WORKLIST ENTRIES (1):
5HT2ARECEPTR View alignment View Structure 5-hydroxytryptamine 2A receptor signature
Type of fingerprint: COMPOUND with 7 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR01101 5HTRECEPTOR; PR00651 5HT2BRECEPTR; PR00517 5HT2CRECEPTR
INTERPRO; IPR000455
Creation date 04-JUN-1996; UPDATE 06-JUN-1999
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.
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 [1,2]. 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.
5HT2ARECEPTR is a 7-element fingerprint that provides a signature for the
5HT2A receptors. The fingerprint was derived from an initial alignment of
4 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 5HT2A receptors but distinguish them from the rest of
teh 5HT family - motifs 1-3 lie at the N-terminus; motifs 4 and 5 span the
third cytoplasmic loop; and motifs 6 and 7 lie at the C-terminus. Two
iterations on OWL28.0 were required to reach convergence, at which point a
true set comprising 6 sequences was identified. A single partial match was
also found (5H2A_CAVPO), a 5HT2A receptor fragment that matches motifs 4
and 5.
An update on SPTR37_9f identified a true set of 6 sequences.
SUMMARY INFORMATION
6 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 FINGERPRINT INDEX
7| 6 6 6 6 6 6 6
6| 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0
--+------------------------------------
| 1 2 3 4 5 6 7
True positives..
5H2A_HUMAN 5H2A_RAT 5H2A_MACMU 5H2A_CRIGR
5H2A_PIG 5H2A_MOUSE
PROTEIN TITLES
5H2A_HUMAN 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTO
5H2A_RAT 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTO
5H2A_MACMU 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTO
5H2A_CRIGR 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTO
5H2A_PIG 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTO
5H2A_MOUSE 5-HYDROXYTRYPTAMINE 2A RECEPTOR (5-HT-2A) (SEROTONIN RECEPTO
SCAN HISTORY
OWL28_0 2 50 NSINGLE
SPTR37_9f 2 7 NSINGLE
INITIAL MOTIF SETS
5HT2ARECEPTR1 Length of motif = 20 Motif number = 1
5HT2A receptor motif I - 1
PCODE ST INT
LYSNDFNSGEANTSDAFNWT 5H2A_HUMAN 27 27
LYHNDFNSRDANTSEASNWT 5H2A_RAT 27 27
LYPNDFNSRDANTSEASNWT 5H2A_MOUSE 27 27
LYRNDFNSRDANSSDASNWT 5H2A_CRIGR 27 27
5HT2ARECEPTR2 Length of motif = 15 Motif number = 2
5HT2A receptor motif II - 1
PCODE ST INT
VDSENRTNLSCEGCL 5H2A_HUMAN 47 0
IDAENRTNLSCEGYL 5H2A_RAT 47 0
IDAENRTNLSCEGYL 5H2A_MOUSE 47 0
IDGENRTNLSFEGYL 5H2A_CRIGR 47 0
5HT2ARECEPTR3 Length of motif = 15 Motif number = 3
5HT2A receptor motif III - 1
PCODE ST INT
PSCLSLLHLQEKNWS 5H2A_HUMAN 63 1
PTCLSILHLQEKNWS 5H2A_RAT 63 1
PTCLSILHLQEKNWS 5H2A_MOUSE 63 1
PTCLSILHLQEKNWS 5H2A_CRIGR 63 1
5HT2ARECEPTR4 Length of motif = 18 Motif number = 4
5HT2A receptor motif IV - 1
PCODE ST INT
CVSDLGTRAKLASFSFLP 5H2A_HUMAN 268 190
CVSDLSTRAKLASFSFLP 5H2A_RAT 268 190
CVSDLSTRAKLSSFSFLP 5H2A_MOUSE 268 190
CVSDLSTRAKLASFSFLP 5H2A_CRIGR 268 190
