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PR01823

Identifier
JANUSKINASE  [View Relations]  [View Alignment]  
Accession
PR01823
No. of Motifs
3
Creation Date
02-DEC-2002
Title
Janus kinase family signature
Database References
PRINTS; PR01824 JANUSKINASE1; PR01825 JANUSKINASE2; PR01826 JANUSKINASE3
PRINTS; PR01827 YKINASETYK2
PRODOM; PD186830
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].
 
JANUSKINASE is a 3-element fingerprint that provides a signature for the
janus kinase family. The fingerprint was derived from an initial alignment
of 10 sequences: the motifs were drawn from conserved regions spanning the 
C-terminal two thirds of the alignment - motif 1 lies in the JH4 domain; 
motif 2 resides in the JH2 domain; and motif 3 lies in the JH1 domain. Two
iterations on SPTR40_20f were required to reach convergence, at which point
a true set comprising 27 sequences was identified. A single partial match
was also found, Q9TTJ0, a porcine kinase-defective JAK2 splice variant that
fails to match motif 3.
Summary Information
  27 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3272727
2110
123
True Positives
JAK1_CYPCA    JAK1_HUMAN    JAK1_MOUSE    JAK2_HUMAN    
JAK2_MOUSE JAK2_RAT JAK3_HUMAN JAK3_MOUSE
JAK3_RAT O12990 O19064 O42291
O57612 O93596 P97423 Q96CH0
Q99699 Q9PTN6 Q9PVI2 Q9PWD0
Q9PWD1 Q9PWM9 Q9TTI9 Q9TTJ1
Q9Y6S2 TYK2_HUMAN TYK2_MOUSE
True Positive Partials
Codes involving 2 elements
Q9TTJ0
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).
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).
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).
O12990 TYROSINE-PROTEIN KINASE JAK1 (EC 2.7.1.112) (JANUS KINASE 1) (JAK-1) (JAK1 KINASE) - Brachydanio rerio (Zebrafish) (Zebra danio).
O19064 JAK2 - Sus scrofa (Pig).
O42291 JANUS TYROSINE KINASE - Gallus gallus (Chicken).
O57612 JAK1 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
O93596 PROTEIN TYROSINE KINASE (EC 2.7.1.112) - Brachydanio rerio (Zebrafish) (Zebra danio).
P97423 JAK3 - Mus musculus (Mouse).
Q96CH0 HYPOTHETICAL 133.7 KDA PROTEIN - Homo sapiens (Human).
Q99699 JAK3 - Homo sapiens (Human).
Q9PTN6 JANUS KINASE 3 - Cyprinus carpio (Common carp).
Q9PVI2 JAK2 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
Q9PWD0 JAK3 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
Q9PWD1 TYK2 TYROSINE KINASE - Tetraodon fluviatilis (Puffer fish).
Q9PWM9 TYROSINE KINASE JAK1 - Gallus gallus (Chicken).
Q9TTI9 KINASE-DEFECTIVE JAK2 VARIANT - Sus scrofa (Pig).
Q9TTJ1 JANUS KINASE 1 - Sus scrofa (Pig).
Q9Y6S2 JAK3_HUMAN - Homo sapiens (Human).
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).

Q9TTJ0 KINASE-DEFECTIVE JAK2 VARIANT - Sus scrofa (Pig).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
FVSLVDGYFRLTADAHHYLCTDVAP JAK1_HUMAN 393 393 -
FVSLIDGYFRLTADAHHYLCTDVAP Q9TTJ1 392 392 -
FASLIDGYFRLTADAHHYLCTDVAP Q9PWM9 399 399 -
FAALVDGYFRLTVDAHHYLCTDVAP O12990 401 401 -
FVALVDGYFRLTVDAHHYLCKDVAP O57612 413 413 -
FAALVDGYFRLTVDAHHYLCTEVAP JAK1_CYPCA 404 404 -
FVSLVDGYFRLTADAHHYLCTDVAP JAK1_MOUSE 405 405 -
FVSLVDGYFRLTADSSHYLCHEVAP TYK2_HUMAN 416 416 -
FVALVDGYFRLTADSSHYLCHEVAP TYK2_MOUSE 411 411 -
FISLLDGYYRLTADAHHYLCHDVAP Q9PWD1 377 377 -

Motif 2 width=25
Element Seqn Id St Int Rpt
PFIKLSDPGIPITVLSRQECIERIP JAK1_HUMAN 721 303 -
PFIKLSDPGIPITVLSRQECIERIP Q9TTJ1 720 303 -
PFIKLSDPGIPITVLSRQECVERIP Q9PWM9 727 303 -
PFIKLSDPGIPITVLSREECVDRIP O12990 732 306 -
PFIKLSDPGIPITVLTREECVHRIP O57612 746 308 -
PFIKLSDPGIPITVLSREECVDRLP JAK1_CYPCA 735 306 -
PFIKLSDPGIPVSVLTRQECIERIP JAK1_MOUSE 732 302 -
PFIKLSDPGVGLGALSREERVERIP TYK2_HUMAN 753 312 -
PFIKLSDPGVGQGALSREERVERIP TYK2_MOUSE 746 310 -
PCIKLSDPGIAMSVLTREERLERIP Q9PWD1 703 301 -

