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PR01572

Identifier
NPFFRECEPTR2  [View Relations]  [View Alignment]  
Accession
PR01572
No. of Motifs
6
Creation Date
13-SEP-2001
Title
Type 2 neuropeptide FF receptor 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].
 
The type 2 neuropeptide FF receptor is expressed at high levels in the
thymus and placenta, with moderate levels in the pituitary, spleen, testis
and brain. Low levels were detected in the spinal cord, pancreas, small
intestine, uterus, stomach, lung, heart and skeletal muscle. No expression
was detected in liver or kidney [7].
 
NPFFRECEPTR2 is a 6-element fingerprint that provides a signature for the 
type 2 neuropeptide FF receptors. 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 type 2 neuropeptide FF receptors but
distinguish them from the rest of the neuropeptide FF receptor family -
motif 1 lies at the N-terminus; motif 2 is located at the C-terminus of TM
domain 2, leading into the first external loop; motif 3 resides in the
second external loop; motif 4 lies in the third external loop; and motifs 5
and 6 reside at the C-terminus. A single iteration on SPTR39.22_17.3f was
required to reach convergence, no further sequences being identified beyond
the starting set.
Summary Information
2 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
6222222
5000000
4000000
3000000
2000000
123456
True Positives
NFF2_HUMAN    NFF2_RAT      
Sequence Titles
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  200  NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
KWDTNSSENWHPIWNVNDT NFF2_HUMAN 106 106 -
RWDSNSSGSWDHIWSGNDT NFF2_RAT 4 4 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VGIFCMPITLLDN NFF2_HUMAN 196 71 -
VGIFCMPITLLDN NFF2_RAT 94 71 -

Motif 3 width=21
Element Seqn Id St Int Rpt
MLHVQEEKYYRVRLNSQNKTS NFF2_HUMAN 283 74 -
MLHVQEEKYYRVRLSSHNKTS NFF2_RAT 181 74 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LSDYADLSPNEL NFF2_HUMAN 398 94 -
LSDYADLSPNKL NFF2_RAT 295 93 -

Motif 5 width=16
Element Seqn Id St Int Rpt
CQKRAKPMEAYALKAK NFF2_HUMAN 455 45 -
CQKKVKPQEAYGLRAK NFF2_RAT 350 43 -

Motif 6 width=12
Element Seqn Id St Int Rpt
MEELKETTNSSE NFF2_HUMAN 510 39 -
MEETGEATNSTE NFF2_RAT 405 39 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
KWDTNSSENWHPIWNVNDT NFF2_HUMAN 106 106 -
RWDSNSSGSWDHIWSGNDT NFF2_RAT 4 4 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VGIFCMPITLLDN NFF2_HUMAN 196 71 -
VGIFCMPITLLDN NFF2_RAT 94 71 -

Motif 3 width=21
Element Seqn Id St Int Rpt
MLHVQEEKYYRVRLNSQNKTS NFF2_HUMAN 283 74 -
MLHVQEEKYYRVRLSSHNKTS NFF2_RAT 181 74 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LSDYADLSPNEL NFF2_HUMAN 398 94 -
LSDYADLSPNKL NFF2_RAT 295 93 -

Motif 5 width=16
Element Seqn Id St Int Rpt
CQKRAKPMEAYALKAK NFF2_HUMAN 455 45 -
CQKKVKPQEAYGLRAK NFF2_RAT 350 43 -

Motif 6 width=12
Element Seqn Id St Int Rpt
MEELKETTNSSE NFF2_HUMAN 510 39 -
MEETGEATNSTE NFF2_RAT 405 39 -