WORKLIST ENTRIES (1):

PSYCHOSINER View alignment View Structure     Psychosine receptor signature
 Type of fingerprint: COMPOUND with 10 elements
Links:
   PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
   PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
   PRINTS; PR00251 BACTRLOPSIN

 Creation date 18-DEC-2001

   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. IM, D.S., HEISE, C.E., NGUYEN, T., O'DOWD, B.F. AND LYNCH, K.R.
   Identification of a molecular target of psychosine and its role in globoid
   cell formation.
   J.CELL BIOL. 153(2) 429-434 (2001).

   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].
   
   Psychosine is a glycosphingolipid implicated in the pathology of globoid
   cell leukodystrophy (GLD), a hereditary metabolic disorder that results from
   the absence of the enzyme galactosyl ceramide. This deficiency results in
   the accumulation of psychosine in the brain, leading to apoptosis of
   oligodendrocytes, progressive demyelination and the existence of large,
   multinuclear cells (globoid cells) derived from microglia [6]. 
   
   The molecular mechanism by which these toxic effects might be mediated has
   recently been elucidated by the identification of TDAG8, an orphan G
   protein-coupled receptor, as a receptor for psychosine [6]. TDAG8 is
   expressed at high levels in the spleen, peripheral blood leukocytes, lymph
   nodes and lung. Activation of the receptor in RH7777 hepatoma cells by
   psychosine and related lysoglycolipids results in a pertussis toxin-
   insensitive inhibition of forskolin-induced cAMP accummulation, possibly 
   through coupling to Gz proteins [6].
  
   PSYCHOSINER is a 10-element fingerprint that provides a signature for the
   psychosine receptor. The fingerprint was derived from an initial alignment
   of 2 sequences: the motifs were drawn from conserved sections within N- and
   C-terminal and loop regions, focusing on those areas of the alignment that
   characterise the psychosine receptors but distinguish them from the rest of
   the rhodopsin-like superfamily - motif 1 resides at the N-terminus; motif 2
   spans the first cytoplasmic loop; motif 3 encodes the first external loop;
   motif 4 spans the second cytoplasmic loop; motifs 5 and 6 reside in the
   second external loop; motif 7 lies in the third cytoplasmic loop; motif 8 
   resides in the C-terminal portion of the third external loop; and motifs 9
   and 10 lie at the C-terminus. A single iteration on SPTR40_18f was required
   to reach convergence, no further sequences being identified beyond the 
   starting set.

  SUMMARY INFORMATION
      2 codes involving 10 elements
      0 codes involving  9 elements
      0 codes involving  8 elements
      0 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
  
   10|   2    2    2    2    2    2    2    2    2    2  
    9|   0    0    0    0    0    0    0    0    0    0  
    8|   0    0    0    0    0    0    0    0    0    0  
    7|   0    0    0    0    0    0    0    0    0    0  
    6|   0    0    0    0    0    0    0    0    0    0  
    5|   0    0    0    0    0    0    0    0    0    0  
    4|   0    0    0    0    0    0    0    0    0    0  
    3|   0    0    0    0    0    0    0    0    0    0  
    2|   0    0    0    0    0    0    0    0    0    0  
   --+---------------------------------------------------
     |   1    2    3    4    5    6    7    8    9   10  

True positives..
 O75819         TDA8_MOUSE     


  PROTEIN TITLES
   O75819           T CELL-DEATH ASSOCIATED PROTEIN - Homo sapiens (Human).
   TDA8_MOUSE       Probable G protein-coupled receptor TDAG8 - Mus musculus (Mo

