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PR01059

Identifier
5HT4RECEPTR  [View Relations]  [View Alignment]  
Accession
PR01059
No. of Motifs
11
Creation Date
26-JAN-1999  (UPDATE 06-JUN-1999)
Title
5-hydroxytryptamine 4 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01101 5HTRECEPTOR
INTERPRO; IPR001520
GCRDB; GCR_1447; GCR_1448; GCR_1480; GCR_1315
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 5H4 receptor is found in neurons in the CNS, with highest levels in
colliculus and hippocampus [6]. In the periphery, it is found in myenteric
neurons in ileum and in smoothe muscle (e.g., rat oesophagus and heart
muscle) [6]. The receptor is linked to the adenylyl cyclase pathway via
Gs [6].
 
5HT4RECEPTR is an 11-element fingerprint that provides a signature for
5-hydroxytryptamine 4 receptors. The fingerprint was derived from an initial
alignment of 13 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that
characterise the 5HT4 receptors but distinguish them from the rest of the
5HT family - motif 1 resides at the N-terminus; motif 2 spans the first
cytoplasmic loop; motif 3 spans the C-terminus of TM domain 2, leading into
the first external loop; motif 4 spans the second cytoplasmic loop; motifs 
5 and 6 span the second external loop; motifs 7 and 8 span the third 
cytoplasmic loop; motif 9 lies in the third external loop; and motifs 10
and 11 reside at the C-terminus. A single iteration on OWL31.1 was required
to reach convergence, no further sequences being identified beyond the 
starting set. Three partial matches were also found, all of which are
fragments that lack portions of sequence bearing the N- and C-terminal
motifs.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 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
1166666666666
1000000000000
900000000000
800000000000
700000000000
600000000000
500000000000
400000000000
300000000000
200000000000
1234567891011
True Positives
5H4_MOUSE     5H4_RAT       O70528        O89003        
O89004 O89034
Sequence Titles
5H4_MOUSE   5-HYDROXYTRYPTAMINE 4 RECEPTOR (5-HT-4) (SEROTONIN RECEPTOR) (5-HT4) - MUS MUSCULUS (MOUSE). 
5H4_RAT 5-HYDROXYTRYPTAMINE 4 RECEPTOR (5-HT-4) (SEROTONIN RECEPTOR) (5-HT4) - RATTUS NORVEGICUS (RAT).
O70528 SEROTONIN RECEPTOR 4 - CAVIA PORCELLUS (GUINEA PIG).
O89003 SEROTONIN 4 RECEPTOR - MUS MUSCULUS (MOUSE).
O89004 SEROTONIN 4 RECEPTOR - MUS MUSCULUS (MOUSE).
O89034 SEROTONIN 4 RECEPTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    1  100  NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
DRLDANVSSNEGFGSVEK 5H4_RAT 2 2 -
DKLDANVSSNEGFRSVEK 5H4_MOUSE 2 2 -
DRLDANVSSNEGFGSVEK RNAJ1370 2 2 -
DKLDANVSSEEGFGSVEK HSAJ1371 2 2 -
DKLDANVSSKEGFGSVEK CPY13585 2 2 -
DKLDANVSSEEGFGSVEK HSY12506 2 2 -
DKLDANVSSEEGFGSVEK HS5HT4AR 2 2 -
DRLDANVSSNEGFGSVEK S55550 2 2 -
DKLDANVSSNEGFRSVEK MM5HT4SAR 2 2 -
DKLDANVSSNEGFRSVEK MM5HT4SBR 2 2 -
DKLDANVSSNEGFRSVEK MMAJ1369 2 2 -
DKLDANVSSEEGFGSVEK HSY12507 2 2 -
DKLDANVSSEEGFGSVEK HSSERR4 2 2 -

