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PR00514

Identifier
5HT1DRECEPTR  [View Relations]  [View Alignment]  
Accession
PR00514
No. of Motifs
5
Creation Date
04-JUN-1996  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 1D receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR000505
GCRDB; GCR_0184; GCR_0356; GCR_0309; GCR_0016
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.
5-Hydroxytryptamine.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.159-180.

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]. 
 
5-Hydroxytryptamine (or serotonin) is ubiquitous in plants and animals.
It is an important neurotransmitter and local hormone in the CNS and
instestine, and is implicated in a vast array of physiological and patho-
physiological pathways [6]. In the periphery, 5HT contracts a number of
smooth muscles, and induces endothelium-dependent vasodilation through
the formation of NO [6]. It is a mediator of peristalsis, and may be
involved in platelet aggregation and homeostasis. In the CNS, 5HT is
believed to be involved in a wide range of functions, including the
control of appetite, mood, anxiety, hallucinations, sleep, vomiting and
pain perception [6]. 5HT receptor ligands are of clinical use in the
treatment of depression, migraine and post-operative vomiting.
 
Numerous receptor subtypes have been classified according to their
antagonist susceptibilities and their affinities for 5HT. Five 5HT1
subtypes and at least three 5HT2 subtypes have now been identified, in
addition to subtypes 5HT3-7 [6]. All share a high degree of sequence
similarity, and have overlapping pharmacological specificities.
 
5HT1-like receptors were originally classified according to their nano-
molar affinity for 5HT, susceptibility to antagonism by methiothepin and/or
methysegide, resistance to antagonism by 5HT2 and 5HT3 antagonists, and
high affinity for the agonist 5-carboxamidotryptamine [6]. Five subtypes
of 5HT1-like receptors have now been identified - these do not fit all the
above criteria, and 5HT1C has been reclassified 5HT2C [6]. All are linked
to the inhibition of adenylyl cyclase, share a high degree of sequence
similarity, and have overlapping pharmacological specificities.
 
Human 5HT1D and 5HT1B receptors share virtually identical pharmacological
profiles, and no selective ligands have been described [6]. 5HT1D receptors
are found in neurons in the CNS, and in vascular smooth muscles in the
periphery. 5HT1D/5HT1B receptors may be the therapeutic substrate of the
anti-migraine drug, sumatriptan; these sites are also implicated in feeding
behaviour, anxiety, depression, cardiac function and movement [6].
 
5HT1DRECEPTR is a 5-element fingerprint that provides a signature for the
5HT1D receptors. The fingerprint was derived from an initial alignment of
4 sequences: the motifs were drawn from conserved sections within either
loop or N-terminal regions, focusing on those areas of the alignment that
characterise the 5HT1D receptors but distinguish them from the rest of the
5HT family - motifs 1 and 2 lie at the N-terminus; and motifs 3-5 lie in the 
third cytoplasmic loop. Two iterations on OWL28.0 were required to reach 
convergence, at which point a true set comprising 6 sequences was identified.
Two partial matches were also found (S45394 and S45399), both of which are
C-terminal fragments.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
566666
400000
300000
200000
12345
True Positives
5H1D_CANFA    5H1D_CAVPO    5H1D_HUMAN    5H1D_MOUSE    
5H1D_RABIT 5H1D_RAT
Sequence Titles
5H1D_CANFA  5-HYDROXYTRYPTAMINE 1D RECEPTOR (5-HT-1D) (SEROTONIN RECEPTOR) - CANIS FAMILIARIS (DOG). 
5H1D_CAVPO 5-HYDROXYTRYPTAMINE 1D RECEPTOR (5-HT-1D) (SEROTONIN RECEPTOR) - CAVIA PORCELLUS (GUINEA PIG).
5H1D_HUMAN 5-HYDROXYTRYPTAMINE 1D RECEPTOR (5-HT-1D) (SEROTONIN RECEPTOR) (5-HT-1D-ALPHA) - HOMO SAPIENS (HUMAN).
5H1D_MOUSE 5-HYDROXYTRYPTAMINE 1D RECEPTOR (5-HT-1D) (SEROTONIN RECEPTOR) - MUS MUSCULUS (MOUSE).
5H1D_RABIT 5-HYDROXYTRYPTAMINE 1D RECEPTOR (5-HT-1D) (SEROTONIN RECEPTOR) (5-HT-1D-ALPHA) - ORYCTOLAGUS CUNICULUS (RABBIT).
5H1D_RAT 5-HYDROXYTRYPTAMINE 1D RECEPTOR (5-HT-1D) (SEROTONIN RECEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_0    2  150  NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
NQSAEGLPQEASNRSLNAT 5H1D_HUMAN 5 5 -
NQSLEGLPQEASNRSLNAT 5H1D_RAT 5 5 -
NQSAEGLPQEAANRSLNAT 5H1D_RABIT 5 5 -
NQSLEGLLQEASNRSLNAT 5H1D_CANFA 5 5 -

