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PR00516

Identifier
5HT2ARECEPTR  [View Relations]  [View Alignment]  
Accession
PR00516
No. of Motifs
7
Creation Date
04-JUN-1996  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 2A receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR000455
GCRDB; GCR_0294; GCR_0546; GCR_0110; GCR_0161; GCR_0162
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 5HT2 receptor was originally classified according to its ability to
display micromolar affinity for 5HT, to be labelled with [3H]spiperone,
and by its susceptibility to 5HT antagonists [6]. At least 3 members of
the family exist (including the re-classified 5HT1C receptor), all of
which share a high degree of sequence similarity and stimulate the
phosphoinositide pathway. 
 
5HT2ARECEPTR is a 7-element fingerprint that provides a signature for the
5HT2A receptors. The fingerprint was derived from an initial alignment of
4 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 5HT2A receptors but distinguish them from the rest of
teh 5HT family - motifs 1-3 lie at the N-terminus; motifs 4 and 5 span the 
third cytoplasmic loop; and motifs 6 and 7 lie at the C-terminus. Two 
iterations on OWL28.0 were required to reach convergence, at which point a
true set comprising 6 sequences was identified. A single partial match was
also found (5H2A_CAVPO), a 5HT2A receptor fragment that matches motifs 4 
and 5.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
76666666
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
5H2A_CRIGR    5H2A_HUMAN    5H2A_MACMU    5H2A_MOUSE    
5H2A_PIG 5H2A_RAT
Sequence Titles
5H2A_CRIGR  5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTOR) (5-HT-2) - CRICETULUS GRISEUS (CHINESE HAMSTER). 
5H2A_HUMAN 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTOR) (5-HT-2) - HOMO SAPIENS (HUMAN).
5H2A_MACMU 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTOR) (5-HT-2) - MACACA MULATTA (RHESUS MACAQUE).
5H2A_MOUSE 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTOR) (5-HT-2) - MUS MUSCULUS (MOUSE).
5H2A_PIG 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTOR) (5-HT-2) (5-HT2A) - SUS SCROFA (PIG).
5H2A_RAT 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTOR) (5-HT-2) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_0    2  50   NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
LYSNDFNSGEANTSDAFNWT 5H2A_HUMAN 27 27 -
LYHNDFNSRDANTSEASNWT 5H2A_RAT 27 27 -
LYRNDFNSRDANSSDASNWT 5H2A_CRIGR 27 27 -
LYPNDFNSRDANTSEASNWT 5H2A_MOUSE 27 27 -

Motif 2 width=15
Element Seqn Id St Int Rpt
VDSENRTNLSCEGCL 5H2A_HUMAN 47 0 -
IDAENRTNLSCEGYL 5H2A_RAT 47 0 -
IDGENRTNLSFEGYL 5H2A_CRIGR 47 0 -
IDAENRTNLSCEGYL 5H2A_MOUSE 47 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
PSCLSLLHLQEKNWS 5H2A_HUMAN 63 1 -
PTCLSILHLQEKNWS 5H2A_RAT 63 1 -
PTCLSILHLQEKNWS 5H2A_CRIGR 63 1 -
PTCLSILHLQEKNWS 5H2A_MOUSE 63 1 -

Motif 4 width=18
Element Seqn Id St Int Rpt
CVSDLGTRAKLASFSFLP 5H2A_HUMAN 268 190 -
CVSDLSTRAKLASFSFLP 5H2A_RAT 268 190 -
CVSDLSTRAKLASFSFLP 5H2A_CRIGR 268 190 -
CVSDLSTRAKLSSFSFLP 5H2A_MOUSE 268 190 -

Motif 5 width=18
Element Seqn Id St Int Rpt
LSSEKLFQRSIHREPGSY 5H2A_HUMAN 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_RAT 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_CRIGR 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_MOUSE 289 3 -

Motif 6 width=18
Element Seqn Id St Int Rpt
PLQLILVNTIPALAYKSS 5H2A_HUMAN 405 98 -
PLQLILVNTIPALAYKSS 5H2A_RAT 405 98 -
PLQLILVNTIPALAYKSS 5H2A_CRIGR 405 98 -
PLQLILVNTIPTLAYKSS 5H2A_MOUSE 405 98 -

