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PR01773

Identifier
P38MAPKINASE  [View Relations]  [View Alignment]  
Accession
PR01773
No. of Motifs
5
Creation Date
16-JUL-2002
Title
P38 MAP kinase signature
Database References

PDB; 1CM8
SCOP; 1CM8
CATH; 1CM8
Literature References
1. LEWIS, T.S., SHAPIRO, P.S. AND AHN, N.G.
Signal transduction through kinase cascades. 
ADV.CANCER RES. 74 49-139 (1998).
 
2. ERREDE, B., CADE, R.M., YASHAR, B.M., KAMADA, Y., LEVIN, D.E., IRIE, K.
AND MATSUMOTO, K. 
Dynamics and organization of MAP kinases signal pathways. 
MOL.REPROD.DEV. 42 477-485 (1995).
 
3. HAN, J., LEE, J-D., BIBBS, L. AND ULEVITCH, R.J.
A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells.
SCIENCE 265 808-811 (1994).
 
4. LEE, J.C., LAYDON, J.T., MCDONNELL, P.C., GALLAGHER, T.F., KUMAR, S., 
GREEN, D., MCNULTY, D., BLUMENTHAL, M.J., HEYS, J.R., ET AL.
A protein kinase involved in the regulation of inflammatory cytokine 
biosynthesis. 
NATURE 372 739-746 (1994).
 
5. ROUSE, J., COHEN, P., TRIGON, S., MORANGE, M., ALONSO-LLAMAZARES, A., 
ZAMANILLO, D., HUNT, T. AND NEBREDA, A.R.
A novel kinase cascade triggered by stress and heat shock that stimulates 
MAPKAP kinase-2 and phosphorylation of the small heat shock proteins.
CELL 78 1027-1037 (1994).

Documentation
MAP (Mitogen Activated Protein) kinases participate in kinase cascades,  
whereby at least 3 protein kinases act in series, culminating in activation 
of MAP kinase [1-2]. MAP kinases are activated by dual phosphorylation 
on both tyrosine and threonine residues of a conserved TXY motif.
 
P38 proteins belong to the MAP kinase family and were discovered in 3
different contexts independently: first, as tyrosine phosphoproteins found
in extracts of cells treated with inflammatory cytokines [3]; second, as 
targets of a pyrinidyl imidazole drug that blocks production of TNFalpha 
[4]; and third, as reactivating kinases for MAP kinase-activated protein 
(MAPKAP) [5]. The proteins are activated by cytokines, hormones, GPCRs, 
osmotic shock, heat shock and other stresses.
 
