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PR00629

Identifier
SHCPIDOMAIN  [View Relations]  [View Alignment]  
Accession
PR00629
No. of Motifs
6
Creation Date
11-DEC-1996  (UPDATE 07-JUN-1999)
Title
SHC phosphotyrosine interaction domain signature
Database References

INTERPRO; IPR000050
PDB; 1MIL
Literature References
1. ECK, M.J., DHE-PAGANON, S., TRUB, T., NOITE, R.T. AND SHOELSON, S.E.  
Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the
insulin receptor.
CELL 85 695-705 (1996).
 
2. DIKIC, I., BATZER, G., BLAIKIE, P., OBERMEIER, A., ULLRICH, A.,
SCHLESSINGER, J. AND MARGOLIS, B.
Shc binding to nerve growth factor receptor is mediated by the
phosphotyrosine interaction domain.
J.BIOL.CHEM. 270 15125-15129 (1995).
 
3.ZHOU, M., HUANG, B., OLEJNICZAK, E.T., MEADOWS, R.P., SHUKER, S.B., 
MIYAZAKI, M.,  TRUB, T., SHOELSON, S.E. AND FESIK, S.W.
Structural basis for IL-4 receptor phosphopeptide recognition by the IRS1-1
PTB domain.
NAT.STRUCT.BIOL. 3 388-393 (1996).

Documentation
Shc proteins contain an SH2 domain and a phosphotyrosine interaction (PI)
domain. These domains facilitate interaction with various activated
tyrosine-phosphorylated receptors, including those of growth factors,
insulin, cytokines and lymphocytes. The PI domain comprises 165 residues,
4 of which (Arg67, Arg175, Ser151 and Lys169 [1]) are responsible for
binding phosphotyrosine on a `IIENPQYFSDA'(NPxPY) peptide [2]. 
 
The PI domain has a similar structure to the insulin receptor substrate-1 
PTB domain, a 7-stranded beta-sandwich, capped by a C-terminal helix.
However, the PI domain contains an additional short N-terminal helix and a
large insertion between strands 1 and 2, which forms a helix and 2 long
connecting loops. The substrate peptide fits into a surface cleft formed
from the C-terminal helix and strand 5 [3]. 
 
SHCPIDOMAIN is a 6-element fingerprint that provides a signature for the
SHC PI domain. The fingerprint was derived from an initial alignment of 6
sequences: motif 1 spans strand 1; motif 2 encodes most of the additional
helix; motif 3 lies in one of the connecting loops; motif 4 includes strand
2; motif 5 spans strands 4, 5 and 6; and motif 6 encodes the C-terminal
helix. A single iteration on OWL28.3 was required to reach convergence, no
further sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 7 sequences.
Summary Information
7 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6777777
5000000
4000000
3000000
2000000
123456
True Positives
O15290        O70143        Q24080        Q61120        
Q92529 SHC_HUMAN SHC_MOUSE
Sequence Titles
O15290      P66SHC - HOMO SAPIENS (HUMAN).                
O70143 N-SHC ISOFORMS P52 AND P56 - RATTUS NORVEGICUS (RAT).
Q24080 DSHC - DROSOPHILA MELANOGASTER (FRUIT FLY).
Q61120 SHC TRANSFORMING PROTEIN 3, SRC HOMOLOGY 2 DOMAIN-CONTAINING (SHCC) - MUS MUSCULUS (MOUSE).
Q92529 P64 ISOFORM OF N-SHC (P52 ISOFORM OF N-SHC) - HOMO SAPIENS (HUMAN).
SHC_HUMAN SHC TRANSFORMING PROTEIN - HOMO SAPIENS (HUMAN).
SHC_MOUSE SHC TRANSFORMING PROTEIN - MUS MUSCULUS (MOUSE).
Scan History
OWL28_3    1  100  NSINGLE    
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GPGVSYLVRYMGCVEV MMU46956 156 156 -
GPGVTYVVKYLGCIEV MMU46854 30 30 -
GPGVSYLVRYMGCVEV SHC_HUMAN 47 47 -
GPGVSYVVRYMGCIEV SCK_HUMAN 35 35 -
GVGVAFNVRYTGCVEV DMU26445 29 29 -
GPGVSYLVRYMGCVEV SHC_MOUSE 47 47 -

Motif 2 width=23
Element Seqn Id St Int Rpt
SMRALDFNTRTQVTREAISLVCE MMU46956 174 2 -
SMRSLDFNTRTQVTREAINRLHE SCK_HUMAN 53 2 -
SMRSLDFSTRTQVTREAISRVCE MMU46854 48 2 -
SMKSLDFETRTQLARECINRVCE DMU26445 47 2 -
SMRALDFNTRTQVTREAISLVCE SHC_MOUSE 65 2 -
SMRALDFNTRTQVTREAISLVCE SHC_HUMAN 65 2 -

Motif 3 width=12
Element Seqn Id St Int Rpt
PGAKGATRRRKP SHC_MOUSE 90 2 -
PGAKGATRRRKP MMU46956 199 2 -
PGVRGSWKKKAP SCK_HUMAN 78 2 -
PGAKGALKKRKP MMU46854 73 2 -
AGLKSAGKRRLT DMU26445 71 1 -
PGAKGATRRRKP SHC_HUMAN 90 2 -

