SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01855

Identifier
NRPEPTIDEWR  [View Relations]  [View Alignment]  
Accession
PR01855
No. of Motifs
8
Creation Date
23-FEB-2003
Title
Neuropeptide W receptor family signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
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. SHIMOMURA, Y., HARADA, M., GOTO, M., SUGO, T., MATSUMOTO, Y., ABE, M.,
WATANABE, T., ASAMI, T., KITADA, C., MORI, M., ONDA, H. AND FUJINO, M.
Identification of neuropeptide W as the endogenous ligand for orphan
G-protein-coupled receptors GPR7 and GPR8.
J.BIOL.CHEM. 277(39) 35826-35832 (2002).
 
7. BREZILLON, S., LANNOY, V., FRANSSEN, J.D., LE POUL, E., DUPRIEZ, V.,
LUCCHETTI, J., DETHEUX, M. AND PARMENTIER, M.
Identification of natural ligands for the orphan G protein-coupled receptors
GPR7 and GPR8.
J.BIOL.CHEM. 278(2) 776-783 (2003).
 
8. FUJII, R., YOSHIDA, H., FUKUSUMI, S., HABATA, Y., HOSOYA, M., KAWAMATA,
Y., YANO, T., HINUMA, S., KITADA, C., ASAMI, T., MORI, M., FUJISAWA, Y. AND
FUJINO, M.
Identification of a neuropeptide modified with bromine as an endogenous
ligand for GPR7.
J.BIOL.CHEM. 277(37) 34010-34016 (2002).

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].
 
Two closely related neuropeptide precursors, which share no significant
sequence similarity with other known neuropeptides, have recently been
identified and named preproneuropeptide B and preproneuropeptide W [6-8]. In
humans, each precursor contains a signal sequence and two dibasic cleavage
sites. Alternative cleavage of these sites results in long (29 or 30 amino
acids) and short (23 amino acids) forms of the neuropeptides being produced
[6,7]. The mouse, rat and bovine versions of preproneuropeptide B, however,
contain only the second cleavage site, resulting in only the long form of
neuropeptide B [7,8].
 
Neuropeptide B is expressed in both the central nervous system (CNS) and in
the periphery. In the CNS, highest levels of the peptide are found in the
substantia nigra and hypothalamus, suggesting a possible role in locomotor
control and the release of pituitary hormones [7]. In the periphery, the
peptide is most abundant in testis, ovary, uterus, placenta, spleen, lymph
nodes and peripheral blood leukocytes, indicating potential roles in the
reproductive and immune systems [7]. Unusually, neuropeptide B purified from
bovine hypothalamus was found to be brominated at its N-terminus [8].
 
Neuropeptide W has a more limited distribution in the brain than
neuropeptide B and is found at highest levels in the substantial nigra,
again suggesting an involvement in locomotor control [7]. In the periphery,
neuropeptide W is more widespread than neuropeptide B. In addition to the
reproductive and immune tissues in which neuropeptide B is expressed,
neuropeptide W has been found at high levels in the liver, stomach and
trachea [7]. Intracerebroventricular administration of neuropeptide W in
rats has been reported to produce an acute increase in food intake and to
stimulate prolactin release [6].
 
Two orphan G protein-coupled receptors, GPR7 and GPR8 have recently been
identified as receptors for the neuropeptides [6-8]. GPR7 is expressed at
highest levels in the hippocampus, amygdala, trachea and in lung carcinoma
and at moderate levels in fetal brain, pituitary and prostate [7]. GPR8 is
most highly expressed in the caudate nucleus, hippocampus and amygdala, and
moderately expressed in the adult brain, thalamus, parietal cortex,
pituitary, adrenal gland, lymph nodes and in lymphoblastic leukemia [7].
Upon activation by neuropeptide B or W, GPR7 and GPR8 couple to pertussis
toxin-sensitive G proteins to inhibit adenylate cyclase [7].
 
NRPEPTIDEWR is an 8-element fingerprint that provides a signature for the
neuropeptide W receptor family. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved sections
within loop, TM and C-terminal regions, focusing on those areas of the
alignment that characterise the neuropeptide W receptors but distinguish
them from the rest of the rhodopsin-like superfamily - motif 1 is located
in the C-terminal portion of TM domain 2; motif 2 encodes the second 
cytoplasmic loop; motifs 3 and 4 span TM domain 4; motifs 5 and 6 lie in 
the second external loop, leading into TM domain 5; motif 7 resides in 
the third cytoplasmic loop; and motif 8 encompasses the C-terminal portion
of TM domain 6. A single iteration on SPTR40_22f was required to reach
convergence, no further sequences being identified beyond the starting set.
Summary Information
4 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 Feature Index
844444444
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
GPR7_HUMAN    GPR8_HUMAN    Q8MJV2        Q8MJV3        
Sequence Titles
GPR7_HUMAN  Probable G protein-coupled receptor GPR7 - Homo sapiens (Human). 
GPR8_HUMAN Probable G protein-coupled receptor GPR8 - Homo sapiens (Human).
Q8MJV2 G protein coupled receptor 8 - Bos taurus (Bovine).
Q8MJV3 G protein coupled receptor 7 - Bos taurus (Bovine).
Scan History
SPTR40_22f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
DELFTLVLPINIAD GPR7_HUMAN 83 83 -
DELFTLVPPVNIAD Q8MJV3 86 86 -
DGLFTLVLPTNIAE Q8MJV2 91 91 -
DGLFTLVLPVNIAE GPR8_HUMAN 91 91 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LATAESRRVAGRT GPR7_HUMAN 139 42 -
LATAESRRVAGRT Q8MJV3 142 42 -
LATARSRRMPRRT Q8MJV2 147 42 -
LATVRSRHMPWRT GPR8_HUMAN 147 42 -