P38MAPKINASE is a 5-element fingerprint that provides a signature for the 
p38 MAP kinases. The fingerprint was derived from an initial alignment of 12
sequences: the motifs were drawn from regions spanning virtually the full 
alignment length, focusing on those sections that characterise the p38 
proteins but distinguish them from the rest of the MAP kinase family - 
motif 1 includes beta-strand 2; motif 2 includes the C-terminus of helix 6;
motif 3 spans helix 11 and the N-terminus of helix 12; motif 4 encodes the
C-terminus of helix 12; and motif 5 includes helix 14. Two iterations on
SPTR40_20f were required to reach convergence, at which point a true set
comprising 23 sequences was identified. Several partial matches were also
found: MK13_PANTR and Q9D0M4 are p38 proteins from chimp and mouse that 
fail to match motif 1; the rest are hypothetical proteins or closely
related MAP kinases that match 2 or 3 motifs.
Summary Information
  23 codes involving  5 elements
2 codes involving 4 elements
1 codes involving 3 elements
5 codes involving 2 elements
Composite Feature Index
52323232323
402222
311010
211404
12345
True Positives
MK11_HUMAN    MK11_MOUSE    MK12_HUMAN    MK12_MOUSE    
MK12_RAT MK13_HUMAN MK13_MOUSE MK13_RAT
MK14_CANFA MK14_CYPCA MK14_HUMAN MK14_MOUSE
MK14_RAT MK14_XENLA O61443 O76806
Q17446 Q95NE7 Q99M57 Q99MG4
Q9DGE1 Q9DGE2 Q9I958
True Positive Partials
Codes involving 4 elements
MK13_PANTR Q9D0M4
Codes involving 3 elements
Q17445
Codes involving 2 elements
ERK1_DICDI O42376 O42781 Q9UQY5
STY1_SCHPO
Sequence Titles
MK11_HUMAN  Mitogen-activated protein kinase 11 (EC 2.7.1.-) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (p38-2) (Stress- activated protein kinase-2) - Homo sapiens (Human). 
MK11_MOUSE Mitogen-activated protein kinase 11 (EC 2.7.1.-) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38B) - Mus musculus (Mouse).
MK12_HUMAN Mitogen-activated protein kinase 12 (EC 2.7.1.-) (Extracellular signal-regulated kinase 6) (ERK-6) (ERK5) (Stress-activated protein kinase-3) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) - Homo sapiens (Human).
MK12_MOUSE Mitogen-activated protein kinase 12 (EC 2.7.1.-) (Extracellular signal-regulated kinase 6) (ERK-6) (Stress-activated protein kinase-3) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) - Mus musculus (Mouse).
MK12_RAT Mitogen-activated protein kinase 12 (EC 2.7.1.-) (Extracellular signal-regulated kinase 6) (ERK-6) (Stress-activated protein kinase-3) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) - Rattus norvegicus (Rat).
MK13_HUMAN Mitogen-activated protein kinase 13 (EC 2.7.1.-) (Stress-activated protein kinase-4) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) - Homo sapiens (Human).
MK13_MOUSE Mitogen-activated protein kinase 13 (EC 2.7.1.-) (Stress-activated protein kinase-4) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) - Mus musculus (Mouse).
MK13_RAT Mitogen-activated protein kinase 13 (EC 2.7.1.-) (Stress-activated protein kinase-4) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) - Rattus norvegicus (Rat).
MK14_CANFA Mitogen-activated protein kinase 14 (EC 2.7.1.-) (Mitogen-activated protein kinase p38) (MAP kinase p38) - Canis familiaris (Dog).
MK14_CYPCA Mitogen-activated protein kinase 14 (EC 2.7.1.-) (Mitogen-activated protein kinase p38) (MAP kinase p38) - Cyprinus carpio (Common carp).
MK14_HUMAN Mitogen-activated protein kinase 14 (EC 2.7.1.-) (Mitogen-activated protein kinase p38) (MAP kinase p38) (Cytokine suppressive anti- inflammatory drug binding protein) (CSAID binding protein) (CSBP) (MAX-interacting protein 2) (MAP kinase MXI2) - Homo sapiens (Human).
MK14_MOUSE Mitogen-activated protein kinase 14 (EC 2.7.1.-) (Mitogen-activated protein kinase p38) (MAP kinase p38) (CRK1) - Mus musculus (Mouse).
MK14_RAT Mitogen-activated protein kinase 14 (EC 2.7.1.-) (Mitogen-activated protein kinase p38) (MAP kinase p38) - Rattus norvegicus (Rat).
MK14_XENLA Mitogen-activated protein kinase 2 (EC 2.7.1.-) (MAP kinase 2) (MPK2) - Xenopus laevis (African clawed frog).
O61443 P38B PROTEIN (LD24658P) - Drosophila melanogaster (Fruit fly).
O76806 MATURATION INHIBITED PROTEIN KINASE P40 - Pisaster ochraceus (Sea star).
Q17446 B0218.3 PROTEIN - Caenorhabditis elegans.
Q95NE7 STRESS-ACTIVATED PROTEIN KINASE 2A - Pan troglodytes (Chimpanzee).
Q99M57 MITOGEN ACTIVATED PROTEIN KINASE 13 - Mus musculus (Mouse).
Q99MG4 P38 MITOGEN-ACTIVATED PROTEIN KINASE ALPHA1 - Rattus norvegicus (Rat).
Q9DGE1 P38B - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9DGE2 P38A - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9I958 MITOGEN ACTIVATED PROTEIN (MAP) KINASE P38 - Cyprinus carpio (Common carp).

MK13_PANTR Mitogen-activated protein kinase 13 (EC 2.7.1.-) (Stress-activated protein kinase-4) - Pan troglodytes (Chimpanzee).
Q9D0M4 MITOGEN-ACTIVATED PROTEIN KINASE 12 - Mus musculus (Mouse).

