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PR00628

Identifier
INSULINRSI  [View Relations]  [View Alignment]  
Accession
PR00628
No. of Motifs
6
Creation Date
03-DEC-1996  (UPDATE 28-JUL-1999)
Title
Insulin receptor substrate-1 PTB domain signature
Database References

INTERPRO; IPR002404
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. 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
Insulin receptor substrate-1 proteins contain both a pleckstrin homology
domain and a phosphotyrosine binding (PTB) domain. These domains facilitate 
interaction with the activated tyrosine-phosphorylated insulin receptor.
The PTB domain, which is situated towards the N-terminus, comprises 105
residues. Two of its arginines (Arg212 and Arg227) are responsible for
hydrogen bonding phosphotyrosine residues on a Ac-LYASSNPApY-NH2 peptide
in the juxtamembrane region of the insulin receptor. Further interactions
via `bridged' water molecules are coordinated by residues Asn210 and Ser228
[1].
 
The PTB domain has a compact, 7-stranded beta-sandwich structure, capped by
a C-terminal helix. The substrate peptide fits into an L-shaped surface
cleft formed from the C-terminal helix and strands 5 and 6 [2].
 
INSULINRSI is a 6-element fingerprint that provides a signature for the
insulin receptor substrate-1 PTB domain. The fingerprint was derived from
an initial alignment of 6 sequences: motif 1 includes the first beta-strand;
motif 2 spans strands 2 and 3; motif 3 spans strands 4 and 5; motifs 4 and
5 include strands 6 and 7 res.; and motif 6 spans the alpha-helix. A single
iteration of OWL28.3 was required to reach convergence, no further sequences
being identified beyond the starting set. A single partial match was also
found, XLU27842, a C-terminal fragment that lacks motifs 1-3.
 
An update on SPTR37_9f identified a true set of 8 sequences, and 1
partial match.
Summary Information
   8 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6888888
5000000
4000000
3000111
2000000
123456
True Positives
IRS1_HUMAN    IRS1_MOUSE    IRS1_RAT      IRS2_MOUSE    
O08724 O14654 P79773 Q28224
True Positive Partials
Codes involving 3 elements
Q91615
Sequence Titles
IRS1_HUMAN  INSULIN RECEPTOR SUBSTRATE-1 (IRS-1) - HOMO SAPIENS (HUMAN). 
IRS1_MOUSE INSULIN RECEPTOR SUBSTRATE-1 - MUS MUSCULUS (MOUSE).
IRS1_RAT INSULIN RECEPTOR SUBSTRATE-1 - RATTUS NORVEGICUS (RAT).
IRS2_MOUSE INSULIN RECEPTOR SUBSTRATE-2 (IRS-2) (4PS) - MUS MUSCULUS (MOUSE).
O08724 INSULIN RECEPTOR SUBSTRATE-3 - RATTUS NORVEGICUS (RAT).
O14654 INSULIN RECEPTOR SUBSTRATE 4 - HOMO SAPIENS (HUMAN).
P79773 INSULIN RECEPTOR SUBSTRATE 1 - GALLUS GALLUS (CHICKEN).
Q28224 IRS-1 - CERCOPITHECUS AETHIOPS (GREEN MONKEY) (GRIVET).

Q91615 INSULIN RECEPTOR SUBSTRATE-1-LIKE PROTEIN - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
OWL28_3    1  100  NSINGLE    
SPTR37_9f 3 50 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
AFKEVWQVILKPKGLGQTKN S30185 154 154 -
AFKEVWQVILKPKGLGQTKN AGMPRIIRS1 159 159 -
AFKEVWQVILKPKGLGQTKN S85963 160 160 -
AFKEVWQVILKPKGLGQTKN IRS1_HUMAN 159 159 -
AFKEVWQVILKPKGLGQTKN IRS1_RAT 154 154 -
AFKEVWQVILKPKGLGQTKN IRS1_MOUSE 154 154 -

Motif 2 width=21
Element Seqn Id St Int Rpt
IGIYRLCLTSKTISFVKLNSE S85963 181 1 -
IGIYRLCLTSKTISFVKLNSE IRS1_HUMAN 180 1 -
IGIYRLCLTSKTISFVKLNSE IRS1_RAT 175 1 -
IGIYRLCLTSKTISFVKLNSE IRS1_MOUSE 175 1 -
IGIYRLCLTSKTISFVKLNSE S30185 175 1 -
IGIYRLCLTSKTISFVKLNSE AGMPRIIRS1 180 1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AAVVLQLMNIRRCGHSE S30185 197 1 -
AAVVLQLMNIRRCGHSE S85963 203 1 -
AAVVLQLMNIRRCGHSE AGMPRIIRS1 202 1 -
AAVVLQLMNIRRCGHSE IRS1_MOUSE 197 1 -
AAVVLQLMNIRRCGHSE IRS1_RAT 197 1 -
AAVVLQLMNIRRCGHSE IRS1_HUMAN 202 1 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NFFFIEVGRSAVT S85963 220 0 -
NFFFIEVGRSAVT IRS1_HUMAN 219 0 -
NFFFIEVGRSAVT IRS1_RAT 214 0 -
NFFFIEVGRSAVT IRS1_MOUSE 214 0 -
NFFFIEVGRSAVT S30185 214 0 -
NFFFIEVGRSAVT AGMPRIIRS1 219 0 -

