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PR01708

Identifier
5HT3RECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01708
No. of Motifs
3
Creation Date
15-MAY-2002
Title
5-hydroxytryptamine 3 receptor signature
Database References
PRINTS; PR01709 5HT3ARECEPTR; PR01710 5HT3BRECEPTR
Literature References
1. WANG, Z.Y., INGEGURD, K., OLSON, E.B.JNR., VIDRUK, E.H. AND BISGARD, G.E.
Expression of 5-HT3 receptors in primary sensory neurons of the petrosal 
ganglion of adult rats.
AUTON.NEUROSCI. 95 121-124 (2002).
 
2. LEITE, J.F. AND CASCIO, M.
Structure of ligand-gated ion channels: critical assessment of biochemical
data supports novel topology.
MOL.CELL.NEUROSCI. 17(5) 777-792 (2001).         
 
3. YAN, D., SCHULTE, M.K., BLOOM, K.E. AND WHITE M.M.
Structural features of the ligand-binding domain of the serotonin 5HT3 
receptor.
J.BIOL.CHEM. 274 5537-5541 (1999).
 
4. DAVIES, P.A., PISTIS, M., HANNA, M.C., PETERS, J.A., LAMBERT, J.J., HALES,
T.G. AND KIRKNESS, E.F.
The 5-HT3B subunit is a major determinant of serotonin-receptor function.
NATURE 397 359-363 (1999). 
 
5. DANG, H., ENGLAND, P.M., FARIVAR, S.S., DOUGHERTY, D.A. AND LESTER, H.A.
Probing the role of a conserved M1 proline residue in 5-hydroxytryptamine 3
receptor gating.
MOL.PHARMACOL. 57 1114-1122 (2000).
 
6. LOVINGER, D.
5-HT3 receptors and the neural actions of alcohols: an increasingly exciting
topic.
NEUROCHEM.INT. 35 125-130 (1999).

Documentation
Serotonin (5-hydroxytryptamine, 5-HT) is widely distributed in both the
central and peripheral nervous system, where it acts as a neurotransmitter
and neuromodulator [1]. It has been implicated in several aspects of brain
function, including regulation of affective states, ingestive behavior and
addiction. 5-HT can activate a number of different receptor subtypes that
produce diverse neuronal responses, principally through activation of
G-protein-mediated signalling pathways. Signalling through the 5-HT3
receptor (5-HT3R) differs, since this subtype belongs to the ligand-gated
ion channel (LGIC) superfamily, which also includes the inhibitory
gamma-aminobutyric acid type A and glycine receptors, and excitatory
nicotinic acetylcholine receptors (nAChR) [2]. 5-HT3 receptor function has
been implicated in a variety of neural processes, including pain perception,
emesis, anxiety and drug abuse.
 
Like the other members of the LGIC superfamily, the 5HT3R exhibits a high
degree of sequence similarity, and therefore putative structural similarity,
with nAChRs [3]. Thus, funtional 5HT3Rs comprise a pentamer: the ion channel
is formed at the centre of a rosette formed between five homologous
subunits. Two classes of 5-HT3R subunit are currently known, termed 5-HT3A
and 5-HT3B. Whilst homomeric pentamers of 5-HT3A form functional receptors,
heteromeric assemblies display channel conductances, cation permeabilities
and current-voltage relationships typical of characterised neuronal 5-HT3 
channels [4].
 
The proposed topology of 5-HT3R subunits comprises four putative
transmembrane (TM) domains (designated M1-4); a large extracellular 
N-terminal region (~200 amino acids); and a variable cytoplasmic loop 
between M3 and M4. The M2 domains from each subunit are thought to form the 
channel pore [5]. The agonist binding site is formed by the N-terminus,
which, on binding, induces a conformational change in the channel pore, a
process often referred to as "gating" [5]. Opening of the pore allows cation
flux through the neuronal membrane and depolarises the membrane potential.
Thus, 5-HT3Rs may be thought of as excitatory receptors [6].
 