Motif 3 width=27
Element Seqn Id St Int Rpt
EDGGNGIKLIMEFLPSGSLKEYLPKNK JAK1_HUMAN 934 188 -
EDGGNGIKLIMEFLPSGSLKEYLPKNK Q9TTJ1 933 188 -
EDGGNGIKLIMEFLPSGSLKEYLPRNK Q9PWM9 940 188 -
EEGGRSIKLIMEFLPAGSLKEYLPRNK O12990 943 186 -
EEGGQAFKLIMEYVPMGSLKDYLPRHK O57612 958 187 -
EEGGRSIKLIMEFLPAGSLKEYLPRNK JAK1_CYPCA 946 186 -
EDGGNGIKLIMEFLPSGSLKEYLPKNK JAK1_MOUSE 945 188 -
DQGEKSLQLVMEYVPLGSLRDYLPRHS TYK2_HUMAN 968 190 -
DQGEKSVQLVMEYVPLGSLRDYLPRHC TYK2_MOUSE 961 190 -
EGGGQGLLLIMEFLPLGSLLKYLPKNK Q9PWD1 913 185 -
Final Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
FVSLIDGYYRLTADAHHYLCKEVAP JAK2_MOUSE 365 365 -
FVSLIDGYYRLTADAHHYLCKEVAP JAK2_RAT 365 365 -
FVSLIDGYYRLTADAHHYLCKEVAP O19064 365 365 -
FVSLIDGYYRLTADAHHYLCKEVAP Q9TTI9 365 365 -
FVSLIDGYYRLTADAHHYLCKEVAP JAK2_HUMAN 365 365 -
FVSLIDGYYRLTTDAHHYLCKEVAP Q9PVI2 352 352 -
FVSLIDGYYRLTTDAHHYLCKEVAP O93596 331 331 -
FVSLVDGYFRLTADAHHYLCTDVAP JAK1_HUMAN 393 393 -
FVSLIDGYFRLTADAHHYLCTDVAP Q9TTJ1 392 392 -
FVALVDGYFRLTTDSQHFFCKEVAP Q9Y6S2 341 341 -
FASLIDGYFRLTADAHHYLCTDVAP Q9PWM9 399 399 -
FMALVDGYYRLTADAHHYFCKEVAP O42291 339 339 -
FAALVDGYFRLTVDAHHYLCTDVAP O12990 401 401 -
FVALVDGYFRLTVDAHHYLCKDVAP O57612 413 413 -
FVALVDGYFRLTTDSQHFFCKEVAP JAK3_HUMAN 341 341 -
FVALVDGYFRLICDSRHYFCKEVAA JAK3_MOUSE 526 526 -
FVALVDGYFRLICDSRHYFCKEVAA P97423 336 336 -
FVALVDGYFRLICDSRHFFCKEVAP JAK3_RAT 338 338 -
FAALVDGYFRLTVDAHHYLCTEVAP JAK1_CYPCA 404 404 -
FVSLVDGYFRLTADAHHYLCTDVAP JAK1_MOUSE 405 405 -
FVALVDGYFRLTTDSQHFFCKEVAP Q99699 341 341 -
FVSLVDGYFRLTADSSHYLCHEVAP Q96CH0 416 416 -
FVSLVDGYFRLTADSSHYLCHEVAP TYK2_HUMAN 416 416 -
FVALVDGYFRLTADSSHYLCHEVAP TYK2_MOUSE 411 411 -
FISLLDGYYRLTADAHHYLCHDVAP Q9PWD1 377 377 -
FVSLVDGYFRLTTDSTHYSCAEVAP Q9PTN6 344 344 -
LVSLVDGYFRLTTDSTHYFCQDTAP Q9PWD0 348 348 -