Q17445 F42G8.3 PROTEIN - Caenorhabditis elegans.

ERK1_DICDI Extracellular signal-regulated kinase 1 (EC 2.7.1.-) (ERK1) (MAP kinase 1) - Dictyostelium discoideum (Slime mold).
O42376 STRESS-ACTIVATED PROTEIN KINASE-3 - Brachydanio rerio (Zebrafish) (Zebra danio).
O42781 MITOGEN-ACTIVATED PROTEIN KINASE - Pneumocystis carinii, and Pneumocystis carinii f. sp. carinii.
Q9UQY5 PUTATIVE MAP KINASE KPP2 - Ustilago maydis (Smut fungus).
STY1_SCHPO Mitogen-activated protein kinase sty1 (EC 2.7.1.-) (MAP kinase sty1) (MAP kinase spc1) - Schizosaccharomyces pombe (Fission yeast).
Scan History
SPTR40_20f 2  78   NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
ELNKTIWEVP MK14_HUMAN 12 12 -
ELNKTVWEVP MK14_RAT 12 12 -
EVNKTIWEVP MK14_CYPCA 13 13 -
ELNKTVWEVP MK11_MOUSE 12 12 -
ELNKTVWEVP MK11_HUMAN 12 12 -
DVNKTAWELP MK13_HUMAN 13 13 -
ELNKTIWEVP MK14_CANFA 12 12 -
DINKTAWELP MK13_RAT 13 13 -
EVTKTAWEVR MK12_HUMAN 15 15 -
EVTKTAWEVR MK12_RAT 15 15 -
DINKTAWELP MK13_MOUSE 13 13 -
EVTKTAWEVR MK12_MOUSE 15 15 -

Motif 2 width=11
Element Seqn Id St Int Rpt
IMLNWMHYNQT MK14_CANFA 193 171 -
IMLNWMHYNQT MK14_HUMAN 193 171 -
IMLNWMHYNQT MK14_RAT 193 171 -
IMLNWMHYNMT MK14_CYPCA 194 171 -
IMLNWMHYNQT MK11_MOUSE 193 171 -
IMLNWMHYNQT MK11_HUMAN 201 179 -
VILSWMHYNQT MK13_HUMAN 193 170 -
VILSWMHYNQT MK13_RAT 193 170 -
VILNWMRYTQT MK12_HUMAN 196 171 -
VILNWMRYTQT MK12_RAT 196 171 -
VILSWMHYNQT MK13_MOUSE 193 170 -
VILNWMRYTQT MK12_MOUSE 196 171 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FTQLFPRASPQAAD MK13_HUMAN 270 66 -
FANVFIGANPLAVD MK14_CANFA 270 66 -
FANVFIGANPLAVD MK14_HUMAN 270 66 -
FANVFIGANPLAVD MK14_RAT 270 66 -
FSEVFIGANPQAVD MK14_CYPCA 271 66 -
LSSVFHGANPLAID MK11_MOUSE 270 66 -
LSSIFRGANPLAID MK11_HUMAN 278 66 -
FTQLFPRASPQAVD MK13_RAT 270 66 -
FASILTNASPLAVN MK12_HUMAN 273 66 -
FASVLTNASPQAVN MK12_RAT 273 66 -
FTQLFPRASPQAAD MK13_MOUSE 270 66 -
FASVLTNASPQAVN MK12_MOUSE 273 66 -

