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PR01092

Identifier
SULFNYLUREAR  [View Relations]  [View Alignment]  
Accession
PR01092
No. of Motifs
5
Creation Date
25-FEB-1999  (UPDATE 07-JUN-1999)
Title
Sulphonylurea receptor family signature
Database References
PRINTS; PR01093 SULFNYLUR1; PR01094 SULFNYLUR2
PRODOM; PD005222; PD005248; PD005449
INTERPRO; IPR000388
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 SUR1 may associate with
the inward rectifier subunit Kir6.2 to form the pancreatic beta cell KATP 
channel. Splice variants of SUR2 (termed SUR2A and SUR2B) may form the
cardiac and smooth muscle isoforms, respectively, again when combined with
Kir 6.2. This co-assembly likely occurs with an obligate 4:4 stoichiometry,
giving rise to an octameric channel.
 
Mutations in SUR genes have been characterised; these can result in
truncations of the second predicted nucleotide binding fold, leading to
persistent hyperinsulinemic hypoglycaemia of infancy, a rare familial
disorder characterised by excessive, unregulated insulin secretion.
 
SULFNYLUREAR is a 5-element fingerprint that provides a signature for the 
sulphonylurea receptor family. The fingerprint was derived from an initial
alignment of 13 sequences: the motifs were drawn from the N-terminal 380
residues of the molecule - motif 1 spans part of the N-terminal putative
extracellular domain and TM domain 1; motif 2 lies within the first
cytoplasmic loop; motif 3 encodes part of the second extracellular loop;
motif 4 lies at the N-terminus of the third extracellular loop; and motif 
5 spans TM domain 6 and the following extracellular loop. Two iterations on 
OWL31.1 were required to reach convergence, at which point a true set
comprising 17 sequences was identified.
 
An update on SPTR37_9f identified a true set of 15 sequences.
Summary Information
15 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51515151515
400000
300000
200000
12345
True Positives
O08902        O08920        O54989        O60706        
O60707 O75948 O89115 P70170
P70171 P70532 Q16583 Q63563
SUR_CRICR SUR_HUMAN SUR_RAT
Sequence Titles
O08902      SULFONYLUREA RECEPTOR 2A - MUS MUSCULUS (MOUSE). 
O08920 SULFONYLUREA RECEPTOR 2B - MUS MUSCULUS (MOUSE).
O54989 SULFONYLUREA RECEPTOR 1B - RATTUS NORVEGICUS (RAT).
O60706 SULFONYLUREA RECEPTOR 2A - HOMO SAPIENS (HUMAN).
O60707 SULFONYLUREA RECEPTOR 2B - HOMO SAPIENS (HUMAN).
O75948 SULFONYLUREA RECEPTOR 1 - HOMO SAPIENS (HUMAN).
O89115 SULFONYLUREA RECEPTOR 2B - RATTUS NORVEGICUS (RAT).
P70170 SULFONYLUREA RECEPTOR 2A - MUS MUSCULUS (MOUSE).
P70171 SULFONYLUREA RECEPTOR 2B - MUS MUSCULUS (MOUSE).
P70532 SULFONYLUREA RECEPTOR - RATTUS NORVEGICUS (RAT).
Q16583 SULFONYLUREA RECEPTOR - HOMO SAPIENS (HUMAN).
Q63563 SULFONYLUREA RECEPTOR - RATTUS NORVEGICUS (RAT).
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 16 NSINGLE
Initial Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
GCFVDALNVVPHVFLLFITFPILFIGWG A56248 25 25 -
GCFVDVLNVVPHVFLLFITFPILFIGWG SUR_HUMAN 24 24 -
GCFVDALNVVPHVFLLFITFPILFIGWG SUR_RAT 24 24 -
GCFVDALNVVPHVFLLFITFPILFIGWG SUR_CRICR 24 24 -
PCFVDALNLVPHVFLLFITFPILFIGWG AF019628 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG MMU97066 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG RATSURES1 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG MMAF003531 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG D86037 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG D86038 23 23 -
GCFVDALNVVPHVFLLFITFPILFIGWG RNSULFUR 25 25 -
GCFVDALNVVPHVFLLFITFPILFIGWG AF039595 25 25 -
GCFVDALNVVPHVFLLFITFPILFIGWG AF087138 25 25 -

