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PR00652

Identifier
5HT7RECEPTR  [View Relations]  [View Alignment]  
Accession
PR00652
No. of Motifs
8
Creation Date
07-APR-1997  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 7 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR001069
GCRDB; GCR_0656; GCR_0687; GCR_0688; GCR_0789; GCR_0749; GCR_0792
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. 
 
5HT7RECEPTR is an 8-element fingerprint that provides a signature for the
5HT7 receptors. The fingerprint was derived from an initial alignment of
5 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 5HT7 receptors but distinguish them from the rest of
the 5HT family - motifs 1-3 span the N-terminus; motif 4 spans the second
cytoplasmic loop; motifs 5 and 6 lie in the third cytoplasmic loop; and
motifs 7 and 8 lie at the C-terminus. A single iteration on OWL29.1 was
required to reach convergence, no further sequences being identified beyond
the starting set. Several partial matches were found, all of which are 5HT7
receptors that lack the portions of sequence bearing the N- and C-terminal
motifs.
 
An update on SPTR37_9f identified a true set of 6 sequences, and 1
partial match.
Summary Information
   6 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
866666666
700000000
600000000
500000000
400000000
300011010
200000000
12345678
True Positives
5H7_CAVPO     5H7_HUMAN     5H7_MOUSE     5H7_RAT       
P78336 P97842
True Positive Partials
Codes involving 3 elements
5H7_XENLA
Sequence Titles
5H7_CAVPO   5-HYDROXYTRYPTAMINE 7 RECEPTOR (5-HT-7) (5-HT-X) (SEROTONIN RECEPTOR) - CAVIA PORCELLUS (GUINEA PIG). 
5H7_HUMAN 5-HYDROXYTRYPTAMINE 7 RECEPTOR (5-HT-7) (5-HT-X) (SEROTONIN RECEPTOR) (5HT7) - HOMO SAPIENS (HUMAN).
5H7_MOUSE 5-HYDROXYTRYPTAMINE 7 RECEPTOR (5-HT-7) (5-HT-X) (SEROTONIN RECEPTOR) (5HT7) - MUS MUSCULUS (MOUSE).
5H7_RAT 5-HYDROXYTRYPTAMINE 7 RECEPTOR (5-HT-7) (5-HT-X) (SEROTONIN RECEPTOR) (5HT7) (GPRFO) - RATTUS NORVEGICUS (RAT).
P78336 5-HYDROXYTRYPTAMINE7 RECEPTOR ISOFORM D - HOMO SAPIENS (HUMAN).
P97842 5-HYDROXYTRYPTAMINE7 RECEPTOR ISOFORM C - RATTUS NORVEGICUS (RAT).

5H7_XENLA 5-HYDROXYTRYPTAMINE 7 RECEPTOR (5-HT-7) (SEROTONIN RECEPTOR) - XENOPUS LAEVIS (AFRICAN CLAWED FROG).
Scan History
OWL29_1    1  50   NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
MDVNSSGRPDLYGHLRSLILP 5H7_MOUSE 2 2 -
MDVNSSGRPDLYGHLRSLILP 5H7_RAT 2 2 -
MDVNSSGRPDLYGHLRSFLLP 5H7_HUMAN 2 2 -
MGVNSSGRPDLYGHLHSILLP 5H7_CAVPO 2 2 -
MDVNSSGRPDLYGHLRSLILP S40687 2 2 -

Motif 2 width=21
Element Seqn Id St Int Rpt
DWSPDGGADPGVSTWTPRLLS 5H7_CAVPO 28 5 -
DLSPDGGAHPVVSSWMPHLLS S40687 30 7 -
DLSPDGGAHPVVSSWMPHLLS 5H7_RAT 30 7 -
DLSPDGGAHSVVSSWMPHLLS 5H7_MOUSE 30 7 -
DLSPDGGADPVAGSWAPHLLS 5H7_HUMAN 30 7 -

Motif 3 width=20
Element Seqn Id St Int Rpt
EVTASPAPTWDAPPDNVSGC S40687 54 3 -
EVTASPAPTWDAPPDNVSGC 5H7_RAT 54 3 -
EVTASPAPTWDAPPDNVSGC 5H7_MOUSE 54 3 -
EVTASPAPTWDAPPDNASGC 5H7_HUMAN 51 0 -
EVAASPSPSWDGTWDNVSGC 5H7_CAVPO 52 3 -

Motif 4 width=17
Element Seqn Id St Int Rpt
TYPVRQNGKCMAKMILS 5H7_RAT 192 118 -
TYPVSQNEKCMAKMILS S40687 192 118 -
TYPVRQNGKCMAKMILS 5H7_MOUSE 192 118 -
TYPVRQNGKCMAKMILS 5H7_HUMAN 189 118 -
TYPVRQNGKCMPKMILS 5H7_CAVPO 190 118 -

Motif 5 width=19
Element Seqn Id St Int Rpt
IYKAARKSAAKHKFSGFPR 5H7_MOUSE 265 56 -
IYKAARKSAAKHKFPGFPR S40687 265 56 -
IYKAARKSAAKHKFPGFPR 5H7_CAVPO 263 56 -
IYKAARKSAAKHKFPGFPR 5H7_HUMAN 262 56 -
IYKAARKSAAKHKFPGFPR 5H7_RAT 265 56 -

Motif 6 width=22
Element Seqn Id St Int Rpt
LNGVVKLQKEVEECANLSRLLK S40687 292 8 -
LNGVVKLQKEVEECANLSRLLK 5H7_RAT 292 8 -
LNGVVKLQKEVEECANLSRLLK 5H7_MOUSE 292 8 -
LNGIVKLQKEVEECANLSRLLK 5H7_HUMAN 289 8 -
LNGMVKLQKEVEECANLSRLLK 5H7_CAVPO 290 8 -

