WORKLIST ENTRIES (1):

NPFFRECEPTOR View alignment View Structure    Neuropeptide FF receptor family signature
 Type of fingerprint: COMPOUND with 6  elements
Links:
   PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
   PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
   PRINTS; PR00251 BACTRLOPSIN
   PRINTS; PR01571 NPFFRECEPTR1; PR01572 NPFFRECEPTR2

 Creation date 13-SEP-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. PANULA, P., AARNISALO, A.A. AND WASOWICZ, K.
   Neuropeptide FF, a mammalian neuropeptide with multiple functions.
   PROG.NEUROBIOL. 48(4-5) 461-487 (1996).

   7. KOTANI, M., MOLLEREAU, C., DETHEUX, M., LE POUL, E., BREZILLON, S.,
   VAKILI, J., MAZARGUIL, H., VASSART, G., ZAJAC, J.M. AND PARMENTIER, M.
   Functional characterization of a human receptor for neuropeptide FF and
   related peptides.
   BR.J.PHARMACOL. 133 138-144 (2001).

   8. BONINI, J.A., JONES, K.A., ADHAM, N., FORRAY, C., ARTYMYSHYN, R., DURKIN,
   M.M., SMITH, K.E., TAMM, J.A., BOTEJU, L.W., LAKHLANI, P.P., RADDATZ, R.,
   YAO, W.J., OGOZALEK, K.L., BOYLE, N., KOURANOVA, E.V., QUAN, Y., VAYSSE,
   P.J., WETZEL, J.M., BRANCHEK, T.A., GERALD, C. AND BOROWSKY, B.
   Identification and characterization of two G protein-coupled receptors for
   neuropeptide FF.
   J.BIOL.CHEM. 275(50) 39324-39331 (2000).

   9. HINUMA, S., SHINTANI, Y., FUKUSUMI, S., IIJIMA, N., MATSUMOTO, Y.,
   HOSOYA, M., FUJII, R., WATANABE, T., KIKUCHI, K., TERAO, Y., YANO, T.,
   YAMAMOTO, T., KAWAMATA, Y., HABATA, Y., ASADA, M., KITADA, C., KUROKAWA, T.,
   ONDA, H., NISHIMURA, O., TANAKA, M., IBATA, Y. AND FUJINO, M.
   New neuropeptides containing carboxy-terminal RFamide and their receptor in
   mammals.
   NAT.CELL BIOL. 2(10) 703-708 (2000).

   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].
   
   Neuropeptide FF (and neuropeptide AF, which is also derived from the same
   precursor) belong to a family of neuropeptides containing an RF-amide motif
   at their C-terminus [6]. Neuropeptide FF (NPFF) is found at high
   concentrations in the posterior pituitary, spinal cord, hypothalamus and
   medulla and is believed to be involved in pain modulation, opioid tolerance,
   cardiovascular regulation, memory and neuroendocrine regulation [6,7]. Two G
   protein-coupled receptors for NPFF have been identified; both are expressed
   in the central nervous system and couple to Gi proteins to inhibit adenylyl
   cyclase [7-9].
  
   NPFFRECEPTOR is a 6-element fingerprint that provides a signature for the
   neuropeptide FF receptor family. The fingerprint was derived from an initial
   alignment of 4 sequences: the motifs were drawn from conserved regions
   spanning virtually the full alignment length, focusing on those sections 
   that characterise the neuropeptide FF receptors but distinguish them from 
   the rest of the rhodopsin-like superfamily - motif 1 resides at the 
   N-terminus; motif 2 lies in TM domain 1; motif 3 is located at the 
   C-terminus of TM domain 2, leading into the first external loop; motif 4 
   spans the C-terminal portion of TM domain 3 and the second cytoplasmic loop;
   motif 5 lies in the third external loop, leading into TM domain 7; and 
   motif 6 resides at the C-terminus of TM domain 7. A single iteration on 
   SPTR39.22_17.3f was required to reach convergence, no further sequences 
   being identified beyond the starting set.

  SUMMARY INFORMATION
      4 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
  
    6|   4    4    4    4    4    4  
    5|   0    0    0    0    0    0  
    4|   0    0    0    0    0    0  
    3|   0    0    0    0    0    0  
    2|   0    0    0    0    0    0  
   --+-------------------------------
     |   1    2    3    4    5    6  

True positives..
 NFF1_HUMAN     NFF1_RAT       NFF2_RAT       NFF2_HUMAN     


  PROTEIN TITLES
   NFF1_HUMAN       NEUROPEPTIDE FF RECEPTOR 1 (RFAMIDE-RELATED PEPTIDE RECEPTOR
   NFF1_RAT         NEUROPEPTIDE FF RECEPTOR 1 (RFAMIDE-RELATED PEPTIDE RECEPTOR
   NFF2_RAT         NEUROPEPTIDE FF RECEPTOR 2 (NEUROPEPTIDE G PROTEIN-COUPLED R
   NFF2_HUMAN       NEUROPEPTIDE FF RECEPTOR 2 (NEUROPEPTIDE G PROTEIN-COUPLED R

