WORKLIST ENTRIES (1):

5HT2CRECEPTR View alignment View Structure    5-hydroxytryptamine 2C receptor signature
 Type of fingerprint: COMPOUND with 8  elements
Links:
   PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
   PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
   PRINTS; PR00251 BACTRLOPSIN
   PRINTS; PR01101 5HTRECEPTOR; PR00516 5HT2ARECEPTR; PR00651 5HT2BRECEPTR
   INTERPRO; IPR000377

 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. 
  
   5HT2CRECEPTR is an 8-element fingerprint that provides a signature for the
   5HT2C receptors. The fingerprint was derived from an initial alignment of
   3 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 5HT2C receptors but distinguish them from the rest of
   the 5HT family - motifs 1 and 2 lie at the N-terminus; motifs 3 and 4 span
   the third cytoplasmic loop; and motifs 6-8 lie at the C-terminus. A single
   iteration on OWL28.0 was required to reach convergence, no further sequences
   being identified beyond the starting set. A single partial match was also
   found (HS5HT2C), a 5HT2C receptor fragment that matches motifs 1 and 2.
  
   An update on SPTR37_9f identified a true set of 3 sequences, and 2
   partial matches.

  SUMMARY INFORMATION
      3 codes involving  8 elements
      0 codes involving  7 elements
      1 codes involving  6 elements
      0 codes involving  5 elements
      0 codes involving  4 elements
      0 codes involving  3 elements
      1 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    8|   3    3    3    3    3    3    3    3  
    7|   0    0    0    0    0    0    0    0  
    6|   0    0    1    1    1    1    1    1  
    5|   0    0    0    0    0    0    0    0  
    4|   0    0    0    0    0    0    0    0  
    3|   0    0    0    0    0    0    0    0  
    2|   1    1    0    0    0    0    0    0  
   --+-----------------------------------------
     |   1    2    3    4    5    6    7    8  

True positives..
 5H2C_MOUSE     5H2C_RAT       5H2C_HUMAN     
Subfamily:  Codes involving 6 elements
 Subfamily True positives..
 Q62842         
Subfamily:  Codes involving 2 elements
 Subfamily True positives..
 Q13638         


  PROTEIN TITLES
   5H2C_MOUSE       5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT-2C) (SEROTONIN RECEPTO
   5H2C_RAT         5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT-2C) (SEROTONIN RECEPTO
   5H2C_HUMAN       5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT-2C) (SEROTONIN RECEPTO
 
   Q62842           SEROTONIN 5-HT2C - RATTUS NORVEGICUS (RAT).
 
   Q13638           5-HT2C RECEPTOR - HOMO SAPIENS (HUMAN).

