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PR01566

Identifier
NEUROMEDNU1R  [View Relations]  [View Alignment]  
Accession
PR01566
No. of Motifs
9
Creation Date
04-SEP-2001
Title
Neuromedin U type 1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01565 NEUROMEDINUR
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].
 
The neuromedin U type 1 receptor (NMU1) is expressed predominantly in the
periphery, with highest levels in the gastrointestinal and urogenital
systems, particularly in the testes [6]. The receptor is also found in the
kidney, pancreas, lung, trachea, adrenal cortex, liver and mammary glands
[6,7]. Within the small intestine and ileum, NMU1 is specifically expressed
in goblet cells [7]. In the central nervous system, the receptor is
expressed only at much lower levels and has been detected most abundantly
in the cerebellum, dorsal root ganglia, hippocampus and spinal cord [6].
Binding of neuromedin U to the receptor results in phospholipase C
activation and increased intracellular calcium concentrations through
coupling to Gq proteins [6].
 
NEUROMEDNU1R is a 9-element fingerprint that provides a signature for the
neuromedin U type 1 receptors. The fingerprint was derived from an initial
alignment of 5 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 type 1 neuromedin U receptors but distinguish 
them from the rest of the neuromedin U receptor family - motifs 1 and 2 
reside at the N-terminus; motif 3 spans the second cytoplasmic loop, leading
into TM domain 4; motif 4 lies in the second external loop; motifs 5 and 6
reside in the third cytoplasmic loop; and motifs 7-9 span 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
5 codes involving  9 elements
0 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
9555555555
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
O43664        O55040        Q9HB89        Q9JIB2        
Q9JJI5
Sequence Titles
O43664      ORPHAN G PROTEIN-COUPLED RECEPTOR - Homo sapiens (Human). 
O55040 ORPHAN G PROTEIN-COUPLED RECEPTOR - Mus musculus (Mouse).
Q9HB89 NEUROMEDIN U RECEPTOR 1 - Homo sapiens (Human).
Q9JIB2 NEUROMEDIN U RECEPTOR 1 - Rattus norvegicus (Rat).
Q9JJI5 G PROTEIN-COUPLED RECEPTOR FM-3 - Rattus norvegicus (Rat).
Scan History
SPTR39.22_17.3f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
CNDSEFKEHFDLED Q9JIB2 3 3 -
CNDSEFKEHFDLED Q9JJI5 13 13 -
CNGSAARGHFDPED O43664 3 3 -
CNGSAARGHFDPED Q9HB89 26 26 -
CNISEFKWPYQPED O55040 3 3 -

Motif 2 width=15
Element Seqn Id St Int Rpt
LTHEDLRLKYLGPQQ Q9JIB2 19 2 -
LTHEDLRLKYLGPQQ Q9JJI5 29 2 -
LTDEALRLKYLGPQQ O43664 19 2 -
LTDEALRLKYLGPQQ Q9HB89 42 2 -
LTDEALRLKYLGPQQ O55040 19 2 -

Motif 3 width=13
Element Seqn Id St Int Rpt
LQAKSVMTRTHVR Q9JIB2 144 110 -
LQAKSVMTRTHVR Q9JJI5 154 110 -
LQARSMVTRAHVR O43664 144 110 -
LQARSMVTRAHVR Q9HB89 167 110 -
LQAKSVMTRAHVR O55040 144 110 -

Motif 4 width=11
Element Seqn Id St Int Rpt
SPLYVPCRGPV Q9JIB2 180 23 -
SPLYVPCRGPV Q9JJI5 190 23 -
RQLHVPCRGPV O43664 180 23 -
RQLHVPCRGPV Q9HB89 203 23 -
SQLTVPCRGPV O55040 180 23 -

Motif 5 width=14
Element Seqn Id St Int Rpt
LQEEVKGRISAAAR Q9JIB2 242 51 -
LQEEVKGRISAAAR Q9JJI5 252 51 -
LMQEAKGRGSAAAR O43664 242 51 -
LMQEAKGRGSAAAR Q9HB89 265 51 -
LQVEVKGRKTAATQ O55040 242 51 -

Motif 6 width=11
Element Seqn Id St Int Rpt
SIQLRDRERRQ Q9JIB2 261 5 -
SIQLRDRERRQ Q9JJI5 271 5 -
RLQQHDRGRRQ O43664 261 5 -
RLQQHDRGRRQ Q9HB89 284 5 -
RIQLQDRGRRQ O55040 261 5 -