Motif 2 width=15
Element Seqn Id St Int Rpt
WLHFPGHNLRWILTF MMAF003531 63 12 -
WLHFPGHNLRWILTF D86037 63 12 -
WLHFPGHNLRWILTF D86038 63 12 -
WLHFPGHNLRWILTF RNSULFUR 65 12 -
WLHFPGHNLRWILTF AF039595 65 12 -
WLHFPGHNLRWILTF AF087138 65 12 -
WLHFPGHNLRWILTF A56248 65 12 -
WLHFPGHNLRWILTF SUR_HUMAN 64 12 -
WLHFPGHNLRWILTF SUR_RAT 64 12 -
WLHFPGHNLRWILTF SUR_CRICR 64 12 -
WLHFPGHNLRWILTF RATSURES1 63 12 -
WLHFPGHNLRWILTF AF019628 63 12 -
WLHFPGHNLRWILTF MMU97066 63 12 -

Motif 3 width=15
Element Seqn Id St Int Rpt
VYYHNIETSNFPKLL RNSULFUR 122 42 -
VYYHNIETSNFPKLL SUR_HUMAN 121 42 -
VYYHNIETSNFPKLL SUR_RAT 121 42 -
VYYHNIETSNFPKLL SUR_CRICR 121 42 -
VYYHNIETSNFPKLL AF039595 122 42 -
VYYHNIETSNFPKLL AF087138 122 42 -
VYYHNIETSNFPKLL A56248 122 42 -
VYYHNIETSNFPKLL RATSURES1 120 42 -
VYYHNIETSNFPKLL AF019628 120 42 -
VYYHNIETSNFPKLL MMU97066 120 42 -
VYYHNIETSNFPKLL MMAF003531 120 42 -
VYYHNIETSNFPKLL D86037 120 42 -
VYYHNIETSNFPKLL D86038 120 42 -

Motif 4 width=24
Element Seqn Id St Int Rpt
VKPPEDLQDLGVRFLQPFVNLLSK MMU97066 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK RATSURES1 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK AF019628 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK MMAF003531 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK D86037 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK D86038 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK RNSULFUR 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK AF039595 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK AF087138 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK A56248 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK SUR_CRICR 203 67 -
VKPPEDLQDLGVRFLQPFVNLLSK SUR_RAT 203 67 -
VKPPEDLQDLGVRFLQPFVNLLSK SUR_HUMAN 203 67 -

Motif 5 width=23
Element Seqn Id St Int Rpt
VLAVLLFLALLLQRTFLQASYYV RNSULFUR 357 129 -
VLAVLLFLALILQRTFLQASYYV D86038 351 125 -
VLAVLLFLALILQRTFLQASYYV D86037 351 125 -
VLAVLLFLALILQRTFLQASYYV MMAF003531 351 125 -
VLAVLLFLALILQRTFLQASYYV MMU97066 351 125 -
VLAVLLFLALILQRTFLQASYYV AF019628 350 124 -
VLAVLLFLALILQRTFLQASYYV RATSURES1 350 124 -
VLAVLLFLALLLQRTFLQASYYV SUR_CRICR 356 129 -
VLAVLLFLALLLQRTFLQASYYV SUR_RAT 356 129 -
VLAVLLFLALLLQRTFLQASYYV SUR_HUMAN 356 129 -
VLAVLLFLALLLQRTFLQASYYV A56248 357 129 -
VLAVLLFLALLLQRTFLQASYYV AF087138 357 129 -
VLAVLLFLALLLQRTFLQASYYV AF039595 357 129 -
Final Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
PCFVDALNLVPHVFLLFITFPILFIGWG O08902 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG Q63563 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG P70171 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG P70170 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG O89115 23 23 -
PCFVDALNLVPHVFLLFITFPILFIGWG O08920 23 23 -
GCFVDALNVVPHVFLLFITFPILFIGWG O54989 25 25 -
GCFVDALNVVPHVFLLFITFPILFIGWG O75948 25 25 -
GCFVDALNVVPHVFLLFITFPILFIGWG P70532 25 25 -
GCFVDALNVVPHVFLLFITFPILFIGWG SUR_CRICR 24 24 -
GCFVDALNVVPHVFLLFITFPILFIGWG SUR_RAT 24 24 -
SCFVDALNLVPHVFLLFITFPILFIGWG O60706 23 23 -
SCFVDALNLVPHVFLLFITFPILFIGWG O60707 23 23 -
GCFVDVLNVVPHVFLLFITFPILFIGWG SUR_HUMAN 24 24 -
GCFVDALNVVPHVFLLFITFPILFIGWG Q16583 25 25 -