Motif 5 width=9
Element Seqn Id St Int Rpt
GPGEFWMQV IRS1_HUMAN 232 0 -
GPGEFWMQV S85963 233 0 -
GPGEFWMQV AGMPRIIRS1 232 0 -
GPGEFWMQV IRS1_RAT 227 0 -
GPGEFWMQV IRS1_MOUSE 227 0 -
GPGEFWMQV S30185 227 0 -

Motif 6 width=25
Element Seqn Id St Int Rpt
SVVAQNMHETILEAMRAMSDEFRPR IRS1_HUMAN 243 2 -
SVVAQNMHETILEAMRAMSDEFRPR AGMPRIIRS1 243 2 -
SVVAQNMHETILEAMRAMSDEFRPR S30185 238 2 -
SVVAQNMHETILEAMRAMSDEFRPR IRS1_RAT 238 2 -
SVVAQNMHETILEAMRAMSDEFRPR IRS1_MOUSE 238 2 -
SVVAQNMHETILEAMRAMSDEFRPR S85963 244 2 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
AFKEVWQVILKPKGLGQTKN IRS1_HUMAN 159 159 -
AFKEVWQVILKPKGLGQTKN Q28224 159 159 -
AFKEVWQVILKPKGLGQTKN IRS1_RAT 154 154 -
AFKEVWQVILKPKGLGQTKN IRS1_MOUSE 154 154 -
AFKEVWQVILKPKGLGQTKN P79773 157 157 -
VYREVWQVNLKPKGLGQSKN IRS2_MOUSE 190 190 -
FYKDVWQVIVKPRGLGHRKE O14654 230 230 -
PFQDVWPVTLRSKGLGRAPG O08724 158 158 -

Motif 2 width=21
Element Seqn Id St Int Rpt
IGIYRLCLTSKTISFVKLNSE IRS1_HUMAN 180 1 -
IGIYRLCLTSKTISFVKLNSE Q28224 180 1 -
IGIYRLCLTSKTISFVKLNSE IRS1_RAT 175 1 -
IGIYRLCLTSKTISFVKLNSE IRS1_MOUSE 175 1 -
IGIYRLCLTSKTISFVKLNSD P79773 178 1 -
TGVYRLCLSARTIGFVKLNCE IRS2_MOUSE 211 1 -
SGVFRLCLTDEEVVFVRLNTE O14654 251 1 -
SGSYRLCLGSGALSLLRKPGS O08724 180 2 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AAVVLQLMNIRRCGHSE IRS1_HUMAN 202 1 -
AAVVLQLMNIRRCGHSE Q28224 202 1 -
AAVVLQLMNIRRCGHSE IRS1_RAT 197 1 -
AAVVLQLMNIRRCGHSE IRS1_MOUSE 197 1 -
AAVVLQLLNIRRCGHSE P79773 200 1 -
PSVTLQLNNIRRCGHSD IRS2_MOUSE 233 1 -
ASVVVQLLSIRRCGHSE O14654 273 1 -
PVLRLSLLSVRRCGHAD O08724 212 11 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NFFFIEVGRSAVT IRS1_HUMAN 219 0 -
NFFFIEVGRSAVT Q28224 219 0 -
NFFFIEVGRSAVT IRS1_RAT 214 0 -
NFFFIEVGRSAVT IRS1_MOUSE 214 0 -
NFFFIEVGRSAVT P79773 217 0 -
SFFFIEVGRSAVT IRS2_MOUSE 250 0 -
QYFFLEVGRSTVI O14654 290 0 -
SFFFLELGRSAPI O08724 229 0 -

Motif 5 width=9
Element Seqn Id St Int Rpt
GPGEFWMQV IRS1_HUMAN 232 0 -
GPGEFWMQV Q28224 232 0 -
GPGEFWMQV IRS1_RAT 227 0 -
GPGEFWMQV IRS1_MOUSE 227 0 -
VPGEFWMQV P79773 230 0 -
GPGELWMQA IRS2_MOUSE 263 0 -
GPGELWMQV O14654 303 0 -
GPGELWLQA O08724 242 0 -

Motif 6 width=25
Element Seqn Id St Int Rpt
SVVAQNMHETILEAMRAMSDEFRPR IRS1_HUMAN 243 2 -
SVVAQNMHETILEAMRAMSDEFRPR Q28224 243 2 -
SVVAQNMHETILEAMRAMSDEFRPR IRS1_RAT 238 2 -
SVVAQNMHETILEAMRAMSDEFRPR IRS1_MOUSE 238 2 -
SVVAQNMHETILEAMRAMSEEFRPR P79773 241 2 -
SVVAQNIHETILEAMKALKELFEFR IRS2_MOUSE 274 2 -
CVVAQNMHELFLEKMRALCADEYRA O14654 314 2 -
AVVAQSIHETVLAAMKRLGSSAASG O08724 253 2 -