5HT3RECEPTOR is a 3-element fingerprint that provides a signature for
5-hydroxytryptamine type 3 receptor subunits. The fingerprint was derived
from an initial alignment of 13 sequences: the motifs were drawn from 
conserved regions spanning the central portion of the alignment, focusing on
those sections that characterise the 5HT3Rs but distinguish them from other
members of the ligand-gated ion channel superfamily - motif 1 lies in the 
N-terminal domain; and motifs 3 and 4 reside within the variable cytoplasmic
loop between TM domains M3 and M4. A single iteration on SPTR40_20f was
required to reach convergence, no further sequences being identified beyond
the starting set. A single partial match was found, Q9UEP2, a putative 
truncated human 5-HT3A subunit lacking the N-terminus and TM domain M1.      
Summary Information
  13 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3131313
2011
123
True Positives
5HT3_HUMAN    5HT3_MOUSE    5HT3_RAT      O60854        
O70212 O70213 O95264 Q61225
Q62999 Q9BSZ9 Q9JHJ5 Q9JJ16
Q9N0F4
True Positive Partials
Codes involving 2 elements
Q9UEP2
Sequence Titles
5HT3_HUMAN  5-hydroxytryptamine 3 receptor precursor (5-HT-3) (Serotonin-gated ion channel receptor) (5-HT3R) - Homo sapiens (Human). 
5HT3_MOUSE 5-hydroxytryptamine 3 receptor precursor (5-HT-3) (Serotonin-gated ion channel receptor) (5-HT3R) - Mus musculus (Mouse).
5HT3_RAT 5-hydroxytryptamine 3 receptor precursor (5-HT-3) (Serotonin-gated ion channel receptor) (5-HT3R) - Rattus norvegicus (Rat).
O60854 5-HYDROXYTRYPTAMINE 3 RECEPTOR PRECURSOR (5-HT-3) (SEROTONIN-GATED ION CHANNEL RECEPTOR) (5-HT3R) (5-HT3 RECEPTOR) (SEROTONIN 3 RECEPTOR) - Homo sapiens (Human).
O70212 5-HT3-AL RECEPTOR PRECURSOR - Cavia porcellus (Guinea pig).
O70213 5-HT3-AS RECEPTOR PRECURSOR - Cavia porcellus (Guinea pig).
O95264 5-HYDROXYTRYPTAMINE 3 RECEPTOR B SUBUNIT PRECURSOR - Homo sapiens (Human).
Q61225 5HT3 RECEPTOR - Mus musculus (Mouse).
Q62999 5HT3 RECEPTOR - Rattus norvegicus (Rat).
Q9BSZ9 HYPOTHETICAL 55.9 KDA PROTEIN - Homo sapiens (Human).
Q9JHJ5 5-HYDROXYTRYPTAMINE 3 RECEPTOR B SUBUNIT PRECURSOR - Mus musculus (Mouse).
Q9JJ16 5-HYDROXYTRYPTAMINE 3 RECEPTOR B SUBUNIT - Rattus norvegicus (Rat).
Q9N0F4 FERRET 5-HT3A RECEPTOR - Mustela putorius furo (Ferret).

Q9UEP2 SEROTONIN RECEPTOR - Homo sapiens (Human).
Scan History
SPTR40_20f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
NEFVDVGKSPSIPYVYV 5HT3_RAT 128 128 -
NEFVDVGKSPSIPYVYV Q62999 122 122 -
NEFVDVGKSPNIPYVYV O70212 128 128 -
NEFVDVGKSPNIPYVYV O70213 128 128 -
NEFVDVGKSPNIPYVYI 5HT3_HUMAN 123 123 -
NEFVDVGKSPNIPYVYI O60854 123 123 -
NEFVDVGKSPNIPYVYI Q9BSZ9 129 129 -
NEFVDVGKSPNIPYVYV 5HT3_MOUSE 127 127 -
NEFVDVGKSPNIPYVYV Q61225 128 128 -
NEFVDVGKSPSIPYVYV Q9N0F4 128 128 -
NEFVDVERSPDLPYVYV Q9JJ16 117 117 -
NEFVDVERSPDLPYVYV Q9JHJ5 117 117 -
NEFVDIERYPDLPYVYV O95264 121 121 -

