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PR00513

Identifier
5HT1BRECEPTR  [View Relations]  [View Alignment]  
Accession
PR00513
No. of Motifs
5
Creation Date
04-JUN-1996  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 1B receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR002147
GCRDB; GCR_0286; GCR_0282; GCR_0311; GCR_0301; GCR_0357; GCR_0382

GCRDB; GCR_0399
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.
 
The 5HT1B receptor was first identified in rats, where it has a distinct
pharmacological profile [6]. In humans, however, it shares an almost
identical pharmacology with the 5HT1D receptor. In the CNS, the receptor
is found in the striatum, medulla, hippocampus, frontal cortex and
amygdala. In the periphery, it is found in vascular smooth muscle [6].
The 5HT1B/5HT1D receptor 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].
 
5HT1BRECEPTR is a 5-element fingerprint that provides a signature for the
5HT1B receptors. The fingerprint was derived from an initial alignment of
5 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 5HT1B 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 7 sequences was identified. 
A single partial match was also found (5H1D_RAT), a 5HT1D receptor that
matches motifs 3 and 5.
 
An update on SPTR37_9f identified a true set of 7 sequences, and 1
partial match.
Summary Information
   7 codes involving  5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
577777
401111
300000
200000
12345
True Positives
5H1B_CRIGR    5H1B_DIDMA    5H1B_HUMAN    5H1B_MOUSE    
5H1B_RABIT 5H1B_RAT 5H1B_SPAEH
True Positive Partials
Codes involving 4 elements
5H1B_CAVPO
Sequence Titles
5H1B_CRIGR  5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) - CRICETULUS GRISEUS (CHINESE HAMSTER). 
5H1B_DIDMA 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) - DIDELPHIS MARSUPIALIS VIRGINIANA (NORTH AMERICAN OPOSSUM).
5H1B_HUMAN 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) (5-HT-1D-BETA) (S12) - HOMO SAPIENS (HUMAN).
5H1B_MOUSE 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) - MUS MUSCULUS (MOUSE).
5H1B_RABIT 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) (5-HT-1D-BETA) - ORYCTOLAGUS CUNICULUS (RABBIT).
5H1B_RAT 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) - RATTUS NORVEGICUS (RAT).
5H1B_SPAEH 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) - SPALAX LEUCODON EHRENBERGI (EHRENBERG'S MOLE RAT).

5H1B_CAVPO 5-HYDROXYTRYPTAMINE 1B RECEPTOR (5-HT-1B) (SEROTONIN RECEPTOR) (5-HT1B RECEPTOR) - CAVIA PORCELLUS (GUINEA PIG).
Scan History
OWL28_0    2  100  NSINGLE    
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
EEQGIQCAPPPP 5H1B_MOUSE 2 2 -
EEQGIQCAPPPP 5H1B_CRIGR 2 2 -
EEPGAQCAPPPP 5H1B_HUMAN 2 2 -
EEPGAQCAPPLA 5H1B_RABIT 2 2 -
EQPSRLCSPPAS 5H1B_DIDMA 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
YQDSIALPWKVLL 5H1B_MOUSE 36 22 -
YQDSIALPWKVLL 5H1B_CRIGR 36 22 -
YQDSISLPWKVLL 5H1B_HUMAN 40 26 -
YQDSIALPWKVLL 5H1B_RABIT 40 26 -
YQDSIALPWKVLL 5H1B_DIDMA 39 25 -

Motif 3 width=17
Element Seqn Id St Int Rpt
QTPNKTGKRLTRAQLIT 5H1B_MOUSE 238 189 -
QTPNKTGKRLTRAQLIT 5H1B_CRIGR 238 189 -
QTPNRTGKRLTRAQLIT 5H1B_HUMAN 242 189 -
QTPNRTGKRLTRAQLIT 5H1B_RABIT 242 189 -
QTPNRTGKRLTRAQLIT 5H1B_DIDMA 240 188 -