5HT2ARECEPTR5 Length of motif = 18 Motif number = 5
5HT2A receptor motif V - 1
PCODE ST INT
LSSEKLFQRSIHREPGSY 5H2A_HUMAN 289 3
LSSEKLFQRSIHREPGSY 5H2A_RAT 289 3
LSSEKLFQRSIHREPGSY 5H2A_MOUSE 289 3
LSSEKLFQRSIHREPGSY 5H2A_CRIGR 289 3
5HT2ARECEPTR6 Length of motif = 18 Motif number = 6
5HT2A receptor motif VI - 1
PCODE ST INT
PLQLILVNTIPALAYKSS 5H2A_HUMAN 405 98
PLQLILVNTIPALAYKSS 5H2A_RAT 405 98
PLQLILVNTIPTLAYKSS 5H2A_MOUSE 405 98
PLQLILVNTIPALAYKSS 5H2A_CRIGR 405 98
5HT2ARECEPTR7 Length of motif = 17 Motif number = 7
5HT2A receptor motif VII - 1
PCODE ST INT
TDNDCSMVALGKQHSEE 5H2A_HUMAN 439 16
TVDDCSMVTLGKQQSEE 5H2A_RAT 439 16
TANDCSMVTLGNQHSEE 5H2A_MOUSE 439 16
TDNDCSMVTLGKQQSEE 5H2A_CRIGR 439 16
FINAL MOTIF SETS
5HT2ARECEPTR1 Length of motif = 20 Motif number = 1
5HT2A receptor motif I - 2
PCODE ST INT
LYSNDFNSGEANTSDAFNWT 5H2A_HUMAN 27 27
LYHNDFNSRDANTSEASNWT 5H2A_RAT 27 27
LYSNDFNSGEANTSDAFNWT 5H2A_MACMU 27 27
LYRNDFNSRDANSSDASNWT 5H2A_CRIGR 27 27
LYHNDFNSGEANTSDAFNWT 5H2A_PIG 27 27
LYPNDFNSRDANTSEASNWT 5H2A_MOUSE 27 27
5HT2ARECEPTR2 Length of motif = 15 Motif number = 2
5HT2A receptor motif II - 2
PCODE ST INT
VDSENRTNLSCEGCL 5H2A_HUMAN 47 0
IDAENRTNLSCEGYL 5H2A_RAT 47 0
VESENRTNLSCEGCL 5H2A_MACMU 47 0
IDGENRTNLSFEGYL 5H2A_CRIGR 47 0
VDSENRTNLSCEGCL 5H2A_PIG 47 0
IDAENRTNLSCEGYL 5H2A_MOUSE 47 0
5HT2ARECEPTR3 Length of motif = 15 Motif number = 3
5HT2A receptor motif III - 2
PCODE ST INT
PSCLSLLHLQEKNWS 5H2A_HUMAN 63 1
PTCLSILHLQEKNWS 5H2A_RAT 63 1
PSCLSLLHLQEKNWS 5H2A_MACMU 63 1
PTCLSILHLQEKNWS 5H2A_CRIGR 63 1
PPCFSLLHLQEKNWS 5H2A_PIG 63 1
PTCLSILHLQEKNWS 5H2A_MOUSE 63 1
5HT2ARECEPTR4 Length of motif = 18 Motif number = 4
5HT2A receptor motif IV - 2
PCODE ST INT
CVSDLGTRAKLASFSFLP 5H2A_HUMAN 268 190
CVSDLSTRAKLASFSFLP 5H2A_RAT 268 190
CVSDLGTRAKLASFSFLP 5H2A_MACMU 268 190
CVSDLSTRAKLASFSFLP 5H2A_CRIGR 268 190
CVSDLGTRAKLASFSFLP 5H2A_PIG 268 190
CVSDLSTRAKLSSFSFLP 5H2A_MOUSE 268 190
5HT2ARECEPTR5 Length of motif = 18 Motif number = 5
5HT2A receptor motif V - 2
PCODE ST INT
LSSEKLFQRSIHREPGSY 5H2A_HUMAN 289 3
LSSEKLFQRSIHREPGSY 5H2A_RAT 289 3
LSSEKLFQRSIHRDPGSY 5H2A_MACMU 289 3
LSSEKLFQRSIHREPGSY 5H2A_CRIGR 289 3
LSSEKLFQRSIHREPGSY 5H2A_PIG 289 3
LSSEKLFQRSIHREPGSY 5H2A_MOUSE 289 3
5HT2ARECEPTR6 Length of motif = 18 Motif number = 6
5HT2A receptor motif VI - 2
PCODE ST INT
PLQLILVNTIPALAYKSS 5H2A_HUMAN 405 98
PLQLILVNTIPALAYKSS 5H2A_RAT 405 98
PLQLILVNTIPALAYKSS 5H2A_MACMU 405 98
PLQLILVNTIPALAYKSS 5H2A_CRIGR 405 98
PLQLILVNTIPALAYKSS 5H2A_PIG 404 97
PLQLILVNTIPTLAYKSS 5H2A_MOUSE 405 98
5HT2ARECEPTR7 Length of motif = 17 Motif number = 7
5HT2A receptor motif VII - 2
PCODE ST INT
TDNDCSMVALGKQHSEE 5H2A_HUMAN 439 16
TVDDCSMVTLGKQQSEE 5H2A_RAT 439 16
TDNDCSMVALGKQHSED 5H2A_MACMU 439 16
TDNDCSMVTLGKQQSEE 5H2A_CRIGR 439 16
TENDCTMVALGKQHSED 5H2A_PIG 438 16
TANDCSMVTLGNQHSEE 5H2A_MOUSE 439 16
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