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PR01770

Identifier
ERK1ERK2MAPK  [View Relations]  [View Alignment]  
Accession
PR01770
No. of Motifs
6
Creation Date
16-JUL-2002
Title
ERK1/2 MAP kinase signature
Database References

PDB; 1ERK
SCOP; 1ERK
CATH; 1ERK
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. BOULTON, T.G., NYE, S.H., ROBBINS, D.J., IP, N.Y., RADZIEJEWSKA, E.,
MORGENBESSE S.D., DEPINHO, R.A., PANAYOTATOS, N., COBB, M.H. AND 
YANCOPOULOS, G.D.
ERKs: a family of protein serine/threonine kinases that are activated and 
tyrosine phosphorylated in response to insulin and NGF.
CELL 65 663-675 (1991).
 
4. TARREGA, C., BLANCO-APARICIO, C., MUNOS, J.J. AND PULIDO, R. 
Two clusters of residues at the docking groove of mitogen-activated protein
kinases differentially mediate their functional interaction with the
tyrosine phosphatases PTP-SL and STEP.
J.BIOL.CHEM. 277(4) 2629-2636 (2002).

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.
 
ERKs (Extracellularly Regulated Kinases) belong to the family of MAP 
kinases. ERK1 and ERK2, proteins of 43 and 41kDa respectively, are ~85% 
identical, even higher levels of similarity being seen in substrate binding 
regions [3]. Both are ubiquitously expressed, although levels vary from 
tissue to tissue. They are activated, for example, by serum, growth factors 
and cytokines. They phosphorylate both cytoskeletal proteins and 
transcription factors, resulting ultimately in cell growth. Substrates carry
a PX(T/S)P motif; other such "docking domains" also exist within ERK, which 
interact with specific motifs in the substrate: e.g., ERK1 and ERK2 possess 
2 DXXD docking sites capable of interaction with a Kinase Interaction Motif 
(KIM), which can be found on activators (MAPKK), inhibitors (PTP-SL and dual
specificity phosphatases) and substrates (Elk-1) [4].
 
ERK1ERK2MAPK is a 6-element fingerprint that provides a signature for the 
ERK1/2 MAP kinases. The fingerprint was derived from an initial alignment of 
5 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the 
ERK1/2 enzymes but distinguish them from the rest of the MAP kinase family
- motif 1 includes alpha-helix 1 and the N-terminus of beta-strand 1; motif
2 encodes the N-terminus of helix 4; motif 3 includes helix 6; motif 4 spans
helix 10; motif 5 includes the N-terminus of helix 12; and motif 6 includes
helix 17. Two iterations on SPTR40_20f were required to reach convergence,
at which point a true set comprising 12 sequences was identified. Several 
partial matches were also found: O35558, murine ERK2, failed to match motifs
5 and 6 and is probably a fragment; and FUS3_YEAST and ERK1_CANAL are yeast
MAP kinases that matched only motifs 2 and 6.
Summary Information
  12 codes involving  6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
6121212121212
5000000
4111100
3000000
2020002
123456
True Positives
ERKA_DROME    MK01_BOVIN    MK01_HUMAN    MK01_MOUSE    
MK01_XENLA MK03_HUMAN MK03_RAT Q8UWG6
Q9DGR5 Q9DGR6 Q9U3F3 SUR1_CAEEL
True Positive Partials
Codes involving 4 elements
O35558
Codes involving 2 elements
ERK1_CANAL FUS3_YEAST
Sequence Titles
ERKA_DROME  Mitogen-activated protein kinase ERK-A (EC 2.7.1.-) (Extracellular- regulated kinase A) (Rolled protein) - Drosophila melanogaster (Fruit fly). 
MK01_BOVIN Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (P42-MAPK) (ERT1) - Bos taurus (Bovine).
MK01_HUMAN Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (p42-MAPK) (ERT1) - Homo sapiens (Human).
MK01_MOUSE Mitogen-activated protein kinase 1 (EC 2.7.1.-) (Extracellular signal- regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) (P42-MAPK) (ERT1) - Mus musculus (Mouse), and Rattus norvegicus (Rat).
MK01_XENLA Mitogen-activated protein kinase (EC 2.7.1.-) (Myelin XP42 protein kinase) (Myelin basic protein kinase) (MBP kinase) (M phase MAP kinase) - Xenopus laevis (African clawed frog).
MK03_HUMAN Mitogen-activated protein kinase 3 (EC 2.7.1.-) (Extracellular signal- regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (p44-ERK1) (ERT2) (p44-MAPK) (Microtubule- associated protein-2 kinase) - Homo sapiens (Human).
MK03_RAT Mitogen-activated protein kinase 3 (EC 2.7.1.-) (Extracellular signal- regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase 1) (MAPK 1) (P44-ERK1) (ERT2) (P44-MAPK) (Microtubule- associated protein-2 kinase) (MNK1) - Rattus norvegicus (Rat).
Q8UWG6 EXTRACELLULAR SIGNAL-REGULATED KINASE 2 - Gallus gallus (Chicken).
Q9DGR5 ERK2 - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9DGR6 ERK1 - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9U3F3 F43C1.2B PROTEIN - Caenorhabditis elegans.
SUR1_CAEEL Mitogen-activated protein kinase SUR-1 (EC 2.7.1.-) (MAP kinase SUR-1) - Caenorhabditis elegans.

