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PR00644

Identifier
GPRORPHANR  [View Relations]  [View Alignment]  
Accession
PR00644
No. of Motifs
8
Creation Date
09-DEC-1996  (UPDATE 07-JUN-1999)
Title
GPR orphan receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00650 GPR12ORPHANR; PR00648 GPR3ORPHANR; PR00649 GPR6ORPHANR

INTERPRO; IPR000723
GCRDB; GCR_0288; GCR_0902; GCR_0906
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. EIDNE, K.A., ZABAVNIK, J., PETERS, T., YOSHIDA, S., ANDERSON, L.
AND TAYLOR, P.L. 
Cloning, sequencing and tissue distribution of a candidate G protein-coupled
receptor from rat pituitary gland.
FEBS LETT. 292 243-248 (1991).
 
7. SONG, Z.H., MODI, W. AND BONNER, T.I.  
Molecular cloning and chromosomal localization of human genes encoding
three closely related G protein-coupled receptors.
GENOMICS 28 347-349 (1995).
 
8. WATSON, S. AND ARKINSTALL,
Orphan receptors.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp223-230.

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 rhodopsin-like GPCRs themselves represent a widespread protein family 
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary 
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural 
framework comprising 7 transmembrane (TM) helices [3-5]. 
 
Several 7TM receptors have been cloned but their endogenous ligands are
unknown; these have been termed orphan receptors. A new GPCR, GPR12, was
isolated from a rat pituitary library, and is found in discrete regions
of the brain, pituitary and testis, but is absent in other tissues [6-8].
Three human homologues (GPR12, GPR6 and GPR3) have also been isolated [7].
The 3 genes have been localised to human chromosomal regions 13q12, 6q21
and 1p34.3-p36.1 respectively. 
 
GPRORPHANR is an 8-element fingerprint that provides a signature for the
GPR family of orphan receptors. The fingerprint was derived from an
initial alignment of 8 sequences: the motifs were drawn from conserved
sections within either loop or N- and C-terminal regions, focusing on
those areas of the alignment that characterise the GPR receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
lies at the N-terminus of TM domain 1; motif 2 spans the first cytoplasmic
loop; motif 3 spans the first external loop, leading into TM domain 3;
motif 4 lies in the second cytoplasmic loop; motifs 5 and 6 span the third
cytoplasmic loop; motif 7 spans the the third external loop, leading into
TM domain 7; and motif 8 resides at the C-terminus. A single iteration
on OWL29.0 was required to reach convergence, no further sequences being
identified beyond the starting set. Two partial matches were found: RATGPCRA
is an N-terminal fragment that matches motifs 1-3; and MSHR_BOVIN is a
melanocyte stimulating hormone receptor that matches motifs 4 and 8. 
 
An update on SPTR37_9f identified a true set of 7 sequences.
Summary Information
7 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
0 codes involving 2 elements
Composite Feature Index
877777777
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
GPR3_HUMAN    GPR3_MOUSE    GPR6_HUMAN    GPR6_RAT      
GPRC_HUMAN GPRC_MOUSE GPRC_RAT
Sequence Titles
GPR3_HUMAN  Probable G-protein coupled receptor 3 (ACCA orphan receptor) - Homo sapiens (Human). 
GPR3_MOUSE Probable G-protein coupled receptor 3 (GPCR21) - Mus musculus (Mouse).
GPR6_HUMAN Sphingosine 1-phosphate receptor GPR6 (G-protein coupled receptor 6) - Homo sapiens (Human).
GPR6_RAT Sphingosine 1-phosphate receptor GPR6 (G-protein coupled receptor 6) - Rattus norvegicus (Rat).
GPRC_HUMAN PROBABLE G PROTEIN-COUPLED RECEPTOR GPR12 - HOMO SAPIENS (HUMAN).
GPRC_MOUSE PROBABLE G PROTEIN-COUPLED RECEPTOR GPR12 (GPCR01) - MUS MUSCULUS (MOUSE).
GPRC_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR GPR12 (R334) - RATTUS NORVEGICUS (RAT).
Scan History
OWL29_0    1  100  NSINGLE    
SPTR37_9f 2 8 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
PWDIVLCSSGTL GPRC_MOUSE 46 46 -
PWDIVLCSSGTL GPRC_RAT 46 46 -
PWDIVLCTSGTL GPRC_HUMAN 46 46 -
PWDVLLCVSGTV GPR6_HUMAN 74 74 -
PWDVLLCVSGTV GPR6_RAT 75 75 -
AWDVVLCISGTL GPR3_HUMAN 42 42 -
AWDVVLCISGTL GPR3_MOUSE 42 42 -
PWDIVLCSSGTL RNCGPCR 46 46 -

