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Q9R117 (TYK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-receptor tyrosine-protein kinase TYK2

EC=2.7.10.2
Gene names
Name:Tyk2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1180 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Subunit structure

Interacts with JAKMIP1 By similarity.

Domain

The FERM domain mediates interaction with JAKMIP1 By similarity.

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.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

Contains 1 FERM domain.

Contains 2 protein kinase domains.

Contains 1 SH2 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11801180Non-receptor tyrosine-protein kinase TYK2
PRO_0000088178

Regions

Domain29 – 426398FERM
Domain445 – 52581SH2; atypical
Domain585 – 862278Protein kinase 1
Domain890 – 1162273Protein kinase 2
Nucleotide binding896 – 9049ATP By similarity

Sites

Active site10161Proton acceptor By similarity
Binding site9231ATP By similarity

Amino acid modifications

Modified residue2911Phosphotyrosine By similarity
Modified residue6001Phosphotyrosine Ref.4
Modified residue8771Phosphoserine By similarity
Modified residue10471Phosphotyrosine; by autocatalysis By similarity

Experimental info

Sequence conflict1911C → F in AAC34580. Ref.1
Sequence conflict2341H → R in AAC34580. Ref.1
Sequence conflict3551K → E in AAC34580. Ref.1
Sequence conflict8311C → S in AAD49423. Ref.1
Sequence conflict10991T → M in AAD49423. Ref.1

Secondary structure

.................................................... 1180
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9R117 [UniParc].

Last modified August 15, 2003. Version 2.
Checksum: 65E060079F08B1C9

FASTA1,180132,861
        10         20         30         40         50         60 
MPLCGRRAIL EDSKADGTEA QPLVPTGCLM VLLHWPGPEG GEPWVTFSQT SLTAEEVCIH 

        70         80         90        100        110        120 
IAHKVGITPP CLNLFALYNA QAKVWLPPNH ILDTSQDMNL YFRMRFYFRN WHGMNPQEPA 

       130        140        150        160        170        180 
VYRCGFPGAE TSSDRAEQGV QLLDSASFEY LFEQGKHEFM NDVVSLRDLS SEEEIHHFKN 

       190        200        210        220        230        240 
ESLGMAFLHL CHLALSRGVP LEEMAREISF KNCIPHSFRQ HIRQHNVLTR LRLHRVFRRF 

       250        260        270        280        290        300 
LRAFRPGHLS QQVVMVKYLA TLERLAPRFG SERIPVCHLE VLAQPERDPC YIQNSGQTAG 

       310        320        330        340        350        360 
DPGPELPSGP PTHEVLVTGT GGIQWHPLQT QESERGNSRG NPHGSRSGKK PKAPKAGEHL 

       370        380        390        400        410        420 
TESPQEPPWT YFCDFQDISH VVLKERRVHI HLQDNKCLLL CLCSQAEALS FVALVDGYFR 

       430        440        450        460        470        480 
LTADSSHYLC HEVAPPRLVT SIQNGIHGPL MDPFVQAKLW PEDGLYLIQW STSHLHRLIL 

       490        500        510        520        530        540 
TVAHRNPAXS NGPRGLRLRK FPITQQPGAF VLDGWGRSFA SLGDLRLALQ GCSLRAGDDC 

       550        560        570        580        590        600 
FPLHXCCLPR PREISNLVIM RGSRAHTRPL NLSQLSFHRV HQDEITQLSH LGQGTRTNVY 

       610        620        630        640        650        660 
EGLLRVGGPD EGKVDNGCPP EPGGTSGQQL RVVLKVLDPS HHDIALAFYE XASLMSQVSH 

       670        680        690        700        710        720 
MHLAFLHGVC VRGSENIIVT EFVEHGPLDV WLRRQRGQVP MTWKMVVAQQ LASALSYLED 

       730        740        750        760        770        780 
KNLVHGNVCG RNILLARLGL EEGTNPFIKL SDPGVGQGAL SREERVERIP WTAPECLSGG 

       790        800        810        820        830        840 
TSSLGTATDM WGFGATLLEI CFDGEAPLQG RGPSEKERFY TKKHQLPEPS CPELATLTRQ 

       850        860        870        880        890        900 
CLTYEPAQRP SFRTILRDLT RLQPQNLVGT SAVNSDSPAS DPTVFHKRYL KKIRDLGEGH 

       910        920        930        940        950        960 
FGKVSLYCYD PTNDGTGEMV AVKALKEGCG PQLRSGWQRE IEILRTLYHE HIVKYKGCCE 

       970        980        990       1000       1010       1020 
DQGEKSVQLV MEYVPLGSLR DYLPRHCVGL AQLLLFAQQI CEGMAYLHAQ HYIHRDLAAR 

      1030       1040       1050       1060       1070       1080 
NVLLDNDRLV KIGDFGLAKA VPEGHEYYRV REDGDSPVFW YAPECLKECK FYYASDVWSF 

      1090       1100       1110       1120       1130       1140 
GVTLYELLTY CDSNQSPHTK FTELIGHTQG QMTVLRLTEL LERGERLPRP DRCPCEIYHL 

      1150       1160       1170       1180 
MKNCWETEAS FRPTFQNLVP ILQTAQEKYQ GQVPSVFSVC 

« Hide

References

« Hide 'large scale' references
[1]"Partial impairment of cytokine responses in Tyk2-deficient mice."
Karaghiosoff M., Neubauer H., Lassnig C., Kovarik P., Schindler H., Pircher H., McCoy B., Bogdan C., Decker T., Brem G., Pfeffer K., Mueller M.
Immunity 13:549-560(2000) [PubMed] [Europe PMC] [Abstract]
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]"Enabling structure-based drug design of Tyk2 through co-crystallization with a stabilizing aminoindazole inhibitor."
Argiriadi M.A., Goedken E.R., Banach D., Borhani D.W., Burchat A., Dixon R.W., Marcotte D., Overmeyer G., Pivorunas V., Sadhukhan R., Sousa S., Moore N.S., Tomlinson M., Voss J., Wang L., Wishart N., Woller K., Talanian R.V.
BMC Struct. Biol. 12:22-22(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 880-1170 IN COMPLEX WITH INHIBITOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF173032 mRNA. Translation: AAD49423.1.
AF052607 Genomic DNA. Translation: AAC34580.2.
BC019789 mRNA. Translation: AAH19789.1.
UniGeneMm.20249.
Mm.450004.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4E1ZX-ray2.50A880-1170[»]
4E20X-ray2.60A881-1170[»]
ProteinModelPortalQ9R117.
SMRQ9R117. Positions 27-562, 573-863, 880-1170.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-1513145.

PTM databases

PhosphoSiteQ9R117.

Proteomic databases

PaxDbQ9R117.
PRIDEQ9R117.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1929470. Tyk2.

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG006195.
InParanoidQ9R117.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

CleanExMM_TYK2.
GenevestigatorQ9R117.

Family and domain databases

InterProIPR019749. 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]
PfamPF07714. Pkinase_Tyr. 2 hits.
[Graphical view]
PIRSFPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSPR01823. JANUSKINASE.
PR00109. TYRKINASE.
PR01827. YKINASETYK2.
SMARTSM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]
SUPFAMSSF47031. SSF47031. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTYK2. mouse.
PROQ9R117.
SOURCESearch...

Entry information

Entry nameTYK2_MOUSE
AccessionPrimary (citable) accession number: Q9R117
Secondary accession number(s): O88431, Q8VE41
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: August 15, 2003
Last modified: July 9, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot