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PR01054

Identifier
MTABOTROPC4R  [View Relations]  [View Alignment]  
Accession
PR01054
No. of Motifs
9
Creation Date
30-JAN-1999  (UPDATE 28-JUL-1999)
Title
Metabotropic glutamate receptor 4 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00248 GPCRMGR
PRINTS; PR00593 MTABOTROPICR
INTERPRO; IPR001786
GCRDB; GCR_0352; GCR_0363; GCR_1891; GCR_2069
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., LELCHUK, R., OXER, M., HARRINGTON, K. AND EMSON, P.
Molecular characterization and localization of human metabotropic glutamate
receptor type 4.
BRAIN RES.MOL.BRAIN RES. 37 239-248 (1996). 

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]. MGR4 is brain-specific, 
showing a distinct distribution (excluding the cerebellum), being expressed
in the thalamus, hypothalamus and caudate nucleus [7]. In rat, the strongest
MGR4 mRNA signal is found in the cerebellar granule cells [7]. The principal
difference from rat brain is the presence in human brain of MGR4 mRNA in 
the caudate nucleus and putamen [7]. MGR4 inhibits adenylyl cyclase through 
a pertussis-toxin-sensitive G protein, probably of the Gi/Go class [6].
 
MTABOTROPC4R is a 9-element fingerprint that provides a signature for the
metabotropic glutamate receptor 4 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 4 receptors but 
distinguish them from the rest of the metabotropic glutamate receptor family
- motifs 1-6 reside in the N-terminal extracellular domain; and motifs 7-9
lie in the C-terminal cytoplasmic domain. A single iteration on OWL31.1 was 
required to reach convergence, no further sequences being identified beyond 
the starting set. A single partial match was found, RNU47331, a rat
metabotropic glutamate 4b receptor that fails to match motifs 8 and 9.
 
An update on SPTR37_9f identified a true set of 2 sequences, and 8
partial matches.
Summary Information
   2 codes involving  9 elements
0 codes involving 8 elements
1 codes involving 7 elements
1 codes involving 6 elements
2 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
4 codes involving 2 elements
Composite Feature Index
9222222222
8000000000
7111111100
6001110111
5002200222
4000000000
3000000000
2002400200
123456789
True Positives
MGR4_HUMAN    MGR4_RAT      
True Positive Partials
Codes involving 7 elements
Q62916
Codes involving 6 elements
MGR8_MOUSE
Codes involving 5 elements
MGR8_HUMAN MGR8_RAT
Codes involving 2 elements
MGR6_HUMAN MGR6_RAT MGR7_HUMAN MGR7_RAT
Sequence Titles
MGR4_HUMAN  METABOTROPIC GLUTAMATE RECEPTOR 4 PRECURSOR - HOMO SAPIENS (HUMAN). 
MGR4_RAT METABOTROPIC GLUTAMATE RECEPTOR 4 PRECURSOR - RATTUS NORVEGICUS (RAT).

Q62916 METABOTROPIC GLUTAMATE RECEPTOR 4B - RATTUS NORVEGICUS (RAT).

MGR8_MOUSE METABOTROPIC GLUTAMATE RECEPTOR 8 PRECURSOR - MUS MUSCULUS (MOUSE).

MGR8_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 8 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR8_RAT METABOTROPIC GLUTAMATE RECEPTOR 8 PRECURSOR - RATTUS NORVEGICUS (RAT).

MGR6_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 6 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR6_RAT METABOTROPIC GLUTAMATE RECEPTOR 6 PRECURSOR - RATTUS NORVEGICUS (RAT).
MGR7_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 7 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR7_RAT METABOTROPIC GLUTAMATE RECEPTOR 7 PRECURSOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    1  50   NSINGLE    
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
WWWARLPLCLLLSLYGPW MGR4_HUMAN 9 9 -
WWWARLPLCLLLSLYAPW MGR4_RAT 9 9 -

Motif 2 width=19
Element Seqn Id St Int Rpt
WMPSSLGKPKGHPHMNSIR MGR4_HUMAN 26 -1 -
WVPSSLGKPKGHPHMNSIR MGR4_RAT 26 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GTEVRCGSGGPPIITKP MGR4_HUMAN 131 86 -
GTEVRCGSGGPPIITKP MGR4_RAT 131 86 -

Motif 4 width=18
Element Seqn Id St Int Rpt
RVLEAARRANQTGHFFWM MGR4_HUMAN 292 144 -
RVLEAARRANQTGHFFWM MGR4_RAT 292 144 -

Motif 5 width=16
Element Seqn Id St Int Rpt
KLSRHALKKGSHVKKC MGR4_HUMAN 373 63 -
KLSRHALKKGSHIKKC MGR4_RAT 373 63 -

Motif 6 width=19
Element Seqn Id St Int Rpt
DHLHLRIERMHWPGSGQQL MGR4_HUMAN 497 108 -
DHLHLRIERMQWPGSGQQL MGR4_RAT 497 108 -

Motif 7 width=15
Element Seqn Id St Int Rpt
VDFQDQRTLDPRFAR MGR4_HUMAN 727 211 -
VDFQDQRTLDPRFAR MGR4_RAT 727 211 -

Motif 8 width=15
Element Seqn Id St Int Rpt
SNKFTQKGNFRPNGE MGR4_HUMAN 870 128 -
SNKFTQKGNFRPNGE MGR4_RAT 870 128 -

Motif 9 width=20
Element Seqn Id St Int Rpt
NLEAPALATKQTYVTYTNHA MGR4_HUMAN 892 7 -
NLETPALATKQTYVTYTNHA MGR4_RAT 892 7 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
WWWARLPLCLLLSLYGPW MGR4_HUMAN 9 9 -
WWWARLPLCLLLSLYAPW MGR4_RAT 9 9 -

Motif 2 width=19
Element Seqn Id St Int Rpt
WMPSSLGKPKGHPHMNSIR MGR4_HUMAN 26 -1 -
WVPSSLGKPKGHPHMNSIR MGR4_RAT 26 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GTEVRCGSGGPPIITKP MGR4_HUMAN 131 86 -
GTEVRCGSGGPPIITKP MGR4_RAT 131 86 -

Motif 4 width=18
Element Seqn Id St Int Rpt
RVLEAARRANQTGHFFWM MGR4_HUMAN 292 144 -
RVLEAARRANQTGHFFWM MGR4_RAT 292 144 -

Motif 5 width=16
Element Seqn Id St Int Rpt
KLSRHALKKGSHVKKC MGR4_HUMAN 373 63 -
KLSRHALKKGSHIKKC MGR4_RAT 373 63 -

Motif 6 width=19
Element Seqn Id St Int Rpt
DHLHLRIERMHWPGSGQQL MGR4_HUMAN 497 108 -
DHLHLRIERMQWPGSGQQL MGR4_RAT 497 108 -

Motif 7 width=15
Element Seqn Id St Int Rpt
VDFQDQRTLDPRFAR MGR4_HUMAN 727 211 -
VDFQDQRTLDPRFAR MGR4_RAT 727 211 -

Motif 8 width=15
Element Seqn Id St Int Rpt
SNKFTQKGNFRPNGE MGR4_HUMAN 870 128 -
SNKFTQKGNFRPNGE MGR4_RAT 870 128 -

Motif 9 width=20
Element Seqn Id St Int Rpt
NLEAPALATKQTYVTYTNHA MGR4_HUMAN 892 7 -
NLETPALATKQTYVTYTNHA MGR4_RAT 892 7 -