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PR01053

Identifier
MTABOTROPC3R  [View Relations]  [View Alignment]  
Accession
PR01053
No. of Motifs
10
Creation Date
28-JAN-1999  (UPDATE 03-JUL-1999)
Title
Metabotropic glutamate receptor 3 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00248 GPCRMGR
PRINTS; PR00593 MTABOTROPICR
INTERPRO; IPR001234
GCRDB; GCR_0362; GCR_2070
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., VOLPE, F., LELCHUK, R., HARRINGTON, K. AND EMSON, P.
Molecular characterization and localization of human metabotropic glutamate
receptor type 3.
BRAIN RES.MOL.BRAIN RES. 40 55-63 (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]. MGR3 is brain-specific,
and is expressed in neurones in the cerebral cortex, caudate-putamen, 
thalamus and cerebellum [7]. MGR3 inhibits adenylyl cyclase through a 
pertussis-toxin-sensitive G protein, probably of the Gi/Go class [6].
 
MTABOTROPC3R is a 10-element fingerprint that provides a signature for the
metabotropic glutamate receptor 3 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 3 receptors but 
distinguish them from the rest of the metabotropic glutamate receptor family
- motifs 1-8 reside in the N-terminal extracellular domain; and motifs 9 and
10 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. Two partial matches were found, MGR2_HUMAN and
MGR2_RAT, both of which are type 2 receptors that match motifs 4 and 10.
 
An update on SPTR37_9f identified a true set of 2 sequences, and 2
partial matches.
Summary Information
   2 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
102222222222
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20002000002
12345678910
True Positives
MGR3_HUMAN    MGR3_RAT      
True Positive Partials
Codes involving 2 elements
MGR2_HUMAN MGR2_RAT
Sequence Titles
MGR3_HUMAN  METABOTROPIC GLUTAMATE RECEPTOR 3 PRECURSOR - HOMO SAPIENS (HUMAN). 
MGR3_RAT METABOTROPIC GLUTAMATE RECEPTOR 3 PRECURSOR - RATTUS NORVEGICUS (RAT).

MGR2_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 2 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR2_RAT METABOTROPIC GLUTAMATE RECEPTOR 2 PRECURSOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL31_1    1  100  NSINGLE    
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
LTRLQVLTLALFSKGFL MGR3_HUMAN 2 2 -
LTRLQILMLALFSKGFL MGR3_RAT 4 4 -

Motif 2 width=17
Element Seqn Id St Int Rpt
LLSLGDHNFLRREIKIE MGR3_HUMAN 18 -1 -
LLSLGDHNFMRREIKIE MGR3_RAT 20 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FPINEKGTGTEE MGR3_HUMAN 43 8 -
FPINEKGTGTEE MGR3_RAT 45 8 -

Motif 4 width=22
Element Seqn Id St Int Rpt
TKVDEAEYMCPDGSYAIQENIP MGR3_HUMAN 116 61 -
TKVDEAEYMCPDGSYAIQENIP MGR3_RAT 118 61 -

Motif 5 width=15
Element Seqn Id St Int Rpt
RSNIRKSYDSVIREL MGR3_HUMAN 247 109 -
RSNIRKSYDSVIREL MGR3_RAT 249 109 -

Motif 6 width=18
Element Seqn Id St Int Rpt
QNKRNHRRVCDKHLAIDS MGR3_HUMAN 362 100 -
QNKRNHRQVCDKHLAIDS MGR3_RAT 364 100 -

Motif 7 width=13
Element Seqn Id St Int Rpt
FNPNKDADSIVKF MGR3_HUMAN 442 62 -
FNPNKGADSIVKF MGR3_RAT 444 62 -

Motif 8 width=16
Element Seqn Id St Int Rpt
DVNSIHWSRNSVPTSQ MGR3_HUMAN 491 36 -
DVDSIHWSRNSVPTSQ MGR3_RAT 493 36 -

Motif 9 width=17
Element Seqn Id St Int Rpt
LHLNRFSVSGTGTTYSQ MGR3_HUMAN 837 330 -
LHLNRFSVSGTATTYSQ MGR3_RAT 839 330 -

Motif 10 width=23
Element Seqn Id St Int Rpt
QSSASTYVPTVCNGREVLDSTTS MGR3_HUMAN 853 -1 -
QSSASTYVPTVCNGREVLDSTTS MGR3_RAT 855 -1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
LTRLQVLTLALFSKGFL MGR3_HUMAN 2 2 -
LTRLQILMLALFSKGFL MGR3_RAT 4 4 -

Motif 2 width=17
Element Seqn Id St Int Rpt
LLSLGDHNFLRREIKIE MGR3_HUMAN 18 -1 -
LLSLGDHNFMRREIKIE MGR3_RAT 20 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FPINEKGTGTEE MGR3_HUMAN 43 8 -
FPINEKGTGTEE MGR3_RAT 45 8 -

Motif 4 width=22
Element Seqn Id St Int Rpt
TKVDEAEYMCPDGSYAIQENIP MGR3_HUMAN 116 61 -
TKVDEAEYMCPDGSYAIQENIP MGR3_RAT 118 61 -

Motif 5 width=15
Element Seqn Id St Int Rpt
RSNIRKSYDSVIREL MGR3_HUMAN 247 109 -
RSNIRKSYDSVIREL MGR3_RAT 249 109 -

Motif 6 width=18
Element Seqn Id St Int Rpt
QNKRNHRRVCDKHLAIDS MGR3_HUMAN 362 100 -
QNKRNHRQVCDKHLAIDS MGR3_RAT 364 100 -

Motif 7 width=13
Element Seqn Id St Int Rpt
FNPNKDADSIVKF MGR3_HUMAN 442 62 -
FNPNKGADSIVKF MGR3_RAT 444 62 -

Motif 8 width=16
Element Seqn Id St Int Rpt
DVNSIHWSRNSVPTSQ MGR3_HUMAN 491 36 -
DVDSIHWSRNSVPTSQ MGR3_RAT 493 36 -

Motif 9 width=17
Element Seqn Id St Int Rpt
LHLNRFSVSGTGTTYSQ MGR3_HUMAN 837 330 -
LHLNRFSVSGTATTYSQ MGR3_RAT 839 330 -

Motif 10 width=23
Element Seqn Id St Int Rpt
QSSASTYVPTVCNGREVLDSTTS MGR3_HUMAN 853 -1 -
QSSASTYVPTVCNGREVLDSTTS MGR3_RAT 855 -1 -