Motif 2 width=12
Element Seqn Id St Int Rpt
IFHSPSLRAPMF GPRC_MOUSE 69 11 -
IFHNPSLRAPMF GPRC_HUMAN 69 11 -
IASTPALRTPMF GPR6_HUMAN 97 11 -
IASTPALRTPMF GPR6_RAT 98 11 -
IVGTPAFRAPMF GPR3_HUMAN 65 11 -
IVGTPAFRAPMF GPR3_MOUSE 65 11 -
IFHSPSLRAPMF RNCGPCR 69 11 -
IFHSPSLRAPMF GPRC_RAT 69 11 -

Motif 3 width=18
Element Seqn Id St Int Rpt
FVFAYLLQSEATKLVTIG GPRC_RAT 101 20 -
FVFQYLVPSETVSLLTVG GPR6_HUMAN 129 20 -
FVFAYLLQSEATKLVTIG RNCGPCR 101 20 -
FAADFCIGSPEMSLMLVG GPR3_MOUSE 97 20 -
FAAVFCIGSAEMSLVLVG GPR3_HUMAN 97 20 -
FVFQYVVPSETVSLLMVG GPR6_RAT 130 20 -
FVFAYLLQSEATKLVTIG GPRC_MOUSE 101 20 -
FVFAYLLQSEATKLVTIG GPRC_HUMAN 101 20 -

Motif 4 width=12
Element Seqn Id St Int Rpt
YLSLYNALTYYS GPR6_HUMAN 167 20 -
YLSLYYALTYHS RNCGPCR 139 20 -
YLSLYYALTYHS GPRC_MOUSE 139 20 -
YLSLYYALTYHS GPRC_RAT 139 20 -
YLSLYYALTYHS GPRC_HUMAN 139 20 -
YLSLYNALTYYS GPR6_RAT 168 20 -
YLSLYNALTYYS GPR3_HUMAN 135 20 -
YLSLYNALTYYS GPR3_MOUSE 135 20 -

Motif 5 width=16
Element Seqn Id St Int Rpt
CQVVWRHAHQIALQQH GPR6_RAT 250 70 -
CKIVMRHAHQIALQHH RNCGPCR 220 69 -
CRIVCRHAQQIALQRH GPR3_MOUSE 217 70 -
CRIVCRHAQQIALQRH GPR3_HUMAN 217 70 -
CKIVMRHAHQIALQHH GPRC_MOUSE 221 70 -
CKIVMRHAHQIALQHH GPRC_RAT 221 70 -
CKIVMRHAHQIALQHH GPRC_HUMAN 221 70 -
CQVVWRHAHQIALQQH GPR6_HUMAN 249 70 -

Motif 6 width=17
Element Seqn Id St Int Rpt
HLLPASHYVATRKGIAT GPR3_HUMAN 232 -1 -
HFLATSHYVTTRKGVST GPRC_MOUSE 236 -1 -
HFLATSHYVTTRKGIST GPRC_RAT 236 -1 -
HFLATSHYVTTRKGVST GPRC_HUMAN 236 -1 -
HCLAPPHLAATRKGVGT GPR6_HUMAN 264 -1 -
HCLAPPHLAATRKGVGT GPR6_RAT 265 -1 -
HLLPASHYVATRKGIAT GPR3_MOUSE 232 -1 -
HFLATSHYVTTRKGIST RNCGPCR 235 -1 -

Motif 7 width=15
Element Seqn Id St Int Rpt
PRLYTYLTLLPATYN GPR3_MOUSE 275 26 -
PSIYTYATLLPATYN GPRC_MOUSE 279 26 -
PSIYTYATLLPATYN GPRC_RAT 279 26 -
PSIYTYATLLPATYN GPRC_HUMAN 279 26 -
PAVYTYATLLPATYN GPR6_HUMAN 307 26 -
PSIYTYATLLPATYN RNCGPCR 278 26 -
PAIYTYATLLPATYN GPR6_RAT 308 26 -
PPLYTYLTLLPATYN GPR3_HUMAN 275 26 -

Motif 8 width=12
Element Seqn Id St Int Rpt
AFRNQEIQKALC GPRC_RAT 302 8 -
AFRNQEIQKALC GPRC_HUMAN 302 8 -
AFRNQDVQKVLW GPR3_MOUSE 298 8 -
AFRNQDVQKVLW GPR3_HUMAN 298 8 -
AFRNQEIQKALC GPRC_MOUSE 302 8 -
AFRNQEIQKAPL RNCGPCR 301 8 -
AFRNQEIQRALW GPR6_HUMAN 330 8 -
AFRNQEIQRALW GPR6_RAT 331 8 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
PWDIVLCSSGTL GPRC_MOUSE 46 46 -
PWDIVLCSSGTL GPRC_RAT 46 46 -
PWDIVLCTSGTL GPRC_HUMAN 46 46 -
PWDVLLCVSGTV GPR6_HUMAN 74 74 -
PWDVLLCVSGTV GPR6_RAT 75 75 -
AWDVVLCISGTL GPR3_HUMAN 42 42 -
AWDVVLCISGTL GPR3_MOUSE 42 42 -