Motif 2 width=12
Element Seqn Id St Int Rpt
VCRDRQLRKIKT 5H4_MOUSE 44 24 -
VCRDRQLRKIKT CPY13585 44 24 -
VCWDRQLRKIKT HSSERR4 44 24 -
VCRDRQLRKIKT MM5HT4SAR 44 24 -
VCRDRQLRKIKT S55550 44 24 -
VCWDRQLRKIKT HS5HT4AR 44 24 -
VCWDRQLRKIKT HSY12506 44 24 -
VCWDRQLRKIKT HSAJ1371 44 24 -
VCRDRQLRKIKT RNAJ1370 44 24 -
VCRDRQLRKIKT MM5HT4SBR 44 24 -
VCRDRQLRKIKT MMAJ1369 44 24 -
VCWDRQLRKIKT HSY12507 44 24 -
VCRDRQLRKIKT 5H4_RAT 44 24 -

Motif 3 width=17
Element Seqn Id St Int Rpt
FGAIELVQDIWIYGEVF HS5HT4AR 76 20 -
FGAIELVQDIWIYGEVF HSY12506 76 20 -
FGAIELVQDIWIYGEVF HSAJ1371 76 20 -
FGAIELVQDIWFYGEMF RNAJ1370 76 20 -
FGAIELVQDIWAYGEMF MM5HT4SBR 76 20 -
FGAIELVQDIWAYGEMF MMAJ1369 76 20 -
FGAIELVQDIWIYGEVF HSY12507 76 20 -
FGAIELVQDIWAYGEMF MM5HT4SAR 76 20 -
FGAIELVQDIWIYGEVF HSSERR4 76 20 -
FGAIELVQDIWFYGEMF 5H4_RAT 76 20 -
FGAIELVQDIWAYGEMF 5H4_MOUSE 76 20 -
FGAIELVQDIWVYGEMF CPY13585 76 20 -
FGAIELVQDIWFYGEMF S55550 76 20 -

Motif 4 width=16
Element Seqn Id St Int Rpt
YYAICCQPLVYRNKMT HSAJ1371 119 26 -
YYAICCQPLVYRNKMT 5H4_RAT 119 26 -
YYAICCQPLVYRNKMT 5H4_MOUSE 119 26 -
YYAICCQPLVYRNKMT CPY13585 119 26 -
YYAICCQPLVYRNKMT HSSERR4 119 26 -
YYAICCQPLVYRNKMT MM5HT4SAR 119 26 -
YYAICCQPLVYRNKMT S55550 119 26 -
YYAICCQPLVYRNKMT HS5HT4AR 119 26 -
YYAICCQPLVYRNKMT HSY12506 119 26 -
YYAICCQPLVYRNKMT RNAJ1370 119 26 -
YYAICCQPLVYRNKMT MM5HT4SBR 119 26 -
YYAICCQPLVYRNKMT MMAJ1369 119 26 -
YYAICCQPLVYRNKMT HSY12507 119 26 -

Motif 5 width=14
Element Seqn Id St Int Rpt
SFLPIMQGWNNIGI MMAJ1369 153 18 -
SFLPIMQGWNNIGI RNAJ1370 153 18 -
SFLPIMQGWNNIGI HSAJ1371 153 18 -
SFLPIMQGWNNIGI HSY12506 153 18 -
SFLPIMQGWNNIGI HS5HT4AR 153 18 -
SFLPIMQGWNNIGI S55550 153 18 -
SFLPIMQGWNNIGI MM5HT4SAR 153 18 -
SFLPIMQGWNNIGI HSSERR4 153 18 -
SFLPIMQGWNNIGI CPY13585 153 18 -
SFLPIMQGWNNIGI HSY12507 153 18 -
SFLPIMQGWNNIGI 5H4_MOUSE 153 18 -
SFLPIMQGWNNIGI 5H4_RAT 153 18 -
SFLPIMQGWNNIGI MM5HT4SBR 153 18 -

