P29597 (TYK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Non-receptor tyrosine-protein kinase TYK2
EC=2.7.10.2

Gene names

Name:

TYK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1187 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain. Ref.7
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Interacts with JAKMIP1. Ref.8
Tissue specificity	Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines. Ref.5
Domain	The FERM domain mediates interaction with JAKMIP1.
Involvement in disease	Protein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:611521]: Consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. Note: The disease is caused by mutations affecting the gene represented in this entry.
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.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat SH2 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from electronic annotation. Source: InterPro regulation of type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: InterPro cytosol Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: InterPro nucleus Inferred from direct assay PubMed 10502458. Source: BHF-UCL
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSP90AB1	P08238	2	EBI-1383454,EBI-352572

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1187

1187

Non-receptor tyrosine-protein kinase TYK2

PRO_0000088177

Regions

Domain

26 – 431

406

FERM

Domain

450 – 529

80

SH2; atypical

Domain

589 – 875

287

Protein kinase 1

Domain

897 – 1176

280

Protein kinase 2

Nucleotide binding

903 – 911

9

ATP By similarity

Sites

Active site

1023

1

Proton acceptor By similarity

Binding site

930

1

ATP By similarity

Amino acid modifications

Modified residue

292

1

Phosphotyrosine Ref.10 Ref.11

Modified residue

604

1

Phosphotyrosine By similarity

Modified residue

884

1

Phosphoserine Ref.10 Ref.11

Modified residue

1054

1

Phosphotyrosine; by autocatalysis By similarity

Natural variations

Natural variant

4

1

R → C.
Corresponds to variant rs35163004 [ dbSNP | Ensembl ].

VAR_037796

Natural variant

4

1

R → H. Ref.2
Corresponds to variant rs12720343 [ dbSNP | Ensembl ].

VAR_020597

Natural variant

81

1

A → V.
Corresponds to variant rs1049619 [ dbSNP | Ensembl ].

VAR_037797

Natural variant

197

1

R → H. Ref.2
Corresponds to variant rs12720263 [ dbSNP | Ensembl ].

VAR_020598

Natural variant

362

1

V → F. Ref.1 Ref.2 Ref.12
Corresponds to variant rs2304256 [ dbSNP | Ensembl ].

VAR_020599

Natural variant

363

1

G → S. Ref.2 Ref.12
Corresponds to variant rs2304255 [ dbSNP | Ensembl ].

VAR_020600

Natural variant

386

1

V → M. Ref.12
Corresponds to variant rs55956017 [ dbSNP | Ensembl ].

VAR_041870

Natural variant

442

1

R → Q.
Corresponds to variant rs2304254 [ dbSNP | Ensembl ].

VAR_037798

Natural variant

684

1

I → S. Ref.1 Ref.2 Ref.12
Corresponds to variant rs12720356 [ dbSNP | Ensembl ].

VAR_020286

Natural variant

703

1

R → W. Ref.12
Corresponds to variant rs55882956 [ dbSNP | Ensembl ].

VAR_041871

Natural variant

732

1

H → R in a colorectal adenocarcinoma sample; somatic mutation. Ref.12

VAR_041872

Natural variant

820

1

P → H.
Corresponds to variant rs34046749 [ dbSNP | Ensembl ].

VAR_037799

Natural variant

928

1

A → V. Ref.12
Corresponds to variant rs35018800 [ dbSNP | Ensembl ].

VAR_041873

Natural variant

1104

1

P → A. Ref.12
Corresponds to variant rs34536443 [ dbSNP | Ensembl ].

VAR_041874

Natural variant

1163

1

E → G. Ref.12
Corresponds to variant rs55886939 [ dbSNP | Ensembl ].

VAR_041875

Experimental info

Sequence conflict

869

1

L → V in CAA38449. Ref.1

Sequence conflict

882

1

P → R in CAA38449. Ref.1

Sequence conflict

887 – 888

2

SD → VG in CAA38449. Ref.1

Sequence conflict

891

1

V → T in CAA38449. Ref.1

Sequence conflict

1016

1

A → S in AAH14243. Ref.3

Sequence conflict

1017 – 1018

2

QH → HD in CAA38449. Ref.1

Secondary structure

1

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1187

Helix Strand Turn

Details...