Motif 7 width=11
Element Seqn Id St Int Rpt
RESFRETLGLG Q9JIB2 341 69 -
RESFRETLGLG Q9JJI5 351 69 -
RETFQEALCLG O43664 341 69 -
RETFQEALCLG Q9HB89 364 69 -
RETFLQALGLG O55040 342 70 -

Motif 8 width=25
Element Seqn Id St Int Rpt
CCHRHQPRHDSHSHLRLTTVSTLCD Q9JIB2 354 2 -
CCHRHQPRHDSHSHLRLTTVSTLCD Q9JJI5 364 2 -
CCHRLRPRHSSHSLSRMTTGSTLCD O43664 353 1 -
CCHRLRPRHSSHSLSRMTTGSTLCD Q9HB89 376 1 -
CCHRRQPYHGSHNHIRLTTGSTLCD O55040 355 2 -

Motif 9 width=16
Element Seqn Id St Int Rpt
PLAENRDPGCEQETDP Q9JIB2 385 6 -
PLAENRDPGCEQETDP Q9JJI5 395 6 -
PLAGNDGPEAQQETDP O43664 387 9 -
PLAGNDGPEAQQETDP Q9HB89 410 9 -
PLAVNEDPGCQQETDP O55040 389 9 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
CNDSEFKEHFDLED Q9JIB2 3 3 -
CNDSEFKEHFDLED Q9JJI5 13 13 -
CNGSAARGHFDPED O43664 3 3 -
CNGSAARGHFDPED Q9HB89 26 26 -
CNISEFKWPYQPED O55040 3 3 -

Motif 2 width=15
Element Seqn Id St Int Rpt
LTHEDLRLKYLGPQQ Q9JIB2 19 2 -
LTHEDLRLKYLGPQQ Q9JJI5 29 2 -
LTDEALRLKYLGPQQ O43664 19 2 -
LTDEALRLKYLGPQQ Q9HB89 42 2 -
LTDEALRLKYLGPQQ O55040 19 2 -

Motif 3 width=13
Element Seqn Id St Int Rpt
LQAKSVMTRTHVR Q9JIB2 144 110 -
LQAKSVMTRTHVR Q9JJI5 154 110 -
LQARSMVTRAHVR O43664 144 110 -
LQARSMVTRAHVR Q9HB89 167 110 -
LQAKSVMTRAHVR O55040 144 110 -

Motif 4 width=11
Element Seqn Id St Int Rpt
SPLYVPCRGPV Q9JIB2 180 23 -
SPLYVPCRGPV Q9JJI5 190 23 -
RQLHVPCRGPV O43664 180 23 -
RQLHVPCRGPV Q9HB89 203 23 -
SQLTVPCRGPV O55040 180 23 -

Motif 5 width=14
Element Seqn Id St Int Rpt
LQEEVKGRISAAAR Q9JIB2 242 51 -
LQEEVKGRISAAAR Q9JJI5 252 51 -
LMQEAKGRGSAAAR O43664 242 51 -
LMQEAKGRGSAAAR Q9HB89 265 51 -
LQVEVKGRKTAATQ O55040 242 51 -

Motif 6 width=11
Element Seqn Id St Int Rpt
SIQLRDRERRQ Q9JIB2 261 5 -
SIQLRDRERRQ Q9JJI5 271 5 -
RLQQHDRGRRQ O43664 261 5 -
RLQQHDRGRRQ Q9HB89 284 5 -
RIQLQDRGRRQ O55040 261 5 -

Motif 7 width=11
Element Seqn Id St Int Rpt
RESFRETLGLG Q9JIB2 341 69 -
RESFRETLGLG Q9JJI5 351 69 -
RETFQEALCLG O43664 341 69 -
RETFQEALCLG Q9HB89 364 69 -
RETFLQALGLG O55040 342 70 -

Motif 8 width=25
Element Seqn Id St Int Rpt
CCHRHQPRHDSHSHLRLTTVSTLCD Q9JIB2 354 2 -
CCHRHQPRHDSHSHLRLTTVSTLCD Q9JJI5 364 2 -
CCHRLRPRHSSHSLSRMTTGSTLCD O43664 353 1 -
CCHRLRPRHSSHSLSRMTTGSTLCD Q9HB89 376 1 -
CCHRRQPYHGSHNHIRLTTGSTLCD O55040 355 2 -

Motif 9 width=16
Element Seqn Id St Int Rpt
PLAENRDPGCEQETDP Q9JIB2 385 6 -
PLAENRDPGCEQETDP Q9JJI5 395 6 -
PLAGNDGPEAQQETDP O43664 387 9 -
PLAGNDGPEAQQETDP Q9HB89 410 9 -
PLAVNEDPGCQQETDP O55040 389 9 -