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PR01827

Identifier
YKINASETYK2  [View Relations]  [View Alignment]  
Accession
PR01827
No. of Motifs
3
Creation Date
09-OCT-2002
Title
Non-receptor tyrosine-protein kinase TYK2 signature
Database References
PRINTS; PR01823 JANUSKINASE
MIM; 176941
Literature References
1. IHLE, J.N.
Cytokine receptor signalling.
NATURE 377 591-594 (1995).
 
2. LEONARD, W.J. AND O'SHEA, J.J.
JAKS AND STATS: Biological Implications.
ANNU.REV.IMMUNOL. 16 293-322 (1998).
 
3. IMADA K. AND LEONARD, W.J.
The Jak-STAT pathway.
MOL.IMMUNOL. 37 1-11 (2000).
 
4. HARPUR, A.G, ANDRES, A.C., ZIEMIECKI, A., ASTON, R.R. AND WILKS, A.F.
JAK2, a third member of the JAK family of protein tyrosine kinases.
ONCOGENE 7 1347-1353 (1992).
 
5. WILKS, A.F., HARPUR, A.G., KURBAN, R.R., RALPH, S.J., ZURCHER, G. AND
ZIEMIEKI, A.
Two novel protein-tyrosine kinases, each with a second phosphotransferase-
related catalytic domain, define a new class of protein kinase.
MOL.CELL BIOL. 11 2057-2065 (1991).
 
6. LUO, H., ROSE, P., BARBER, D., HANRATTY, W.P., LEE, S., ROBERTS, T.M. 
D'ANDREA, A.D. AND DEAROLF, C.R.
Mutation in the Jak kinase JH2 domain hyperactivates Drosophila and 
mammalian  Jak-Stat pathways.
MOL.CELL BIOL. 17 1562-1571 (1997).
 
7. FRANK, S.J., GILLILAND, G., KRAFT, A.S. AND ARNOLD, C.S.
Interaction of the growth hormone receptor cytoplasmic domain with the JAK2 
tyrosine kinase.
ENDOCRINOLOGY 135 2228-2239 (1994).
 
8. KROLEWSKI, J., LEE, R., EDDY, R., SHOWS, T. AND DALLA-FAVERA, R.
Identification and chromosomal mapping of new human tyrosine kinase genes.
ONCOGENE 5 277-82 (1990).

Documentation
Janus kinases (JAKs) are tyrosine kinases that function in membrane-proximal
signalling events initiated by a variety of extracellular factors binding to
cell surface receptors. Many type I and II cytokine receptors lack a protein
tyrosine kinase domain and rely on JAKs to initiate the cytoplasmic signal 
transduction cascade [1,2]. Ligand binding induces oligomerisation of the
receptors, which then activates the cytoplasmic receptor-associated JAKs.
These subsequently phosphorylate tyrosine residues along the receptor chains
with which they are associated. The phosphotyrosine residues are a target
for a variety of SH2 domain-containing transducer proteins. Amongst these
are the signal transducers and activators of transcription (STAT) proteins,
which, after binding to the receptor chains, are phosphorylated by the JAK
proteins. Phosphorylation enables the STAT proteins to dimerise and
translocate into the nucleus, where they alter the expression of cytokine-
regulated genes. This system is known as the JAK-STAT pathway [3]
 
Four mammalian JAK family members have been identified: JAK1, JAK2, JAK3, 
and TYK2. They are relatively large kinases of approximately 1150 amino 
acids, with molecular weights of ~120-130kDa. Their amino acid sequences
are characterised by the presence of 7 highly conserved domains, termed
JAK homology (JH) domains [4]. The C-terminal domain (JH1) is responsible 
for the tyrosine kinase function. The next domain in the sequence (JH2) is 
known as the tyrosine kinase-like domain, as its sequence shows high 
similarity to functional kinases but does not possess any catalytic 
activity [5]. Although the function of this domain is not well established,
there is some evidence for a regulatory role on the JH1 domain, thus
modulating catalytic activity [6]. The N-terminal portion of the JAKs 
(spanning JH7 to JH3) is important for receptor association and 
non-catalytic activity [7].
 
TYK2 was first identified by low-stringency hybridisation screening of a
human lymphoid cDNA library with the catalytic domain of proto-oncogene 
c-fms [8]. Mouse and puffer fish orthlogues have also been identified. In 
common with JAK1 and JAK2, and by contrast with JAK3, TYK2 appears to be 
ubiquitously expressed [2]. 
 
YKINASETYK2 is a 3-element fingerprint that provides a signature for the
non-receptor tyrosine-protein kinase TYK2 proteins. The fingerprint was 
derived from an initial alignment of 2 sequences: the motifs were drawn from
conserved regions in the N-terminal half of the alignment, focusing on those
sections that characterise TYK2 but distinguish it from other family members
- motif 1 lies in the JH6 domain; motif 2 resides in the JH5 domain; and 
motif 3 lies in the JH3 domain. Two iterations on SPTR40_20f were required 
to reach convergence, at which point a true set comprising 4 sequences was 
identified. 
Summary Information
4 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3444
2000
123
True Positives
Q96CH0        Q9PWD1        TYK2_HUMAN    TYK2_MOUSE    
Sequence Titles
Q96CH0      HYPOTHETICAL 133.7 KDA PROTEIN - Homo sapiens (Human). 
Q9PWD1 TYK2 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
TYK2_HUMAN Non-receptor tyrosine-protein kinase TYK2 (EC 2.7.1.112) - Homo sapiens (Human).
TYK2_MOUSE Non-receptor tyrosine-protein kinase TYK2 (EC 2.7.1.112) - Mus musculus (Mouse).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
ELSTEEEIHHFKNE TYK2_HUMAN 169 169 -
DMKTEEEISCFKNE Q9PWD1 160 160 -

Motif 2 width=11
Element Seqn Id St Int Rpt
LAPRFGTERVP TYK2_HUMAN 266 83 -
LVPSFGVESFY Q9PWD1 262 88 -

Motif 3 width=11
Element Seqn Id St Int Rpt
LEGWGRSFPSV TYK2_HUMAN 516 239 -
LDGWNREFSSV Q9PWD1 477 204 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
ELSTEEEIHHFKNE Q96CH0 169 169 -
ELSTEEEIHHFKNE TYK2_HUMAN 169 169 -
DLSSEEEIHHFKNE TYK2_MOUSE 168 168 -
DMKTEEEISCFKNE Q9PWD1 160 160 -

Motif 2 width=11
Element Seqn Id St Int Rpt
LAPRFGTERVP Q96CH0 266 83 -
LAPRFGTERVP TYK2_HUMAN 266 83 -
LAPRFGSERIP TYK2_MOUSE 265 83 -
LVPSFGVESFY Q9PWD1 262 88 -

Motif 3 width=11
Element Seqn Id St Int Rpt
LEGWGRSFPSV Q96CH0 516 239 -
LEGWGRSFPSV TYK2_HUMAN 516 239 -
LDGWGRSFASL TYK2_MOUSE 512 236 -
LDGWNREFSSV Q9PWD1 477 204 -