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PR01567

Identifier
NEUROMEDNU2R  [View Relations]  [View Alignment]  
Accession
PR01567
No. of Motifs
8
Creation Date
04-SEP-2001
Title
Neuromedin U type 2 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. 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 2 receptor (NMU2) is expressed most abundantly in the
central nervous system, particularly in the medulla oblongata, pontine
reticular formation, substantia nigra, spinal cord and thalamus [6,7]. High
levels of expression have also been found in the thymus, thyroid and testes
[7]. NMU2 has been detected at much lower levels in some peripheral tissues,
including the kidney, lung, trachea and gastrointestinal tract [6].
 
NEUROMEDNU2R is an 8-element fingerprint that provides a signature for the
neuromedin U type 2 receptors. The fingerprint was derived from an initial
alignment of 4 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 2 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 encodes the second cytoplasmic loop, 
leading into TM domain 4; motif 4 lies in the second external loop; motif 5
lies in the third cytoplasmic loop; motif 6 is located at the C-terminus of
TM domain 6, leading into the third external loop; and motifs 7 and 8 
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
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
Q9ESQ4        Q9GZQ4        Q9JIB1        Q9NRA6        
Sequence Titles
Q9ESQ4      G PROTEIN-COUPLED RECEPTOR TGR-1 - Rattus norvegicus (Rat). 
Q9GZQ4 NEUROMEDIN U RECEPTOR 2 (NEUROMEDIN U RECEPTOR-TYPE 2) - Homo sapiens (Human).
Q9JIB1 NEUROMEDIN U RECEPTOR 2 - Rattus norvegicus (Rat).
Q9NRA6 NEUROMEDIN U RECEPTOR 2 (G PROTEIN-COUPLED RECEPTOR TGR-1) - Homo sapiens (Human).
Scan History
SPTR39.22_17.3f 1  120  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
MGKLENASWI Q9ESQ4 1 1 -
MEKLQNASWI Q9NRA6 1 1 -
MGKLENASWI Q9JIB1 1 1 -
MEKLQNASWI Q9GZQ4 4 4 -

Motif 2 width=15
Element Seqn Id St Int Rpt
YLAHLCGPKRSDLSL Q9ESQ4 24 13 -
YLAFLCGPRRSHFFL Q9NRA6 29 18 -
YLAHLCGPKRSDLSL Q9JIB1 24 13 -
YLAFLCGPRRSHFFL Q9GZQ4 32 18 -

Motif 3 width=15
Element Seqn Id St Int Rpt
FRAKLESTRRRALRI Q9ESQ4 144 105 -
FRAKLQSTRRRALRI Q9NRA6 149 105 -
FRAKLESTRRRALRI Q9JIB1 144 105 -
FRAKLQSTRRRALRI Q9GZQ4 152 105 -

Motif 4 width=12
Element Seqn Id St Int Rpt
FQHFPNGSSVPG Q9ESQ4 181 22 -
FHYFPNGSLVPG Q9NRA6 186 22 -
FQHFPNGSSVPG Q9JIB1 181 22 -
FHYFPNGSLVPG Q9GZQ4 189 22 -

Motif 5 width=14
Element Seqn Id St Int Rpt
SLEANKVAVNIHRP Q9ESQ4 240 47 -
SLEADEGNANIQRP Q9NRA6 245 47 -
SLEANKVAVNIHRP Q9JIB1 240 47 -
SLEADEGNANIQRP Q9GZQ4 248 47 -

Motif 6 width=12
Element Seqn Id St Int Rpt
LFFSFVEEWTES Q9ESQ4 281 27 -
LFFSFVEEWSES Q9NRA6 286 27 -
LFFSFVEEWTES Q9JIB1 281 27 -
LFFSFVEEWSES Q9GZQ4 289 27 -

Motif 7 width=16
Element Seqn Id St Int Rpt
PQGPPAQKIIFLTECH Q9ESQ4 347 54 -
PQLPPAQRNIFLTECH Q9NRA6 352 54 -
PQGPPAQKIIFLTECH Q9JIB1 347 54 -
PQLPPAQRNIFLTECH Q9GZQ4 355 54 -

Motif 8 width=18
Element Seqn Id St Int Rpt
ELTEDAGPQFPGQSSIHN Q9ESQ4 365 2 -
ELTEDIGPQFPCQSSMHN Q9NRA6 370 2 -
ELTEDAGPQFPGQSSIHN Q9JIB1 365 2 -
ELTEDIGPQFPCQSSMHN Q9GZQ4 373 2 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
MGKLENASWI Q9ESQ4 1 1 -
MEKLQNASWI Q9NRA6 1 1 -
MGKLENASWI Q9JIB1 1 1 -
MEKLQNASWI Q9GZQ4 4 4 -

Motif 2 width=15
Element Seqn Id St Int Rpt
YLAHLCGPKRSDLSL Q9ESQ4 24 13 -
YLAFLCGPRRSHFFL Q9NRA6 29 18 -
YLAHLCGPKRSDLSL Q9JIB1 24 13 -
YLAFLCGPRRSHFFL Q9GZQ4 32 18 -

Motif 3 width=15
Element Seqn Id St Int Rpt
FRAKLESTRRRALRI Q9ESQ4 144 105 -
FRAKLQSTRRRALRI Q9NRA6 149 105 -
FRAKLESTRRRALRI Q9JIB1 144 105 -
FRAKLQSTRRRALRI Q9GZQ4 152 105 -

Motif 4 width=12
Element Seqn Id St Int Rpt
FQHFPNGSSVPG Q9ESQ4 181 22 -
FHYFPNGSLVPG Q9NRA6 186 22 -
FQHFPNGSSVPG Q9JIB1 181 22 -
FHYFPNGSLVPG Q9GZQ4 189 22 -

Motif 5 width=14
Element Seqn Id St Int Rpt
SLEANKVAVNIHRP Q9ESQ4 240 47 -
SLEADEGNANIQRP Q9NRA6 245 47 -
SLEANKVAVNIHRP Q9JIB1 240 47 -
SLEADEGNANIQRP Q9GZQ4 248 47 -

Motif 6 width=12
Element Seqn Id St Int Rpt
LFFSFVEEWTES Q9ESQ4 281 27 -
LFFSFVEEWSES Q9NRA6 286 27 -
LFFSFVEEWTES Q9JIB1 281 27 -
LFFSFVEEWSES Q9GZQ4 289 27 -

Motif 7 width=16
Element Seqn Id St Int Rpt
PQGPPAQKIIFLTECH Q9ESQ4 347 54 -
PQLPPAQRNIFLTECH Q9NRA6 352 54 -
PQGPPAQKIIFLTECH Q9JIB1 347 54 -
PQLPPAQRNIFLTECH Q9GZQ4 355 54 -

Motif 8 width=18
Element Seqn Id St Int Rpt
ELTEDAGPQFPGQSSIHN Q9ESQ4 365 2 -
ELTEDIGPQFPCQSSMHN Q9NRA6 370 2 -
ELTEDAGPQFPGQSSIHN Q9JIB1 365 2 -
ELTEDIGPQFPCQSSMHN Q9GZQ4 373 2 -