WORKLIST ENTRIES (1):

GABAARALPHA6 View alignment     Gamma-aminobutyric-acid A receptor alpha 6 subunit signature
 Type of fingerprint: COMPOUND with 5  elements
Links:
   PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR; PR01079 GABAARALPHA
   PRINTS; PR01614 GABAARALPHA1; PR01615 GABAARALPHA2; PR01616 GABAARALPHA3
   PRINTS; PR01617 GABAARALPHA4; PR01618 GABAARALPHA5 
   MIM; 137143 

 Creation date 05-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. SCHWARTZKROIN, P.A.
   GABA synapses enter the molecular big time.
   NAT.MED. 4 1115-1116 (1998).

   9. 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]. Amongst family members, the large
   cytoplasmic loop displays the most divergence in terms of primary structure,
   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]. The BZ binding site is located at the interface of adjacent alpha
   and gamma subunits; therefore, the type of alpha subunit present is
   instrumental in determining BZ selectivity and sensitivity. Receptors can be
   categorised into 3 groups based on their alpha subunit content and, hence,
   sensitivity to BZs: alpha 1-containing receptors have greatest sensitivity 
   towards BZs (type I); alpha 2, 3 and 5-containing receptors have similar but
   distinguishable properties (type II); and alpha 4- and 6-containing
   assemblies have very low BZ affinity [1]. A conserved histidine residue in
   the alpha subunit of type I and II receptors is believed to be responsible
   for BZ affinity [7]. It is becoming clear that GABAA receptors represent an
   important point of therapuetic intervention in some neurological disorders.
   For example, a predominance of type II over type I receptors in hippocampal
   dentate granule cells, together with receptor density at the synapse, has 
   been linked to epilepsy [8].
  
   Alpha 4- and 6-containing receptors are often referred to as 'diazepam-
   insensitive' receptors, since inclusion of such subunits in place of type I
   and II polypeptides virtually eliminates sensitivity to BZs. The alpha 6
   subunit is found exclusively in the cerebellar granule cells. It also
   undergoes alternative splicing, generating a non-functional isoform that
   lacks 10 residues from the N-terminal domain [2].
  
   GABAARALPHA6 is a 5-element fingerprint that provides a signature for GABAA
   receptor alpha 6 subunits. The fingerprint was derived from an initial
   alignment of 4 sequences: the motifs were drawn from conserved regions 
   spanning the full alignment length, focusing on those sections that 
   characterise alpha 6 subunits but distinguish them from the rest of the
   GABAA receptor alpha subunit family - motifs 1 and 2 lie in the N-terminal
   region of the long extracellular loop preceding TM domain 1; and motifs 3-5 
   reside in the cytoplasmic loop separating TM domains 3 and 4 [9]. A single 
   iteration on SPTR40_18f was required to reach convergence, no further 
   sequences being identified beyond the starting set.             

  SUMMARY INFORMATION
      4 codes involving  5 elements
      0 codes involving  4 elements
      0 codes involving  3 elements
      0 codes involving  2 elements

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

True positives..
 GAA6_MOUSE     GAA6_RAT       GAA6_HUMAN     GAA6_CHICK     


  PROTEIN TITLES
   GAA6_MOUSE       Gamma-aminobutyric-acid receptor alpha-6 subunit precursor (
   GAA6_RAT         Gamma-aminobutyric-acid receptor alpha-6 subunit precursor (
   GAA6_HUMAN       Gamma-aminobutyric-acid receptor alpha-6 subunit precursor (
   GAA6_CHICK       Gamma-aminobutyric-acid receptor alpha-6 subunit precursor (

