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PR00517

Identifier
5HT2CRECEPTR  [View Relations]  [View Alignment]  
Accession
PR00517
No. of Motifs
8
Creation Date
04-JUN-1996  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 2C receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR000377
GCRDB; GCR_0217; GCR_0510; GCR_0830; GCR_0407; GCR_0160
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. 
 
5HT2CRECEPTR is an 8-element fingerprint that provides a signature for the
5HT2C receptors. The fingerprint was derived from an initial alignment of
3 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 5HT2C receptors but distinguish them from the rest of
the 5HT family - motifs 1 and 2 lie at the N-terminus; motifs 3 and 4 span
the third cytoplasmic loop; and motifs 6-8 lie at the C-terminus. A single
iteration on OWL28.0 was required to reach convergence, no further sequences
being identified beyond the starting set. A single partial match was also
found (HS5HT2C), a 5HT2C receptor fragment that matches motifs 1 and 2.
 
An update on SPTR37_9f identified a true set of 3 sequences, and 2
partial matches.
Summary Information
   3 codes involving  8 elements
0 codes involving 7 elements
1 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
833333333
700000000
600111111
500000000
400000000
300000000
211000000
12345678
True Positives
5H2C_HUMAN    5H2C_MOUSE    5H2C_RAT      
True Positive Partials
Codes involving 6 elements
Q62842
Codes involving 2 elements
Q13638
Sequence Titles
5H2C_HUMAN  5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT-2C) (SEROTONIN RECEPTOR) (5HT-1C) - HOMO SAPIENS (HUMAN). 
5H2C_MOUSE 5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT-2C) (SEROTONIN RECEPTOR) (5HT-1C) - MUS MUSCULUS (MOUSE).
5H2C_RAT 5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT-2C) (SEROTONIN RECEPTOR) (5HT-1C) - RATTUS NORVEGICUS (RAT).

Q62842 SEROTONIN 5-HT2C - RATTUS NORVEGICUS (RAT).

Q13638 5-HT2C RECEPTOR - HOMO SAPIENS (HUMAN).
Scan History
OWL28_0    1  50   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
AVRSLLVHLIGLLVWQFDIS 5H2C_MOUSE 7 7 -
AVRSLLMHLIGLLVWQFDIS 5H2C_RAT 7 7 -
AVHSFLVHLIGLLVWQCDIS 5H2C_HUMAN 7 7 -

Motif 2 width=18
Element Seqn Id St Int Rpt
SPVAAIVTDTFNSSDGGR 5H2C_MOUSE 28 1 -
SPVAAIVTDTFNSSDGGR 5H2C_RAT 28 1 -
SPVAAIVTDIFNTSDGGR 5H2C_HUMAN 28 1 -

Motif 3 width=13
Element Seqn Id St Int Rpt
EEENAPNPNPDQK 5H2C_MOUSE 275 229 -
EEENAPNPNPDQK 5H2C_RAT 276 230 -
EEENSANPNQDQN 5H2C_HUMAN 273 227 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RRKKKEKRPRGT 5H2C_MOUSE 289 1 -
RRKKKEKRPRGT 5H2C_RAT 290 1 -
RRKKKERRPRGT 5H2C_HUMAN 288 2 -

Motif 5 width=17
Element Seqn Id St Int Rpt
PPVRQIPRVAATALSGR 5H2C_MOUSE 394 93 -
PPVRQIPRVAATALSGR 5H2C_RAT 395 93 -
PPVRQIPRVAATALSGR 5H2C_HUMAN 393 93 -

Motif 6 width=17
Element Seqn Id St Int Rpt
ELNVNIYRHTNERVVRK 5H2C_MOUSE 411 0 -
ELNVNIYRHTNERVARK 5H2C_RAT 412 0 -
ELNVNIYRHTNEPVIEK 5H2C_HUMAN 410 0 -

Motif 7 width=16
Element Seqn Id St Int Rpt
ANDTEPGIEMQVENLE 5H2C_MOUSE 428 0 -
ANDPEPGIEMQVENLE 5H2C_RAT 429 0 -
ASDNEPGIEMQVENLE 5H2C_HUMAN 427 0 -

Motif 8 width=15
Element Seqn Id St Int Rpt
ELPVNPSNVVSERIS 5H2C_MOUSE 443 -1 -
ELPVNPSNVVSERIS 5H2C_RAT 444 -1 -
ELPVNPSSVVSERIS 5H2C_HUMAN 442 -1 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
AVRSLLVHLIGLLVWQFDIS 5H2C_MOUSE 7 7 -
AVRSLLMHLIGLLVWQFDIS 5H2C_RAT 7 7 -
AVHSFLVHLIGLLVWQCDIS 5H2C_HUMAN 7 7 -

Motif 2 width=18
Element Seqn Id St Int Rpt
SPVAAIVTDTFNSSDGGR 5H2C_MOUSE 28 1 -
SPVAAIVTDTFNSSDGGR 5H2C_RAT 28 1 -
SPVAAIVTDIFNTSDGGR 5H2C_HUMAN 28 1 -

Motif 3 width=13
Element Seqn Id St Int Rpt
EEENAPNPNPDQK 5H2C_MOUSE 275 229 -
EEENAPNPNPDQK 5H2C_RAT 276 230 -
EEENSANPNQDQN 5H2C_HUMAN 273 227 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RRKKKEKRPRGT 5H2C_MOUSE 289 1 -
RRKKKEKRPRGT 5H2C_RAT 290 1 -
RRKKKERRPRGT 5H2C_HUMAN 288 2 -

Motif 5 width=17
Element Seqn Id St Int Rpt
PPVRQIPRVAATALSGR 5H2C_MOUSE 394 93 -
PPVRQIPRVAATALSGR 5H2C_RAT 395 93 -
PPVRQIPRVAATALSGR 5H2C_HUMAN 393 93 -

Motif 6 width=17
Element Seqn Id St Int Rpt
ELNVNIYRHTNERVVRK 5H2C_MOUSE 411 0 -
ELNVNIYRHTNERVARK 5H2C_RAT 412 0 -
ELNVNIYRHTNEPVIEK 5H2C_HUMAN 410 0 -

Motif 7 width=16
Element Seqn Id St Int Rpt
ANDTEPGIEMQVENLE 5H2C_MOUSE 428 0 -
ANDPEPGIEMQVENLE 5H2C_RAT 429 0 -
ASDNEPGIEMQVENLE 5H2C_HUMAN 427 0 -

Motif 8 width=15
Element Seqn Id St Int Rpt
ELPVNPSNVVSERIS 5H2C_MOUSE 443 -1 -
ELPVNPSNVVSERIS 5H2C_RAT 444 -1 -
ELPVNPSSVVSERIS 5H2C_HUMAN 442 -1 -