SCAN HISTORY SPTR39.22_17.3f 1 80 NSINGLE INITIAL MOTIF SETS NPFFRECEPTOR1 Length of motif = 14 Motif number = 1 Neuropeptide FF receptor family motif I - 1 PCODE ST INT NLTFSSYYQHTSPV NFF1_HUMAN 29 29 SLTFSSYYQHSSPV NFF1_RAT 29 29 NITYVNYYLHQPQV NFF2_HUMAN 133 133 NITYMNYYLHQPHV NFF2_RAT 31 31 NPFFRECEPTOR2 Length of motif = 13 Motif number = 2 Neuropeptide FF receptor family motif II - 1 PCODE ST INT FLLCMVGNTLVCF NFF1_HUMAN 54 11 FLLCMVGNTLVCF NFF1_RAT 54 11 FFLCMMGNTVVCF NFF2_HUMAN 158 11 FFLCMVGNTVVCF NFF2_RAT 56 11 NPFFRECEPTOR3 Length of motif = 18 Motif number = 3 Neuropeptide FF receptor family motif III - 1 PCODE ST INT GIFCMPTTLVDNLITGWP NFF1_HUMAN 93 26 GIFCMPTTLVDNLITGWP NFF1_RAT 93 26 GIFCMPITLLDNIIAGWP NFF2_HUMAN 197 26 GIFCMPITLLDNIIAGWP NFF2_RAT 95 26 NPFFRECEPTOR4 Length of motif = 15 Motif number = 4 Neuropeptide FF receptor family motif IV - 1 PCODE ST INT FRCIVHPFREKLTLR NFF1_HUMAN 142 31 FRCIVHPFREKLTLR NFF1_RAT 142 31 FQCVVYPFKPKLTIK NFF2_HUMAN 246 31 FRCVVYPFKPKLTVK NFF2_RAT 144 31 NPFFRECEPTOR5 Length of motif = 13 Motif number = 5 Neuropeptide FF receptor family motif V - 1 PCODE ST INT TVYAFPFAHWLAF NFF1_HUMAN 307 150 SVYAFPLAHWLAF NFF1_RAT 309 152 NIYIYPFAHWLAF NFF2_HUMAN 413 152 NIYVYPFAHWLAF NFF2_RAT 310 151 NPFFRECEPTOR6 Length of motif = 11 Motif number = 6 Neuropeptide FF receptor family motif VI - 1 PCODE ST INT ENFRRGFQAAF NFF1_HUMAN 334 14 ENFRRGFQAAF NFF1_RAT 336 14 ENFRRGFQEAF NFF2_HUMAN 440 14 ENFRSGFQDAF NFF2_RAT 337 14 FINAL MOTIF SETS NPFFRECEPTOR1 Length of motif = 14 Motif number = 1 Neuropeptide FF receptor family motif I - 1 PCODE ST INT NLTFSSYYQHTSPV NFF1_HUMAN 29 29 SLTFSSYYQHSSPV NFF1_RAT 29 29 NITYMNYYLHQPHV NFF2_RAT 31 31 NITYVNYYLHQPQV NFF2_HUMAN 133 133 NPFFRECEPTOR2 Length of motif = 13 Motif number = 2 Neuropeptide FF receptor family motif II - 1 PCODE ST INT FLLCMVGNTLVCF NFF1_HUMAN 54 11 FLLCMVGNTLVCF NFF1_RAT 54 11 FFLCMVGNTVVCF NFF2_RAT 56 11 FFLCMMGNTVVCF NFF2_HUMAN 158 11 NPFFRECEPTOR3 Length of motif = 18 Motif number = 3 Neuropeptide FF receptor family motif III - 1 PCODE ST INT GIFCMPTTLVDNLITGWP NFF1_HUMAN 93 26 GIFCMPTTLVDNLITGWP NFF1_RAT 93 26 GIFCMPITLLDNIIAGWP NFF2_RAT 95 26 GIFCMPITLLDNIIAGWP NFF2_HUMAN 197 26 NPFFRECEPTOR4 Length of motif = 15 Motif number = 4 Neuropeptide FF receptor family motif IV - 1 PCODE ST INT FRCIVHPFREKLTLR NFF1_HUMAN 142 31 FRCIVHPFREKLTLR NFF1_RAT 142 31 FRCVVYPFKPKLTVK NFF2_RAT 144 31 FQCVVYPFKPKLTIK NFF2_HUMAN 246 31 NPFFRECEPTOR5 Length of motif = 13 Motif number = 5 Neuropeptide FF receptor family motif V - 1 PCODE ST INT TVYAFPFAHWLAF NFF1_HUMAN 307 150 SVYAFPLAHWLAF NFF1_RAT 309 152 NIYVYPFAHWLAF NFF2_RAT 310 151 NIYIYPFAHWLAF NFF2_HUMAN 413 152 NPFFRECEPTOR6 Length of motif = 11 Motif number = 6 Neuropeptide FF receptor family motif VI - 1 PCODE ST INT ENFRRGFQAAF NFF1_HUMAN 334 14 ENFRRGFQAAF NFF1_RAT 336 14 ENFRSGFQDAF NFF2_RAT 337 14 ENFRRGFQEAF NFF2_HUMAN 440 14

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