Motif 6 width=25
Element Seqn Id St Int Rpt
DVIEKRKFNHNSNSTFCVFMVNKPY 5H4_RAT 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY CPY13585 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY HSSERR4 168 1 -
DVIEKRKFSHNSNSTWCVFMVNKPY MM5HT4SAR 168 1 -
DVIEKRKFNHNSNSTFCVFMVNKPY S55550 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY HS5HT4AR 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY HSY12506 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY HSAJ1371 168 1 -
DVIEKRKFNHNSNSTFCVFMVNKPY RNAJ1370 168 1 -
DVIEKRKFSHNSNSTWCVFMVNKPY MM5HT4SBR 168 1 -
DVIEKRKFSHNSNSTWCVFMVNKPY MMAJ1369 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY HSY12507 168 1 -
DVIEKRKFSHNSNSTWCVFMVNKPY 5H4_MOUSE 168 1 -

Motif 7 width=17
Element Seqn Id St Int Rpt
TAKEHAHQIQMLQRAGA HSY12506 218 25 -
TAKEHARQIQVLQRAGA CPY13585 218 25 -
TAKEHAHQIQMLQRAGA HSSERR4 218 25 -
TAKEHAQQIQMLQRAGA MM5HT4SAR 218 25 -
TAKEHAQQIQMLQRAGA S55550 218 25 -
TAKEHAHQIQMLQRAGA HS5HT4AR 218 25 -
TAKEHAHQIQMLQRAGA HSAJ1371 218 25 -
TAKEHAQQIQMLQRAGA RNAJ1370 218 25 -
TAKEHAQQIQMLQRAGA MM5HT4SBR 218 25 -
TAKEHAQQIQMLQRAGA MMAJ1369 218 25 -
TAKEHAHQIQMLQRAGA HSY12507 218 25 -
TAKEHAQQIQMLQRAGA 5H4_MOUSE 218 25 -
TAKEHAQQIQMLQRAGA 5H4_RAT 218 25 -

Motif 8 width=20
Element Seqn Id St Int Rpt
ATSESRPQTADQHSTHRMRT S55550 234 -1 -
ASSESRPQSADQHSTHRMRT HS5HT4AR 234 -1 -
ASSESRPQSADQHSTHRMRT HSY12506 234 -1 -
ASSESRPQSADQHSTHRMRT HSAJ1371 234 -1 -
ATSESRPQTADQHSTHRMRT RNAJ1370 234 -1 -
ATSESRPQPADQHSTHRMRT MM5HT4SBR 234 -1 -
ATSESRPQPADQHSTHRMRT MMAJ1369 234 -1 -
ASSESRPQSADQHSTHRMRT HSY12507 234 -1 -
ATSESRPQTADQHSTHRMRT 5H4_RAT 234 -1 -
ATSESRPQPADQHSTHRMRT 5H4_MOUSE 234 -1 -
APAEGRPQPADQHSTHRMRT CPY13585 234 -1 -
ASSESRPQSADQHSTHRMRT HSSERR4 234 -1 -
ATSESRPQPADQHSTHRMRT MM5HT4SAR 234 -1 -

Motif 9 width=16
Element Seqn Id St Int Rpt
DPFIDYTVPEKVWTAF S55550 282 28 -
DPFIDYTVPGQVWTAF HS5HT4AR 282 28 -
DPFIDYTVPGQVWTAF HSY12506 282 28 -
DPFIDYTVPGQVWTAF HSAJ1371 282 28 -
DPFIDYTVPEKVWTAF RNAJ1370 282 28 -
DPFIDYTVPEQVWTAF MM5HT4SBR 282 28 -
DPFIDYTVPEQVWTAF MMAJ1369 282 28 -
DPFIDYTVPGQVWTAF HSY12507 282 28 -
DPFIDYTVPGQLWTAF CPY13585 282 28 -
DPFIDYTVPEQVWTAF 5H4_MOUSE 282 28 -
DPFIDYTVPEKVWTAF 5H4_RAT 282 28 -
DPFIDYTVPGQVWTAF HSSERR4 282 28 -
DPFIDYTVPEQVWTAF MM5HT4SAR 282 28 -