Motif 4 width=9
Element Seqn Id St Int Rpt
EKMLVLDSD MK14_CANFA 286 2 -
EKMLVLDSD MK14_HUMAN 286 2 -
EKMLVLDSD MK14_RAT 286 2 -
EKMLVLDTD MK14_CYPCA 287 2 -
GRMLVLDSD MK11_MOUSE 286 2 -
GRMLVLDSD MK11_HUMAN 294 2 -
DKMLELDVD MK13_RAT 286 2 -
EKMLVLDAE MK12_HUMAN 289 2 -
EKMLVLDAE MK12_RAT 289 2 -
EKMLELDVD MK13_HUMAN 286 2 -
DKMLELDVD MK13_MOUSE 286 2 -
ERMLVLDAE MK12_MOUSE 289 2 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FFEPFRDPEEE MK13_MOUSE 307 12 -
YFAQYHDPDDE MK14_CANFA 307 12 -
YFAQYHDPDDE MK14_HUMAN 307 12 -
YFAQYHDPDDE MK14_RAT 307 12 -
YFAQYHDPDDE MK14_CYPCA 308 12 -
YFSQYRDPDDE MK11_MOUSE 307 12 -
YFSQYHDPEDE MK11_HUMAN 315 12 -
FFEPFRDPEEE MK13_HUMAN 307 12 -
LFEPLRDPEEE MK13_RAT 307 12 -
YFESLHDTEDE MK12_HUMAN 310 12 -
YFESLRDTEDE MK12_RAT 310 12 -
YFESLRDTEDE MK12_MOUSE 310 12 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
ELNKTIWEVP Q95NE7 12 12 -
ELNKTIWEVP MK14_MOUSE 12 12 -
ELNKTIWEVP MK14_HUMAN 12 12 -
ELNKTVWEVP MK14_RAT 12 12 -
ELNKTVWEVP Q99MG4 12 12 -
ELNKTIWEVP Q9DGE1 13 13 -
EVNKTIWEVP Q9DGE2 13 13 -
ELNKTLWEVP MK14_XENLA 13 13 -
ELNKTIWEVP Q9I958 13 13 -
EVNKTIWEVP MK14_CYPCA 13 13 -
ELNKTVWEVP MK11_MOUSE 12 12 -
ELNKTIWEVP MK14_CANFA 12 12 -
ELNKTVWEVP MK11_HUMAN 12 12 -
DINRTEWEIP O61443 12 12 -
ELNKTTWEVP O76806 21 21 -
DVNKTAWELP MK13_HUMAN 13 13 -
DINKTAWELP MK13_RAT 13 13 -
EVTKTAWEVR MK12_HUMAN 15 15 -
EVTKTAWEVR MK12_RAT 15 15 -
DINKTAWELP MK13_MOUSE 13 13 -
DINKTAWELP Q99M57 13 13 -
ELNRSVWVVP Q17446 23 23 -
EVTKTAWEVR MK12_MOUSE 15 15 -

Motif 2 width=11
Element Seqn Id St Int Rpt
IMLNWMHYNQT MK14_CANFA 193 171 -
IMLNWMHYNQT Q95NE7 193 171 -
IMLNWMHYNQT MK14_MOUSE 193 171 -
IMLNWMHYNQT MK14_HUMAN 193 171 -
IMLNWMHYNQT MK14_RAT 193 171 -
IMLNWMHYNQT Q99MG4 193 171 -
IMLNWMHYNMT Q9DGE1 194 171 -
IMLNWMHYNVT Q9DGE2 194 171 -
IMLNWMHYNQT MK14_XENLA 194 171 -
IMLNWMHYNMT Q9I958 194 171 -
IMLNWMHYNMT MK14_CYPCA 194 171 -
IMLNWMHYNQT MK11_MOUSE 193 171 -
IMLNWMHYNQT MK11_HUMAN 201 179 -
IMLNWMHYNQT O61443 196 174 -
IMLNWMHYTNT O76806 202 171 -
VILSWMHYNQT MK13_HUMAN 193 170 -
VILSWMHYNQT MK13_RAT 193 170 -
VILNWMRYTQT MK12_HUMAN 196 171 -
VILNWMRYTQT MK12_RAT 196 171 -
VILSWMHYNQT MK13_MOUSE 193 170 -
VILSWMHYNQT Q99M57 193 170 -
IMLNWMHYTQT Q17446 204 171 -
VILNWMRYTQT MK12_MOUSE 196 171 -