Motif 3 width=13
Element Seqn Id St Int Rpt
ARAVSLAVWGIVT GPR7_HUMAN 155 3 -
ARAVSLAVWGVAT Q8MJV3 158 3 -
AKVASLCVWLGVT Q8MJV2 163 3 -
AKVASLCVWLGVT GPR8_HUMAN 163 3 -

Motif 4 width=10
Element Seqn Id St Int Rpt
VLPFAVFARL GPR7_HUMAN 170 2 -
VLPFAVFARL Q8MJV3 173 2 -
VLPFLTFAGV Q8MJV2 178 2 -
VLPFFSFAGV GPR8_HUMAN 178 2 -

Motif 5 width=10
Element Seqn Id St Int Rpt
QCVLVFPQPE GPR7_HUMAN 187 7 -
QCVLVFPQPE Q8MJV3 190 7 -
SCGLSFPRPE Q8MJV2 196 8 -
SCGLSFPWPE GPR8_HUMAN 196 8 -

Motif 6 width=13
Element Seqn Id St Int Rpt
WWRASRLYTLVLG GPR7_HUMAN 199 2 -
WWRASRLYTLVLG Q8MJV3 202 2 -
WFQASRIYTLVLG Q8MJV2 208 2 -
WFKASRVYTLVLG GPR8_HUMAN 208 2 -

Motif 7 width=14
Element Seqn Id St Int Rpt
RLHAMRLDSHAKAL GPR7_HUMAN 229 17 -
RLRAIRLDSHAKAL Q8MJV3 232 17 -
RLRALRLHSGAKAL Q8MJV2 238 17 -
RLRAVRLRSGAKAL GPR8_HUMAN 238 17 -

Motif 8 width=15
Element Seqn Id St Int Rpt
LLCWTPYHLSTVVAL GPR7_HUMAN 261 18 -
LLVWTPYHLSTVVAL Q8MJV3 264 18 -
LLCWTPFHLASIVAL Q8MJV2 270 18 -
LLCWTPFHLASVVAL GPR8_HUMAN 270 18 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
DELFTLVLPINIAD GPR7_HUMAN 83 83 -
DELFTLVPPVNIAD Q8MJV3 86 86 -
DGLFTLVLPTNIAE Q8MJV2 91 91 -
DGLFTLVLPVNIAE GPR8_HUMAN 91 91 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LATAESRRVAGRT GPR7_HUMAN 139 42 -
LATAESRRVAGRT Q8MJV3 142 42 -
LATARSRRMPRRT Q8MJV2 147 42 -
LATVRSRHMPWRT GPR8_HUMAN 147 42 -

Motif 3 width=13
Element Seqn Id St Int Rpt
ARAVSLAVWGIVT GPR7_HUMAN 155 3 -
ARAVSLAVWGVAT Q8MJV3 158 3 -
AKVASLCVWLGVT Q8MJV2 163 3 -
AKVASLCVWLGVT GPR8_HUMAN 163 3 -

Motif 4 width=10
Element Seqn Id St Int Rpt
VLPFAVFARL GPR7_HUMAN 170 2 -
VLPFAVFARL Q8MJV3 173 2 -
VLPFLTFAGV Q8MJV2 178 2 -
VLPFFSFAGV GPR8_HUMAN 178 2 -

Motif 5 width=10
Element Seqn Id St Int Rpt
QCVLVFPQPE GPR7_HUMAN 187 7 -
QCVLVFPQPE Q8MJV3 190 7 -
SCGLSFPRPE Q8MJV2 196 8 -
SCGLSFPWPE GPR8_HUMAN 196 8 -

Motif 6 width=13
Element Seqn Id St Int Rpt
WWRASRLYTLVLG GPR7_HUMAN 199 2 -
WWRASRLYTLVLG Q8MJV3 202 2 -
WFQASRIYTLVLG Q8MJV2 208 2 -
WFKASRVYTLVLG GPR8_HUMAN 208 2 -

Motif 7 width=14
Element Seqn Id St Int Rpt
RLHAMRLDSHAKAL GPR7_HUMAN 229 17 -
RLRAIRLDSHAKAL Q8MJV3 232 17 -
RLRALRLHSGAKAL Q8MJV2 238 17 -
RLRAVRLRSGAKAL GPR8_HUMAN 238 17 -

Motif 8 width=15
Element Seqn Id St Int Rpt
LLCWTPYHLSTVVAL GPR7_HUMAN 261 18 -
LLVWTPYHLSTVVAL Q8MJV3 264 18 -
LLCWTPFHLASIVAL Q8MJV2 270 18 -
LLCWTPFHLASVVAL GPR8_HUMAN 270 18 -