SCAN HISTORY SPTR40_18f 1 300 NSINGLE INITIAL MOTIF SETS GABAARALPHA61 Length of motif = 15 Motif number = 1 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif I - 1 PCODE ST INT MALLIAWVCVAVSIE GAA6_CHICK 1 1 MASSLPWLCIILWLE GAA6_HUMAN 1 1 MVLLLPWLFIILWLE GAA6_MOUSE 1 1 MLLLLPWLFSLLWIE GAA6_RAT 1 1 GABAARALPHA62 Length of motif = 14 Motif number = 2 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif II - 1 PCODE ST INT ALGGQGDGGDLYSE GAA6_CHICK 17 1 ALGKLEVEGNFYSE GAA6_HUMAN 17 1 AQAQLEDEGNFYSE GAA6_MOUSE 17 1 AQAQLEDEGNFYSE GAA6_RAT 17 1 GABAARALPHA63 Length of motif = 13 Motif number = 3 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif III - 1 PCODE ST INT QTQRAMRKAARAA GAA6_CHICK 331 300 QTQKAKRKAQFAA GAA6_HUMAN 331 300 QSQKAERQAQTAA GAA6_MOUSE 331 300 QSQKAERQAQTAA GAA6_RAT 331 300 GABAARALPHA64 Length of motif = 21 Motif number = 4 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif IV - 1 PCODE ST INT LSAATVPAEDEIVSHSDSNCN GAA6_CHICK 349 5 ISKATEPLEAEIVLHPDSKYH GAA6_HUMAN 349 5 KSKASESLEAEIVVHSDSKYH GAA6_MOUSE 349 5 KSKTTESLEAEIVVHSDSKYH GAA6_RAT 349 5 GABAARALPHA65 Length of motif = 20 Motif number = 5 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif V - 1 PCODE ST INT RVNSVTSQADQSPEASIVSN GAA6_CHICK 373 3 RITSLSLPIVSSSEANKVLT GAA6_HUMAN 373 3 RISSLTLPIVPSSEASKALS GAA6_MOUSE 373 3 RISSLTLPIVPSSEASKVLS GAA6_RAT 373 3 FINAL MOTIF SETS GABAARALPHA61 Length of motif = 15 Motif number = 1 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif I - 1 PCODE ST INT MVLLLPWLFIILWLE GAA6_MOUSE 1 1 MLLLLPWLFSLLWIE GAA6_RAT 1 1 MASSLPWLCIILWLE GAA6_HUMAN 1 1 MALLIAWVCVAVSIE GAA6_CHICK 1 1 GABAARALPHA62 Length of motif = 14 Motif number = 2 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif II - 1 PCODE ST INT AQAQLEDEGNFYSE GAA6_MOUSE 17 1 AQAQLEDEGNFYSE GAA6_RAT 17 1 ALGKLEVEGNFYSE GAA6_HUMAN 17 1 ALGGQGDGGDLYSE GAA6_CHICK 17 1 GABAARALPHA63 Length of motif = 13 Motif number = 3 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif III - 1 PCODE ST INT QSQKAERQAQTAA GAA6_MOUSE 331 300 QSQKAERQAQTAA GAA6_RAT 331 300 QTQKAKRKAQFAA GAA6_HUMAN 331 300 QTQRAMRKAARAA GAA6_CHICK 331 300 GABAARALPHA64 Length of motif = 21 Motif number = 4 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif IV - 1 PCODE ST INT KSKASESLEAEIVVHSDSKYH GAA6_MOUSE 349 5 KSKTTESLEAEIVVHSDSKYH GAA6_RAT 349 5 ISKATEPLEAEIVLHPDSKYH GAA6_HUMAN 349 5 LSAATVPAEDEIVSHSDSNCN GAA6_CHICK 349 5 GABAARALPHA65 Length of motif = 20 Motif number = 5 Gamma-aminobutyric-acid A receptor alpha 6 subunit motif V - 1 PCODE ST INT RISSLTLPIVPSSEASKALS GAA6_MOUSE 373 3 RISSLTLPIVPSSEASKVLS GAA6_RAT 373 3 RITSLSLPIVSSSEANKVLT GAA6_HUMAN 373 3 RVNSVTSQADQSPEASIVSN GAA6_CHICK 373 3

User query: Display/Full Code "GABAARALPHA6"