Motif 4 width=18
Element Seqn Id St Int Rpt
TDSPGSTSSVTSINSRAP 5H1B_MOUSE 254 -1 -
TDSPGSTTSVTSINSRAP 5H1B_CRIGR 254 -1 -
TDSPGSTSSVTSINSRVP 5H1B_HUMAN 258 -1 -
TDSPGSTTSVTSINSRAP 5H1B_RABIT 258 -1 -
TDSPGSSSSGTSINSRAP 5H1B_DIDMA 256 -1 -

Motif 5 width=16
Element Seqn Id St Int Rpt
PVYVNQVKVRVSDALL 5H1B_MOUSE 280 8 -
PVYVNQVKVRVSDALL 5H1B_CRIGR 280 8 -
PVYVNQVKVRVSDALL 5H1B_HUMAN 284 8 -
PVYVNQVKVRVSDALL 5H1B_RABIT 284 8 -
PVYVNQVKVKVSDALL 5H1B_DIDMA 282 8 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
EEQGIQCAPPPP 5H1B_MOUSE 2 2 -
EEQGIQCAPPPP 5H1B_RAT 2 2 -
EEQGIQCAPPPP 5H1B_CRIGR 2 2 -
EEPGAQCAPPPP 5H1B_HUMAN 2 2 -
EEPGAQCAPPLA 5H1B_RABIT 2 2 -
EEPGARCAPPPP 5H1B_SPAEH 2 2 -
EQPSRLCSPPAS 5H1B_DIDMA 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
YQDSIALPWKVLL 5H1B_MOUSE 36 22 -
YQDSIALPWKVLL 5H1B_RAT 36 22 -
YQDSIALPWKVLL 5H1B_CRIGR 36 22 -
YQDSISLPWKVLL 5H1B_HUMAN 40 26 -
YQDSIALPWKVLL 5H1B_RABIT 40 26 -
YQDSIALPWKVLL 5H1B_SPAEH 36 22 -
YQDSIALPWKVLL 5H1B_DIDMA 39 25 -

Motif 3 width=17
Element Seqn Id St Int Rpt
QTPNKTGKRLTRAQLIT 5H1B_MOUSE 238 189 -
QTPNKTGKRLTRAQLIT 5H1B_RAT 238 189 -
QTPNKTGKRLTRAQLIT 5H1B_CRIGR 238 189 -
QTPNRTGKRLTRAQLIT 5H1B_HUMAN 242 189 -
QTPNRTGKRLTRAQLIT 5H1B_RABIT 242 189 -
QTPNKTGKRLSRAQLIS 5H1B_SPAEH 238 189 -
QTPNRTGKRLTRAQLIT 5H1B_DIDMA 240 188 -

Motif 4 width=18
Element Seqn Id St Int Rpt
TDSPGSTSSVTSINSRAP 5H1B_MOUSE 254 -1 -
TDSPGSTSSVTSINSRVP 5H1B_RAT 254 -1 -
TDSPGSTTSVTSINSRAP 5H1B_CRIGR 254 -1 -
TDSPGSTSSVTSINSRVP 5H1B_HUMAN 258 -1 -
TDSPGSTTSVTSINSRAP 5H1B_RABIT 258 -1 -
SDSPGSTSSVTSINSRVP 5H1B_SPAEH 254 -1 -
TDSPGSSSSGTSINSRAP 5H1B_DIDMA 256 -1 -

Motif 5 width=16
Element Seqn Id St Int Rpt
PVYVNQVKVRVSDALL 5H1B_MOUSE 280 8 -
PVYVNQVKVRVSDALL 5H1B_RAT 280 8 -
PVYVNQVKVRVSDALL 5H1B_CRIGR 280 8 -
PVYVNQVKVRVSDALL 5H1B_HUMAN 284 8 -
PVYVNQVKVRVSDALL 5H1B_RABIT 284 8 -
PVYVNQVKVRVSDALL 5H1B_SPAEH 280 8 -
PVYVNQVKVKVSDALL 5H1B_DIDMA 282 8 -