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PR00570

Identifier
ENDOTHELINAR  [View Relations]  [View Alignment]  
Accession
PR00570
No. of Motifs
7
Creation Date
10-SEP-1996  (UPDATE 14-JUN-1999)
Title
Endothelin-A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00366 ENDOTHELINR
INTERPRO; IPR002175
GCRDB; GCR_0403; GCR_O473; GCR_0491; GCR_0512; GCR_0602; GCR_0727

GCRDB; GCR_0737
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. WATSON, S. AND ARKINSTALL, S.
Endothelin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp111-116.

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that 
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the 
sequence level, on the basis of which they can be separated into distinct 
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship, 
but between which there is no statistically significant similarity in 
sequence [1]. The currently known clan members include the rhodopsin-like 
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
 
The rhodopsin-like GPCRs themselves represent a widespread protein family 
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary 
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural 
framework comprising 7 transmembrane (TM) helices [3-5]. 
 
Endothelins play an important role in the regulation of the cardiovascular
system [6]. They are the most potent vasoconstrictors identified, they
stimulate cardiac contraction, regulate release of vasoactive substances,
and stimulate mitogenesis in blood vessels in primary culture. They also
stimulate contraction in almost all other smooth muscles (e.g., uterus,
bronchus, vas deferens, stomach) and stimulate secretion in several tissues
(e.g., kidney, liver and adrenals) [6]. Endothelin receptors have also been
found in the brain (e.g., in the cerebral cortex, cerebellum and glial
cells). Endothelins have been implicated in a variety of pathophysiological
conditions associated with stress [6].
 
The ETA receptor is the predominant type of endothelin receptor [6]. It
mediates contraction in blood vessels, bronchus, uterus and heart; it also
inhibits aldosterone secretion. The receptors have been identified in glial
cells in the CNS. They activate the phosphoinositide pathway through a
pertussis-toxin-insensitive G protein, probably of the Gq/G11 class [6].
 
ENDOTHELINAR is a 7-element fingerprint that provides a signature for
the endothelin-A receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections   
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the endothelin-A receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs
1-3 span the N-terminus; motif 4 spans the first external loop; motif 5
spans the second external loop; and motifs 6 and 7 lie at the C-terminus.
A single iteration on OWL28.1 was required to reach convergence, no further
sequences being identified beyond the starting set. A single partial match
was also found, A54126, an endothelin AX-receptor that matches motifs 4-7.
 
An update on SPTR37_9f identified a true set of 6 sequences, and 2
partial matches.
Summary Information
   6 codes involving  7 elements
0 codes involving 6 elements
1 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
76666666
60000000
51110011
41111000
30000000
20000000
1234567
True Positives
ET1R_BOVIN    ET1R_HUMAN    ET1R_PIG      ET1R_RAT      
O73739 Q91548
True Positive Partials
Codes involving 5 elements
Q16433
Codes involving 4 elements
Q16432
Sequence Titles
ET1R_BOVIN  ENDOTHELIN-1 RECEPTOR PRECURSOR (ET-A) - BOS TAURUS (BOVINE). 
ET1R_HUMAN ENDOTHELIN-1 RECEPTOR PRECURSOR (ET-A) - HOMO SAPIENS (HUMAN).
ET1R_PIG ENDOTHELIN-1 RECEPTOR PRECURSOR (ET-A) - SUS SCROFA (PIG).
ET1R_RAT ENDOTHELIN-1 RECEPTOR PRECURSOR (ET-A) - RATTUS NORVEGICUS (RAT).
O73739 ENDOTHELIN TYPE A RECEPTOR - GALLUS GALLUS (CHICKEN).
Q91548 ENDOTHELIN RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).

Q16433 ENDOTHELIN-A RECEPTOR DELTA 3-4 - HOMO SAPIENS (HUMAN).

Q16432 ENDOTHELIN-A RECEPTOR DELTA 4 - HOMO SAPIENS (HUMAN).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 4 100 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
ASFWLALVGGAIADNAERY ET1R_RAT 8 8 -
LSFWVALVGGVISDNPESY ET1R_BOVIN 8 8 -
ASFWLALVGCVISDNPERY ET1R_HUMAN 8 8 -
VSFWVALLGCVISDNPESH S80652 8 8 -
ASFWLALVGCVISDNPERY HUMEDNRA 8 8 -

Motif 2 width=18
Element Seqn Id St Int Rpt
STNLSNHVDDFTTFRGTE ET1R_HUMAN 27 0 -
STNLSNHVDDFTTFRGTE HUMEDNRA 27 0 -
STNLSTHVDDFTTFRGTE S80652 27 0 -
STNLSIHVDSVATFHGTE ET1R_BOVIN 27 0 -
SANLSSHVEDFTPFPGTE ET1R_RAT 27 0 -

Motif 3 width=19
Element Seqn Id St Int Rpt
NLVLPSNGSMHNYCPQQTK ET1R_HUMAN 56 11 -
NLALPSNGSMHNYCPQQTK S80652 56 11 -
NLVLPSNGSMHNYCPQQTK HUMEDNRA 56 11 -
NLALPSNGSMHGYCPQQTK ET1R_RAT 56 11 -
NLALPSNGSMHNYCPQQTK ET1R_BOVIN 56 11 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GRWPFDHNDFGVFLC HUMEDNRA 144 69 -
GRWPFDHNDFGVFLC ET1R_RAT 144 69 -
GRWPFEQNDFGVFLC ET1R_BOVIN 144 69 -
GRWPFDHNDFGVFLC ET1R_HUMAN 144 69 -
GRWPFENHDFGVFLC S80652 144 69 -

