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PR01055

Identifier
MTABOTROPC5R  [View Relations]  [View Alignment]  
Accession
PR01055
No. of Motifs
12
Creation Date
30-JAN-1999  (UPDATE 10-JUN-1999)
Title
Metabotropic glutamate receptor 5 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00248 GPCRMGR
PRINTS; PR00593 MTABOTROPICR
INTERPRO; IPR000202
GCRDB; GCR_0444; GCR_0760; GCR_0761; GCR_1002; GCR_1003; GCR_1317
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994). 
 
2. MASU, M., TANABE, Y., TSUCHIDA, K., SHIGEMOTO, R. AND NAKANISHI, S.
Sequence and expression of a metabotropic glutamate receptor.
NATURE 349 760-765 (1991).
 
3. HOUAMED, K.M., KUIJPER, J.L., GILBERT, T.L., HALDEMAN, B.A., OHARA, P.J.,
MULVIHILL, E.R., ALMERS, W. AND HAGEN, F.S.
Cloning, expression and gene structure of a G protein-coupled glutamate
receptor from rat brain.
SCIENCE 252 1318-1321 (1991).
 
4. ABE, T., SUGIHARA, H., NAWA, H., SHIGEMOTO, R., MIZUNO, N. AND 
NAKANISHI, S.
Molecular characterisation of a novel metabotropic glutamate receptor
MGLUR5 coupled to inositol phosphate/Ca2+ signal transduction.
J.BIOL.CHEM. 267(19) 13361-13368 (1992).
 
5. TANABE, Y., MASU, M., ISHII, T., SHIGEMOTO, R. AND NAKANISHI, S.
A family of metabotropic glutamate receptors.
NEURON 8(1) 169-179 (1992).
 
6. WATSON, S. AND ARKINSTALL, S.
Glutamate receptors.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.130-141.

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 metabotropic glutamate receptors are functionally and pharmacologically
distinct from the ionotropic glutamate receptors. They are coupled to G-
proteins and stimulate the inositol phophate/Ca2+ intracellular signalling 
pathway [2-5]. The amino acid sequences of the receptors contain 2 domains:
a large extracellular domain, and a membrane-associated domain that contains
high proportions of hydrophobic residues grouped into 7 regions, in a manner
reminiscent of the rhodopsins and other receptors believed to interact with
G proteins. However, while a similar 3D framework has been proposed to
account for this, there is no significant sequence identity between these
and receptors of the rhodopsin-type family: the metabotropic glutamate
receptors thus bear their own distinctive `7TM' signature. This 7TM
signature is also shared by the calcium-sensing receptors.
 
At least eight sub-types of metabotropic receptor (MGR1-8) have been 
identified in cloning studies. The sub-types differ in their agonist 
pharmacology and signal transduction pathways [6]. mRNA for MGR5 is 
widespread in the brain, with a unique distribution; it is found in high
levels in the striatum, cerebral cortex, hippocampus and olfactory bulb [6].
MGR5 activates the phosphoinositide pathway, probably via a G protein of
the Gq/G11 class; pertussis toxin partially inhibits the response to MGR1,
but not to MGR5 [6]. 
 
MTABOTROPC5R is a 12-element fingerprint that provides a signature for the
metabotropic glutamate receptor 5 precursor. The fingerprint was derived
from an initial alignment of 2 sequences: the motifs were drawn from short
conserved regions spanning the full alignment length, focusing on those
sections that characterise the metabotropic glutamate type 5 receptors but 
distinguish them from the rest of the metabotropic glutamate receptor family
- motifs 1-7 reside in the N-terminal extracellular domain, motif 7 spanning
the N-terminus of putative TM domain 1; motif 8 spans the C-terminus of TM
domain 4; and motifs 9-12 lie in the C-terminal cytoplasmic domain. Two
iterations on OWL31.1 were required to reach convergence, at which point a
true set comprising 3 sequences was identified. Two partial matches were
also found, MGR1_HUMAN and MGR1_RAT, both of which are type 1 receptors
that match motifs 10 and 12.
 
An update on SPTR37_9f identified a true set of 2 sequences, and 2
partial matches.
Summary Information
   2 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 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
2 codes involving 2 elements
Composite Feature Index
12222222222222
11000000000000
10000000000000
9000000000000
8000000000000
7000000000000
6000000000000
5000000000000
4000000000000
3000000000000
2000000000202
123456789101112
True Positives
MGR5_HUMAN    MGR5_RAT      
True Positive Partials
Codes involving 2 elements
MGR1_HUMAN MGR1_RAT
Sequence Titles
MGR5_HUMAN  METABOTROPIC GLUTAMATE RECEPTOR 5 PRECURSOR - HOMO SAPIENS (HUMAN). 
MGR5_RAT METABOTROPIC GLUTAMATE RECEPTOR 5 PRECURSOR - RATTUS NORVEGICUS (RAT).