Motif 2 width=12
Element Seqn Id St Int Rpt
IFHSPSLRAPMF GPRC_MOUSE 69 11 -
IFHSPSLRAPMF GPRC_RAT 69 11 -
IFHNPSLRAPMF GPRC_HUMAN 69 11 -
IASTPALRTPMF GPR6_HUMAN 97 11 -
IASTPALRTPMF GPR6_RAT 98 11 -
IVGTPAFRAPMF GPR3_HUMAN 65 11 -
IVGTPAFRAPMF GPR3_MOUSE 65 11 -

Motif 3 width=18
Element Seqn Id St Int Rpt
FVFAYLLQSEATKLVTIG GPRC_MOUSE 101 20 -
FVFAYLLQSEATKLVTIG GPRC_RAT 101 20 -
FVFAYLLQSEATKLVTIG GPRC_HUMAN 101 20 -
FVFQYLVPSETVSLLTVG GPR6_HUMAN 129 20 -
FVFQYVVPSETVSLLMVG GPR6_RAT 130 20 -
FAAVFCIGSAEMSLVLVG GPR3_HUMAN 97 20 -
FAADFCIGSPEMSLMLVG GPR3_MOUSE 97 20 -

Motif 4 width=12
Element Seqn Id St Int Rpt
YLSLYYALTYHS GPRC_MOUSE 139 20 -
YLSLYYALTYHS GPRC_RAT 139 20 -
YLSLYYALTYHS GPRC_HUMAN 139 20 -
YLSLYNALTYYS GPR6_HUMAN 167 20 -
YLSLYNALTYYS GPR6_RAT 168 20 -
YLSLYNALTYYS GPR3_HUMAN 135 20 -
YLSLYNALTYYS GPR3_MOUSE 135 20 -

Motif 5 width=16
Element Seqn Id St Int Rpt
CKIVMRHAHQIALQHH GPRC_MOUSE 221 70 -
CKIVMRHAHQIALQHH GPRC_RAT 221 70 -
CKIVMRHAHQIALQHH GPRC_HUMAN 221 70 -
CQVVWRHAHQIALQQH GPR6_HUMAN 249 70 -
CQVVWRHAHQIALQQH GPR6_RAT 250 70 -
CRIVCRHAQQIALQRH GPR3_HUMAN 217 70 -
CRIVCRHAQQIALQRH GPR3_MOUSE 217 70 -

Motif 6 width=17
Element Seqn Id St Int Rpt
HFLATSHYVTTRKGVST GPRC_MOUSE 236 -1 -
HFLATSHYVTTRKGIST GPRC_RAT 236 -1 -
HFLATSHYVTTRKGVST GPRC_HUMAN 236 -1 -
HCLAPPHLAATRKGVGT GPR6_HUMAN 264 -1 -
HCLAPPHLAATRKGVGT GPR6_RAT 265 -1 -
HLLPASHYVATRKGIAT GPR3_HUMAN 232 -1 -
HLLPASHYVATRKGIAT GPR3_MOUSE 232 -1 -

Motif 7 width=15
Element Seqn Id St Int Rpt
PSIYTYATLLPATYN GPRC_MOUSE 279 26 -
PSIYTYATLLPATYN GPRC_RAT 279 26 -
PSIYTYATLLPATYN GPRC_HUMAN 279 26 -
PAVYTYATLLPATYN GPR6_HUMAN 307 26 -
PAIYTYATLLPATYN GPR6_RAT 308 26 -
PPLYTYLTLLPATYN GPR3_HUMAN 275 26 -
PRLYTYLTLLPATYN GPR3_MOUSE 275 26 -

Motif 8 width=12
Element Seqn Id St Int Rpt
AFRNQEIQKALC GPRC_MOUSE 302 8 -
AFRNQEIQKALC GPRC_RAT 302 8 -
AFRNQEIQKALC GPRC_HUMAN 302 8 -
AFRNQEIQRALW GPR6_HUMAN 330 8 -
AFRNQEIQRALW GPR6_RAT 331 8 -
AFRNQDVQKVLW GPR3_HUMAN 298 8 -
AFRNQDVQKVLW GPR3_MOUSE 298 8 -