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PR01093

Identifier
SULFNYLUR1  [View Relations]  [View Alignment]  
Accession
PR01093
No. of Motifs
5
Creation Date
25-FEB-1999  (UPDATE 07-JUN-1999)
Title
Sulphonylurea receptor type 1 family signature
Database References
PRINTS; PR01092 SULFNYLUREAR
PRODOM; PD011659; PD016038; PD010694
INTERPRO; IPR000844
Literature References
1. AGUILAR-BRYAN, L., NICHOLS, C.G., WECHSLER, S.W., CLEMENT, J.P. IV,
BOYD, A.E. III, GONZALEZ, G., HERRERA-SOSA, H., NGUY, K., BRYAN, J. AND
NELSON, D.A.
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator
of insulin secretion.
SCIENCE 268 423-426 (1995).
 
2. INAGAKI, N., GONOI, T., CLEMENT, J.P., IV, NAMBA, N., INAZAWA, J.,
GONZALEZ, G., AGUILAR-BRYAN, L., SEINO, S. AND BRYAN, J.
Reconstitution of IKATP: an inward rectifier plus the sulfonylurea receptor.
SCIENCE 270 1166-1170 (1995).
 
3. ASHCROFT, F.M. AND GRIBBLE, F.M.
Correlating structure and function in ATP-sensitive K+ channels.
TRENDS NEUROSCIENCE 21 288-294 (1998).
 
4. HANSEN, T., ECHWALD, S.M., HANSEN, L., MOLLER, A.M., ALMIND, K.,
CLAUSEN, J.O., URHAMMER, S.A., INOUE, H., FERRER, J., BRYAN, J.,
AGUILAR-BRYAN, L., PERMUTT, M.A. AND PEDERSEN O.
Decreased tolbutamide-stimulated insulin secretion in healthy subjects
with sequence variants in the high-affinity sulfonylurea receptor gene.
DIABETES 47 598-605 (1998).

Documentation
The sulphonylurea receptor (SUR) is a member of the ATP-binding cassette
superfamily that associates with certain K+ channel inward rectifier
subunits to form ATP-sensitive K+ channels (KATP channels) [1,2].  These are
a family of K+ channels that are inhibited by intracellular ATP, which can
couple metabolic state to cell excitability. Their presence on pancreatic
islet beta cells allows the cells to function as metabolic sensors,
regulating insulin release in relation to glucose metabolism. Furthermore,
SUR is the site of action for the sulphonylurea oral hypoglycaemic agents 
that are used widely for the treatment of non-insulin dependent diabetes
mellitus. When these agents bind to the sulphonlyurea receptor, they reduce
KATP channel activity, stimulating insulin release.
 
As mentioned, SUR is a member of the ATP-binding cassette superfamily
(traffic adenosine triphsophatase superfamily), other members including the
P-glycoprotein multi-drug resistance (MDR) proteins and the cystic
fibrosis transconductance regulators (CFTRs). This raises the possibility
that SUR may transport some endogenous substance, as yet unidentified.
Two closely related genes have been found to encode the sulphonylurea
receptors, SUR1 and SUR2, there being three splice variants of the second
form [3]. They are thought to contain 13-17 transmembrane (TM) domains,
with two potential nucleotide binding folds, and a large number of possible
protein kinase A, or C phosphorylation sites. 
 
SUR1 is thought to be the sulphonylurea receptor isoform that is a 
constituent of the pancreatic beta cell KATP channel. Several mutations
have been characterised in the human SUR1 gene, some of which are thought
to be responsible for the rare inheritable metabolic disorder, familial 
persistent hyperinsulinemic hypoglycemia of infancy, which is characterised
by excessive unregulated insulin secretion. SUR1 gene mutations may also
underlie the varying sensitivity of some individuals to sulphonylurea
oral hypoglycaemic agents [4]. 
 
SULFNYLUR1 is a 5-element fingerprint that provides a signature for type 1
sulphonylurea receptors. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from the first two thirds
of the alignment, focusing on those regions that distingush type 1
sulphonlyurea receptors from type 2 - motif 1 resides within the N-terminal
putative extracellular domain; motif 2 lies in the third extracellular loop;
motifs 3-4 span the fifth cytoplasmic loop (which contains the first
putative nucleotode-binding domain); and motif 5 lies within the sixth 
extracellular domain. Two iterations on OWL31.1 were required to reach
convergence, at which point a true set comprising 9 sequences was identified.
 
