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PR01709

Identifier
5HT3ARECEPTR  [View Relations]  [View Alignment]  
Accession
PR01709
No. of Motifs
5
Creation Date
15-MAY-2002
Title
5-hydroxytryptamine 3 receptor A subunit signature
Database References
PRINTS; PR01708 5HT3RECEPTOR
MIM; 182139
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).
 
7. MARICQ, A.V., PETERSON, A.S., BRAKE, A.J., MYERS, R.M. AND JULIUS, D.
Primary structure and functional expression of the 5HT3 receptor, a 
serotonin-gated ion channel.
SCIENCE 254 432-437 (1991).               

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 (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].
 
Cloning of the 5-HT3A subunit from a neuroblastoma expression library was
reported in 1991 [7]. Whilst recombinant expression of 5-HT3A yields
functional receptors, the channel conductance and permeability to cations
are different from that observed for native receptors [4]. Alternative exon
splicing gives rise to two isoforms of 5-HT3A, termed 5-HT3AS and 5-HT3AL
for short and long variants, respectively. The 5-HT3RA subunit is widely
expressed throughout the peripheral and central nervous systems, including
several regions of the brain.
 
5HT3ARECEPTR is a 5-element fingerprint that provides a signature for 5-HT3A
receptor subunits. The fingerprint was derived from an initial alignment of
3 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the 
5-HT3A receptor subunits but distinguish them from 5-HT3B receptors - motifs
1 and 2 reside within the N-terminal domain; motifs 3 and 4 lie in the
variable cytoplasmic loop between M3 and M4; and motif 5 spans the 
C-terminal portion of M4. Two iterations on SPTR40_20f were required to 
reach convergence, at which point a true set comprising 10 sequences was
identified. A single partial match was also found, a putative truncated 
human 5-HT3A subunit lacking the N-terminus and TM domain M1.          
Summary Information
  10 codes involving  5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51010101010
400000
300111
200000
12345
True Positives
5HT3_HUMAN    5HT3_MOUSE    5HT3_RAT      O60854        
O70212 O70213 Q61225 Q62999
Q9BSZ9 Q9N0F4
True Positive Partials
Codes involving 3 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).
Q61225 5HT3 RECEPTOR - Mus musculus (Mouse).
Q62999 5HT3 RECEPTOR - Rattus norvegicus (Rat).
Q9BSZ9 HYPOTHETICAL 55.9 KDA PROTEIN - Homo sapiens (Human).
Q9N0F4 FERRET 5-HT3A RECEPTOR - Mustela putorius furo (Ferret).

Q9UEP2 SEROTONIN RECEPTOR - Homo sapiens (Human).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
NEFVDVGKSPNIPYVYI 5HT3_HUMAN 123 123 -
NEFVDVGKSPSIPYVYV 5HT3_RAT 128 128 -
NEFVDVGKSPNIPYVYV 5HT3_MOUSE 127 127 -

Motif 2 width=20
Element Seqn Id St Int Rpt
LHTIQDINISLWRLPEKVKS 5HT3_HUMAN 179 39 -
LHTIQDINISLWRTPEEVRS 5HT3_RAT 184 39 -
LHTIQDINITLWRSPEEVRS 5HT3_MOUSE 183 39 -

Motif 3 width=15
Element Seqn Id St Int Rpt
RPPATSQATKTDDCS 5HT3_HUMAN 365 166 -
RPPATFQANKTDDCS 5HT3_RAT 370 166 -
RPPATFQANKTDDCS 5HT3_MOUSE 368 165 -

Motif 4 width=17
Element Seqn Id St Int Rpt
ASLAVCGLLQELSSIRQ 5HT3_HUMAN 411 31 -
ASLAVRGLLQELSSIRH 5HT3_RAT 416 31 -
ASLAVRGLLQELSSIRH 5HT3_MOUSE 420 37 -

