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PR01094

Identifier
SULFNYLUR2  [View Relations]  [View Alignment]  
Accession
PR01094
No. of Motifs
4
Creation Date
25-FEB-1999  (UPDATE 07-JUN-1999)
Title
Sulphonylurea receptor type 2 family signature
Database References
PRINTS; PR01092 SULFNYLUREAR
PRODOM; PD009273; PD011658
INTERPRO; IPR001475
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).

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. 
 
Comparison of the properties of cloned and wild-type KATP channels suggests
that splice variants of SUR2 (termed SUR2A and SUR2B) may form the cardiac
and smooth muscle KATP channel isoforms, when combined with the inward
rectifier subunit Kir 6.2.
 
SULFNYLUR2 is a 4-element fingerprint that provides a signature for type 2
sulphonylurea receptors. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from the N-terminal half
of the alignment, focusing on those regions that distinguish type 2 
sulphonylurea receptors from type 1 - motif 1 spans ~1/3 of the N-terminal
hydrophilic domain; motif 2 lies within the third putative extracellular
domain; motif 3 encodes the fifth extracellular domain; and motif 4 lies
within the first putative nucleotide binding fold. Two iterations on OWL31.1
were required to reach convergence, at which point a true set comprising 8
sequences was identified.
 
An update on SPTR37_9f identified a true set of 8 sequences.
Summary Information
8 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
48888
30000
20000
1234
True Positives
O08902        O08920        O60706        O60707        
O89115 P70170 P70171 Q63563
Sequence Titles
O08902      SULFONYLUREA RECEPTOR 2A - MUS MUSCULUS (MOUSE). 
O08920 SULFONYLUREA RECEPTOR 2B - MUS MUSCULUS (MOUSE).
O60706 SULFONYLUREA RECEPTOR 2A - HOMO SAPIENS (HUMAN).
O60707 SULFONYLUREA RECEPTOR 2B - HOMO SAPIENS (HUMAN).
O89115 SULFONYLUREA RECEPTOR 2B - RATTUS NORVEGICUS (RAT).
P70170 SULFONYLUREA RECEPTOR 2A - MUS MUSCULUS (MOUSE).
P70171 SULFONYLUREA RECEPTOR 2B - MUS MUSCULUS (MOUSE).
Q63563 SULFONYLUREA RECEPTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  150  NSINGLE    
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
NNISSYNIY RATSURES1 8 8 -
NNISSYNIY MMU97066 8 8 -
NNISSYNIY MMAF003531 8 8 -
NNISSYNIY D86037 8 8 -
NNISSYNIY AF019628 8 8 -
NNISSYNIY D86038 8 8 -

Motif 2 width=9
Element Seqn Id St Int Rpt
VCLKEAYEE RATSURES1 262 245 -
VCLKEAYEE MMU97066 262 245 -
VCLKEAYEE MMAF003531 262 245 -
VCLKEAYEE D86037 262 245 -
VCLKEAYEE AF019628 262 245 -
VCLKEAYEE D86038 262 245 -

Motif 3 width=14
Element Seqn Id St Int Rpt
THAYASGNNLKPAE RATSURES1 554 283 -
THAYASGNNLKPAE MMU97066 555 284 -
THAYASGNNLKPAE MMAF003531 555 284 -
THAYASGNNLKPAE D86037 555 284 -
THAYASGNNLKPAE AF019628 554 283 -
THAYASGNNLKPAE D86038 555 284 -

Motif 4 width=19
Element Seqn Id St Int Rpt
NVNESEPSFEATRSRSRYS RATSURES1 729 161 -
NVNESEPSFEATRSRSRYS MMU97066 730 161 -
NVNESEPSFEATRSRSRYS MMAF003531 695 126 -
NVNESEPSFEATRSRSRYS D86037 730 161 -
NVNESEPSFEATRSRSRYS AF019628 729 161 -
NVNESEPSFEATRSRSRYS D86038 730 161 -
Final Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
NNISSYNIY O08902 8 8 -
NNISSYNIY Q63563 8 8 -
NNISSYNIY P70171 8 8 -
NNISSYNIY P70170 8 8 -
NNISSYNIY O89115 8 8 -
NNISSYNIY O08920 8 8 -
NNISSYNIN O60706 8 8 -
NNISSYNIN O60707 8 8 -

Motif 2 width=9
Element Seqn Id St Int Rpt
VCLKEAYEE O08902 262 245 -
VCLKEAYEE Q63563 262 245 -
VCLKEAYEE P70171 262 245 -
VCLKEAYEE P70170 262 245 -
VCLKEAYEE O89115 262 245 -
VCLKEAYEE O08920 262 245 -
VCLKDAYEE O60706 262 245 -
VCLKDAYEE O60707 262 245 -

Motif 3 width=14
Element Seqn Id St Int Rpt
THAYASGNNLKPAE O08902 555 284 -
THAYASGNNLKPAE Q63563 554 283 -
THAYASGNNLKPAE P70171 555 284 -
THAYASGNNLKPAE P70170 555 284 -
THAYASGNNLKPAE O89115 554 283 -
THAYASGNNLKPAE O08920 555 284 -
THAYASGNNLKPAE O60706 557 286 -
THAYASGNNLKPAE O60707 557 286 -

Motif 4 width=19
Element Seqn Id St Int Rpt
NVNESEPSFEATRSRSRYS O08902 695 126 -
NVNESEPSFEATRSRSRYS Q63563 729 161 -
NVNESEPSFEATRSRSRYS P70171 730 161 -
NVNESEPSFEATRSRSRYS P70170 730 161 -
NVNESEPSFEATRSRSRYS O89115 729 161 -
NVNESEPSFEATRSRSRYS O08920 730 161 -
NVNESEPSFEATRSRNRYS O60706 733 162 -
NVNESEPSFEATRSRNRYS O60707 733 162 -