Helix

894 – 896

3

Beta strand

897 – 905

9

Beta strand

907 – 916

10

Beta strand

920 – 922

3

Beta strand

925 – 932

8

Helix

938 – 953

16

Beta strand

962 – 968

7

Turn

969 – 972

4

Beta strand

973 – 978

6

Helix

986 – 989

4

Helix

990 – 992

3

Helix

997 – 1016

20

Helix

1026 – 1028

3

Beta strand

1029 – 1031

3

Beta strand

1037 – 1039

3

Helix

1042 – 1044

3

Beta strand

1053 – 1056

4

Helix

1065 – 1067

3

Helix

1070 – 1075

6

Beta strand

1077 – 1079

3

Helix

1080 – 1095

16

Turn

1096 – 1098

3

Helix

1100 – 1102

3

Helix

1104 – 1112

9

Helix

1117 – 1129

13

Helix

1142 – 1151

10

Helix

1156 – 1158

3

Helix

1162 – 1177

16

Sequences

	Sequence		Length	Mass (Da)
	P29597 [UniParc]. Last modified December 7, 2004. Version 3. Checksum: F76C25D6A919EDBC	FASTA	1,187	133,650
	10 20 30 40 50 60 MPLRHWGMAR GSKPVGDGAQ PMAAMGGLKV LLHWAGPGGG EPWVTFSESS LTAEEVCIHI 70 80 90 100 110 120 AHKVGITPPC FNLFALFDAQ AQVWLPPNHI LEIPRDASLM LYFRIRFYFR NWHGMNPREP 130 140 150 160 170 180 AVYRCGPPGT EASSDQTAQG MQLLDPASFE YLFEQGKHEF VNDVASLWEL STEEEIHHFK 190 200 210 220 230 240 NESLGMAFLH LCHLALRHGI PLEEVAKKTS FKDCIPRSFR RHIRQHSALT RLRLRNVFRR 250 260 270 280 290 300 FLRDFQPGRL SQQMVMVKYL ATLERLAPRF GTERVPVCHL RLLAQAEGEP CYIRDSGVAP 310 320 330 340 350 360 TDPGPESAAG PPTHEVLVTG TGGIQWWPVE EEVNKEEGSS GSSGRNPQAS LFGKKAKAHK 370 380 390 400 410 420 AVGQPADRPR EPLWAYFCDF RDITHVVLKE HCVSIHRQDN KCLELSLPSR AAALSFVSLV 430 440 450 460 470 480 DGYFRLTADS SHYLCHEVAP PRLVMSIRDG IHGPLLEPFV QAKLRPEDGL YLIHWSTSHP 490 500 510 520 530 540 YRLILTVAQR SQAPDGMQSL RLRKFPIEQQ DGAFVLEGWG RSFPSVRELG AALQGCLLRA 550 560 570 580 590 600 GDDCFSLRRC CLPQPGETSN LIIMRGARAS PRTLNLSQLS FHRVDQKEIT QLSHLGQGTR 610 620 630 640 650 660 TNVYEGRLRV EGSGDPEEGK MDDEDPLVPG RDRGQELRVV LKVLDPSHHD IALAFYETAS 670 680 690 700 710 720 LMSQVSHTHL AFVHGVCVRG PENIMVTEYV EHGPLDVWLR RERGHVPMAW KMVVAQQLAS 730 740 750 760 770 780 ALSYLENKNL VHGNVCGRNI LLARLGLAEG TSPFIKLSDP GVGLGALSRE ERVERIPWLA 790 800 810 820 830 840 PECLPGGANS LSTAMDKWGF GATLLEICFD GEAPLQSRSP SEKEHFYQRQ HRLPEPSCPQ 850 860 870 880 890 900 LATLTSQCLT YEPTQRPSFR TILRDLTRLQ PHNLADVLTV NPDSPASDPT VFHKRYLKKI 910 920 930 940 950 960 RDLGEGHFGK VSLYCYDPTN DGTGEMVAVK ALKADCGPQH RSGWKQEIDI LRTLYHEHII 970 980 990 1000 1010 1020 KYKGCCEDQG EKSLQLVMEY VPLGSLRDYL PRHSIGLAQL LLFAQQICEG MAYLHAQHYI 1030 1040 1050 1060 1070 1080 HRDLAARNVL LDNDRLVKIG DFGLAKAVPE GHEYYRVRED GDSPVFWYAP ECLKEYKFYY 1090 1100 1110 1120 1130 1140 ASDVWSFGVT LYELLTHCDS SQSPPTKFLE LIGIAQGQMT VLRLTELLER GERLPRPDKC 1150 1160 1170 1180 PCEVYHLMKN CWETEASFRP TFENLIPILK TVHEKYQGQA PSVFSVC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TYK2, prototype of a novel class of non-receptor tyrosine kinase genes." Firmbach-Kraft I., Byers M., Shows T., Dalla-Favera R., Krolewski J.J. Oncogene 5:1329-1336(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PHE-362 AND SER-684.
[2]	SeattleSNPs variation discovery resource Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-4; HIS-197; PHE-362; SER-363 AND SER-684.
[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]. Tissue: Kidney.
[4]	"A protein tyrosine kinase in the interferon alpha/beta signaling pathway." Velazquez L., Fellous M., Stark G.R., Pellegrini S. Cell 70:313-322(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-1187.
[5]	"Identification and chromosomal mapping of new human tyrosine kinase genes." Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R. Oncogene 5:277-282(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1007-1162, TISSUE SPECIFICITY.
[6]	"Putative tyrosine kinases expressed in K-562 human leukemia cells." Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K. Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1025-1082.
[7]	"Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase." Colamonici O., Yan H., Domanski P., Handa R., Smalley D., Mullersman J., Witte M., Krishnan K., Krolewski J. Mol. Cell. Biol. 14:8133-8142(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF IFNAR1.
[8]	"Jamip1 (marlin-1) defines a family of proteins interacting with Janus kinases and microtubules." Steindler C., Li Z., Algarte M., Alcover A., Libri V., Ragimbeau J., Pellegrini S. J. Biol. Chem. 279:43168-43177(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH JAKMIP1.
[9]	"Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity." Minegishi Y., Saito M., Morio T., Watanabe K., Agematsu K., Tsuchiya S., Takada H., Hara T., Kawamura N., Ariga T., Kaneko H., Kondo N., Tsuge I., Yachie A., Sakiyama Y., Iwata T., Bessho F., Ohishi T. , Joh K., Imai K., Kogawa K., Shinohara M., Fujieda M., Wakiguchi H., Pasic S., Abinun M., Ochs H.D., Renner E.D., Jansson A., Belohradsky B.H., Metin A., Shimizu N., Mizutani S., Miyawaki T., Nonoyama S., Karasuyama H. Immunity 25:745-755(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN TYK2 DEFICIENCY.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-884, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-292 AND SER-884, MASS SPECTROMETRY.
[12]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-362; SER-363; MET-386; SER-684; TRP-703; ARG-732; VAL-928; ALA-1104 AND GLY-1163.
+	Additional computationally mapped references.