Motif 2 width=25
Element Seqn Id St Int Rpt
PFIKLSDPGISITVLPKDILQERIP JAK2_MOUSE 693 303 -
PFIKLSDPGISITVLPKDILQERIP JAK2_RAT 693 303 -
PFIKLSDPGISITVLPKDILQERIP O19064 693 303 -
PFIKLSDPGISITVLPKDILQERIP Q9TTI9 693 303 -
PFIKLSDPGISITVLPKDILQERIP JAK2_HUMAN 693 303 -
PFIKLSDPGISITVLPKEILVERIP Q9PVI2 679 302 -
PFIKLSDPGISITVQPREILLERIP O93596 657 301 -
PFIKLSDPGIPITVLSRQECIERIP JAK1_HUMAN 721 303 -
PFIKLSDPGIPITVLSRQECIERIP Q9TTJ1 720 303 -
PFIKLSDPGVSPAVLSLEMLTDRIP Q9Y6S2 665 299 -
PFIKLSDPGIPITVLSRQECVERIP Q9PWM9 727 303 -
PFIKLNDPGVSITVLAKEWLVERIP O42291 665 301 -
PFIKLSDPGIPITVLSREECVDRIP O12990 732 306 -
PFIKLSDPGIPITVLTREECVHRIP O57612 746 308 -
PFIKLSDPGVSPAVLSLEMLTDRIP JAK3_HUMAN 665 299 -
PFIKLSDPGVSPTVLSLEMLTDRIP JAK3_MOUSE 876 325 -
PFIKLSDPGVSPTVLSLEMLTDRIP P97423 657 296 -
PFIKLSDPGVSPTVLSLEMLTDRIP JAK3_RAT 661 298 -
PFIKLSDPGIPITVLSREECVDRLP JAK1_CYPCA 735 306 -
PFIKLSDPGIPVSVLTRQECIERIP JAK1_MOUSE 732 302 -
PFIKLSDPGVSPAVLSLEMLTDRIP Q99699 665 299 -
PFIKLSDPGVGLGALSREERVERIP Q96CH0 753 312 -
PFIKLSDPGVGLGALSREERVERIP TYK2_HUMAN 753 312 -
PFIKLSDPGVGQGALSREERVERIP TYK2_MOUSE 746 310 -
PCIKLSDPGIAMSVLTREERLERIP Q9PWD1 703 301 -
PFIKLSDPGINMALLGKDVVLDRIP Q9PTN6 667 298 -
PFIKLSDPGISVLMLGKDVIVDRIP Q9PWD0 670 297 -

Motif 3 width=27
Element Seqn Id St Int Rpt
SAGRRNLRLIMEYLPYGSLRDYLQKHK JAK2_MOUSE 919 201 -
SAGRRNLRLIMEYLPYGSLRDYLQKHK JAK2_RAT 919 201 -
SAGRRNLRLIMEYLPYGSLRDYLQKHK O19064 919 201 -
SAGRRNLRLIMEYLPYGSLRDYLQKHK Q9TTI9 919 201 -
SAGRRNLKLIMEYLPYGSLRDYLQKHK JAK2_HUMAN 919 201 -
SAGRRNLRLVMEYLPFGSLRDYLIKNK Q9PVI2 905 201 -
SAGRNNLRLVMEFLPFGSLRDYLSKNR O93596 882 200 -
EDGGNGIKLIMEFLPSGSLKEYLPKNK JAK1_HUMAN 934 188 -
EDGGNGIKLIMEFLPSGSLKEYLPKNK Q9TTJ1 933 188 -
GPGRQSLRLVMEYLPSGCLRDFLQRHR Q9Y6S2 892 202 -
EDGGNGIKLIMEFLPSGSLKEYLPRNK Q9PWM9 940 188 -
SRGRRGLRLVMEYLPDGCLRDYLQKNQ O42291 891 201 -
EEGGRSIKLIMEFLPAGSLKEYLPRNK O12990 943 186 -
EEGGQAFKLIMEYVPMGSLKDYLPRHK O57612 958 187 -
GPGRPELRLVMEYLPSGCLRDFLQRHR JAK3_HUMAN 892 202 -
GPGRQSLRLVMEYLPSGCLRDFLQRHR JAK3_MOUSE 1101 200 -
GPGRQSLRLVMEYLPSGCLRDFLQRHR P97423 883 201 -
GPGRQELRLVMEYLPSGCLRDFLQRHR JAK3_RAT 888 202 -
EEGGRSIKLIMEFLPAGSLKEYLPRNK JAK1_CYPCA 946 186 -
EDGGNGIKLIMEFLPSGSLKEYLPKNK JAK1_MOUSE 945 188 -
GPGEPELRLVMEYLPSGCLRDFLQRHR Q99699 892 202 -
DQGEKSLQLVMEYVPLGSLRDYLPRHS Q96CH0 968 190 -
DQGEKSLQLVMEYVPLGSLRDYLPRHS TYK2_HUMAN 968 190 -
DQGEKSVQLVMEYVPLGSLRDYLPRHC TYK2_MOUSE 961 190 -
EGGGQGLLLIMEFLPLGSLLKYLPKNK Q9PWD1 913 185 -
STGRLSTKLVMEYLPYGSLIGYMEKHR Q9PTN6 891 199 -
SMGRLSMGLVTEYLPYGSLIGYLENNR Q9PWD0 891 196 -