Motif 5 width=20
Element Seqn Id St Int Rpt
KTCMLNATSKFMEFYQDVKD S80652 237 78 -
KTCMLNATSKFMEFYQDVKD ET1R_HUMAN 237 78 -
RTCMLNATSKFMEFYQDVKD ET1R_BOVIN 237 78 -
RTCMLNATTKFMEFYQDVKD ET1R_RAT 237 78 -
KTCMLNATSKFMEFYQDVKD HUMEDNRA 237 78 -

Motif 6 width=20
Element Seqn Id St Int Rpt
QSKSLMTSVPMNGTSIQWKN S80652 390 133 -
QSKSLMTSVPMNGTSIQWKN ET1R_RAT 390 133 -
QSKSLMTSVPMNGTSIQWKN HUMEDNRA 390 133 -
QSKSLMTSVPMNGTSIQWKN ET1R_HUMAN 390 133 -
QSKSLMTSVPMNGTSIQWKN ET1R_BOVIN 390 133 -

Motif 7 width=15
Element Seqn Id St Int Rpt
QNNHNTDRSSHKDSM HUMEDNRA 412 2 -
EQNHNTERSSHKDSM ET1R_RAT 411 1 -
QNNHNTDRSSHKDSM ET1R_HUMAN 412 2 -
QNNHNTERSSHKDSI ET1R_BOVIN 412 2 -
QNNHNTERSSHKDSI S80652 412 2 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
ASFWLALVGCVISDNPERY ET1R_HUMAN 8 8 -
VSFWVALLGCVISDNPESH ET1R_PIG 8 8 -
LSFWVALVGGVISDNPESY ET1R_BOVIN 8 8 -
ASFWLALVGGAIADNAERY ET1R_RAT 8 8 -
VSSLLLLLGFVLCDSSDKY O73739 8 8 -
LRFTVLLVLAGIAVSSSFG Q91548 6 6 -

Motif 2 width=18
Element Seqn Id St Int Rpt
STNLSNHVDDFTTFRGTE ET1R_HUMAN 27 0 -
STNLSTHVDDFTTFRGTE ET1R_PIG 27 0 -
STNLSIHVDSVATFHGTE ET1R_BOVIN 27 0 -
SANLSSHVEDFTPFPGTE ET1R_RAT 27 0 -
ATNWSDVGIYLPTSSGIE O73739 27 0 -
YQNRTDASTDFTMLNRSH Q91548 27 2 -

Motif 3 width=19
Element Seqn Id St Int Rpt
NLVLPSNGSMHNYCPQQTK ET1R_HUMAN 56 11 -
NLALPSNGSMHNYCPQQTK ET1R_PIG 56 11 -
NLALPSNGSMHNYCPQQTK ET1R_BOVIN 56 11 -
NLALPSNGSMHGYCPQQTK ET1R_RAT 56 11 -
TTRRPPVSNQTVKCSQQTK O73739 50 5 -
TSPVRKGNRSADLCPEKTK Q91548 45 0 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GRWPFDHNDFGVFLC ET1R_HUMAN 144 69 -
GRWPFENHDFGVFLC ET1R_PIG 144 69 -
GRWPFEQNDFGVFLC ET1R_BOVIN 144 69 -
GRWPFDHNDFGVFLC ET1R_RAT 144 69 -
QKWPFGDSEFGQFLC O73739 138 69 -
QRWPFDQSPVGAFLC Q91548 133 69 -

Motif 5 width=20
Element Seqn Id St Int Rpt
KTCMLNATSKFMEFYQDVKD ET1R_HUMAN 237 78 -
KTCMLNATSKFMEFYQDVKD ET1R_PIG 237 78 -
RTCMLNATSKFMEFYQDVKD ET1R_BOVIN 237 78 -
RTCMLNATTKFMEFYQDVKD ET1R_RAT 237 78 -
VTCMLNPTNKFMLFYKDAKD O73739 231 78 -
RTCMFHATSPFMMFYKNAKD Q91548 226 78 -

Motif 6 width=20
Element Seqn Id St Int Rpt
QSKSLMTSVPMNGTSIQWKN ET1R_HUMAN 390 133 -
QSKSLMTSVPMNGTSIQWKN ET1R_PIG 390 133 -
QSKSLMTSVPMNGTSIQWKN ET1R_BOVIN 390 133 -
QSKSLMTSVPMNGTSIQWKN ET1R_RAT 390 133 -
QSKSLATSVPMNGTSIQWKN O73739 384 133 -
QSKTHINTAPMNVTSIQWKN Q91548 378 132 -

Motif 7 width=15
Element Seqn Id St Int Rpt
QNNHNTDRSSHKDSM ET1R_HUMAN 412 2 -
QNNHNTERSSHKDSI ET1R_PIG 412 2 -
QNNHNTERSSHKDSI ET1R_BOVIN 412 2 -
EQNHNTERSSHKDSM ET1R_RAT 411 1 -
LNNHNTDRSSHKDSI O73739 406 2 -
QNYYGADRSIHKDSI Q91548 400 2 -