Web resources

TYK2base

TYK2 mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54637 mRNA. Translation: CAA38449.1.
AY549314 Genomic DNA. Translation: AAS37680.1.
BC014243 mRNA. Translation: AAH14243.1.

IPI

IPI00022353.

PIR

TVHUY2. S12127.

RefSeq

NP_003322.3. NM_003331.4.

UniGene

Hs.75516.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LXN	X-ray	2.50	A	888-1182	[»]
3LXP	X-ray	1.65	A	888-1182	[»]
3NYX	X-ray	2.50	A	885-1176	[»]
3NZ0	X-ray	2.00	A	885-1176	[»]

ProteinModelPortal

P29597.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1062N.

IntAct

P29597. 2 interactions.

MINT

MINT-107878.

STRING

9606.ENSP00000264818.

PTM databases

PhosphoSite

P29597.

Polymorphism databases

DMDM

56405328.

Proteomic databases

PaxDb

P29597.

PRIDE

P29597.

Protocols and materials databases

DNASU

7297.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264818; ENSP00000264818; ENSG00000105397.
ENST00000525621; ENSP00000431885; ENSG00000105397.

GeneID

7297.

KEGG

hsa:7297.

UCSC

uc002moc.4. human.

Organism-specific databases

CTD

7297.

GeneCards

GC19M010461.

H-InvDB

HIX0202831.

HGNC

HGNC:12440. TYK2.

HPA

HPA005157.

MIM

176941. gene.
611521. phenotype.

neXtProt

NX_P29597.

Orphanet

169446. Autosomal recessive hyper IgE syndrome.
748. Mendelian susceptibility to mycobacterial diseases.

PharmGKB

PA37094.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000049158.

HOVERGEN

HBG006195.

InParanoid

P29597.

KO

K11219.

OMA

HAQHYIH.

OrthoDB

EOG4FXR6W.

PhylomeDB

P29597.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
ptp1bpathway. Signaling events mediated by PTP1B.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P29597.

Bgee

P29597.

CleanEx

HS_TYK2.

Genevestigator

P29597.

GermOnline

ENSG00000105397. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR019749. Band_41_domain.
IPR019748. FERM_central.
IPR000299. FERM_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_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]

Pfam

PF07714. Pkinase_Tyr. 2 hits.
[Graphical view]

PIRSF

PIRSF000636. TyrPK_Jak. 1 hit.

PRINTS

PR01823. JANUSKINASE.
PR00109. TYRKINASE.
PR01827. YKINASETYK2.

SMART

SM00295. B41. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 2 hits.
[Graphical view]

SUPFAM

SSF47031. FERM_3-hlx. 1 hit.
SSF56112. Kinase_like. 2 hits.

PROSITE

PS00660. FERM_1. False negative.
PS00661. FERM_2. False negative.
PS50057. FERM_3. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 2 hits.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P29597.

ChEMBL

CHEMBL3553.

ChiTaRS

TYK2. human.

EvolutionaryTrace

P29597.

GenomeRNAi

7297.

NextBio

28539.

SOURCE

Search...

Entry information

Entry name

TYK2_HUMAN

Accession

Primary (citable) accession number: P29597
Secondary accession number(s): Q6QB10, Q96CH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	December 7, 2004
Last modified:	May 1, 2013
This is version 144 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.