AF052607 Genomic DNA. Translation: AAC34580.2.
BC019789 mRNA. Translation: AAH19789.1.
UniGeneiMm.20249.
Mm.450004.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF173032 mRNA. Translation: AAD49423.1.
AF052607 Genomic DNA. Translation: AAC34580.2.
BC019789 mRNA. Translation: AAH19789.1.
UniGeneiMm.20249.
Mm.450004.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4E1ZX-ray2.50A880-1170[»]
4E20X-ray2.60A881-1170[»]
ProteinModelPortaliQ9R117.
SMRiQ9R117. Positions 27-562, 573-863, 880-1170.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1513145.

Chemistry

ChEMBLiCHEMBL2321619.

PTM databases

PhosphoSiteiQ9R117.

Proteomic databases

MaxQBiQ9R117.
PaxDbiQ9R117.
PRIDEiQ9R117.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1929470. Tyk2.

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG006195.
InParanoidiQ9R117.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.

Miscellaneous databases

ChiTaRSiTyk2. mouse.
PROiQ9R117.
SOURCEiSearch...

Gene expression databases

CleanExiMM_TYK2.
GenevestigatoriQ9R117.

Family and domain databases

InterProiIPR019749. 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]
PfamiPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR00109. TYRKINASE.
PR01827. YKINASETYK2.
SMARTiSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE.
    Strain: 129/Sv.
    Tissue: Liver.
  2. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (JAN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 732-737, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: OF1.
    Tissue: Hippocampus.
  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] OF 769-1180.
  4. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-600, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  5. Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 880-1170 IN COMPLEX WITH INHIBITOR.

Entry informationi

Entry nameiTYK2_MOUSE
AccessioniPrimary (citable) accession number: Q9R117
Secondary accession number(s): O88431, Q8VE41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: August 15, 2003
Last modified: February 4, 2015
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Tyk2 deficient mice display reduced responses to interferon-alpha/beta and IL-12 and a selective deficiency in STAT3 activation in these pathways. Interferon-gamma signaling is also impaired.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.