MGR1_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 1 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR1_RAT METABOTROPIC GLUTAMATE RECEPTOR 1 PRECURSOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  50   NSINGLE    
SPTR37_9f 2 27 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
VLLLILSVLLLKEDVR MGR5_HUMAN 2 2 -
VLLLILSVLLLKEDVR MGR5_RAT 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
RGSAQSSERRVVAHMPG MGR5_HUMAN 17 -1 -
RGSAQSSERRVVAHMPG MGR5_RAT 17 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
SSEEEEGLVRCVDGSSS MGR5_HUMAN 119 85 -
SSEEEEGLVRCVDGSSS MGR5_RAT 119 85 -

Motif 4 width=20
Element Seqn Id St Int Rpt
LEGFPQENSKYNKTCNSSLT MGR5_HUMAN 367 231 -
LEGFAQENSKYNKTCNSSLT MGR5_RAT 366 230 -

Motif 5 width=13
Element Seqn Id St Int Rpt
FKEMGKDYFDYIN MGR5_HUMAN 471 84 -
FKEMGKDYFDYIN MGR5_RAT 470 84 -

Motif 6 width=21
Element Seqn Id St Int Rpt
WDNGELKMDDDEVWSKKSNII MGR5_HUMAN 487 3 -
WDNGELKMDDDEVWSKKNNII MGR5_RAT 486 3 -

Motif 7 width=12
Element Seqn Id St Int Rpt
RWGDPEPIAAVV MGR5_HUMAN 574 66 -
RWGDPEPIAAVV MGR5_RAT 573 66 -

Motif 8 width=17
Element Seqn Id St Int Rpt
GIIVALFIMEPPDIMHD MGR5_HUMAN 706 120 -
GIIVALFIMEPPDIMHD MGR5_RAT 705 120 -

Motif 9 width=24
Element Seqn Id St Int Rpt
KSSSAASRSSSLVNLWKRRGSSGE MGR5_HUMAN 851 128 -
KSSSAASRSSSLVNLWKRRGSSGE MGR5_RAT 850 128 -

Motif 10 width=25
Element Seqn Id St Int Rpt
WQRLSIHINKKENPNQTAVIKPFPK MGR5_HUMAN 930 55 -
WQRLSVHINKKENPNQTAVIKPFPK MGR5_RAT 929 55 -

Motif 11 width=24
Element Seqn Id St Int Rpt
RPRSPSPISTLSHRAGSASRTDDD MGR5_HUMAN 1015 60 -
RPRSPSPISTLSHLAGSAGRTDDD MGR5_RAT 1011 57 -

Motif 12 width=24
Element Seqn Id St Int Rpt
PVSESALCIPSSPKYDTLIIRDYT MGR5_HUMAN 1183 144 -
PVSESALCIPSSPKYDTLIIRDYT MGR5_RAT 1174 139 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
VLLLILSVLLLKEDVR MGR5_HUMAN 2 2 -
VLLLILSVLLLKEDVR MGR5_RAT 2 2 -

Motif 2 width=17
Element Seqn Id St Int Rpt
RGSAQSSERRVVAHMPG MGR5_HUMAN 17 -1 -
RGSAQSSERRVVAHMPG MGR5_RAT 17 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
SSEEEEGLVRCVDGSSS MGR5_HUMAN 119 85 -
SSEEEEGLVRCVDGSSS MGR5_RAT 119 85 -

Motif 4 width=20
Element Seqn Id St Int Rpt
LEGFPQENSKYNKTCNSSLT MGR5_HUMAN 367 231 -
LEGFAQENSKYNKTCNSSLT MGR5_RAT 366 230 -

Motif 5 width=13
Element Seqn Id St Int Rpt
FKEMGKDYFDYIN MGR5_HUMAN 471 84 -
FKEMGKDYFDYIN MGR5_RAT 470 84 -

Motif 6 width=21
Element Seqn Id St Int Rpt
WDNGELKMDDDEVWSKKSNII MGR5_HUMAN 487 3 -
WDNGELKMDDDEVWSKKNNII MGR5_RAT 486 3 -

Motif 7 width=12
Element Seqn Id St Int Rpt
RWGDPEPIAAVV MGR5_HUMAN 574 66 -
RWGDPEPIAAVV MGR5_RAT 573 66 -

Motif 8 width=17
Element Seqn Id St Int Rpt
GIIVALFIMEPPDIMHD MGR5_HUMAN 706 120 -
GIIVALFIMEPPDIMHD MGR5_RAT 705 120 -

Motif 9 width=24
Element Seqn Id St Int Rpt
KSSSAASRSSSLVNLWKRRGSSGE MGR5_HUMAN 851 128 -
KSSSAASRSSSLVNLWKRRGSSGE MGR5_RAT 850 128 -

Motif 10 width=25
Element Seqn Id St Int Rpt
WQRLSIHINKKENPNQTAVIKPFPK MGR5_HUMAN 930 55 -
WQRLSVHINKKENPNQTAVIKPFPK MGR5_RAT 929 55 -

Motif 11 width=24
Element Seqn Id St Int Rpt
RPRSPSPISTLSHRAGSASRTDDD MGR5_HUMAN 1015 60 -
RPRSPSPISTLSHLAGSAGRTDDD MGR5_RAT 1011 57 -

Motif 12 width=24
Element Seqn Id St Int Rpt
PVSESALCIPSSPKYDTLIIRDYT MGR5_HUMAN 1183 144 -
PVSESALCIPSSPKYDTLIIRDYT MGR5_RAT 1174 139 -