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PR00593

Identifier
MTABOTROPICR  [View Relations]  [View Alignment]  
Accession
PR00593
No. of Motifs
6
Creation Date
13-AUG-1996  (UPDATE 10-JUN-1999)
Title
Metabotropic glutamate receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00248 GPCRMGR
PRINTS; PR01051 MTABOTROPC1R; PR01052 MTABOTROPC2R; PR01053 MTABOTROPC3R
PRINTS; PR01054 MTABOTROPC4R; PR01055 MTABOTROPC5R; PR01056 MTABOTROPC6R
PRINTS; PR01057 MTABOTROPC7R; PR01058 MTABOTROPC8R
INTERPRO; IPR000162
GCRDB; GCR_01002; GCR_1003; GCR_0444; GCR_0760; GCR_0352; GCR_0363

GCRDB; GCR_0216
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].
 
MTABOTROPICR is a 6-element fingerprint that provides a signature for the 
metabotropic glutamate receptors. The fingerprint was derived from an
initial alignment of 8 sequences: the motifs were drawn from conserved
sections within both the extracellular and 7TM domains, focusing on those
areas of the alignment that characterise the metabotropic receptors but
distinguish them from the rest of the metabotropic receptor superfamily 
- motifs 1-3 lie in the extracellular domain; motif 4 lies at the N-terminus
of TM domain 1; motif 5 lies in TM domain 3; and motif 6 spans the N-
terminus of TM domain 7. Two iterations on OWL28.1 were required to reach
convergence, at which point a true set comprising 15 sequences was
identified. A single partial match was also found, CEZC5063, a fragment
matching motifs 3-6.
 
An update on SPTR37_9f identified a true set of 19 sequences, and 2
partial matches.
Summary Information
  19 codes involving  6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6191919191919
5000000
4001111
3000000
2100001
123456
True Positives
MGR1_HUMAN    MGR1_RAT      MGR2_HUMAN    MGR2_RAT      
MGR3_HUMAN MGR3_RAT MGR4_HUMAN MGR4_RAT
MGR5_HUMAN MGR5_RAT MGR6_HUMAN MGR6_RAT
MGR7_HUMAN MGR7_RAT MGR8_HUMAN MGR8_MOUSE
MGR8_RAT MGR_DROME Q62916
True Positive Partials
Codes involving 4 elements
MGR1_CAEEL
Codes involving 2 elements
Q93564
Sequence Titles
MGR1_HUMAN  METABOTROPIC GLUTAMATE RECEPTOR 1 PRECURSOR - HOMO SAPIENS (HUMAN). 
MGR1_RAT METABOTROPIC GLUTAMATE RECEPTOR 1 PRECURSOR - RATTUS NORVEGICUS (RAT).
MGR2_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 2 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR2_RAT METABOTROPIC GLUTAMATE RECEPTOR 2 PRECURSOR - RATTUS NORVEGICUS (RAT).
MGR3_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 3 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR3_RAT METABOTROPIC GLUTAMATE RECEPTOR 3 PRECURSOR - RATTUS NORVEGICUS (RAT).
MGR4_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 4 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR4_RAT METABOTROPIC GLUTAMATE RECEPTOR 4 PRECURSOR - RATTUS NORVEGICUS (RAT).
MGR5_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 5 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR5_RAT METABOTROPIC GLUTAMATE RECEPTOR 5 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).
MGR8_HUMAN METABOTROPIC GLUTAMATE RECEPTOR 8 PRECURSOR - HOMO SAPIENS (HUMAN).
MGR8_MOUSE METABOTROPIC GLUTAMATE RECEPTOR 8 PRECURSOR - MUS MUSCULUS (MOUSE).
MGR8_RAT METABOTROPIC GLUTAMATE RECEPTOR 8 PRECURSOR - RATTUS NORVEGICUS (RAT).
MGR_DROME METABOTROPIC GLUTAMATE RECEPTOR PRECURSOR - DROSOPHILA MELANOGASTER (FRUIT FLY).
Q62916 METABOTROPIC GLUTAMATE RECEPTOR 4B - RATTUS NORVEGICUS (RAT).