An update on SPTR37_9f identified a true set of 7 sequences.
Summary Information
7 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
577777
400000
300000
200000
12345
True Positives
O54989        O75948        P70532        Q16583        
SUR_CRICR SUR_HUMAN SUR_RAT
Sequence Titles
O54989      SULFONYLUREA RECEPTOR 1B - RATTUS NORVEGICUS (RAT). 
O75948 SULFONYLUREA RECEPTOR 1 - HOMO SAPIENS (HUMAN).
P70532 SULFONYLUREA RECEPTOR - RATTUS NORVEGICUS (RAT).
Q16583 SULFONYLUREA RECEPTOR - HOMO SAPIENS (HUMAN).
SUR_CRICR SULFONYLUREA RECEPTOR - CRICETUS CRICETUS (BLACK-BELLIED HAMSTER).
SUR_HUMAN SULFONYLUREA RECEPTOR - HOMO SAPIENS (HUMAN).
SUR_RAT SULFONYLUREA RECEPTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  200  NSINGLE    
SPTR37_9f 2 8 NSINGLE
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
ENHSAAYRVDQ SUR_RAT 8 8 -
ENHSAAYRVDQ AF039595 9 9 -
ENHSAAYRVDQ AF087138 9 9 -
ENHSAAYRVDQ A56248 9 9 -
ENHSAAYRVDQ RNSULFUR 9 9 -
ENHSAAYRVDQ SUR_HUMAN 8 8 -
ENHSAAYRVDQ SUR_CRICR 8 8 -

Motif 2 width=9
Element Seqn Id St Int Rpt
AFDAQARKD A56248 269 249 -
AFDAQARKD RNSULFUR 269 249 -
AFDAQVRKD SUR_HUMAN 268 249 -
AFDAQARKD SUR_CRICR 268 249 -
AFDAQARKD SUR_RAT 268 249 -
AFDAQVRKD AF087138 269 249 -
AFDAQARKD AF039595 269 249 -

Motif 3 width=13
Element Seqn Id St Int Rpt
AEIREEQCAPHEP SUR_HUMAN 616 339 -
AEIREEQCAPREP RNSULFUR 617 339 -
AEIREEQCAPREP AF039595 617 339 -
AEIREEQCAPHEP AF087138 617 339 -
AEIREEQCAPREP A56248 617 339 -
AEIREEQCAPREP SUR_RAT 616 339 -
AEIREEQCAPREP SUR_CRICR 616 339 -

Motif 4 width=17
Element Seqn Id St Int Rpt
YQAVPLKVVNRKRPARE AF039595 638 8 -
YQAVPLKVVNRKRPARE RNSULFUR 638 8 -
YQAVPLRVVNRKRPARE SUR_HUMAN 637 8 -
YQAVPLKVVNRKRPARE SUR_CRICR 637 8 -
YQAVPLKVVNRKRPARE SUR_RAT 637 8 -
YQAVPLKVVNRKRPARE A56248 638 8 -
YQAVPLRVVNRKRPARE AF087138 638 8 -

Motif 5 width=11
Element Seqn Id St Int Rpt
AARNCSLSQEC SUR_HUMAN 1045 391 -
AARNCSLSQEC RNSULFUR 1047 392 -
AARNCSLSQEC AF039595 1047 392 -
AARNCSLSQEC AF087138 1046 391 -
AARNCSLSQEC A56248 1047 392 -
AARNCSLSQEC SUR_RAT 1045 391 -
AARNCSLSQEC SUR_CRICR 1046 392 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
ENHSAAYRVDQ O54989 9 9 -
ENHSAAYRVDQ SUR_RAT 8 8 -
ENHSAAYRVDQ SUR_CRICR 8 8 -
ENHSAAYRVDQ P70532 9 9 -
ENHSAAYRVDQ O75948 9 9 -
ENHSAAYRVDQ Q16583 9 9 -
ENHSAAYRVDQ SUR_HUMAN 8 8 -

Motif 2 width=9
Element Seqn Id St Int Rpt
AFDAQARKD O54989 269 249 -
AFDAQARKD SUR_RAT 268 249 -
AFDAQARKD SUR_CRICR 268 249 -
AFDAQARKD P70532 269 249 -
AFDAQVRKD O75948 269 249 -
AFDAQVRKD Q16583 269 249 -
AFDAQVRKD SUR_HUMAN 268 249 -

Motif 3 width=13
Element Seqn Id St Int Rpt
AEIREEQCAPREP O54989 617 339 -
AEIREEQCAPREP SUR_RAT 616 339 -
AEIREEQCAPREP SUR_CRICR 616 339 -
AEIREEQCAPREP P70532 617 339 -
AEIREEQCAPHEP O75948 617 339 -
AEIREEQCAPHEP Q16583 617 339 -
AEIREEQCAPHEP SUR_HUMAN 616 339 -

Motif 4 width=17
Element Seqn Id St Int Rpt
YQAVPLKVVNRKRPARE O54989 638 8 -
YQAVPLKVVNRKRPARE SUR_RAT 637 8 -
YQAVPLKVVNRKRPARE SUR_CRICR 637 8 -
YQAVPLKVVNRKRPARE P70532 638 8 -
YQAVPLRVVNRKRPARE O75948 638 8 -
YQAVPLRVVNRKRPARE Q16583 638 8 -
YQAVPLRVVNRKRPARE SUR_HUMAN 637 8 -

Motif 5 width=11
Element Seqn Id St Int Rpt
AARNCSLSQEC O54989 1047 392 -
AARNCSLSQEC SUR_RAT 1045 391 -
AARNCSLSQEC SUR_CRICR 1046 392 -
AARNCSLSQEC P70532 1047 392 -
AARNCSLSQEC O75948 1046 391 -
AARNCSLSQEC Q16583 1046 391 -
AARNCSLSQEC SUR_HUMAN 1045 391 -