Motif 7 width=17
Element Seqn Id St Int Rpt
TDNDCSMVALGKQHSEE 5H2A_HUMAN 439 16 -
TVDDCSMVTLGKQQSEE 5H2A_RAT 439 16 -
TDNDCSMVTLGKQQSEE 5H2A_CRIGR 439 16 -
TANDCSMVTLGNQHSEE 5H2A_MOUSE 439 16 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
LYSNDFNSGEANTSDAFNWT 5H2A_HUMAN 27 27 -
LYHNDFNSRDANTSEASNWT 5H2A_RAT 27 27 -
LYSNDFNSGEANTSDAFNWT 5H2A_MACMU 27 27 -
LYRNDFNSRDANSSDASNWT 5H2A_CRIGR 27 27 -
LYHNDFNSGEANTSDAFNWT 5H2A_PIG 27 27 -
LYPNDFNSRDANTSEASNWT 5H2A_MOUSE 27 27 -

Motif 2 width=15
Element Seqn Id St Int Rpt
VDSENRTNLSCEGCL 5H2A_HUMAN 47 0 -
IDAENRTNLSCEGYL 5H2A_RAT 47 0 -
VESENRTNLSCEGCL 5H2A_MACMU 47 0 -
IDGENRTNLSFEGYL 5H2A_CRIGR 47 0 -
VDSENRTNLSCEGCL 5H2A_PIG 47 0 -
IDAENRTNLSCEGYL 5H2A_MOUSE 47 0 -

Motif 3 width=15
Element Seqn Id St Int Rpt
PSCLSLLHLQEKNWS 5H2A_HUMAN 63 1 -
PTCLSILHLQEKNWS 5H2A_RAT 63 1 -
PSCLSLLHLQEKNWS 5H2A_MACMU 63 1 -
PTCLSILHLQEKNWS 5H2A_CRIGR 63 1 -
PPCFSLLHLQEKNWS 5H2A_PIG 63 1 -
PTCLSILHLQEKNWS 5H2A_MOUSE 63 1 -

Motif 4 width=18
Element Seqn Id St Int Rpt
CVSDLGTRAKLASFSFLP 5H2A_HUMAN 268 190 -
CVSDLSTRAKLASFSFLP 5H2A_RAT 268 190 -
CVSDLGTRAKLASFSFLP 5H2A_MACMU 268 190 -
CVSDLSTRAKLASFSFLP 5H2A_CRIGR 268 190 -
CVSDLGTRAKLASFSFLP 5H2A_PIG 268 190 -
CVSDLSTRAKLSSFSFLP 5H2A_MOUSE 268 190 -

Motif 5 width=18
Element Seqn Id St Int Rpt
LSSEKLFQRSIHREPGSY 5H2A_HUMAN 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_RAT 289 3 -
LSSEKLFQRSIHRDPGSY 5H2A_MACMU 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_CRIGR 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_PIG 289 3 -
LSSEKLFQRSIHREPGSY 5H2A_MOUSE 289 3 -

Motif 6 width=18
Element Seqn Id St Int Rpt
PLQLILVNTIPALAYKSS 5H2A_HUMAN 405 98 -
PLQLILVNTIPALAYKSS 5H2A_RAT 405 98 -
PLQLILVNTIPALAYKSS 5H2A_MACMU 405 98 -
PLQLILVNTIPALAYKSS 5H2A_CRIGR 405 98 -
PLQLILVNTIPALAYKSS 5H2A_PIG 404 97 -
PLQLILVNTIPTLAYKSS 5H2A_MOUSE 405 98 -

Motif 7 width=17
Element Seqn Id St Int Rpt
TDNDCSMVALGKQHSEE 5H2A_HUMAN 439 16 -
TVDDCSMVTLGKQQSEE 5H2A_RAT 439 16 -
TDNDCSMVALGKQHSED 5H2A_MACMU 439 16 -
TDNDCSMVTLGKQQSEE 5H2A_CRIGR 439 16 -
TENDCTMVALGKQHSED 5H2A_PIG 438 16 -
TANDCSMVTLGNQHSEE 5H2A_MOUSE 439 16 -