MGR1_CAEEL PROBABLE METABOTROPIC GLUTAMATE RECEPTOR MGL-1 - CAENORHABDITIS ELEGANS.

Q93564 F45H11.4 PROTEIN - CAENORHABDITIS ELEGANS.
Scan History
OWL28_1    2  25   NSINGLE    
OWL31_1 2 100 NSINGLE
SPTR37_9f 2 139 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
VCIAQSVKIPRE MGR4_RAT 248 248 -
VCIAQSQKIPRE MGR8_MOUSE 245 245 -
VCIAQSIKIPRE MGR6_RAT 237 237 -
LCIAQSVRIPQE MGR7_RAT 248 248 -
ICIATAEKVGRS MGR3_RAT 239 239 -
ICIAHSYKIYSN MGR5_RAT 239 239 -
ICVATSEKVGRA MGR2_RAT 233 233 -
LCIAHSDKIYSN MGR1_RAT 253 253 -

Motif 2 width=13
Element Seqn Id St Int Rpt
FDKIIKRLLETSN MGR4_RAT 265 5 -
FEKIIKRLLETPN MGR8_MOUSE 262 5 -
FHKVIRRLMETPN MGR6_RAT 254 5 -
FDRIIKQLLDTPN MGR7_RAT 267 7 -
YDSVIRELLQKPN MGR3_RAT 256 5 -
FDKLLKKLRSHLP MGR5_RAT 256 5 -
FEGVVRALLQKPS MGR2_RAT 250 5 -
FDRLLRKLRERLP MGR1_RAT 270 5 -

Motif 3 width=16
Element Seqn Id St Int Rpt
GAVTILPKRMSVRGFD MGR4_RAT 330 52 -
GAVTILPKRASIDGFD MGR8_MOUSE 327 52 -
GAITILPKRASIDGFD MGR6_RAT 319 52 -
GAITIQPKRATVEGFD MGR7_RAT 332 52 -
GAITLELASHPVRQFD MGR3_RAT 319 50 -
GGITIKLQSPDVKWFD MGR5_RAT 322 53 -
GAITIELASYPISDFA MGR2_RAT 313 50 -
GGITIKLQSPEVRSFD MGR1_RAT 336 53 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EQEGKVQFVIDA MGR4_RAT 401 55 -
EQEGKVQFVIDA MGR8_MOUSE 397 54 -
EQEGKVQFVIDA MGR6_RAT 390 55 -
EQEGKVQFVIDA MGR7_RAT 403 55 -
EQESKIMFVVNA MGR3_RAT 385 50 -
VQDSKMGFVINA MGR5_RAT 391 53 -
EQESKIMFVVNA MGR2_RAT 373 44 -
VQDSKMGFVINA MGR1_RAT 405 53 -

Motif 5 width=15
Element Seqn Id St Int Rpt
RIFLGLGMSISYAAL MGR4_RAT 656 243 -
RIFLGLGMCFSYAAL MGR8_MOUSE 652 243 -
RLLLGLGTTLSYSAL MGR6_RAT 648 246 -
RVFLGLGMCISYAAL MGR7_RAT 659 244 -
RLGLGTSFAICYSAL MGR3_RAT 645 248 -
RIGIGLSPAMSYSAL MGR5_RAT 647 244 -
RLGLGTAFSVCYSAL MGR2_RAT 636 251 -
RLLVGLSSAMCYSAL MGR1_RAT 661 244 -