SCAN HISTORY SPTR40_18f 1 100 NSINGLE INITIAL MOTIF SETS PSYCHOSINER1 Length of motif = 18 Motif number = 1 Psychosine receptor motif I - 1 PCODE ST INT MNSMCIEEQRHLEHYLFP TDA8_MOUSE 3 3 MNSTCIEEQHDLDHYLFP O75819 1 1 PSYCHOSINER2 Length of motif = 14 Motif number = 2 Psychosine receptor motif II - 1 PCODE ST INT CVSFLQAKKENELG TDA8_MOUSE 39 18 CVSFLQPKKESELG O75819 37 18 PSYCHOSINER3 Length of motif = 23 Motif number = 3 Psychosine receptor motif III - 1 PCODE ST INT WINYTWNKDNWTFSPTLCKGSVF TDA8_MOUSE 72 19 WIDYTWNKDNWTFSPALCKGSAF O75819 70 19 PSYCHOSINER4 Length of motif = 13 Motif number = 4 Psychosine receptor motif IV - 1 PCODE ST INT VYPLKFSFLRTRR TDA8_MOUSE 119 24 VYPLKFFFLRTRR O75819 117 24 PSYCHOSINER5 Length of motif = 20 Motif number = 5 Psychosine receptor motif V - 1 PCODE ST INT WKDETSVEYCDSDKSNFTLC TDA8_MOUSE 153 21 WEDETVVEYCDAEKSNFTLC O75819 151 21 PSYCHOSINER6 Length of motif = 19 Motif number = 6 Psychosine receptor motif VI - 1 PCODE ST INT YDKYPLEKWQINLNLFRTC TDA8_MOUSE 173 0 YDKYPLEKWQINLNLFRTC O75819 171 0 PSYCHOSINER7 Length of motif = 15 Motif number = 7 Psychosine receptor motif VII - 1 PCODE ST INT AVRHNQATENSEKRR TDA8_MOUSE 211 19 AVRHNKATENKEKKR O75819 209 19 PSYCHOSINER8 Length of motif = 12 Motif number = 8 Psychosine receptor motif VIII - 1 PCODE ST INT SGWQTFTVYRVT TDA8_MOUSE 264 38 SGKRTYTMYRIT O75819 264 40 PSYCHOSINER9 Length of motif = 16 Motif number = 9 Psychosine receptor motif IX - 1 PCODE ST INT TETGRADMWNILKLCT TDA8_MOUSE 294 18 TETGRYDMWNILKFCT O75819 294 18 PSYCHOSINER10 Length of motif = 16 Motif number = 10 Psychosine receptor motif X - 1 PCODE ST INT ILSVSTRDAVELEIID TDA8_MOUSE 322 12 ILSVSTKDTMELEVLE O75819 322 12 FINAL MOTIF SETS PSYCHOSINER1 Length of motif = 18 Motif number = 1 Psychosine receptor motif I - 1 PCODE ST INT MNSTCIEEQHDLDHYLFP O75819 1 1 MNSMCIEEQRHLEHYLFP TDA8_MOUSE 3 3 PSYCHOSINER2 Length of motif = 14 Motif number = 2 Psychosine receptor motif II - 1 PCODE ST INT CVSFLQPKKESELG O75819 37 18 CVSFLQAKKENELG TDA8_MOUSE 39 18 PSYCHOSINER3 Length of motif = 23 Motif number = 3 Psychosine receptor motif III - 1 PCODE ST INT WIDYTWNKDNWTFSPALCKGSAF O75819 70 19 WINYTWNKDNWTFSPTLCKGSVF TDA8_MOUSE 72 19 PSYCHOSINER4 Length of motif = 13 Motif number = 4 Psychosine receptor motif IV - 1 PCODE ST INT VYPLKFFFLRTRR O75819 117 24 VYPLKFSFLRTRR TDA8_MOUSE 119 24 PSYCHOSINER5 Length of motif = 20 Motif number = 5 Psychosine receptor motif V - 1 PCODE ST INT WEDETVVEYCDAEKSNFTLC O75819 151 21 WKDETSVEYCDSDKSNFTLC TDA8_MOUSE 153 21 PSYCHOSINER6 Length of motif = 19 Motif number = 6 Psychosine receptor motif VI - 1 PCODE ST INT YDKYPLEKWQINLNLFRTC O75819 171 0 YDKYPLEKWQINLNLFRTC TDA8_MOUSE 173 0 PSYCHOSINER7 Length of motif = 15 Motif number = 7 Psychosine receptor motif VII - 1 PCODE ST INT AVRHNKATENKEKKR O75819 209 19 AVRHNQATENSEKRR TDA8_MOUSE 211 19 PSYCHOSINER8 Length of motif = 12 Motif number = 8 Psychosine receptor motif VIII - 1 PCODE ST INT SGKRTYTMYRIT O75819 264 40 SGWQTFTVYRVT TDA8_MOUSE 264 38 PSYCHOSINER9 Length of motif = 16 Motif number = 9 Psychosine receptor motif IX - 1 PCODE ST INT TETGRYDMWNILKFCT O75819 294 18 TETGRADMWNILKLCT TDA8_MOUSE 294 18 PSYCHOSINER10 Length of motif = 16 Motif number = 10 Psychosine receptor motif X - 1 PCODE ST INT ILSVSTKDTMELEVLE O75819 322 12 ILSVSTRDAVELEIID TDA8_MOUSE 322 12

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