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PR01570

Identifier
NPFFRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01570
No. of Motifs
6
Creation Date
13-SEP-2001
Title
Neuropeptide FF receptor family signature
Database References
Literature References
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).

Documentation
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]. 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 Feature Index
6444444
5000000
4000000
3000000
2000000
123456
True Positives
NFF1_HUMAN    NFF1_RAT      NFF2_HUMAN    NFF2_RAT      
Sequence Titles
NFF1_HUMAN  NEUROPEPTIDE FF RECEPTOR 1 (RFAMIDE-RELATED PEPTIDE RECEPTOR OT7T022) - Homo sapiens (Human). 
NFF1_RAT NEUROPEPTIDE FF RECEPTOR 1 (RFAMIDE-RELATED PEPTIDE RECEPTOR OT7T022) - Rattus norvegicus (Rat).
NFF2_HUMAN NEUROPEPTIDE FF RECEPTOR 2 (NEUROPEPTIDE G PROTEIN-COUPLED RECEPTOR) (G-PROTEIN-COUPLED RECEPTOR HLWAR77) - Homo sapiens (Human).
NFF2_RAT NEUROPEPTIDE FF RECEPTOR 2 (NEUROPEPTIDE G PROTEIN-COUPLED RECEPTOR) - Rattus norvegicus (Rat).
Scan History
SPTR39.22_17.3f 1  80   NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
NLTFSSYYQHTSPV NFF1_HUMAN 29 29 -
SLTFSSYYQHSSPV NFF1_RAT 29 29 -
NITYMNYYLHQPHV NFF2_RAT 31 31 -
NITYVNYYLHQPQV NFF2_HUMAN 133 133 -

Motif 2 width=13
Element Seqn Id St Int Rpt
FLLCMVGNTLVCF NFF1_HUMAN 54 11 -
FLLCMVGNTLVCF NFF1_RAT 54 11 -
FFLCMVGNTVVCF NFF2_RAT 56 11 -
FFLCMMGNTVVCF NFF2_HUMAN 158 11 -

Motif 3 width=18
Element Seqn Id St Int Rpt
GIFCMPTTLVDNLITGWP NFF1_HUMAN 93 26 -
GIFCMPTTLVDNLITGWP NFF1_RAT 93 26 -
GIFCMPITLLDNIIAGWP NFF2_RAT 95 26 -
GIFCMPITLLDNIIAGWP NFF2_HUMAN 197 26 -

Motif 4 width=15
Element Seqn Id St Int Rpt
FRCIVHPFREKLTLR NFF1_HUMAN 142 31 -
FRCIVHPFREKLTLR NFF1_RAT 142 31 -
FRCVVYPFKPKLTVK NFF2_RAT 144 31 -
FQCVVYPFKPKLTIK NFF2_HUMAN 246 31 -

Motif 5 width=13
Element Seqn Id St Int Rpt
TVYAFPFAHWLAF NFF1_HUMAN 307 150 -
SVYAFPLAHWLAF NFF1_RAT 309 152 -
NIYVYPFAHWLAF NFF2_RAT 310 151 -
NIYIYPFAHWLAF NFF2_HUMAN 413 152 -

Motif 6 width=11
Element Seqn Id St Int Rpt
ENFRRGFQAAF NFF1_HUMAN 334 14 -
ENFRRGFQAAF NFF1_RAT 336 14 -
ENFRSGFQDAF NFF2_RAT 337 14 -
ENFRRGFQEAF NFF2_HUMAN 440 14 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
NLTFSSYYQHTSPV NFF1_HUMAN 29 29 -
SLTFSSYYQHSSPV NFF1_RAT 29 29 -
NITYMNYYLHQPHV NFF2_RAT 31 31 -
NITYVNYYLHQPQV NFF2_HUMAN 133 133 -

Motif 2 width=13
Element Seqn Id St Int Rpt
FLLCMVGNTLVCF NFF1_HUMAN 54 11 -
FLLCMVGNTLVCF NFF1_RAT 54 11 -
FFLCMVGNTVVCF NFF2_RAT 56 11 -
FFLCMMGNTVVCF NFF2_HUMAN 158 11 -

Motif 3 width=18
Element Seqn Id St Int Rpt
GIFCMPTTLVDNLITGWP NFF1_HUMAN 93 26 -
GIFCMPTTLVDNLITGWP NFF1_RAT 93 26 -
GIFCMPITLLDNIIAGWP NFF2_RAT 95 26 -
GIFCMPITLLDNIIAGWP NFF2_HUMAN 197 26 -

Motif 4 width=15
Element Seqn Id St Int Rpt
FRCIVHPFREKLTLR NFF1_HUMAN 142 31 -
FRCIVHPFREKLTLR NFF1_RAT 142 31 -
FRCVVYPFKPKLTVK NFF2_RAT 144 31 -
FQCVVYPFKPKLTIK NFF2_HUMAN 246 31 -

Motif 5 width=13
Element Seqn Id St Int Rpt
TVYAFPFAHWLAF NFF1_HUMAN 307 150 -
SVYAFPLAHWLAF NFF1_RAT 309 152 -
NIYVYPFAHWLAF NFF2_RAT 310 151 -
NIYIYPFAHWLAF NFF2_HUMAN 413 152 -

Motif 6 width=11
Element Seqn Id St Int Rpt
ENFRRGFQAAF NFF1_HUMAN 334 14 -
ENFRRGFQAAF NFF1_RAT 336 14 -
ENFRSGFQDAF NFF2_RAT 337 14 -
ENFRRGFQEAF NFF2_HUMAN 440 14 -