Motif 2 width=15
Element Seqn Id St Int Rpt
WLHFPGHNLRWILTF O08902 63 12 -
WLHFPGHNLRWILTF Q63563 63 12 -
WLHFPGHNLRWILTF P70171 63 12 -
WLHFPGHNLRWILTF P70170 63 12 -
WLHFPGHNLRWILTF O89115 63 12 -
WLHFPGHNLRWILTF O08920 63 12 -
WLHFPGHNLRWILTF O54989 65 12 -
WLHFPGHNLRWILTF O75948 65 12 -
WLHFPGHNLRWILTF P70532 65 12 -
WLHFPGHNLRWILTF SUR_CRICR 64 12 -
WLHFPGHNLRWILTF SUR_RAT 64 12 -
WLHFPGHNLRWILTF O60706 63 12 -
WLHFPGHNLRWILTF O60707 63 12 -
WLHFPGHNLRWILTF SUR_HUMAN 64 12 -
WLHFPGHNLRWILTF Q16583 65 12 -

Motif 3 width=15
Element Seqn Id St Int Rpt
VYYHNIETSNFPKLL O08902 120 42 -
VYYHNIETSNFPKLL Q63563 120 42 -
VYYHNIETSNFPKLL P70171 120 42 -
VYYHNIETSNFPKLL P70170 120 42 -
VYYHNIETSNFPKLL O89115 120 42 -
VYYHNIETSNFPKLL O08920 120 42 -
VYYHNIETSNFPKLL O54989 122 42 -
VYYHNIETSNFPKLL O75948 122 42 -
VYYHNIETSNFPKLL P70532 122 42 -
VYYHNIETSNFPKLL SUR_CRICR 121 42 -
VYYHNIETSNFPKLL SUR_RAT 121 42 -
VYYHNIETSNFPKLL O60706 120 42 -
VYYHNIETSNFPKLL O60707 120 42 -
VYYHNIETSNFPKLL SUR_HUMAN 121 42 -
VYYHNIETSNFPKLL Q16583 122 42 -

Motif 4 width=24
Element Seqn Id St Int Rpt
VKPPEDLQDLGVRFLQPFVNLLSK O08902 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK Q63563 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK P70171 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK P70170 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK O89115 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK O08920 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK O54989 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK O75948 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK P70532 204 67 -
VKPPEDLQDLGVRFLQPFVNLLSK SUR_CRICR 203 67 -
VKPPEDLQDLGVRFLQPFVNLLSK SUR_RAT 203 67 -
VKPPEDLQDLGVRFLQPFVNLLSK O60706 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK O60707 202 67 -
VKPPEDLQDLGVRFLQPFVNLLSK SUR_HUMAN 203 67 -
VKPPEDLQDLGVRFLQPFVNLPSK Q16583 204 67 -

Motif 5 width=23
Element Seqn Id St Int Rpt
VLAVLLFLALILQRTFLQASYYV O08902 351 125 -
VLAVLLFLALILQRTFLQASYYV Q63563 350 124 -
VLAVLLFLALILQRTFLQASYYV P70171 351 125 -
VLAVLLFLALILQRTFLQASYYV P70170 351 125 -
VLAVLLFLALILQRTFLQASYYV O89115 350 124 -
VLAVLLFLALILQRTFLQASYYV O08920 351 125 -
VLAVLLFLALLLQRTFLQASYYV O54989 357 129 -
VLAVLLFLALLLQRTFLQASYYV O75948 357 129 -
VLAVLLFLALLLQRTFLQASYYV P70532 357 129 -
VLAVLLFLALLLQRTFLQASYYV SUR_CRICR 356 129 -
VLAVLLFLALLLQRTFLQASYYV SUR_RAT 356 129 -
VLAVLLFLALILQRTFLQASYYV O60706 353 127 -
VLAVLLFLALILQRTFLQASYYV O60707 353 127 -
VLAVLLFLALLLQRTFLQASYYV SUR_HUMAN 356 129 -
VLAVLLFLALLLQRTFLQASYYV Q16583 357 129 -