Motif 6 width=15
Element Seqn Id St Int Rpt
TLTVSVSLSASVSLG MGR4_RAT 821 150 -
TLTVSMSLSASVSLG MGR8_MOUSE 817 150 -
TLTVSLSLSASVSLG MGR6_RAT 813 150 -
TLTISMNLSASVALG MGR7_RAT 824 150 -
TMCISVSLSGFVVLG MGR3_RAT 802 142 -
TMCFSVSLSATVALG MGR5_RAT 800 138 -
TMCVSVSLSGSVVLG MGR2_RAT 793 142 -
TTCFAVSLSVTVALG MGR1_RAT 814 138 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
VCIAQSVKIPRE MGR4_HUMAN 248 248 -
VCIAQSVKIPRE MGR4_RAT 248 248 -
VCIAQSVKIPRE Q62916 248 248 -
VCIAQSQKIPRE MGR8_MOUSE 245 245 -
VCIAQSQKIPRE MGR8_RAT 245 245 -
VCIAQSQKIPRE MGR8_HUMAN 245 245 -
VCIAQSIKIPRE MGR6_HUMAN 243 243 -
VCIAQSIKIPRE MGR6_RAT 237 237 -
LCIAQSVRIPQE MGR7_HUMAN 248 248 -
LCIAQSVRIPQE MGR7_RAT 248 248 -
ICIATAEKVGRS MGR3_RAT 239 239 -
ICIATAEKVGRS MGR3_HUMAN 237 237 -
ICIAHSYKIYSN MGR5_RAT 239 239 -
ICIAHSYKIYSN MGR5_HUMAN 240 240 -
VCIAVAEKVPSA MGR_DROME 246 246 -
ICVATSEKVGRA MGR2_HUMAN 233 233 -
ICVATSEKVGRA MGR2_RAT 233 233 -
LCIAHSDKIYSN MGR1_HUMAN 253 253 -
LCIAHSDKIYSN MGR1_RAT 253 253 -

Motif 2 width=13
Element Seqn Id St Int Rpt
FDKIIRRLLETSN MGR4_HUMAN 265 5 -
FDKIIKRLLETSN MGR4_RAT 265 5 -
FDKIIKRLLETSN Q62916 265 5 -
FEKIIKRLLETPN MGR8_MOUSE 262 5 -
FEKIIKRLLETPN MGR8_RAT 262 5 -
FEKIIKRLLETPN MGR8_HUMAN 262 5 -
FSKVIRRLMETPN MGR6_HUMAN 260 5 -
FHKVIRRLMETPN MGR6_RAT 254 5 -
FDRIIKQLLDTPN MGR7_HUMAN 267 7 -
FDRIIKQLLDTPN MGR7_RAT 267 7 -
YDSVIRELLQKPN MGR3_RAT 256 5 -
YDSVIRELLQKPN MGR3_HUMAN 254 5 -
FDKLLKKLRSHLP MGR5_RAT 256 5 -
FDKLLKKLTSHLP MGR5_HUMAN 257 5 -
FDSIISKLQKKPN MGR_DROME 263 5 -
FEGVVRALLQKPS MGR2_HUMAN 250 5 -
FEGVVRALLQKPS MGR2_RAT 250 5 -
FDRLLRKLRERLP MGR1_HUMAN 270 5 -
FDRLLRKLRERLP MGR1_RAT 270 5 -

Motif 3 width=16
Element Seqn Id St Int Rpt
GAVTILPKRMSVRGFD MGR4_HUMAN 330 52 -
GAVTILPKRMSVRGFD MGR4_RAT 330 52 -
GAVTILPKRMSVRGFD Q62916 330 52 -
GAVTILPKRASIDGFD MGR8_MOUSE 327 52 -
GAVTILPKRASIDGFD MGR8_RAT 327 52 -
GAVTILPKRASIDGFD MGR8_HUMAN 327 52 -
GAITILPKRASIDGFD MGR6_HUMAN 325 52 -
GAITILPKRASIDGFD MGR6_RAT 319 52 -
GAITIQPKRATVEGFD MGR7_HUMAN 332 52 -
GAITIQPKRATVEGFD MGR7_RAT 332 52 -
GAITLELASHPVRQFD MGR3_RAT 319 50 -
GAITLELASQPVRQFD MGR3_HUMAN 317 50 -
GGITIKLQSPDVKWFD MGR5_RAT 322 53 -
GGITIKLQSPDVKWFD MGR5_HUMAN 323 53 -
GAITVELQSEIIADFD MGR_DROME 328 52 -
GAITIELASYPISDFA MGR2_HUMAN 313 50 -
GAITIELASYPISDFA MGR2_RAT 313 50 -
GGITIKLQSPEVRSFD MGR1_HUMAN 336 53 -
GGITIKLQSPEVRSFD MGR1_RAT 336 53 -