Motif 10 width=17
Element Seqn Id St Int Rpt
RAFLIILCCDDERYRRP HS5HT4AR 321 23 -
RAFLIILCCDDERYKRP S55550 321 23 -
RAFLIILCCDDERYKRP MM5HT4SAR 321 23 -
RAFLIILCCDDERYKRP 5H4_RAT 321 23 -
RAFLIILCCDDERYRRP HSY12507 321 23 -
RAFLIILCCDDERYRRP HSSERR4 321 23 -
RAFLIILCCDDERYRRP CPY13585 321 23 -
RAFLIILCCDDERYKRP 5H4_MOUSE 321 23 -
RAFLIILCCDDERYKRP MMAJ1369 321 23 -
RAFLIILCCDDERYKRP MM5HT4SBR 321 23 -
RAFLIILCCDDERYKRP RNAJ1370 321 23 -
RAFLIILCCDDERYRRP HSAJ1371 321 23 -
RAFLIILCCDDERYRRP HSY12506 321 23 -

Motif 11 width=23
Element Seqn Id St Int Rpt
PSILGQTVPCSTTTINGSTHVLS HSAJ1371 337 -1 -
PPILGQTVPCSTTTINGSTHVLS MM5HT4SBR 337 -1 -
PPILGQTVPCSTTTINGSTHVLR MMAJ1369 337 -1 -
PSILGQTVPCSTTTINGSTHVLR HSY12507 337 -1 -
PSILGQTVPCSTTTINGSTHVLR HSSERR4 337 -1 -
PSILGQTVPCSTTTINGSTHVLR CPY13585 337 -1 -
PPILGQTVPCSTTTINGSTHVLR 5H4_MOUSE 337 -1 -
PPILGQTVPCSTTTINGSTHVLR 5H4_RAT 337 -1 -
PPILGQTVPCSTTTINGSTHVLR MM5HT4SAR 337 -1 -
PPILGQTVPCSTTTINGSTHVLR S55550 337 -1 -
PSILGQTVPCSTTTINGSTHVLR HS5HT4AR 337 -1 -
PSILGQTVPCSTTTINGSTHVLS HSY12506 337 -1 -
PPILGQTVPCSTTTINGSTHVLS RNAJ1370 337 -1 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
DKLDANVSSNEGFRSVEK 5H4_MOUSE 2 2 -
DKLDANVSSNEGFRSVEK O89003 2 2 -
DKLDANVSSNEGFRSVEK O89004 2 2 -
DRLDANVSSNEGFGSVEK 5H4_RAT 2 2 -
DRLDANVSSNEGFGSVEK O89034 2 2 -
DKLDANVSSKEGFGSVEK O70528 2 2 -

Motif 2 width=12
Element Seqn Id St Int Rpt
VCRDRQLRKIKT 5H4_MOUSE 44 24 -
VCRDRQLRKIKT O89003 44 24 -
VCRDRQLRKIKT O89004 44 24 -
VCRDRQLRKIKT 5H4_RAT 44 24 -
VCRDRQLRKIKT O89034 44 24 -
VCRDRQLRKIKT O70528 44 24 -

Motif 3 width=17
Element Seqn Id St Int Rpt
FGAIELVQDIWAYGEMF 5H4_MOUSE 76 20 -
FGAIELVQDIWAYGEMF O89003 76 20 -
FGAIELVQDIWAYGEMF O89004 76 20 -
FGAIELVQDIWFYGEMF 5H4_RAT 76 20 -
FGAIELVQDIWFYGEMF O89034 76 20 -
FGAIELVQDIWVYGEMF O70528 76 20 -