Motif 7 width=18
Element Seqn Id St Int Rpt
RNINRKLSAAGMHEALKL S40687 407 93 -
RNINRKLSAAGMHEALKL 5H7_RAT 407 93 -
RNINRKLSAAGMHEALKL 5H7_MOUSE 407 93 -
RNINRKLSAAGMHEALKL 5H7_HUMAN 404 93 -
RNINRKLSAAGMHEALKL 5H7_CAVPO 405 93 -

Motif 8 width=22
Element Seqn Id St Int Rpt
AERPERSEFVLQNSDHCGKKGH S40687 425 0 -
AERPERSEFVLQNCDHCGKKGH 5H7_MOUSE 425 0 -
AERPERPECVLQNSDYCRKKGH 5H7_CAVPO 423 0 -
AERPERPEFVLQNADYCRKKGH 5H7_HUMAN 422 0 -
AERPERSEFVLQNSDHCGKKGH 5H7_RAT 425 0 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
MDVNSSGRPDLYGHLRSLILP 5H7_RAT 2 2 -
MDVNSSGRPDLYGHLRSLILP 5H7_MOUSE 2 2 -
MDVNSSGRPDLYGHLRSFLLP 5H7_HUMAN 2 2 -
MDVNSSGRPDLYGHLRSLILP P97842 2 2 -
MDVNSSGRPDLYGHLRSFLLP P78336 2 2 -
MGVNSSGRPDLYGHLHSILLP 5H7_CAVPO 2 2 -

Motif 2 width=21
Element Seqn Id St Int Rpt
DLSPDGGAHPVVSSWMPHLLS 5H7_RAT 30 7 -
DLSPDGGAHSVVSSWMPHLLS 5H7_MOUSE 30 7 -
DLSPDGGADPVAGSWAPHLLS 5H7_HUMAN 30 7 -
DLSPDGGAHPVVSSWMPHLLS P97842 30 7 -
DLSPDGGADPVAGSWAPHLLS P78336 30 7 -
DWSPDGGADPGVSTWTPRLLS 5H7_CAVPO 28 5 -

Motif 3 width=20
Element Seqn Id St Int Rpt
EVTASPAPTWDAPPDNVSGC 5H7_RAT 54 3 -
EVTASPAPTWDAPPDNVSGC 5H7_MOUSE 54 3 -
EVTASPAPTWDAPPDNASGC 5H7_HUMAN 51 0 -
EVTASPAPTWDAPPDNVSGC P97842 54 3 -
EVTASPAPTWDAPPDNASGC P78336 51 0 -
EVAASPSPSWDGTWDNVSGC 5H7_CAVPO 52 3 -

Motif 4 width=17
Element Seqn Id St Int Rpt
TYPVRQNGKCMAKMILS 5H7_RAT 192 118 -
TYPVRQNGKCMAKMILS 5H7_MOUSE 192 118 -
TYPVRQNGKCMAKMILS 5H7_HUMAN 189 118 -
TYPVRQNGKCMAKMILS P97842 192 118 -
TYPVRQNGKCMAKMILS P78336 189 118 -
TYPVRQNGKCMPKMILS 5H7_CAVPO 190 118 -

Motif 5 width=19
Element Seqn Id St Int Rpt
IYKAARKSAAKHKFPGFPR 5H7_RAT 265 56 -
IYKAARKSAAKHKFSGFPR 5H7_MOUSE 265 56 -
IYKAARKSAAKHKFPGFPR 5H7_HUMAN 262 56 -
IYKAARKSAAKHKFPGFPR P97842 265 56 -
IYKAARKSAAKHKFPGFPR P78336 262 56 -
IYKAARKSAAKHKFPGFPR 5H7_CAVPO 263 56 -

Motif 6 width=22
Element Seqn Id St Int Rpt
LNGVVKLQKEVEECANLSRLLK 5H7_RAT 292 8 -
LNGVVKLQKEVEECANLSRLLK 5H7_MOUSE 292 8 -
LNGIVKLQKEVEECANLSRLLK 5H7_HUMAN 289 8 -
LNGVVKLQKEVEECANLSRLLK P97842 292 8 -
LNGIVKLQKEVEECANLSRLLK P78336 289 8 -
LNGMVKLQKEVEECANLSRLLK 5H7_CAVPO 290 8 -

Motif 7 width=18
Element Seqn Id St Int Rpt
RNINRKLSAAGMHEALKL 5H7_RAT 407 93 -
RNINRKLSAAGMHEALKL 5H7_MOUSE 407 93 -
RNINRKLSAAGMHEALKL 5H7_HUMAN 404 93 -
RNINRKLSAAGMHEALKL P97842 407 93 -
RNINRKLSAAGMHEALKL P78336 404 93 -
RNINRKLSAAGMHEALKL 5H7_CAVPO 405 93 -

Motif 8 width=22
Element Seqn Id St Int Rpt
AERPERSEFVLQNSDHCGKKGH 5H7_RAT 425 0 -
AERPERSEFVLQNCDHCGKKGH 5H7_MOUSE 425 0 -
AERPERPEFVLQNADYCRKKGH 5H7_HUMAN 422 0 -
AERPERSEFVLMTRASGVQQAL P97842 425 0 -
AERPERPEFVLRACTRRVLLRP P78336 422 0 -
AERPERPECVLQNSDYCRKKGH 5H7_CAVPO 423 0 -