Motif 4 width=10
Element Seqn Id St Int Rpt
AGMSISLTIS MMU46854 101 16 -
AGMSISIHIS SCK_HUMAN 105 15 -
AGMPITLTVS SHC_HUMAN 118 16 -
AGMPITLTVS SHC_MOUSE 118 16 -
AGMPITLTVS MMU46956 227 16 -
AGTNIIINVS DMU26445 94 11 -

Motif 5 width=29
Element Seqn Id St Int Rpt
IIANHHMRSISFASGGDPDTTDYVAYVAK MMU46854 124 13 -
IIANHHMQSISFASGGDPDTAEYVAYVAK MMU46956 250 13 -
VIANHHMPSISFASGGDTDMTDYVAYVAK SCK_HUMAN 128 13 -
VIANHNMPRISFASGGDNDTLDFLAYIAK DMU26445 117 13 -
IIANHHMQSISFASGGDPDTAEYVAYVAK SHC_MOUSE 141 13 -
IIANHHMQSISFASGGDPDTAEYVAYVAK SHC_HUMAN 141 13 -

Motif 6 width=27
Element Seqn Id St Int Rpt
ACHILECCEGLAQSIISTVGQAFELRF SCK_HUMAN 163 6 -
ACHILECPEGLAQDVISTIGQAFELRF MMU46956 285 6 -
ACHILECPEGLAQDVISTIGQAFELRF SHC_MOUSE 176 6 -
ACHILECPEGLAQDVISTIGQAFELRF SHC_HUMAN 176 6 -
ACYVLECAGGQSEDLIVTIGKAFALRF DMU26445 152 6 -
ACHILECCDGLAQDVIGSIGQAFELRF MMU46854 159 6 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GPGVSYLVRYMGCVEV O15290 157 157 -
GPGVSYLVRYMGCVEV SHC_MOUSE 47 47 -
GPGVSYLVRYMGCVEV SHC_HUMAN 47 47 -
GPGVTYVVKYLGCIEV Q61120 30 30 -
GPGVTYVVKYLGCIEV Q92529 150 150 -
GSGVTYVVKYLGCIEV O70143 150 150 -
GVGVAFNVRYTGCVEV Q24080 29 29 -

Motif 2 width=23
Element Seqn Id St Int Rpt
SMRALDFNTRTQVTREAISLVCE O15290 175 2 -
SMRALDFNTRTQVTREAISLVCE SHC_MOUSE 65 2 -
SMRALDFNTRTQVTREAISLVCE SHC_HUMAN 65 2 -
SMRSLDFSTRTQVTREAISRVCE Q61120 48 2 -
SMRSLDFSTRTQITREAISRVCE Q92529 168 2 -
SMRSLDFSTRTQVTREAISRVCE O70143 168 2 -
SMKSLDFETRTQLARECINRVCE Q24080 47 2 -

Motif 3 width=12
Element Seqn Id St Int Rpt
PGAKGATRRRKP O15290 200 2 -
PGAKGATRRRKP SHC_MOUSE 90 2 -
PGAKGATRRRKP SHC_HUMAN 90 2 -
PGAKGALKKRKP Q61120 73 2 -
PGAKGAFKKRKP Q92529 193 2 -
PGAKGAFKKRKP O70143 193 2 -
AGLKSAGKRRLT Q24080 71 1 -

Motif 4 width=10
Element Seqn Id St Int Rpt
AGMPITLTVS O15290 228 16 -
AGMPITLTVS SHC_MOUSE 118 16 -
AGMPITLTVS SHC_HUMAN 118 16 -
AGMSISLTIS Q61120 101 16 -
AGMSISLTIS Q92529 221 16 -
AGMSISLTIS O70143 221 16 -
AGTNIIINVS Q24080 94 11 -

Motif 5 width=29
Element Seqn Id St Int Rpt
IIANHHMQSISFASGGDPDTAEYVAYVAK O15290 251 13 -
IIANHHMQSISFASGGDPDTAEYVAYVAK SHC_MOUSE 141 13 -
IIANHHMQSISFASGGDPDTAEYVAYVAK SHC_HUMAN 141 13 -
IIANHHMRSISFASGGDPDTTDYVAYVAK Q61120 124 13 -
IIANHHMRSISFASGGDPDTTDYVAYVAK Q92529 244 13 -
IISNHHMRSISFASGGDPDTTDYVAYVAK O70143 244 13 -
VIANHNMPRISFASGGDNDTLDFLAYIAK Q24080 117 13 -

Motif 6 width=27
Element Seqn Id St Int Rpt
ACHILECPEGLAQDVISTIGQAFELRF O15290 286 6 -
ACHILECPEGLAQDVISTIGQAFELRF SHC_MOUSE 176 6 -
ACHILECPEGLAQDVISTIGQAFELRF SHC_HUMAN 176 6 -
ACHILECCDGLAQDVIGSIGQAFELRF Q61120 159 6 -
ACHILECCDGLAQDVIGSIGQAFELRF Q92529 279 6 -
ACHILECCDGLAQDVIGSIGQAFELRF O70143 279 6 -
ACYVLECAGGQSEDLIVTIGKAFALRF Q24080 152 6 -