Motif 4 width=16
Element Seqn Id St Int Rpt
YYAICCQPLVYRNKMT 5H4_MOUSE 119 26 -
YYAICCQPLVYRNKMT O89003 119 26 -
YYAICCQPLVYRNKMT O89004 119 26 -
YYAICCQPLVYRNKMT 5H4_RAT 119 26 -
YYAICCQPLVYRNKMT O89034 119 26 -
YYAICCQPLVYRNKMT O70528 119 26 -

Motif 5 width=14
Element Seqn Id St Int Rpt
SFLPIMQGWNNIGI 5H4_MOUSE 153 18 -
SFLPIMQGWNNIGI O89003 153 18 -
SFLPIMQGWNNIGI O89004 153 18 -
SFLPIMQGWNNIGI 5H4_RAT 153 18 -
SFLPIMQGWNNIGI O89034 153 18 -
SFLPIMQGWNNIGI O70528 153 18 -

Motif 6 width=25
Element Seqn Id St Int Rpt
DVIEKRKFSHNSNSTWCVFMVNKPY 5H4_MOUSE 168 1 -
DVIEKRKFSHNSNSTWCVFMVNKPY O89003 168 1 -
DVIEKRKFSHNSNSTWCVFMVNKPY O89004 168 1 -
DVIEKRKFNHNSNSTFCVFMVNKPY 5H4_RAT 168 1 -
DVIEKRKFNHNSNSTFCVFMVNKPY O89034 168 1 -
DLIEKRKFNQNSNSTYCVFMVNKPY O70528 168 1 -

Motif 7 width=17
Element Seqn Id St Int Rpt
TAKEHAQQIQMLQRAGA 5H4_MOUSE 218 25 -
TAKEHAQQIQMLQRAGA O89003 218 25 -
TAKEHAQQIQMLQRAGA O89004 218 25 -
TAKEHAQQIQMLQRAGA 5H4_RAT 218 25 -
TAKEHAQQIQMLQRAGA O89034 218 25 -
TAKEHARQIQVLQRAGA O70528 218 25 -

Motif 8 width=20
Element Seqn Id St Int Rpt
ATSESRPQPADQHSTHRMRT 5H4_MOUSE 234 -1 -
ATSESRPQPADQHSTHRMRT O89003 234 -1 -
ATSESRPQPADQHSTHRMRT O89004 234 -1 -
ATSESRPQTADQHSTHRMRT 5H4_RAT 234 -1 -
ATSESRPQTADQHSTHRMRT O89034 234 -1 -
APAEGRPQPADQHSTHRMRT O70528 234 -1 -

Motif 9 width=16
Element Seqn Id St Int Rpt
DPFIDYTVPEQVWTAF 5H4_MOUSE 282 28 -
DPFIDYTVPEQVWTAF O89003 282 28 -
DPFIDYTVPEQVWTAF O89004 282 28 -
DPFIDYTVPEKVWTAF 5H4_RAT 282 28 -
DPFIDYTVPEKVWTAF O89034 282 28 -
DPFIDYTVPGQLWTAF O70528 282 28 -

Motif 10 width=17
Element Seqn Id St Int Rpt
RAFLIILCCDDERYKRP 5H4_MOUSE 321 23 -
RAFLIILCCDDERYKRP O89003 321 23 -
RAFLIILCCDDERYKRP O89004 321 23 -
RAFLIILCCDDERYKRP 5H4_RAT 321 23 -
RAFLIILCCDDERYKRP O89034 321 23 -
RAFLIILCCDDERYRRP O70528 321 23 -

Motif 11 width=23
Element Seqn Id St Int Rpt
PPILGQTVPCSTTTINGSTHVLR 5H4_MOUSE 337 -1 -
PPILGQTVPCSTTTINGSTHVLR O89003 337 -1 -
PPILGQTVPCSTTTINGSTHVLS O89004 337 -1 -
PPILGQTVPCSTTTINGSTHVLR 5H4_RAT 337 -1 -
PPILGQTVPCSTTTINGSTHVLS O89034 337 -1 -
PSILGQTVPCSTTTINGSTHVLR O70528 337 -1 -