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PR01826

Identifier
JANUSKINASE3  [View Relations]  [View Alignment]  
Accession
PR01826
No. of Motifs
4
Creation Date
09-OCT-2002
Title
Janus kinase 3 (JAK3) signature
Database References
PRINTS; PR01823 JANUSKINASE
PRODOM; PD183504;
MIM; 600173
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. TAKAHASHI, T. AND SHIRASAWA, T.
Molecular cloning of rat JAK3, a novel member of the JAK family of protein 
tyrosine kinas
FEBS LETT. 342 124-128 (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].
 
JAK3 was initially cloned using a PCR-based strategy utilising degenerate
primers corresponding to conserved motifs within the catalytic domain of 
protein-tyrosine kinases [8]. By contrast with the relatively ubiquitous 
expression of JAK1, JAK2 and TYK2, JAK3 has more restricted and regulated 
tissue expression. It is expressed constitutively at high levels in NK cells
and thymocytes, and is inducible in T cells, B cells and myeloid cells. JAK3
is also expressed in vascular smooth muscle cells and endothelium [2].
 
JANUSKINASE3 is a 4-element fingerprint that provides a signature for the
janus kinase 3 (JAK3) proteins. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections 
that characterise JAK3 but distinguish it from other family members - 
motif 1 lies in the JH6 domain; motif 2 resides partially within the JH5
domain and partially between the JH5 and JH4 domains; motif 3 lies in the 
JH3 domain; and motif 4 resides in the JH2 tyrosine kinase-like domain. Two
iterations on SPTR40_20f were required to reach convergence, at which point
a true set comprising 6 sequences was identified.
Summary Information
6 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
46666
30000
20000
1234
True Positives
JAK3_HUMAN    JAK3_MOUSE    JAK3_RAT      P97423        
Q99699 Q9Y6S2
Sequence Titles
JAK3_HUMAN  Tyrosine-protein kinase JAK3 (EC 2.7.1.112) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK) - Homo sapiens (Human). 
JAK3_MOUSE Tyrosine-protein kinase JAK3 (EC 2.7.1.112) (Janus kinase 3) (JAK-3) - Mus musculus (Mouse).
JAK3_RAT Tyrosine-protein kinase JAK3 (EC 2.7.1.112) (Janus kinase 3) (JAK-3) - Rattus norvegicus (Rat).
P97423 JAK3 - Mus musculus (Mouse).
Q99699 JAK3 - Homo sapiens (Human).
Q9Y6S2 JAK3_HUMAN - Homo sapiens (Human).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
RSDLVSGRLPVGLSLKE JAK3_HUMAN 142 142 -
RSDLVSGRLPVGLSMKE JAK3_MOUSE 142 142 -
RSDLVSGRLPVGLSLKD JAK3_RAT 142 142 -

Motif 2 width=11
Element Seqn Id St Int Rpt
AETFHVGLPGA JAK3_HUMAN 251 92 -
TETFRVGLPGA JAK3_MOUSE 250 91 -
TESFLVGLPGA JAK3_RAT 251 92 -

Motif 3 width=13
Element Seqn Id St Int Rpt
GLHVDGVAVTLTS JAK3_HUMAN 461 199 -
GLRVDGAALNLTS JAK3_MOUSE 674 413 -
GLQVDGTALNLTS JAK3_RAT 458 196 -

Motif 4 width=10
Element Seqn Id St Int Rpt
EAQTLSLEAD JAK3_HUMAN 698 224 -
EAQTLCLEAD JAK3_MOUSE 909 222 -
EAGTLNLEAD JAK3_RAT 694 223 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
RSDLVSGRLPVGLSLKE JAK3_HUMAN 142 142 -
RSDLVSGRLPVGLSLKE Q9Y6S2 142 142 -
RSDLVSGRLPVGLSLKE Q99699 143 143 -
RSDLVSGRLPVGLSMKE JAK3_MOUSE 142 142 -
RSDLVSGRLPVGLSMKE P97423 142 142 -
RSDLVSGRLPVGLSLKD JAK3_RAT 142 142 -

Motif 2 width=11
Element Seqn Id St Int Rpt
AETFHVGLPGA JAK3_HUMAN 251 92 -
AETFHVGLPGA Q9Y6S2 251 92 -
AETFHVGLPGA Q99699 252 92 -
TETFRVGLPGA JAK3_MOUSE 250 91 -
TETFRVGLPGA P97423 250 91 -
TESFLVGLPGA JAK3_RAT 251 92 -

Motif 3 width=13
Element Seqn Id St Int Rpt
GLHVDGVAVTLTS JAK3_HUMAN 461 199 -
GLHVDGVAVTLTS Q9Y6S2 461 199 -
GLHVDGVAVTLTS Q99699 461 198 -
GLRVDGAALNLTS JAK3_MOUSE 674 413 -
GLRVDGAALNLTS P97423 455 194 -
GLQVDGTALNLTS JAK3_RAT 458 196 -

Motif 4 width=10
Element Seqn Id St Int Rpt
EAQTLSLEAD JAK3_HUMAN 698 224 -
EAQTLSLEAD Q9Y6S2 698 224 -
EAQTLSLEAD Q99699 698 224 -
EAQTLCLEAD JAK3_MOUSE 909 222 -
EAQTLCLEAD P97423 690 222 -
EAGTLNLEAD JAK3_RAT 694 223 -