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PR01565

Identifier
NEUROMEDINUR  [View Relations]  [View Alignment]  
Accession
PR01565
No. of Motifs
6
Creation Date
04-SEP-2001
Title
Neuromedin U receptor family signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01566 NEUROMEDNU1R
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. RADDATZ, R., WILSON, A.E., ARTYMYSHYN, R., BONINI, J.A., BOROWSKY, B.,
BOTEJU, L.W., ZHOU, S., KOURANOVA, E.V., NAGORNY, R., GUEVARRA, M.S., DAI,
M., LERMAN, G.S., VAYSSE, P.J., BRANCHEK, T.A., GERALD, C., FORRAY, C. AND
ADHAM, N.
Identification and characterization of two neuromedin U receptors
differentially expressed in peripheral tissues and the central nervous
system.
J.BIOL.CHEM. 275(42) 32452-32459 (2000).
 
7. HOWARD, A.D., WANG, R., PONG, S.S., MELLIN, T.N., STRACK, A., GUAN, X.M.,
ZENG, Z., WILLIAMS, D.L.JR, FEIGHNER, S.D., NUNES, C.N., MURPHY, B., STAIR,
J.N., YU, H., JIANG, Q., CLEMENTS, M.K., TAN, C.P., MCKEE, K.K., HRENIUK,
D.L., MCDONALD, T.P., LYNCH, K.R., EVANS, J.F., AUSTIN, C.P., CASKEY, C.T.,
VAN DER PLOEG, L.H.T. AND LIU, Q.
Identification of receptors for neuromedin U and its role in feeding.
NATURE 406 70-74 (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].
 
Neuromedin U is a neuropeptide, first isolated from porcine spinal cord and
expressed widely in the gastrointestinal, genitourinary and central nervous
systems [6,7]. Neuromedin U has potent contractile activity on smooth muscle
and this activity is believed to reside within the C-terminal portion of 
the peptide, which is highly conserved between species [6]. Other roles 
for the peptide include: regulation of blood flow and ion transport in 
the intestine, regulation of adrenocortical function and increased blood
pressure [6,7]. The roles of neuromedin U in the central nervous system
are poorly understood, but may include: regulation of food intake,
neuroendocrine control, modulation of dopamine actions and involvement in
neuropsychiatric disorders [6]. Two G protein-coupled receptor subtypes,
with differing expression patterns, have been identified and shown to bind
neuromedin U [6,7].
 
NEUROMEDINUR is a 6-element fingerprint that provides a signature for the
neuromedin U receptor family. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections
within the loop regions, focusing on those areas of the alignment that
characterise the neuromedin U receptors but distinguish them from the rest
of the rhodopsin-like superfamily - motif 1 spans the first cytoplasmic
loop, leading into TM domain 2; motif 2 encodes the C-terminal portion of 
TM domain 2 and the first external loop; motif 3 spans part of TM domain 4,
leading into the second external loop; motif 4 lies in the second external
loop; motif 5 resides at the C-terminus of TM domain 6, leading into the
third external loop; and motif 6 encodes the C-terminal portion of the third
external loop and part of TM domain 7. Two iterations on SPTR39.22_17.3f
were required to reach convergence, at which point a true set comprising 9
sequences was identified. A single partial match was also found, Q9VFN4, a
Drosophila GPCR that matches motifs 1 and 2.
Summary Information
   9 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6999999
5000000
4000000
3000000
2110000
123456
True Positives
O43664        O55040        Q9ESQ4        Q9GZQ4        
Q9HB89 Q9JIB1 Q9JIB2 Q9JJI5
Q9NRA6
True Positive Partials
Codes involving 2 elements
Q9VFN4
Sequence Titles
O43664      ORPHAN G PROTEIN-COUPLED RECEPTOR - Homo sapiens (Human). 
O55040 ORPHAN G PROTEIN-COUPLED RECEPTOR - Mus musculus (Mouse).
Q9ESQ4 G PROTEIN-COUPLED RECEPTOR TGR-1 - Rattus norvegicus (Rat).
Q9GZQ4 NEUROMEDIN U RECEPTOR 2 (NEUROMEDIN U RECEPTOR-TYPE 2) - Homo sapiens (Human).
Q9HB89 NEUROMEDIN U RECEPTOR 1 - Homo sapiens (Human).
Q9JIB1 NEUROMEDIN U RECEPTOR 2 - Rattus norvegicus (Rat).
Q9JIB2 NEUROMEDIN U RECEPTOR 1 - Rattus norvegicus (Rat).
Q9JJI5 G PROTEIN-COUPLED RECEPTOR FM-3 - Rattus norvegicus (Rat).
Q9NRA6 NEUROMEDIN U RECEPTOR 2 (G PROTEIN-COUPLED RECEPTOR TGR-1) - Homo sapiens (Human).