Motif 2 width=15
Element Seqn Id St Int Rpt
AWDPRTLQALKISLA 5H1D_HUMAN 28 4 -
AWDPEVLQALRISLV 5H1D_RAT 25 1 -
AWDPGTLQALKISLA 5H1D_RABIT 28 4 -
AWGPETLQALKISLA 5H1D_CANFA 28 4 -

Motif 3 width=19
Element Seqn Id St Int Rpt
PPSLYGKRFTTAHLITGSA 5H1D_HUMAN 231 188 -
PPSLYGKRFTTAQLITGSA 5H1D_RAT 228 188 -
PPSLYGKRFTTAHLITGSA 5H1D_RABIT 231 188 -
PPSLYGKRFTTAQLITGSA 5H1D_CANFA 231 188 -

Motif 4 width=14
Element Seqn Id St Int Rpt
GSSLCSLNSSLHEG 5H1D_HUMAN 250 0 -
GSSLCSLNPSLHES 5H1D_RAT 247 0 -
GSSLCSLSPSLGEG 5H1D_RABIT 250 0 -
GSSLCSLSPSLQEE 5H1D_CANFA 250 0 -

Motif 5 width=11
Element Seqn Id St Int Rpt
HSHSAGSPLFF 5H1D_HUMAN 264 0 -
HTHTVGSPLFF 5H1D_RAT 261 0 -
HSHSAGSPLFF 5H1D_RABIT 264 0 -
RSHAAGPPLFF 5H1D_CANFA 264 0 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
NQSAEGLPQEASNRSLNAT 5H1D_HUMAN 5 5 -
NQSLEGLPQEASNRSLNAT 5H1D_MOUSE 5 5 -
NQSLEGLPQEASNRSLNAT 5H1D_RAT 5 5 -
NQSAEGLPQEAANRSLNAT 5H1D_RABIT 5 5 -
NQSLEGLLQEASNRSLNAT 5H1D_CANFA 5 5 -
NQSEEGLPQEASNRSLNAT 5H1D_CAVPO 5 5 -

Motif 2 width=15
Element Seqn Id St Int Rpt
AWDPRTLQALKISLA 5H1D_HUMAN 28 4 -
AWDPEVLQALRISLV 5H1D_MOUSE 25 1 -
AWDPEVLQALRISLV 5H1D_RAT 25 1 -
AWDPGTLQALKISLA 5H1D_RABIT 28 4 -
AWGPETLQALKISLA 5H1D_CANFA 28 4 -
DWDPGLLQALKVSLV 5H1D_CAVPO 28 4 -

Motif 3 width=19
Element Seqn Id St Int Rpt
PPSLYGKRFTTAHLITGSA 5H1D_HUMAN 231 188 -
PPSLYGKRFTTAQLITGSA 5H1D_MOUSE 228 188 -
PPSLYGKRFTTAQLITGSA 5H1D_RAT 228 188 -
PPSLYGKRFTTAHLITGSA 5H1D_RABIT 231 188 -
PPSLYGKRFTTAQLITGSA 5H1D_CANFA 231 188 -
PPSLSGKRFTTAHLITGSA 5H1D_CAVPO 231 188 -

Motif 4 width=14
Element Seqn Id St Int Rpt
GSSLCSLNSSLHEG 5H1D_HUMAN 250 0 -
GSSLCSLNPSLHES 5H1D_MOUSE 247 0 -
GSSLCSLNPSLHES 5H1D_RAT 247 0 -
GSSLCSLSPSLGEG 5H1D_RABIT 250 0 -
GSSLCSLSPSLQEE 5H1D_CANFA 250 0 -
GSSLCSLNPSLHEG 5H1D_CAVPO 250 0 -

Motif 5 width=11
Element Seqn Id St Int Rpt
HSHSAGSPLFF 5H1D_HUMAN 264 0 -
HTHTVGSPLFF 5H1D_MOUSE 261 0 -
HTHTVGSPLFF 5H1D_RAT 261 0 -
HSHSAGSPLFF 5H1D_RABIT 264 0 -
RSHAAGPPLFF 5H1D_CANFA 264 0 -
GHMHPGSPLFF 5H1D_CAVPO 263 -1 -