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PR00512

Identifier
5HT1ARECEPTR  [View Relations]  [View Alignment]  
Accession
PR00512
No. of Motifs
7
Creation Date
06-JUN-1996  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 1A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR000610
GCRDB; GCR_0087; GCR_0381; GCR_0624; GCR_0109
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 5HT1A receptor is found pre- and post-synaptically in neurons in the
CNS, and in the periphery [6]. It is also abundant in foetal lymphatic
tissue. Clinically, 5HT1A receptor ligands represent potential anxiolytic
and hypertensive agents [6]. Several potent and selective 5HT1A receptor
agonists have been described; there are no selective antagonists.  
 
5HT1ARECEPTR is a 7-element fingerprint that provides a signature for the
5HT1A 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 5HT1A receptors but distinguish them from the rest of the
5HT family - motifs 1 and 2 lie at the N-terminus; motif 3 spans the second
external loop; and motifs 4-7 lie in the third cytoplasmic loop. A single 
iteration on OWL28.0 was required to reach convergence, no further sequences 
being identified beyond the starting set. Three partial matches were also 
found, all of which are 5HT1A receptor fragments. 
 
An update on SPTR37_9f identified a true set of 3 sequences, and 2
partial matches.
Summary Information
   3 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
1 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
73333333
60000000
50000000
40111010
30011010
20000000
1234567
True Positives
5H1A_HUMAN    5H1A_MOUSE    5H1A_RAT      
True Positive Partials
Codes involving 4 elements
O42385
Codes involving 3 elements
Q98998
Sequence Titles
5H1A_HUMAN  5-HYDROXYTRYPTAMINE 1A RECEPTOR (5-HT-1A) (SEROTONIN RECEPTOR) (5- HT1A) (G-21) - HOMO SAPIENS (HUMAN). 
5H1A_MOUSE 5-HYDROXYTRYPTAMINE 1A RECEPTOR (5-HT-1A) (SEROTONIN RECEPTOR) (5- HT1A) - MUS MUSCULUS (MOUSE).
5H1A_RAT 5-HYDROXYTRYPTAMINE 1A RECEPTOR (5-HT-1A) (SEROTONIN RECEPTOR) (5- HT1A) - RATTUS NORVEGICUS (RAT).

O42385 SEROTONIN RECEPTOR - FUGU RUBRIPES (JAPANESE PUFFERFISH) (TAKIFUGU RUBRIPES).

Q98998 5-HT1A RECEPTOR - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
OWL28_0    1  50   NSINGLE    
SPTR37_9f 2 111 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
GQGNNTTSPPAPFETGG HSPLMERE 7 7 -
GQGNNTTTSLEPFGTGG MMU39391 7 7 -
GQGNNTTASQEPFGTGG 5H1A_RAT 7 7 -
GQGNNTTSPPAPFETGG 5H1A_HUMAN 7 7 -

Motif 2 width=18
Element Seqn Id St Int Rpt
GNDTGLSNVTFSYQVITS MMU39391 23 -1 -
GNVTSISDVTFSYQVITS 5H1A_RAT 23 -1 -
GNTTGISDVTVSYQVITS 5H1A_HUMAN 23 -1 -
GNTTGISDVTVSYQVITS HSPLMERE 23 -1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
RTPEDRSDPDACTISK HSPLMERE 175 134 -
RAPEDRSNPNECTISK MMU39391 176 135 -
RTPEDRSDPDACTISK 5H1A_HUMAN 176 135 -
RTPEDRSDPDACTISK 5H1A_RAT 176 135 -

Motif 4 width=20
Element Seqn Id St Int Rpt
FRIRKTVKKVEKKGAGTSFG MMU39391 224 32 -
FRIRKTVRKVEKKGAGTSLG 5H1A_RAT 224 32 -
FRIRKTVKKVEKTGADTRHG 5H1A_HUMAN 224 32 -
FRIRKTVKKVEKTGADTRHG HSPLMERE 223 32 -

Motif 5 width=17
Element Seqn Id St Int Rpt
CRRSAENRAVGTPCANG MMU39391 263 19 -
WRLGVESKAGGALCANG HSPLMERE 262 19 -
WRRCAENRAVGTPCTNG 5H1A_RAT 263 19 -
WRLGVESKAGGALCANG 5H1A_HUMAN 263 19 -

Motif 6 width=20
Element Seqn Id St Int Rpt
AVRQGDDGAALEVIEVHRVG 5H1A_HUMAN 280 0 -
AVRQGEDDATLEVIEVHRVG MMU39391 280 0 -
AVRQGDDGAALEVIEVHRVG HSPLMERE 279 0 -
AVRQGDDEATLEVIEVHRVG 5H1A_RAT 280 0 -

Motif 7 width=16
Element Seqn Id St Int Rpt
APASFERKNERNAEAK 5H1A_HUMAN 317 17 -
VPACLERKNERTAEAK MMU39391 317 17 -
APACLERKNERNAEAK 5H1A_RAT 317 17 -
APASFERKNERNAEAK HSPLMERE 316 17 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
GQGNNTTASQEPFGTGG 5H1A_RAT 7 7 -
GQGNNTTTSLEPFGTGG 5H1A_MOUSE 7 7 -
GQGNNTTSPPAPFETGG 5H1A_HUMAN 7 7 -

Motif 2 width=18
Element Seqn Id St Int Rpt
GNVTSISDVTFSYQVITS 5H1A_RAT 23 -1 -
GNDTGLSNVTFSYQVITS 5H1A_MOUSE 23 -1 -
GNTTGISDVTVSYQVITS 5H1A_HUMAN 23 -1 -

Motif 3 width=16
Element Seqn Id St Int Rpt
RTPEDRSDPDACTISK 5H1A_RAT 176 135 -
RAPEDRSNPNECTISK 5H1A_MOUSE 176 135 -
RTPEDRSDPDACTISK 5H1A_HUMAN 176 135 -

Motif 4 width=20
Element Seqn Id St Int Rpt
FRIRKTVRKVEKKGAGTSLG 5H1A_RAT 224 32 -
FRIRKTVKKVEKKGAGTSFG 5H1A_MOUSE 224 32 -
FRIRKTVKKVEKTGADTRHG 5H1A_HUMAN 224 32 -

Motif 5 width=17
Element Seqn Id St Int Rpt
WRRCAENRAVGTPCTNG 5H1A_RAT 263 19 -
CRRSAENRAVGTPCANG 5H1A_MOUSE 263 19 -
WRLGVESKAGGALCANG 5H1A_HUMAN 263 19 -

Motif 6 width=20
Element Seqn Id St Int Rpt
AVRQGDDEATLEVIEVHRVG 5H1A_RAT 280 0 -
AVRQGEDDATLEVIEVHRVG 5H1A_MOUSE 280 0 -
AVRQGDDGAALEVIEVHRVG 5H1A_HUMAN 280 0 -

Motif 7 width=16
Element Seqn Id St Int Rpt
APACLERKNERNAEAK 5H1A_RAT 317 17 -
VPACLERKNERTAEAK 5H1A_MOUSE 317 17 -
APASFERKNERNAEAK 5H1A_HUMAN 317 17 -