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PR01825

Identifier
JANUSKINASE2  [View Relations]  [View Alignment]  
Accession
PR01825
No. of Motifs
3
Creation Date
09-OCT-2002
Title
Janus kinase 2 (JAK2) signature 
Database References
PRINTS; PR01823 JANUSKINASE
MIM; 147796
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).

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].
 
JAK2 was initially cloned using a PCR-based strategy utilising primers 
corresponding to conserved motifs within the catalytic domain of protein-
tyrosine kinases [4]. In common with JAK1 and TYK2, and by contrast with
JAK3, JAK2 appears to be ubiquitously expressed [2]. 
 
JANUSKINASE2 is a 3-element fingerprint that provides a signature for the
janus kinase 2 (JAK2) proteins. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved regions 
in the N-terminal half of the alignment, focusing on those sections that 
characterise JAK2 but distinguish it from other family members - motif 1
resides between the JH7 and JH6 domains; motif 2 lies within the JH4 domain;
and motif 3 resides between the JH3 domain and JH2 tyrosine kinase-like 
domain. Three iterations on SPTR40_20f were required to reach convergence, 
at which point a true set comprising 7 sequences was identified.
Summary Information
7 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3777
2000
123
True Positives
JAK2_HUMAN    JAK2_MOUSE    JAK2_RAT      O19064        
Q9PVI2 Q9TTI9 Q9TTJ0
Sequence Titles
JAK2_HUMAN  Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) (JAK-2) - Homo sapiens (Human). 
JAK2_MOUSE Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) (JAK-2) - Mus musculus (Mouse).
JAK2_RAT Tyrosine-protein kinase JAK2 (EC 2.7.1.112) (Janus kinase 2) (JAK-2) - Rattus norvegicus (Rat).
O19064 JAK2 - Sus scrofa (Pig).
Q9PVI2 JAK2 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
Q9TTI9 KINASE-DEFECTIVE JAK2 VARIANT - Sus scrofa (Pig).
Q9TTJ0 KINASE-DEFECTIVE JAK2 VARIANT - Sus scrofa (Pig).
Scan History
SPTR40_20f 3  250  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
YCNGSNRTYR O19064 124 124 -
YCNGSNRTYR Q9TTI9 124 124 -
YCSGSNRAYR JAK2_HUMAN 124 124 -
YCSGSNRTYR JAK2_RAT 124 124 -
YCSGSSRTYR JAK2_MOUSE 124 124 -
YSGGASRAYR Q9PVI2 123 123 -

Motif 2 width=14
Element Seqn Id St Int Rpt
CSPKDFNKYFLTFA O19064 427 293 -
CSPKDFNKYFLTFA Q9TTI9 427 293 -
CSPKDFNKYFLTFA JAK2_HUMAN 427 293 -
CSPKDFNKYFLTFA JAK2_RAT 427 293 -
CSPKDFNKYFLTFA JAK2_MOUSE 427 293 -
CSPKDFNKYFLTFP Q9PVI2 414 281 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FRTNGISDVPTSPT O19064 512 71 -
FRTNGISDVPTSPT Q9TTI9 512 71 -
FRTNGVSDVPTSPT JAK2_HUMAN 512 71 -
FRTNGVSDVQLSPT JAK2_RAT 512 71 -
FRTNGISDVQISPT JAK2_MOUSE 512 71 -
CRTNKGPEVPLSPS Q9PVI2 499 71 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
YCNGSNRTYR O19064 124 124 -
YCNGSNRTYR Q9TTJ0 124 124 -
YCNGSNRTYR Q9TTI9 124 124 -
YCSGSNRAYR JAK2_HUMAN 124 124 -
YCSGSNRTYR JAK2_RAT 124 124 -
YCSGSSRTYR JAK2_MOUSE 124 124 -
YSGGASRAYR Q9PVI2 123 123 -

Motif 2 width=14
Element Seqn Id St Int Rpt
CSPKDFNKYFLTFA O19064 427 293 -
CSPKDFNKYFLTFA Q9TTJ0 427 293 -
CSPKDFNKYFLTFA Q9TTI9 427 293 -
CSPKDFNKYFLTFA JAK2_HUMAN 427 293 -
CSPKDFNKYFLTFA JAK2_RAT 427 293 -
CSPKDFNKYFLTFA JAK2_MOUSE 427 293 -
CSPKDFNKYFLTFP Q9PVI2 414 281 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FRTNGISDVPTSPT O19064 512 71 -
FRTNGISDVPTSPT Q9TTJ0 512 71 -
FRTNGISDVPTSPT Q9TTI9 512 71 -
FRTNGVSDVPTSPT JAK2_HUMAN 512 71 -
FRTNGVSDVQLSPT JAK2_RAT 512 71 -
FRTNGISDVQISPT JAK2_MOUSE 512 71 -
CRTNKGPEVPLSPS Q9PVI2 499 71 -