WORKLIST ENTRIES (1):

GABAARGAMMA3 View alignment     Gamma-aminobutyric-acid A receptor gamma 3 subunit signature
 Type of fingerprint: COMPOUND with 4  elements
Links:
   PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR; PR01620 GABAARGAMMA
   PRINTS; PR01621 GABAARGAMMA1; PR01622 GABAARGAMMA2
   MIM; 600233

 Creation date 12-DEC-2001

   1. WHITING, P.J., MCKERNAN, R.M. AND WAFFORD, K.A.
   Structure and pharmacology of vertebrate GABA(A) receptor subtypes.
   INT.REV.NEUROBIOL. 38 95-138 (1995).

   2. ASHCROFT, F.M.
   GABA(A) receptors.
   IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.325-336.

   3. RUDOLPH, U., CRESTANI, F. AND MOHLER, H.
   GABA(A) receptor subtypes: dissecting their pharmacological functions.
   TRENDS PHARMACOL.SCI. 22 188-194 (2001).

   4. BARNARD, E.A., SKOLNICK, P., OLSEN, R.W., MOHLER, H., SIEGHART, W., 
   BIGGIO, G., BRAESTRUP, C., BATESON, A.N. AND LANGER, S.Z.
   International Union of Pharmacology: XV. Subtypes of gamma-aminobutyric acid
   (A) receptors: classification on the basis of subunit structure and receptor
   function.
   PHARMACOL.REV. 50 291-313 (1998).

   5. BONNERT, T.P., MCKERNAN, R.M., FARRAR, S., LE BOURDELLES, B., HEAVENS, 
   R.P., SMITH, D.W., HEWSON, L., RIGBY, M.R., SIRINATHSINGHJI, BROWN, N., 
   WAFFORD, K.A. AND WHITING, P.J.
   Theta, a novel gamma-aminobutyric acid type A receptor subunit.
   PROC.NATL.ACAD.SCI.U.S.A. 96 9891-9896 (1999).

   6. PRITCHETT, D.B., SONTHEIMER, H., SHIVERS, B.D., YMER, S., KETTENMANN, H.,
   SCHOFIELD, P.R. AND SEEBERG, P.H.
   Importance of a novel GABA(A) receptor subunit for benzodiazepine 
   pharmacology.
   NATURE 338 582-585 (1989).

   7. MOHLER, H., CRESTANI, F. AND RUDOLPH, U.
   GABA(A)-receptor subtypes: a new pharmacology.
   CURR.OPIN.PHARMACOL. 1 22-25 (2001).

   8. HERB, A., WISDEN, W., LUDDENS, H., PUIA, G., VICINI, S. AND SEEBERG, P.H.
   The third gamma subunit of the gamma-aminobutyric acid type A receptor 
   family.
   PROC.NATL.ACAD.SCI.U.S.A. 89 1433-1437 (1992).       

   Gamma-aminobutyric acid type A (GABAA) receptors are members of the neuro-
   transmitter ligand-gated ion channels: they mediate neuronal inhibition on
   binding GABA. The effects of GABA on GABAA receptors are modulated by a range
   of therapeutically important drugs, including barbiturates, anaesthetics and
   benzodiazepines (BZs) [1,2]. The BZs are a diverse range of compounds,
   including widely prescribed drugs, such as librium and valium, and their
   interaction with GABAA receptors provides the most potent pharmacological
   means of distinguishing different GABAA receptor subtypes [1].
  
   GABAA receptors are pentameric membrane proteins that operate GABA-gated
   chloride channels [3]. Eight types of receptor subunit have been cloned,
   with multiple subtypes within some classes: alpha 1-6, beta 1-4, gamma 1-4,
   delta, epsilon, pi, rho 1-3 and theta [4,5]. Subunits are typically 50-60kDa
   in size and comprise a long N-terminal extracellular domain, containing
   a putative signal peptide and a disulphide-bonded beta structural loop; 4
   putative transmembrane (TM) domains; and a large cytoplasmic loop connecting
   the third and fourth TM domains [2]. The large cytoplasmic loop displays the
   most divergence in terms of primary structure amongst family members, with
   the TM domains showing the highest level of sequence conservation [6].
  
   Immunoprecipitation studies have shown that most GABAA receptors contain one
   type of alpha and beta subunit, and a single gamma polypeptide in a ratio of
   2:2:1 [1]. Whilst the critical residue involved in BZ binding is believed to
   be located within the alpha subunit [7], the BZ binding site is considered
   to be located at the interface between adjacent alpha and gamma subunits:
   replacement of gamma subunits with delta and epsilon renders the receptor
   insensitive to BZs due to disruption of the binding site [4]. Three
   mammalian gamma subunits have been identified (gamma 1 to 3), each encoded
   by a separate gene, plus an avian gamma 4 subunit. 
  
