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PR00518

Identifier
5HT5ARECEPTR  [View Relations]  [View Alignment]  
Accession
PR00518
No. of Motifs
5
Creation Date
04-JUN-1996  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 5A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR001397
GCRDB; GCR_0586; GCR_0720
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.
 
The 5HT5 receptor has a similar pharmacology to the 5HT1D receptor. In
the CNS, its mRNA is found in the cerebral cortex, hippocampus, habenula,
olfactory bulb and granular layer of the cerebellum [6]. There are no
selective agonists, and the receptor does not appear to be linked to the
adenylyl cyclase or phosphoinositide pathways [6].
 
5HT5ARECEPTR is a 5-element fingerprint that provides a signature for the
5HT5A 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 5HT5A 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 and 5 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.
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
300000
200000
12345
True Positives
5H5A_HUMAN    5H5A_MOUSE    5H5A_RAT      
Sequence Titles
5H5A_HUMAN  5-HYDROXYTRYPTAMINE 5A RECEPTOR (5-HT-5A) (SEROTONIN RECEPTOR) (5-HT-5) - HOMO SAPIENS (HUMAN). 
5H5A_MOUSE 5-HYDROXYTRYPTAMINE 5A RECEPTOR (5-HT-5A) (SEROTONIN RECEPTOR) (5-HT-5) - MUS MUSCULUS (MOUSE).
5H5A_RAT 5-HYDROXYTRYPTAMINE 5A RECEPTOR (5-HT-5A) (SEROTONIN RECEPTOR) (REC17) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_0    1  50   NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
PINLTSFSLSTPSTLEP 5H5A_RAT 4 4 -
PVNLTSFSLSTPSSLEP 5H5A_MOUSE 4 4 -
PVNLTSFSLSTPSSLEP S28058 4 4 -
PVNLTSFSLSTPSPLET 5H5A_HUMAN 4 4 -

Motif 2 width=18
Element Seqn Id St Int Rpt
NHSLGKDDLRPSSPLLSV 5H5A_HUMAN 21 0 -
NRSLDTEVLRPSRPFLSA S28058 21 0 -
NRSLDTEVLRPSRPFLSA 5H5A_MOUSE 21 0 -
NRSLDTEALRTSQSFLSA 5H5A_RAT 21 0 -

Motif 3 width=9
Element Seqn Id St Int Rpt
ETYSELSEE 5H5A_RAT 183 144 -
ETYSEGSEE 5H5A_HUMAN 183 144 -
ETYSEPSEE S28058 183 144 -
ETYSEPSEE 5H5A_MOUSE 183 144 -

Motif 4 width=17
Element Seqn Id St Int Rpt
SRKTNSVSPVPEAVEVK S28058 233 41 -
SRKTNSVSPVPEAVEVK 5H5A_MOUSE 233 41 -
SRKTNSVSPIPEAVEVK 5H5A_RAT 233 41 -
SRKTNSVSPISEAVEVK 5H5A_HUMAN 233 41 -

Motif 5 width=10
Element Seqn Id St Int Rpt
KDASQHPQMV 5H5A_RAT 249 -1 -
KDSAKQPQMV 5H5A_HUMAN 249 -1 -
KNATQHPQMV 5H5A_MOUSE 249 -1 -
KNATQHPQMV S28058 249 -1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
PVNLTSFSLSTPSSLEP 5H5A_MOUSE 4 4 -
PINLTSFSLSTPSTLEP 5H5A_RAT 4 4 -
PVNLTSFSLSTPSPLET 5H5A_HUMAN 4 4 -

Motif 2 width=18
Element Seqn Id St Int Rpt
NRSLDTEVLRPSRPFLSA 5H5A_MOUSE 21 0 -
NRSLDTEALRTSQSFLSA 5H5A_RAT 21 0 -
NHSLGKDDLRPSSPLLSV 5H5A_HUMAN 21 0 -

Motif 3 width=9
Element Seqn Id St Int Rpt
ETYSEPSEE 5H5A_MOUSE 183 144 -
ETYSELSEE 5H5A_RAT 183 144 -
ETYSEGSEE 5H5A_HUMAN 183 144 -

Motif 4 width=17
Element Seqn Id St Int Rpt
SRKTNSVSPVPEAVEVK 5H5A_MOUSE 233 41 -
SRKTNSVSPIPEAVEVK 5H5A_RAT 233 41 -
SRKTNSVSPISEAVEVK 5H5A_HUMAN 233 41 -

Motif 5 width=10
Element Seqn Id St Int Rpt
KNATQHPQMV 5H5A_MOUSE 249 -1 -
KDASQHPQMV 5H5A_RAT 249 -1 -
KDSAKQPQMV 5H5A_HUMAN 249 -1 -