Motif 4 width=12
Element Seqn Id St Int Rpt
EQEGKVQFVIDA MGR4_HUMAN 401 55 -
EQEGKVQFVIDA MGR4_RAT 401 55 -
EQEGKVQFVIDA Q62916 401 55 -
EQEGKVQFVIDA MGR8_MOUSE 397 54 -
EQEGKVQFVIDA MGR8_RAT 397 54 -
EQEGKVQFVIDA MGR8_HUMAN 397 54 -
EQEGKVQFVIDA MGR6_HUMAN 396 55 -
EQEGKVQFVIDA MGR6_RAT 390 55 -
EQEGKVQFVIDA MGR7_HUMAN 403 55 -
EQEGKVQFVIDA MGR7_RAT 403 55 -
EQESKIMFVVNA MGR3_RAT 385 50 -
EQESKIMFVVNA MGR3_HUMAN 383 50 -
VQDSKMGFVINA MGR5_RAT 391 53 -
VQDSKMGFVINA MGR5_HUMAN 392 53 -
EQESKTQFVVDA MGR_DROME 413 69 -
EQESKIMFVVNA MGR2_HUMAN 373 44 -
EQESKIMFVVNA MGR2_RAT 373 44 -
VQDSKMGFVINA MGR1_HUMAN 405 53 -
VQDSKMGFVINA MGR1_RAT 405 53 -

Motif 5 width=15
Element Seqn Id St Int Rpt
RIFLGLGMSISYAAL MGR4_HUMAN 656 243 -
RIFLGLGMSISYAAL MGR4_RAT 656 243 -
RIFLGLGMSISYAAL Q62916 656 243 -
RIFLGLGMCFSYAAL MGR8_MOUSE 652 243 -
RIFLGLGMCFSYAAL MGR8_RAT 652 243 -
RVFLGLGMCFSYAAL MGR8_HUMAN 652 243 -
RLFLGLGTTLSYSAL MGR6_HUMAN 654 246 -
RLLLGLGTTLSYSAL MGR6_RAT 648 246 -
RVFLGLGMCISYAAL MGR7_HUMAN 659 244 -
RVFLGLGMCISYAAL MGR7_RAT 659 244 -
RLGLGTSFAICYSAL MGR3_RAT 645 248 -
RLGLGSSFAICYSAL MGR3_HUMAN 643 248 -
RIGIGLSPAMSYSAL MGR5_RAT 647 244 -
RIGIGLSPAMSYSAL MGR5_HUMAN 648 244 -
RFGIGVGFSIIYSAL MGR_DROME 695 270 -
RLGLGTAFSVCYSAL MGR2_HUMAN 636 251 -
RLGLGTAFSVCYSAL MGR2_RAT 636 251 -
RLLVGLSSAMCYSAL MGR1_HUMAN 661 244 -
RLLVGLSSAMCYSAL MGR1_RAT 661 244 -

Motif 6 width=15
Element Seqn Id St Int Rpt
TLTVSVSLSASVSLG MGR4_HUMAN 821 150 -
TLTVSVSLSASVSLG MGR4_RAT 821 150 -
TLTVSVSLSASVSLG Q62916 821 150 -
TLTVSMSLSASVSLG MGR8_MOUSE 817 150 -
TLTVSMSLSASVSLG MGR8_RAT 817 150 -
TLTVSMSLSASVSLG MGR8_HUMAN 817 150 -
TLTVSLSLSASVSLG MGR6_HUMAN 819 150 -
TLTVSLSLSASVSLG MGR6_RAT 813 150 -
TLTISMNLSASVALG MGR7_HUMAN 824 150 -
TLTISMNLSASVALG MGR7_RAT 824 150 -
TMCISVSLSGFVVLG MGR3_RAT 802 142 -
TMCISVSLSGFVVLG MGR3_HUMAN 800 142 -
TMCFSVSLSATVALG MGR5_RAT 800 138 -
TMCFSVSLSATVALG MGR5_HUMAN 801 138 -
TLCISISLSASVALV MGR_DROME 850 140 -
TMCVSVSLSGSVVLG MGR2_HUMAN 793 142 -
TMCVSVSLSGSVVLG MGR2_RAT 793 142 -
TTCFAVSLSVTVALG MGR1_HUMAN 814 138 -
TTCFAVSLSVTVALG MGR1_RAT 814 138 -