SCAN HISTORY OWL28_0 1 50 NSINGLE SPTR37_9f 2 6 NSINGLE INITIAL MOTIF SETS 5HT2CRECEPTR1 Length of motif = 20 Motif number = 1 5HT2C receptor motif I - 1 PCODE ST INT AVRSLLVHLIGLLVWQFDIS 5H2C_MOUSE 7 7 AVRSLLMHLIGLLVWQFDIS 5H2C_RAT 7 7 AVHSFLVHLIGLLVWQCDIS 5H2C_HUMAN 7 7 5HT2CRECEPTR2 Length of motif = 18 Motif number = 2 5HT2C receptor motif II - 1 PCODE ST INT SPVAAIVTDTFNSSDGGR 5H2C_MOUSE 28 1 SPVAAIVTDTFNSSDGGR 5H2C_RAT 28 1 SPVAAIVTDIFNTSDGGR 5H2C_HUMAN 28 1 5HT2CRECEPTR3 Length of motif = 13 Motif number = 3 5HT2C receptor motif III - 1 PCODE ST INT EEENAPNPNPDQK 5H2C_MOUSE 275 229 EEENAPNPNPDQK 5H2C_RAT 276 230 EEENSANPNQDQN 5H2C_HUMAN 273 227 5HT2CRECEPTR4 Length of motif = 12 Motif number = 4 5HT2C receptor motif IV - 1 PCODE ST INT RRKKKEKRPRGT 5H2C_MOUSE 289 1 RRKKKEKRPRGT 5H2C_RAT 290 1 RRKKKERRPRGT 5H2C_HUMAN 288 2 5HT2CRECEPTR5 Length of motif = 17 Motif number = 5 5HT2C receptor motif V - 1 PCODE ST INT PPVRQIPRVAATALSGR 5H2C_MOUSE 394 93 PPVRQIPRVAATALSGR 5H2C_RAT 395 93 PPVRQIPRVAATALSGR 5H2C_HUMAN 393 93 5HT2CRECEPTR6 Length of motif = 17 Motif number = 6 5HT2C receptor motif VI - 1 PCODE ST INT ELNVNIYRHTNERVVRK 5H2C_MOUSE 411 0 ELNVNIYRHTNERVARK 5H2C_RAT 412 0 ELNVNIYRHTNEPVIEK 5H2C_HUMAN 410 0 5HT2CRECEPTR7 Length of motif = 16 Motif number = 7 5HT2C receptor motif VII - 1 PCODE ST INT ANDTEPGIEMQVENLE 5H2C_MOUSE 428 0 ANDPEPGIEMQVENLE 5H2C_RAT 429 0 ASDNEPGIEMQVENLE 5H2C_HUMAN 427 0 5HT2CRECEPTR8 Length of motif = 15 Motif number = 8 5HT2C receptor motif VIII - 1 PCODE ST INT ELPVNPSNVVSERIS 5H2C_MOUSE 443 -1 ELPVNPSNVVSERIS 5H2C_RAT 444 -1 ELPVNPSSVVSERIS 5H2C_HUMAN 442 -1 FINAL MOTIF SETS 5HT2CRECEPTR1 Length of motif = 20 Motif number = 1 5HT2C receptor motif I - 2 PCODE ST INT AVRSLLVHLIGLLVWQFDIS 5H2C_MOUSE 7 7 AVRSLLMHLIGLLVWQFDIS 5H2C_RAT 7 7 AVHSFLVHLIGLLVWQCDIS 5H2C_HUMAN 7 7 5HT2CRECEPTR2 Length of motif = 18 Motif number = 2 5HT2C receptor motif II - 2 PCODE ST INT SPVAAIVTDTFNSSDGGR 5H2C_MOUSE 28 1 SPVAAIVTDTFNSSDGGR 5H2C_RAT 28 1 SPVAAIVTDIFNTSDGGR 5H2C_HUMAN 28 1 5HT2CRECEPTR3 Length of motif = 13 Motif number = 3 5HT2C receptor motif III - 2 PCODE ST INT EEENAPNPNPDQK 5H2C_MOUSE 275 229 EEENAPNPNPDQK 5H2C_RAT 276 230 EEENSANPNQDQN 5H2C_HUMAN 273 227 5HT2CRECEPTR4 Length of motif = 12 Motif number = 4 5HT2C receptor motif IV - 2 PCODE ST INT RRKKKEKRPRGT 5H2C_MOUSE 289 1 RRKKKEKRPRGT 5H2C_RAT 290 1 RRKKKERRPRGT 5H2C_HUMAN 288 2 5HT2CRECEPTR5 Length of motif = 17 Motif number = 5 5HT2C receptor motif V - 2 PCODE ST INT PPVRQIPRVAATALSGR 5H2C_MOUSE 394 93 PPVRQIPRVAATALSGR 5H2C_RAT 395 93 PPVRQIPRVAATALSGR 5H2C_HUMAN 393 93 5HT2CRECEPTR6 Length of motif = 17 Motif number = 6 5HT2C receptor motif VI - 2 PCODE ST INT ELNVNIYRHTNERVVRK 5H2C_MOUSE 411 0 ELNVNIYRHTNERVARK 5H2C_RAT 412 0 ELNVNIYRHTNEPVIEK 5H2C_HUMAN 410 0 5HT2CRECEPTR7 Length of motif = 16 Motif number = 7 5HT2C receptor motif VII - 2 PCODE ST INT ANDTEPGIEMQVENLE 5H2C_MOUSE 428 0 ANDPEPGIEMQVENLE 5H2C_RAT 429 0 ASDNEPGIEMQVENLE 5H2C_HUMAN 427 0 5HT2CRECEPTR8 Length of motif = 15 Motif number = 8 5HT2C receptor motif VIII - 2 PCODE ST INT ELPVNPSNVVSERIS 5H2C_MOUSE 443 -1 ELPVNPSNVVSERIS 5H2C_RAT 444 -1 ELPVNPSSVVSERIS 5H2C_HUMAN 442 -1

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