Motif 5 width=12
Element Seqn Id St Int Rpt
LAYSITLVMLWS 5HT3_HUMAN 462 34 -
LAYSITLVTLWS 5HT3_RAT 467 34 -
LAYSITLVTLWS 5HT3_MOUSE 471 34 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
NEFVDVGKSPNIPYVYI 5HT3_HUMAN 123 123 -
NEFVDVGKSPNIPYVYI O60854 123 123 -
NEFVDVGKSPNIPYVYI Q9BSZ9 129 129 -
NEFVDVGKSPSIPYVYV 5HT3_RAT 128 128 -
NEFVDVGKSPSIPYVYV Q62999 122 122 -
NEFVDVGKSPNIPYVYV 5HT3_MOUSE 127 127 -
NEFVDVGKSPNIPYVYV Q61225 128 128 -
NEFVDVGKSPNIPYVYV O70212 128 128 -
NEFVDVGKSPNIPYVYV O70213 128 128 -
NEFVDVGKSPSIPYVYV Q9N0F4 128 128 -

Motif 2 width=20
Element Seqn Id St Int Rpt
LHTIQDINISLWRLPEKVKS 5HT3_HUMAN 179 39 -
LHTIQDINISLWRLPEKVKS O60854 179 39 -
LHTIQDINISLWRLPEKVKS Q9BSZ9 185 39 -
LHTIQDINISLWRTPEEVRS 5HT3_RAT 184 39 -
LHTIQDINISLWRTPEEVRS Q62999 178 39 -
LHTIQDINITLWRSPEEVRS 5HT3_MOUSE 183 39 -
LHTIQDINITLWRSPEEVRS Q61225 184 39 -
LHTIQDINISLWRLPEKVKS O70212 184 39 -
LHTIQDINISLWRLPEKVKS O70213 184 39 -
LHTIQDINISLWRLPEKVKL Q9N0F4 184 39 -

Motif 3 width=15
Element Seqn Id St Int Rpt
RPPATSQATKTDDCS 5HT3_HUMAN 365 166 -
RPPATSQATKTDDCS O60854 397 198 -
RPPATSQATKTDDCS Q9BSZ9 371 166 -
RPPATFQANKTDDCS 5HT3_RAT 370 166 -
RPPATFQANKTDDCS Q62999 364 166 -
RPPATFQANKTDDCS 5HT3_MOUSE 368 165 -
RPPATFQANKTDDCS Q61225 370 166 -
RGPATLQATKTDDFS O70212 371 167 -
RGPATLQATKTDDFS O70213 371 167 -
RPLVISPATKTDDCT Q9N0F4 370 166 -

Motif 4 width=17
Element Seqn Id St Int Rpt
ASLAVCGLLQELSSIRQ 5HT3_HUMAN 411 31 -
ASLAVCGLLQELSSIRQ O60854 443 31 -
ASLAVCGLLQELSSIRQ Q9BSZ9 417 31 -
ASLAVRGLLQELSSIRH 5HT3_RAT 416 31 -
ASLAVRGLLQELSSIRH Q62999 410 31 -
ASLAVRGLLQELSSIRH 5HT3_MOUSE 420 37 -
ASLAVRGLLQELSSIRH Q61225 422 37 -
ASLAMCGLLQELASIRH O70212 423 37 -
ASLAMCGLLQELASIRH O70213 417 31 -
ASLAVRGLLQELASIRR Q9N0F4 416 31 -

Motif 5 width=12
Element Seqn Id St Int Rpt
LAYSITLVMLWS 5HT3_HUMAN 462 34 -
LAYSITLVMLWS O60854 494 34 -
LAYSITLVMLWS Q9BSZ9 468 34 -
LAYSITLVTLWS 5HT3_RAT 467 34 -
LAYSITLVTLWS Q62999 461 34 -
LAYSITLVTLWS 5HT3_MOUSE 471 34 -
LAYSITLVTLWS Q61225 473 34 -
LAYSITLVTLWS O70212 474 34 -
LAYSITLVTLWS O70213 468 34 -
LAYSVTLIALWS Q9N0F4 467 34 -