Motif 3 width=14
Element Seqn Id St Int Rpt
LSSVFHGANPLAID MK11_MOUSE 270 66 -
FANVFIGANPLAVD MK14_CANFA 270 66 -
FANVFIGANPLAVD Q95NE7 270 66 -
FANVFIGANPLAVD MK14_MOUSE 270 66 -
FANVFIGANPLAVD MK14_HUMAN 270 66 -
FANVFIGANPLAVD MK14_RAT 270 66 -
FANVFIGANPLAVD Q99MG4 270 66 -
FADVFIGANPLAVD Q9DGE1 271 66 -
FADVFIGANPQAVD Q9DGE2 271 66 -
FEDVFLGANPQAVD MK14_XENLA 271 66 -
FADVFVGANPMAVD Q9I958 271 66 -
FSEVFIGANPQAVD MK14_CYPCA 271 66 -
LSSIFRGANPLAID MK11_HUMAN 278 66 -
FRDIFRGANPLAID O61443 273 66 -
FRGYFAGANEIAVD O76806 279 66 -
FTQLFPRASPQAAD MK13_HUMAN 270 66 -
FTQLFPRASPQAVD MK13_RAT 270 66 -
FASILTNASPLAVN MK12_HUMAN 273 66 -
FASVLTNASPQAVN MK12_RAT 273 66 -
FTQLFPRASPQAAD MK13_MOUSE 270 66 -
FTQLFPRASPQAAD Q99M57 270 66 -
FKRLFAQATPQAID Q17446 281 66 -
FASVLTNASPQAVN MK12_MOUSE 273 66 -

Motif 4 width=9
Element Seqn Id St Int Rpt
EKMLVLDSD MK14_CANFA 286 2 -
EKMLVLDSD Q95NE7 286 2 -
EKMLVLDSD MK14_MOUSE 286 2 -
EKMLVLDSD MK14_HUMAN 286 2 -
EKMLVLDSD MK14_RAT 286 2 -
EKMLVLDSD Q99MG4 286 2 -
EKMLVLDTD Q9DGE1 287 2 -
EKMLVLDTD Q9DGE2 287 2 -
EKMLVLDTD MK14_XENLA 287 2 -
EKMLVLDTD Q9I958 287 2 -
EKMLVLDTD MK14_CYPCA 287 2 -
GRMLVLDSD MK11_MOUSE 286 2 -
GRMLVLDSD MK11_HUMAN 294 2 -
EKMLELDAD O61443 289 2 -
EKMLLLDVD O76806 295 2 -
DKMLELDVD MK13_RAT 286 2 -
EKMLVLDAE MK12_HUMAN 289 2 -
EKMLVLDAE MK12_RAT 289 2 -
EKMLELDVD MK13_HUMAN 286 2 -
DKMLELDVD MK13_MOUSE 286 2 -
DKMLELDVD Q99M57 286 2 -
EKMLHLDPD Q17446 297 2 -
ERMLVLDAE MK12_MOUSE 289 2 -

Motif 5 width=11
Element Seqn Id St Int Rpt
YLAAYHDETDE Q17446 318 12 -
YFAQYHDPDDE MK14_CANFA 307 12 -
YFAQYHDPDDE Q95NE7 307 12 -
YFAQYHDPDDE MK14_MOUSE 307 12 -
YFAQYHDPDDE MK14_HUMAN 307 12 -
YFAQYHDPDDE MK14_RAT 307 12 -
YFAQYHDPDDE Q99MG4 307 12 -
YFAQYHDPDDE Q9DGE1 308 12 -
YFAQYHDPDDE Q9DGE2 308 12 -
YFAQYHDPDDE MK14_XENLA 308 12 -
YFAQYHDPDDE Q9I958 308 12 -
YFAQYHDPDDE MK14_CYPCA 308 12 -
YFSQYRDPDDE MK11_MOUSE 307 12 -
YFSQYHDPEDE MK11_HUMAN 315 12 -
YMEKYHDPTDE O61443 310 12 -
YVAKYHDESDE O76806 316 12 -
FFEPFRDPEEE MK13_HUMAN 307 12 -
LFEPLRDPEEE MK13_RAT 307 12 -
YFESLHDTEDE MK12_HUMAN 310 12 -
YFESLRDTEDE MK12_RAT 310 12 -
FFEPFRDPEEE MK13_MOUSE 307 12 -
FFEPFRDPEEE Q99M57 307 12 -
YFESLRDTEDE MK12_MOUSE 310 12 -