Q9VFN4 CG9918 PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR39.22_17.3f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
RHKAMRTPTNYY Q9HB89 87 87 -
RHQTLKTPTNYY Q9ESQ4 64 64 -
QHQAMKTPTNYY Q9GZQ4 72 72 -
RQKAMHTPTNFY Q9JJI5 74 74 -
RNKTMRTPTNFY O55040 64 64 -

Motif 2 width=23
Element Seqn Id St Int Rpt
PLEIYEMWHNYPFLFGPVGCYFK Q9ESQ4 92 16 -
PLEVYEMWRNYPFLFGPVGCYFK Q9GZQ4 100 16 -
PLELYEMWHNYPFLLGVGGCYFR Q9HB89 115 16 -
PLELYEMQHNYPFQLGAGGCYFR Q9JJI5 102 16 -
PLELYEMQQNYPFQLGASACYFR O55040 92 16 -

Motif 3 width=12
Element Seqn Id St Int Rpt
SLPNTSLHGLSQ O55040 170 55 -
SLPNTSLHGIRQ Q9HB89 193 55 -
SLPNTSIHGIKF Q9ESQ4 170 55 -
SLPNTSIHGIKF Q9GZQ4 178 55 -
SLPNTSLHGLSP Q9JJI5 180 55 -

Motif 4 width=12
Element Seqn Id St Int Rpt
VPGSATCTVIKP Q9GZQ4 198 8 -
VPDSAVCMLVRP Q9HB89 213 8 -
VPGSATCTVTKP Q9ESQ4 190 8 -
VPDSVTCTLVRP Q9JJI5 200 8 -
VPDSAICSLVGP O55040 190 8 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FHIDRLFFSFV Q9GZQ4 284 74 -
FHADRVMWSVV Q9HB89 313 88 -
FHVDRLFFSFV Q9ESQ4 276 74 -
FHADRLMWSMV Q9JJI5 300 88 -
FHADRIMWSLV O55040 290 88 -

Motif 6 width=14
Element Seqn Id St Int Rpt
FNLVHVVSGVFFYL Q9GZQ4 305 10 -
FQHVHVISGIFFYL Q9HB89 334 10 -
FNLIHVVSGVFFYL Q9ESQ4 297 10 -
FQSVHLASGVFLYL Q9JJI5 321 10 -
YQCVHIASGIFFYL O55040 312 11 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
RHKAMRTPTNYY O43664 64 64 -
RHKAMRTPTNYY Q9HB89 87 87 -
RHQTLKTPTNYY Q9ESQ4 64 64 -
RHQTLKTPTNYY Q9JIB1 64 64 -
QHQAMKTPTNYY Q9NRA6 69 69 -
RQKAMHTPTNFY Q9JIB2 64 64 -
QHQAMKTPTNYY Q9GZQ4 72 72 -
RQKAMHTPTNFY Q9JJI5 74 74 -
RNKTMRTPTNFY O55040 64 64 -

Motif 2 width=23
Element Seqn Id St Int Rpt
PLEIYEMWHNYPFLFGPVGCYFK Q9ESQ4 92 16 -
PLEVYEMWRNYPFLFGPVGCYFK Q9GZQ4 100 16 -
PLEVYEMWRNYPFLFGPVGCYFK Q9NRA6 97 16 -
PLELYEMWHNYPFLLGVGGCYFR O43664 92 16 -
PLELYEMWHNYPFLLGVGGCYFR Q9HB89 115 16 -
PLEIYEMWHNYPFLFGPVGCYFK Q9JIB1 92 16 -
PLELYEMQHNYPFQLGAGGCYFR Q9JIB2 92 16 -
PLELYEMQHNYPFQLGAGGCYFR Q9JJI5 102 16 -
PLELYEMQQNYPFQLGASACYFR O55040 92 16 -

Motif 3 width=12
Element Seqn Id St Int Rpt
SLPNTSLHGLSQ O55040 170 55 -
SLPNTSIHGIKF Q9NRA6 175 55 -
SLPNTSLHGIRQ O43664 170 55 -
SLPNTSLHGIRQ Q9HB89 193 55 -
SLPNTSIHGIKF Q9ESQ4 170 55 -
SLPNTSIHGIKF Q9JIB1 170 55 -
SLPNTSIHGIKF Q9GZQ4 178 55 -
SLPNTSLHGLSP Q9JIB2 170 55 -
SLPNTSLHGLSP Q9JJI5 180 55 -

Motif 4 width=12
Element Seqn Id St Int Rpt
VPDSVTCTLVRP Q9JIB2 190 8 -
VPGSATCTVIKP Q9GZQ4 198 8 -
VPGSATCTVIKP Q9NRA6 195 8 -
VPDSAVCMLVRP O43664 190 8 -
VPDSAVCMLVRP Q9HB89 213 8 -
VPGSATCTVTKP Q9ESQ4 190 8 -
VPGSATCTVTKP Q9JIB1 190 8 -
VPDSVTCTLVRP Q9JJI5 200 8 -
VPDSAICSLVGP O55040 190 8 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FHIDRLFFSFV Q9GZQ4 284 74 -
FHIDRLFFSFV Q9NRA6 281 74 -
FHADRVMWSVV O43664 290 88 -
FHADRVMWSVV Q9HB89 313 88 -
FHVDRLFFSFV Q9ESQ4 276 74 -
FHVDRLFFSFV Q9JIB1 276 74 -
FHADRLMWSMV Q9JIB2 290 88 -
FHADRLMWSMV Q9JJI5 300 88 -
FHADRIMWSLV O55040 290 88 -

Motif 6 width=14
Element Seqn Id St Int Rpt
FNLVHVVSGVFFYL Q9GZQ4 305 10 -
FNLVHVVSGVFFYL Q9NRA6 302 10 -
FQHVHVISGIFFYL O43664 311 10 -
FQHVHVISGIFFYL Q9HB89 334 10 -
FNLIHVVSGVFFYL Q9ESQ4 297 10 -
FNLIHVVSGVFFYL Q9JIB1 297 10 -
FQSVHLASGVFLYL Q9JIB2 311 10 -
FQSVHLASGVFLYL Q9JJI5 321 10 -
YQCVHIASGIFFYL O55040 312 11 -