Motif 2 width=12
Element Seqn Id St Int Rpt
FVVCMALLVISL 5HT3_RAT 314 169 -
FVVCMALLVISL Q62999 308 169 -
FVVCMALLVISL O70212 315 170 -
FVVCMALLVISL O70213 315 170 -
FVVCMALLVISL 5HT3_HUMAN 309 169 -
FVVCMALLVISL O60854 341 201 -
FVVCMALLVISL Q9BSZ9 315 169 -
FVVCMALLVISL 5HT3_MOUSE 312 168 -
FVVCMALLVISL Q61225 314 169 -
FVVCMALLVMSL Q9N0F4 314 169 -
FTVCMALLVLSL Q9JJ16 302 168 -
FTVCMALLVLSL Q9JHJ5 302 168 -
FTICMAFLVLSL O95264 306 168 -

Motif 3 width=10
Element Seqn Id St Int Rpt
LLCLGEQPMA 5HT3_RAT 359 33 -
LLCLGEQPMA Q62999 353 33 -
LLCLGEQLTS O70212 360 33 -
LLCLGEQLTS O70213 360 33 -
LLCLREQSTS 5HT3_HUMAN 354 33 -
LLCLREQSTS O60854 386 33 -
LLCLREQSTS Q9BSZ9 360 33 -
ILCLGEQPMA 5HT3_MOUSE 357 33 -
ILCLGEQPMA Q61225 359 33 -
LLCLGEQPAS Q9N0F4 359 33 -
LMCLRGDSDA Q9JJ16 335 21 -
LMCLQGDSDA Q9JHJ5 335 21 -
FLCLRGDTDA O95264 339 21 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
NEFVDVGKSPSIPYVYV 5HT3_RAT 128 128 -
NEFVDVGKSPSIPYVYV Q62999 122 122 -
NEFVDVGKSPNIPYVYV O70212 128 128 -
NEFVDVGKSPNIPYVYV O70213 128 128 -
NEFVDVGKSPNIPYVYI 5HT3_HUMAN 123 123 -
NEFVDVGKSPNIPYVYI O60854 123 123 -
NEFVDVGKSPNIPYVYI Q9BSZ9 129 129 -
NEFVDVGKSPNIPYVYV 5HT3_MOUSE 127 127 -
NEFVDVGKSPNIPYVYV Q61225 128 128 -
NEFVDVGKSPSIPYVYV Q9N0F4 128 128 -
NEFVDVERSPDLPYVYV Q9JJ16 117 117 -
NEFVDVERSPDLPYVYV Q9JHJ5 117 117 -
NEFVDIERYPDLPYVYV O95264 121 121 -

Motif 2 width=12
Element Seqn Id St Int Rpt
FVVCMALLVISL 5HT3_RAT 314 169 -
FVVCMALLVISL Q62999 308 169 -
FVVCMALLVISL O70212 315 170 -
FVVCMALLVISL O70213 315 170 -
FVVCMALLVISL 5HT3_HUMAN 309 169 -
FVVCMALLVISL O60854 341 201 -
FVVCMALLVISL Q9BSZ9 315 169 -
FVVCMALLVISL 5HT3_MOUSE 312 168 -
FVVCMALLVISL Q61225 314 169 -
FVVCMALLVMSL Q9N0F4 314 169 -
FTVCMALLVLSL Q9JJ16 302 168 -
FTVCMALLVLSL Q9JHJ5 302 168 -
FTICMAFLVLSL O95264 306 168 -

Motif 3 width=10
Element Seqn Id St Int Rpt
LLCLGEQPMA 5HT3_RAT 359 33 -
LLCLGEQPMA Q62999 353 33 -
LLCLGEQLTS O70212 360 33 -
LLCLGEQLTS O70213 360 33 -
LLCLREQSTS 5HT3_HUMAN 354 33 -
LLCLREQSTS O60854 386 33 -
LLCLREQSTS Q9BSZ9 360 33 -
ILCLGEQPMA 5HT3_MOUSE 357 33 -
ILCLGEQPMA Q61225 359 33 -
LLCLGEQPAS Q9N0F4 359 33 -
LMCLRGDSDA Q9JJ16 335 21 -
LMCLQGDSDA Q9JHJ5 335 21 -
FLCLRGDTDA O95264 339 21 -