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PR01710

Identifier
5HT3BRECEPTR  [View Relations]  [View Alignment]  
Accession
PR01710
No. of Motifs
3
Creation Date
15-MAY-2002
Title
5-hydroxytryptamine 3 receptor B subunit signature
Database References
PRINTS; PR01708 5HT3RECEPTOR
MIM; 604654
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 aerotonin 5HT3 
receptor.
J.BIOL.CHEM. 274 5537-5541 (1999).
 
4. 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).
 
5. LOVINGER, D.
5-HT3 receptors and the neural actions of alcohols: an increasingly exciting
topic.
NEUROCHEM.INT. 35 125-130 (1999).
 
7. 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).
 
8. DUBIN, A.E., HUVAR, R., D'ANDREA, M.R., PYATI, J., ZHU, J.Y., JOY, K.C., 
WILSON, S.J., GALINDO, J.E., GLASS, C.A., LUO, L., JACKSON, M.R., LOVENBERG,
T.W. AND ERLANDER, M.G.
The pharmacological and functional characteristics of the serotonin 5-HT3A 
receptor are specifically modified by a 5-HT3B receptor subunit.
J.BIOL.CHEM. 274 30799-30810 (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. The proposed topology of 5-HT3R subunits comprises four putative
transmembrane (TM) domains (designate 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 [4]. 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" [4]. 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 [5].
 
Whilst it was initially thought that 5-HT3Rs comprised a homopentamer of
alpha subunits, the channel conductance and permeability to anions was
different in homomeric receptors from that observed in native channels. More
recently, another 5-HT3 receptor subunit, 5-HT3B, was identified and cloned
from a human brain cDNA library [7]. This subunit was unable to form
functional channels when expressed alone in oocytes, but produced functional
receptors when injected with 5-HT3A into the same cell. It is thought that
5HT3B contributes towards tissue-specific functional changes in
5-HT3-mediated signalling [8].
 
5HT3BRECEPTR is a 3-element fingerprint that provides a signature for 5-HT3B
receptor subunits. The fingerprint was derived from an initial alignment of
2 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the 
5-HT3B receptor subunits but distinguish them from 5-HT3A receptors - motifs
1 and 2 reside within the N-terminal domain; and motif 3 lies in the 
variable cytoplasmic loop between TM domains M3 and M4. Two iterations on 
SPTR40_20f were required to reach convergence, at which point a true set
comprising 3 sequences was identified.                             
Summary Information
3 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3333
2000
123
True Positives
O95264        Q9JHJ5        Q9JJ16        
Sequence Titles
O95264      5-HYDROXYTRYPTAMINE 3 RECEPTOR B SUBUNIT PRECURSOR - Homo sapiens (Human). 
Q9JHJ5 5-HYDROXYTRYPTAMINE 3 RECEPTOR B SUBUNIT PRECURSOR - Mus musculus (Mouse).
Q9JJ16 5-HYDROXYTRYPTAMINE 3 RECEPTOR B SUBUNIT - Rattus norvegicus (Rat).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
VGILGTATPQPGNSSL Q9JHJ5 13 13 -
AGILATDTHHPQDSAL O95264 17 17 -

Motif 2 width=14
Element Seqn Id St Int Rpt
SSTYHIRQSSAGDF Q9JHJ5 209 180 -
SSTYSILQSSAGGF O95264 213 180 -

Motif 3 width=20
Element Seqn Id St Int Rpt
VHQEHRVPSDTLKDFWFQFR Q9JHJ5 363 140 -
LYGEHLAQPGTLKEVWSQLQ O95264 367 140 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
VGILGTATPQPGNSSL Q9JJ16 13 13 -
VGILGTATPQPGNSSL Q9JHJ5 13 13 -
AGILATDTHHPQDSAL O95264 17 17 -

Motif 2 width=14
Element Seqn Id St Int Rpt
TSTYHIRQSSAGDF Q9JJ16 209 180 -
SSTYHIRQSSAGDF Q9JHJ5 209 180 -
SSTYSILQSSAGGF O95264 213 180 -

Motif 3 width=20
Element Seqn Id St Int Rpt
VRQEHQVPSDTLKDFWFQLQ Q9JJ16 363 140 -
VHQEHRVPSDTLKDFWFQFR Q9JHJ5 363 140 -
LYGEHLAQPGTLKEVWSQLQ O95264 367 140 -