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PR01824

Identifier
JANUSKINASE1  [View Relations]  [View Alignment]  
Accession
PR01824
No. of Motifs
4
Creation Date
09-OCT-2002
Title
Janus kinase 1 (JAK1) signature
Database References
PRINTS; PR01823 JANUSKINASE
MIM; 147795
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].
 
JAK1 was initially cloned using a PCR-based strategy utilising degenerate
primers corresponding to conserved motifs within the catalytic domain of 
protein-tyrosine kinases [5]. In common with JAK2 and TYK2, and by contrast
with JAK3, JAK1 appears to be ubiquitously expressed [2].
 
JANUSKINASE1 is a 4-element fingerprint that provides a signature for the
janus kinase 1 (JAK1) 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 JAK1 but distinguish it from other family members - motif
1 lies in the JH6 domain; motif 2 resides between the JH4 and JH3 domains; 
motif 3 lies partially between the JH4 and JH3 domains and partially within 
the JH4 domain; and motif 4 resides within the 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  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
47777
30000
20000
1234
True Positives
JAK1_CYPCA    JAK1_HUMAN    JAK1_MOUSE    O12990        
O57612 Q9PWM9 Q9TTJ1
Sequence Titles
JAK1_CYPCA  Tyrosine-protein kinase JAK1 (EC 2.7.1.112) (Janus kinase 1) (JAK-1) - Cyprinus carpio (Common carp). 
JAK1_HUMAN Tyrosine-protein kinase JAK1 (EC 2.7.1.112) (Janus kinase 1) (JAK-1) - Homo sapiens (Human).
JAK1_MOUSE Tyrosine-protein kinase JAK1 (EC 2.7.1.112) (Janus kinase 1) (JAK-1) - Mus musculus (Mouse).
O12990 TYROSINE-PROTEIN KINASE JAK1 (EC 2.7.1.112) (JANUS KINASE 1) (JAK-1) (JAK1 KINASE) - Brachydanio rerio (Zebrafish) (Zebra danio).
O57612 JAK1 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
Q9PWM9 TYROSINE KINASE JAK1 - Gallus gallus (Chicken).
Q9TTJ1 JANUS KINASE 1 - Sus scrofa (Pig).
Scan History
SPTR40_20f 3  300  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
ETLNKSIRQRN JAK1_HUMAN 211 211 -
ETLNKSIRQRN JAK1_MOUSE 223 223 -
DSLNRTIKQRN JAK1_CYPCA 222 222 -

Motif 2 width=10
Element Seqn Id St Int Rpt
NILMTVTCFE JAK1_HUMAN 462 240 -
NILMTVTCFE JAK1_MOUSE 474 240 -
YIIMTVVCIE JAK1_CYPCA 473 240 -

Motif 3 width=14
Element Seqn Id St Int Rpt
QFKNFQIEVQKGRY JAK1_HUMAN 482 10 -
QFKNFQIEVQKGRY JAK1_MOUSE 493 9 -
QYKNFQIETSPQGY JAK1_CYPCA 493 10 -

Motif 4 width=15
Element Seqn Id St Int Rpt
CYNGEIPLKDKTLIE JAK1_HUMAN 775 279 -
CYNGEIPLKDKTLIE JAK1_MOUSE 786 279 -
CYNGEIPLKDKKLTE JAK1_CYPCA 789 282 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
ETLNKSIRQRN JAK1_HUMAN 211 211 -
ETLNKSIRQRN Q9TTJ1 211 211 -
ETLNKSIRQRN JAK1_MOUSE 223 223 -
ETLNKTIRQRN Q9PWM9 223 223 -
DSLNRTIKQRN JAK1_CYPCA 222 222 -
DSLNRTIKQRN O12990 221 221 -
ETLNRSIKQRS O57612 219 219 -

Motif 2 width=10
Element Seqn Id St Int Rpt
NILMTVTCFE JAK1_HUMAN 462 240 -
NILMTVTCFE Q9TTJ1 461 239 -
NILMTVTCFE JAK1_MOUSE 474 240 -
LILMTVTCLE Q9PWM9 468 234 -
YIIMTVVCIE JAK1_CYPCA 473 240 -
FIIMTVVCIE O12990 470 238 -
YIVITVVCTE O57612 482 252 -

Motif 3 width=14
Element Seqn Id St Int Rpt
QFKNFQIEVQKGRY JAK1_HUMAN 482 10 -
QFKNFQIEVQKGRY Q9TTJ1 480 9 -
QFKNFQIEVQKGRY JAK1_MOUSE 493 9 -
QYKNFQIEVKKGGY Q9PWM9 487 9 -
QYKNFQIETSPQGY JAK1_CYPCA 493 10 -
QYKNFQIETSPQGY O12990 490 10 -
QYKNFQIEESSDGF O57612 502 10 -

Motif 4 width=15
Element Seqn Id St Int Rpt
CYNGEIPLKDKTLIE JAK1_HUMAN 775 279 -
CYNGEIPLKDKTLIE Q9TTJ1 774 280 -
CYNGEIPLKDKTLIE JAK1_MOUSE 786 279 -
CYNGETPLKDKTLAE Q9PWM9 781 280 -
CYNGEIPLKDKKLTE JAK1_CYPCA 789 282 -
CYNGEIPLKDKKLSE O12990 786 282 -
CYDGEVPLKEKKLTE O57612 800 284 -