O35558 ERK2 - Mus musculus (Mouse).

ERK1_CANAL Extracellular signal-regulated kinase 1 (EC 2.7.1.-) (ERK1) (MAP kinase 1) (MAPK 1) - Candida albicans (Yeast).
FUS3_YEAST Mitogen-activated protein kinase FUS3 (EC 2.7.1.-) (MAP kinase FUS3) - Saccharomyces cerevisiae (Baker's yeast).
Scan History
SPTR40_20f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
MVRGQVFDVGPRYTNLSY MK01_BOVIN 13 13 -
MVRGQVFDVGPRYTNLSY MK01_MOUSE 11 11 -
MVRGQVFDVGPRYTNLSY MK01_HUMAN 13 13 -
MVKGQPFDVGPRYTQLQY MK03_HUMAN 30 30 -
VVKGQPFDVGPRYTQLQY MK03_RAT 31 31 -

Motif 2 width=10
Element Seqn Id St Int Rpt
TQHLSNDHIC MK01_BOVIN 118 87 -
TQHLSNDHIC MK01_MOUSE 116 87 -
TQHLSNDHIC MK01_HUMAN 118 87 -
SQQLSNDHIC MK03_HUMAN 135 87 -
SQQLSNDHIC MK03_RAT 136 87 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VADPDHDHTGF MK01_BOVIN 173 45 -
VADPDHDHTGF MK01_MOUSE 171 45 -
VADPDHDHTGF MK01_HUMAN 173 45 -
IADPEHDHTGF MK03_HUMAN 190 45 -
IADPEHDHTGF MK03_RAT 191 45 -

Motif 4 width=12
Element Seqn Id St Int Rpt
KHYLDQLNHILG MK01_BOVIN 231 47 -
KHYLDQLNHILG MK01_MOUSE 229 47 -
KHYLDQLNHILG MK01_HUMAN 231 47 -
KHYLDQLNHILG MK03_HUMAN 248 47 -
KHYLDQLNHILG MK03_RAT 249 47 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LNCIINLKARN MK01_BOVIN 252 9 -
LNCIINLKARN MK01_MOUSE 250 9 -
LNCIINLKARN MK01_HUMAN 252 9 -
LNCIINMKARN MK03_HUMAN 269 9 -
LNCIINMKARN MK03_RAT 270 9 -

Motif 6 width=11
Element Seqn Id St Int Rpt
LEQYYDPSDEP MK01_BOVIN 313 50 -
LEQYYDPSDEP MK01_MOUSE 311 50 -
LEQYYDPSDEP MK01_HUMAN 313 50 -
LEQYYDPTDEP MK03_HUMAN 330 50 -
LEQYYDPTDEP MK03_RAT 331 50 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
MVRGQVFDVGPRYTNLSY MK01_BOVIN 13 13 -
MVRGQVFDVGPRYTNLSY Q8UWG6 21 21 -
MVRGQVFDVGPRYTNLSY MK01_MOUSE 11 11 -
MVRGQVFDVGPRYTNLSY MK01_HUMAN 13 13 -
MVRGQAFDVGPRYTNLSY MK01_XENLA 16 16 -
MVRGQAFDVGPRYSNLSY Q9DGR5 22 22 -
SVKGQNFDVGPRYTDLQY Q9DGR6 43 43 -
MVKGQPFDVGPRYTQLQY MK03_HUMAN 30 30 -
VVKGQPFDVGPRYTQLQY MK03_RAT 31 31 -
VIRGQIFEVGPRYIKLAY ERKA_DROME 26 26 -
EVHGQLFEVAPRYVNLSY Q9U3F3 84 84 -
EVHGQLFEVAPRYVNLSY SUR1_CAEEL 84 84 -