   The presence of a gamma 2 subunit, together with alpha 1, confers 
   'classical' BZ-binding activity to GABAA receptors; substitution for 
   gamma 1 or 3 leads to an altered binding profile for BZs [4]. The gamma 3
   subunit confers a slightly reduced binding affinity for BZs when compared 
   to gamma 2-containing receptors [1], although the difference is not as
   great as that observed for gamma 1-containing receptor subtypes. 
  
   GABAARGAMMA3 is a 4-element fingerprint that provides a signature for GABAA
   gamma 3 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
   gamma 3 subunits but distinguish them from the rest of the GABAA receptor 
   gamma subunit family - motif 1 resides in the extracellular N-terminal
   domain; and motifs 2-4 lie in the cytoplasmic loop between TM domains 3 and
   4 [8]. A single iteration on SPTR40_18f was required to reach convergence,
   no further sequences being identified beyond the starting set.    

  SUMMARY INFORMATION
      3 codes involving  4 elements
      0 codes involving  3 elements
      0 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    4|   3    3    3    3  
    3|   0    0    0    0  
    2|   0    0    0    0  
   --+---------------------
     |   1    2    3    4  

True positives..
 GAC3_MOUSE     GAC3_RAT       GAC3_HUMAN     


  PROTEIN TITLES
   GAC3_MOUSE       Gamma-aminobutyric-acid receptor gamma-3 subunit precursor (
   GAC3_RAT         Gamma-aminobutyric-acid receptor gamma-3 subunit precursor (
   GAC3_HUMAN       Gamma-aminobutyric-acid receptor gamma-3 subunit precursor (

SCAN HISTORY SPTR40_18f 1 300 NSINGLE INITIAL MOTIF SETS GABAARGAMMA31 Length of motif = 23 Motif number = 1 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif I - 1 PCODE ST INT MAAKLLLLLCLFSGLHARSRRVE GAC3_MOUSE 1 1 MAAKLLLLLCLFSGLHARSRRVE GAC3_RAT 1 1 MAPKLLLLLCLFSGLHARSRKVE GAC3_HUMAN 1 1 GABAARGAMMA32 Length of motif = 19 Motif number = 2 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif II - 1 PCODE ST INT CRKPTIRKKKTSLLHPDST GAC3_MOUSE 343 319 CRKPTIRKKKTSLLHPDST GAC3_RAT 343 319 CRKPTTTKKTTSLLHPDSS GAC3_HUMAN 343 319 GABAARGAMMA33 Length of motif = 18 Motif number = 3 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif III - 1 PCODE ST INT WIPDRISLQAPSNYSLLD GAC3_MOUSE 363 1 WIPDRISLQAPSNYSLLD GAC3_RAT 363 1 WIPERISLQAPSNYSLLD GAC3_HUMAN 363 1 GABAARGAMMA34 Length of motif = 14 Motif number = 4 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif IV - 1 PCODE ST INT MITLNNSMYWQEFE GAC3_MOUSE 388 7 MITLNNSMYWQEFE GAC3_RAT 388 7 MITLNNSVYWQEFE GAC3_HUMAN 388 7 FINAL MOTIF SETS GABAARGAMMA31 Length of motif = 23 Motif number = 1 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif I - 1 PCODE ST INT MAAKLLLLLCLFSGLHARSRRVE GAC3_MOUSE 1 1 MAAKLLLLLCLFSGLHARSRRVE GAC3_RAT 1 1 MAPKLLLLLCLFSGLHARSRKVE GAC3_HUMAN 1 1 GABAARGAMMA32 Length of motif = 19 Motif number = 2 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif II - 1 PCODE ST INT CRKPTIRKKKTSLLHPDST GAC3_MOUSE 343 319 CRKPTIRKKKTSLLHPDST GAC3_RAT 343 319 CRKPTTTKKTTSLLHPDSS GAC3_HUMAN 343 319 GABAARGAMMA33 Length of motif = 18 Motif number = 3 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif III - 1 PCODE ST INT WIPDRISLQAPSNYSLLD GAC3_MOUSE 363 1 WIPDRISLQAPSNYSLLD GAC3_RAT 363 1 WIPERISLQAPSNYSLLD GAC3_HUMAN 363 1 GABAARGAMMA34 Length of motif = 14 Motif number = 4 Gamma-aminobutyric-acid A receptor gamma 3 subunit motif IV - 1 PCODE ST INT MITLNNSMYWQEFE GAC3_MOUSE 388 7 MITLNNSMYWQEFE GAC3_RAT 388 7 MITLNNSVYWQEFE GAC3_HUMAN 388 7

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