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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.

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.

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei927ATPPROSITE-ProRule annotation1
Active sitei1020Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi900 – 908ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-447115. Interleukin-12 family signaling.
R-MMU-6783783. Interleukin-10 signaling.
R-MMU-6785807. Interleukin-4 and 13 signaling.
R-MMU-8854691. Interleukin-20 family signaling.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-912694. Regulation of IFNA signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Non-receptor tyrosine-protein kinase TYK2 (EC:2.7.10.2)
Gene namesi
Name:Tyk2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componentsi: Chromosome 9, Unplaced

Organism-specific databases

MGIiMGI:1929470. Tyk2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2321619.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881781 – 1184Non-receptor tyrosine-protein kinase TYK2Add BLAST1184

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei295PhosphotyrosineBy similarity1
Modified residuei525PhosphoserineCombined sources1
Modified residuei604PhosphotyrosineCombined sources1
Modified residuei881PhosphoserineBy similarity1
Modified residuei1051Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9R117.
MaxQBiQ9R117.
PaxDbiQ9R117.
PRIDEiQ9R117.

PTM databases

iPTMnetiQ9R117.
PhosphoSitePlusiQ9R117.

Expressioni

Gene expression databases

CleanExiMM_TYK2.
GenevisibleiQ3TXE3. MM.

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

11184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi891 – 893Combined sources3
Beta strandi894 – 902Combined sources9
Beta strandi904 – 913Combined sources10
Beta strandi917 – 919Combined sources3
Beta strandi922 – 929Combined sources8
Helixi935 – 950Combined sources16
Beta strandi959 – 964Combined sources6
Beta strandi971 – 976Combined sources6
Helixi983 – 986Combined sources4
Helixi987 – 989Combined sources3
Helixi994 – 1013Combined sources20
Helixi1023 – 1025Combined sources3
Beta strandi1026 – 1028Combined sources3
Helixi1030 – 1032Combined sources3
Beta strandi1034 – 1036Combined sources3
Beta strandi1050 – 1053Combined sources4
Beta strandi1058 – 1060Combined sources3
Helixi1062 – 1064Combined sources3
Helixi1067 – 1071Combined sources5
Beta strandi1074 – 1076Combined sources3
Helixi1077 – 1092Combined sources16
Turni1093 – 1095Combined sources3
Helixi1097 – 1099Combined sources3
Helixi1101 – 1109Combined sources9
Helixi1114 – 1127Combined sources14
Helixi1139 – 1148Combined sources10
Helixi1153 – 1155Combined sources3
Helixi1159 – 1172Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4E1ZX-ray2.50A884-1174[»]
4E20X-ray2.60A885-1174[»]
ProteinModelPortaliQ9R117.
SMRiQ9R117.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 430FERMPROSITE-ProRule annotationAdd BLAST398
Domaini449 – 529SH2; atypicalAdd BLAST81
Domaini589 – 866Protein kinase 1PROSITE-ProRule annotationAdd BLAST278
Domaini894 – 1166Protein 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

Keywords - Domaini

Repeat, SH2 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00900000140909.
HOVERGENiHBG006195.
InParanoidiQ9R117.

