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PR01057

Identifier
MTABOTROPC7R  [View Relations]  [View Alignment]  
Accession
PR01057
No. of Motifs
7
Creation Date
30-JAN-1999  (UPDATE 07-JUN-1999)
Title
Metabotropic glutamate receptor 7 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00248 GPCRMGR
PRINTS; PR00593 MTABOTROPICR
INTERPRO; IPR001883
GCRDB; GCR_0945; GCR_0946; GCR_1890; GCR_2071
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.
 
7. MAKOFF, A., PILLING, C., HARRINGTON, K. AND EMSON, P.
Human metabotropic glutamate receptor type 7: molecular cloning and mRNA
distribution in the CNS.
BRAIN RES.MOL.BRAIN RES. 40 165-170 (1996). 
 
8. OKAMOTO, N., HORI, S., AKAZAWA, C., HAYASHI, Y., SHIGEMOTO, R.,
MIZUNO, N. AND NAKANISHI, S.
Molecular characterization of a new metabotropic glutamate receptor mGluR7
coupled to inhibitory cyclic AMP signal transduction.
J.BIOL.CHEM. 269 1231-1236 (1994). 

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]. MGR7 mRNA has a 
widespread distribution in many neuronal cells of the central nervous 
system, with highest levels in the hippocampal formation, cerebral cortex
and cerebellum [7,8]; it is thus different from the more limitedly expressed
MGR4 or MGR6 mRNA [8]. MGR7 and MGR4 are believed to correspond to the
putative L-2-amino-4-phosphonobutyrate receptor, which plays an important
role in modulation of glutamate transmission in the CNS [8].
 
MTABOTROPC7R is a 7-element fingerprint that provides a signature for the
metabotropic glutamate receptor 7 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 7 receptors but 
distinguish them from the rest of the metabotropic glutamate receptor family
- motifs 1-6 reside in the N-terminal extracellular domain; and motif 7 lies
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. Three partial matches were also found: A43643 is
a patent sequence that matches motifs 5-7; and HSU95025 and MGR8_HUMAN are
type 8 receptors that match motifs 6 and 7.
 
An update on SPTR37_9f identified a true set of 2 sequences.
Summary Information
2 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
72222222
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
MGR7_HUMAN    MGR7_RAT      
Sequence Titles
MGR7_HUMAN  METABOTROPIC GLUTAMATE RECEPTOR 7 PRECURSOR - HOMO SAPIENS (HUMAN). 
MGR7_RAT METABOTROPIC GLUTAMATE RECEPTOR 7 PRECURSOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    2  100  NSINGLE    
SPTR37_9f 2 3 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
QLRKLLRVLTLMKFPCCVLE MGR7_HUMAN 3 3 -
QLGKLLRVLTLMKFPCCVLE MGR7_RAT 3 3 -

Motif 2 width=21
Element Seqn Id St Int Rpt
EVLLCALAAAARGQEMYAPHS MGR7_HUMAN 22 -1 -
EVLLCVLAAAARGQEMYAPHS MGR7_RAT 22 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
PQERKDRTIDFD MGR7_HUMAN 257 214 -
PQERKDRTIDFD MGR7_RAT 257 214 -

Motif 4 width=12
Element Seqn Id St Int Rpt
ISGSKKEDTDRK MGR7_HUMAN 378 109 -
ISGSKKEDTDRK MGR7_RAT 378 109 -

Motif 5 width=15
Element Seqn Id St Int Rpt
ADYRGVCPEMEQAGG MGR7_HUMAN 431 41 -
ADYRGVCPEMEQAGG MGR7_RAT 431 41 -

Motif 6 width=13
Element Seqn Id St Int Rpt
FQYQTTNTSNPGY MGR7_HUMAN 480 34 -
FQYQTTNTTNPGY MGR7_RAT 480 34 -

Motif 7 width=16
Element Seqn Id St Int Rpt
SSRLSHKPSDRPNGEA MGR7_HUMAN 873 380 -
SSRLSHKPSDRPNGEA MGR7_RAT 873 380 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
QLRKLLRVLTLMKFPCCVLE MGR7_HUMAN 3 3 -
QLGKLLRVLTLMKFPCCVLE MGR7_RAT 3 3 -

Motif 2 width=21
Element Seqn Id St Int Rpt
EVLLCALAAAARGQEMYAPHS MGR7_HUMAN 22 -1 -
EVLLCVLAAAARGQEMYAPHS MGR7_RAT 22 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
PQERKDRTIDFD MGR7_HUMAN 257 214 -
PQERKDRTIDFD MGR7_RAT 257 214 -

Motif 4 width=12
Element Seqn Id St Int Rpt
ISGSKKEDTDRK MGR7_HUMAN 378 109 -
ISGSKKEDTDRK MGR7_RAT 378 109 -

Motif 5 width=15
Element Seqn Id St Int Rpt
ADYRGVCPEMEQAGG MGR7_HUMAN 431 41 -
ADYRGVCPEMEQAGG MGR7_RAT 431 41 -

Motif 6 width=13
Element Seqn Id St Int Rpt
FQYQTTNTSNPGY MGR7_HUMAN 480 34 -
FQYQTTNTTNPGY MGR7_RAT 480 34 -

Motif 7 width=16
Element Seqn Id St Int Rpt
SSRLSHKPSDRPNGEA MGR7_HUMAN 873 380 -
SSRLSHKPSDRPNGEA MGR7_RAT 873 380 -