Motif 2 width=10
Element Seqn Id St Int Rpt
TQHLSNDHIC MK01_BOVIN 118 87 -
TQHLSNDHIC Q8UWG6 126 87 -
TQHLSNDHIC MK01_MOUSE 116 87 -
TQHLSNDHIC MK01_HUMAN 118 87 -
TQHLSNDHIC MK01_XENLA 121 87 -
TQHLSNDHIC Q9DGR5 127 87 -
TQQLSNDHIC Q9DGR6 148 87 -
SQQLSNDHIC MK03_HUMAN 135 87 -
SQQLSNDHIC MK03_RAT 136 87 -
TQRLSNDHIC ERKA_DROME 131 87 -
TQKLSNDHVC Q9U3F3 189 87 -
TQKLSNDHVC SUR1_CAEEL 189 87 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VADPDHDHTGF MK01_BOVIN 173 45 -
VADPDHDHTGF Q8UWG6 181 45 -
VADPDHDHTGF MK01_MOUSE 171 45 -
VADPDHDHTGF MK01_HUMAN 173 45 -
VADPDHDHTGF MK01_XENLA 176 45 -
VADPDHDHTGF Q9DGR5 182 45 -
IADPEHDHTGF Q9DGR6 203 45 -
IADPEHDHTGF MK03_HUMAN 190 45 -
IADPEHDHTGF MK03_RAT 191 45 -
IADPEHDHTGF ERKA_DROME 186 45 -
VTDPQTDHTGF Q9U3F3 244 45 -
VTDPQTDHTGF SUR1_CAEEL 244 45 -

Motif 4 width=12
Element Seqn Id St Int Rpt
KHYLDQLNHILG MK01_BOVIN 231 47 -
KHYLDQLNHILG Q8UWG6 239 47 -
KHYLDQLNHILG MK01_MOUSE 229 47 -
KHYLDQLNHILG MK01_HUMAN 231 47 -
KHYLDQLNHILG MK01_XENLA 234 47 -
KHYLDQLNHILG Q9DGR5 240 47 -
KHYLDQLNHILG Q9DGR6 261 47 -
KHYLDQLNHILG MK03_HUMAN 248 47 -
KHYLDQLNHILG MK03_RAT 249 47 -
KHYLDQLNHILG ERKA_DROME 244 47 -
KHYLDQLNLILA Q9U3F3 302 47 -
KHYLDQLNLILA SUR1_CAEEL 302 47 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LNCIINLKARN MK01_BOVIN 252 9 -
LNCIINLKARN Q8UWG6 260 9 -
LNCIINLKARN MK01_MOUSE 250 9 -
LNCIINLKARN MK01_HUMAN 252 9 -
LNCIINLKARN MK01_XENLA 255 9 -
LNCIINIKARN Q9DGR5 261 9 -
LNCIINMKARN Q9DGR6 282 9 -
LNCIINMKARN MK03_HUMAN 269 9 -
LNCIINMKARN MK03_RAT 270 9 -
LECIINEKARN ERKA_DROME 265 9 -
LQCIINDKARS Q9U3F3 323 9 -
LQCIINDKARS SUR1_CAEEL 323 9 -

Motif 6 width=11
Element Seqn Id St Int Rpt
LEQYYDPSDEP MK01_BOVIN 313 50 -
LEQYYDPSDEP Q8UWG6 321 50 -
LEQYYDPSDEP MK01_MOUSE 311 50 -
LEQYYDPSDEP MK01_HUMAN 313 50 -
LEQYYDPSDEP MK01_XENLA 316 50 -
LEQYYDPTDEP Q9DGR5 322 50 -
LEQYYDPSDEP Q9DGR6 343 50 -
LEQYYDPTDEP MK03_HUMAN 330 50 -
LEQYYDPTDEP MK03_RAT 331 50 -
LEQYYDPGDEP ERKA_DROME 326 50 -
LEQYYDPGDEP Q9U3F3 384 50 -
LEQYYDPGDEP SUR1_CAEEL 384 50 -