Family and domain databases

Gene3Di1.20.80.10. 1 hit.
3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR019749. Band_41_domain.
IPR014352. FERM/acyl-CoA-bd_prot_sf.
IPR035963. FERM_2.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom_sf.
IPR011993. PH-like_dom_sf.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR036860. SH2_dom_sf.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016251. Tyr_kinase_non-rcpt_Jak/Tyk2.
IPR016045. Tyr_kinase_non-rcpt_TYK2_N.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 2 hits.
PIRSFiPIRSF000636. TyrPK_Jak. 1 hit.
PRINTSiPR01823. JANUSKINASE.
PR00109. TYRKINASE.
PR01827. YKINASETYK2.
SMARTiView protein in SMART
SM00295. B41. 1 hit.
SM00219. TyrKc. 2 hits.
SUPFAMiSSF47031. SSF47031. 1 hit.
SSF50729. SSF50729. 1 hit.
SSF55550. SSF55550. 2 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiView protein in PROSITE
PS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9R117-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVGTMPLCGR RAILEDSKAD GTEAQPLVPT GCLMVLLHWP GPEGGEPWVT
60 70 80 90 100
FSQTSLTAEE VCIHIAHKVG ITPPCLNLFA LYNAQAKVWL PPNHILDTSQ
110 120 130 140 150
DMNLYFRMRF YFRNWHGMNP QEPAVYRCGF PGAETSSDRA EQGVQLLDSA
160 170 180 190 200
SFEYLFEQGK HEFMNDVVSL RDLSSEEEIH HFKNESLGMA FLHLCHLALS
210 220 230 240 250
RGVPLEEMAR EISFKNCIPH SFRQHIRQHN VLTRLRLHRV FRRFLRAFRP
260 270 280 290 300
GHLSQQVVMV KYLATLERLA PRFGSERIPV CHLEVLAQPE RDPCYIQNSG
310 320 330 340 350
QTAGDPGPEL PSGPPTHEVL VTGTGGIQWH PLQTQESERG NSRGNPHGSR
360 370 380 390 400
SGKKPKAPKA GEHLTESPQE PPWTYFCDFQ DISHVVLKER RVHIHLQDNK
410 420 430 440 450
CLLLCLCSQA EALSFVALVD GYFRLTADSS HYLCHEVAPP RLVTSIQNGI
460 470 480 490 500
HGPLMDPFVQ AKLWPEDGLY LIQWSTSHLH RLILTVAHRN PAFSNGPRGL
510 520 530 540 550
RLRKFPITQQ PGAFVLDGWG RSFASLGDLR LALQGCSLRA GDDCFPLHHC
560 570 580 590 600
CLPRPREISN LVIMRGSRAH TRPLNLSQLS FHRVHQDEIT QLSHLGQGTR
610 620 630 640 650
TNVYEGLLRV GGPDEGKVDN GCPPEPGGTS GQQLRVVLKV LDPSHHDIAL
660 670 680 690 700
AFYETASLMS QVSHMHLAFL HGVCVRGSEN IIVTEFVEHG PLDVWLRRQR
710 720 730 740 750
GQVPMTWKMV VAQQLASALS YLEDKNLVHG NVCGRNILLA RLGLEEGTNP
760 770 780 790 800
FIKLSDPGVG QGALSREERV ERIPWTAPEC LSGGTSSLGT ATDMWGFGAT
810 820 830 840 850
LLEICFDGEA PLQGRGPSEK ERFYTKKHQL PEPSSPELAT LTRQCLTYEP
860 870 880 890 900
AQRPSFRTIL RDLTRLQPQN LVGTSAVNSD SPASDPTVFH KRYLKKIRDL
910 920 930 940 950
GEGHFGKVSL YCYDPTNDGT GEMVAVKALK EGCGPQLRSG WQREIEILRT
960 970 980 990 1000
LYHEHIVKYK GCCEDQGEKS VQLVMEYVPL GSLRDYLPRH CVGLAQLLLF
1010 1020 1030 1040 1050
AQQICEGMAY LHAQHYIHRD LAARNVLLDN DRLVKIGDFG LAKAVPEGHE
1060 1070 1080 1090 1100
YYRVREDGDS PVFWYAPECL KECKFYYASD VWSFGVTLYE LLTYCDSNQS
1110 1120 1130 1140 1150
PHMKFTELIG HTQGQMTVLR LTELLERGER LPRPDRCPCE IYHLMKNCWE
1160 1170 1180
TEASFRPTFQ NLVPILQTAQ EKYQGQVPSV FSVC
Length:1,184
Mass (Da):133,315
Last modified:January 31, 2018 - v3
Checksum:i2B42052073463AC8
GO

Sequence cautioni

The sequence AAD49423 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH94240 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EDL25160 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195C → F in AAC34580 (PubMed:11070173).Curated1
Sequence conflicti238H → R in AAC34580 (PubMed:11070173).Curated1
Sequence conflicti359K → E in AAC34580 (PubMed:11070173).Curated1
Sequence conflicti835S → C in AAC34580 (PubMed:11070173).1
Sequence conflicti1103M → T in AAC34580 (PubMed:11070173).1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF173032 mRNA. Translation: AAD49423.1. Different initiation.
AF052607 Genomic DNA. Translation: AAC34580.2.
AK159303 mRNA. Translation: BAE34973.1.
AC163637 Genomic DNA. No translation available.
CH466522 Genomic DNA. Translation: EDL25160.1. Sequence problems.
BC094240 mRNA. Translation: AAH94240.1. Different initiation.
BC019789 mRNA. Translation: AAH19789.1.
RefSeqiNP_061263.2. NM_018793.2.
XP_011240881.1. XM_011242579.2.
UniGeneiMm.20249.
Mm.450004.

Genome annotation databases

EnsembliENSMUST00000214454; ENSMUSP00000150214; ENSMUSG00000032175.
GeneIDi54721.
UCSCiuc009oke.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiTYK2_MOUSE
AccessioniPrimary (citable) accession number: Q9R117
Secondary accession number(s): O88431
, Q3TXE3, Q52KQ2, Q8VE41
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: January 31, 2018
Last modified: January 31, 2018
This is version 156 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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