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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)DescriptionActionsGraphical viewLength
Binding sitei923ATPPROSITE-ProRule annotation1
Active sitei1016Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi896 – 904ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1929470. Tyk2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2321619.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881781 – 1180Non-receptor tyrosine-protein kinase TYK2Add BLAST1180

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei291PhosphotyrosineBy similarity1
Modified residuei521PhosphoserineCombined sources1
Modified residuei600PhosphotyrosineCombined sources1
Modified residuei877PhosphoserineBy similarity1
Modified residuei1047Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9R117.
MaxQBiQ9R117.
PaxDbiQ9R117.
PRIDEiQ9R117.

PTM databases

iPTMnetiQ9R117.
PhosphoSitePlusiQ9R117.

Expressioni

Gene expression databases

CleanExiMM_TYK2.

Interactioni

Subunit structurei

Interacts with JAKMIP1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

MINTiMINT-1513145.
STRINGi10090.ENSMUSP00000001036.

Chemistry databases

BindingDBiQ9R117.

Structurei

Secondary structure

11180
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi887 – 889Combined sources3
Beta strandi890 – 898Combined sources9
Beta strandi900 – 909Combined sources10
Beta strandi913 – 915Combined sources3
Beta strandi918 – 925Combined sources8
Helixi931 – 946Combined sources16
Beta strandi955 – 960Combined sources6
Beta strandi967 – 972Combined sources6
Helixi979 – 982Combined sources4
Helixi983 – 985Combined sources3
Helixi990 – 1009Combined sources20
Helixi1019 – 1021Combined sources3
Beta strandi1022 – 1024Combined sources3
Helixi1026 – 1028Combined sources3
Beta strandi1030 – 1032Combined sources3
Beta strandi1046 – 1049Combined sources4
Beta strandi1054 – 1056Combined sources3
Helixi1058 – 1060Combined sources3
Helixi1063 – 1067Combined sources5
Beta strandi1070 – 1072Combined sources3
Helixi1073 – 1088Combined sources16
Turni1089 – 1091Combined sources3
Helixi1093 – 1095Combined sources3
Helixi1097 – 1105Combined sources9
Helixi1110 – 1123Combined sources14
Helixi1135 – 1144Combined sources10
Helixi1149 – 1151Combined sources3
Helixi1155 – 1168Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4E1ZX-ray2.50A880-1170[»]
4E20X-ray2.60A881-1170[»]
ProteinModelPortaliQ9R117.
SMRiQ9R117.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 426FERMPROSITE-ProRule annotationAdd BLAST398
Domaini445 – 525SH2; atypicalAdd BLAST81
Domaini585 – 862Protein kinase 1PROSITE-ProRule annotationAdd BLAST278
Domaini890 – 1162Protein kinase 2PROSITE-ProRule annotationAdd BLAST273

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

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
HOVERGENiHBG006195.
InParanoidiQ9R117.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
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.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 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)DescriptionActionsGraphical viewLength
Sequence conflicti191C → F in AAC34580 (PubMed:11070173).Curated1
Sequence conflicti234H → R in AAC34580 (PubMed:11070173).Curated1
Sequence conflicti355K → E in AAC34580 (PubMed:11070173).Curated1
Sequence conflicti831C → S in AAD49423 (PubMed:11070173).Curated1
Sequence conflicti1099T → M in AAD49423 (PubMed:11070173).Curated1

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4E1ZX-ray2.50A880-1170[»]
4E20X-ray2.60A881-1170[»]
ProteinModelPortaliQ9R117.
SMRiQ9R117.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-1513145.
STRINGi10090.ENSMUSP00000001036.

Chemistry databases

BindingDBiQ9R117.
ChEMBLiCHEMBL2321619.

PTM databases

iPTMnetiQ9R117.
PhosphoSitePlusiQ9R117.

Proteomic databases

EPDiQ9R117.
MaxQBiQ9R117.
PaxDbiQ9R117.
PRIDEiQ9R117.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1929470. Tyk2.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
HOVERGENiHBG006195.
InParanoidiQ9R117.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.

Miscellaneous databases

ChiTaRSiTyk2. mouse.
PROiQ9R117.
SOURCEiSearch...

Gene expression databases

CleanExiMM_TYK2.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
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.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 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...

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: November 30, 2016
This is version 147 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

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 one 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.