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PR01739

Identifier
RELAXINR  [View Relations]  [View Alignment]  
Accession
PR01739
No. of Motifs
7
Creation Date
26-JUN-2002
Title
Relaxin receptor family signature
Database References
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. HSU, S.Y., NAKABAYASHI, K., NISHI, S., KUMAGAI, J., KUDO, M.,
SHERWOOD, O.D. AND HSUEH, A.J.W.
Activation of orphan receptors by the hormone relaxin.
SCIENCE 295 671-674 (2002).

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine,
paracrine 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].
 
Relaxin has diverse actions in the reproductive tract and in other tissues
during pregnancy [6]. Although binding sites for relaxin have been found in
reproductive tissue, the nature of the receptor was previously unknown.
Recently, two orphan GPCRs, LGR7 and LGR8, have been identified as receptors
for the hormone. These two receptors contain large extracellular N-termini
with leucine-rich repeat regions, and are structurally similar to the
gonadotropin and thyrotropin receptors [6]. LGR7 is expressed in the brain,
kidney, testis, placenta, uterus, ovary, adrenal gland, prostate, skin and
heart, while LGR8 is expressed mainly in the brain, kidney, muscle, testis,
thyroid, uterus, peripheral blood cells and bone marrow [6]. Upon binding to
LGR7 or 8, relaxin stimulates a dose-dependent increase in cyclic AMP
production, indicating coupling of the receptors to Gs proteins [6].
 
RELAXINR is a 7-element fingerprint that provides a signature for the
relaxin receptor family. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections
within external loop and N-terminal regions, focusing on those areas of the
alignment that characterise the relaxin receptors but distinguish them from
the rest of the rhodopsin-like superfamily - motifs 1-4 are located in the
large N-terminal domain; motif 5 lies in the N-terminal portion of the first
external loop; motif 6 resides within the second external loop; and motif 7
spans the final external loop. A single iteration on SPTR40_20f was required
to reach convergence, no further sequences being identified beyond the
starting set. A single partial match was found, GPCR_LYMST, the pond snail
GPCR, which closely resembles the relaxin receptors.
Summary Information
   3 codes involving  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
73333333
60000000
50000000
40000000
30000000
20100010
1234567
True Positives
Q8WXD0        Q91ZZ5        Q9HBX9        
True Positive Partials
Codes involving 2 elements
GPCR_LYMST
Sequence Titles
Q8WXD0      G PROTEIN-COUPLED RECEPTOR AFFECTING TESTICULAR DESCENT - Homo sapiens (Human). 
Q91ZZ5 G PROTEIN COUPLED RECEPTOR AFFECTING TESTICULAR DESCENT - Mus musculus (Mouse).
Q9HBX9 LEUCINE-RICH REPEAT-CONTAINING G PROTEIN-COUPLED RECEPTOR 7 - Homo sapiens (Human).

GPCR_LYMST G-protein coupled receptor GRL101 precursor - Lymnaea stagnalis (Great pond snail).
Scan History
SPTR40_20f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
GYFPCGNLTKCLP Q91ZZ5 31 31 -
GYFPCGNLTKCLP Q8WXD0 48 48 -
GYFPCGNITKCLP Q9HBX9 30 30 -

Motif 2 width=16
Element Seqn Id St Int Rpt
LYLSHNCITSLRPGIF Q91ZZ5 173 129 -
LYLNHNCITTLRPGIF Q8WXD0 190 129 -
LYLSHNRITFLKPGVF Q9HBX9 179 136 -

Motif 3 width=13
Element Seqn Id St Int Rpt
NLSHIYLKTFRYC Q91ZZ5 361 172 -
NLSHIYFKNFRYC Q8WXD0 378 172 -
NLSHIYFKKFQYC Q9HBX9 368 173 -

Motif 4 width=15
Element Seqn Id St Int Rpt
PHVRICMPSTDGISS Q91ZZ5 377 3 -
PHVRICMPLTDGISS Q8WXD0 394 3 -
PHVRSCKPNTDGISS Q9HBX9 384 3 -

Motif 5 width=11
Element Seqn Id St Int Rpt
GVFDIKYRGQY Q91ZZ5 455 63 -
GIFDIKYRGQY Q8WXD0 472 63 -
GGFDLKFRGEY Q9HBX9 462 63 -

Motif 6 width=14
Element Seqn Id St Int Rpt
FGNFYGKNGVCFPL Q91ZZ5 546 80 -
FGNFYGKNGVCFPL Q8WXD0 563 80 -
FKNYYGTNGVCFPL Q9HBX9 553 80 -

Motif 7 width=15
Element Seqn Id St Int Rpt
LSLLQVEIPGTITSW Q91ZZ5 643 83 -
LSLFRVEIPDTMTSW Q8WXD0 660 83 -
LSLLQVEIPGTITSW Q9HBX9 650 83 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
GYFPCGNLTKCLP Q91ZZ5 31 31 -
GYFPCGNLTKCLP Q8WXD0 48 48 -
GYFPCGNITKCLP Q9HBX9 30 30 -

Motif 2 width=16
Element Seqn Id St Int Rpt
LYLSHNCITSLRPGIF Q91ZZ5 173 129 -
LYLNHNCITTLRPGIF Q8WXD0 190 129 -
LYLSHNRITFLKPGVF Q9HBX9 179 136 -

Motif 3 width=13
Element Seqn Id St Int Rpt
NLSHIYLKTFRYC Q91ZZ5 361 172 -
NLSHIYFKNFRYC Q8WXD0 378 172 -
NLSHIYFKKFQYC Q9HBX9 368 173 -

Motif 4 width=15
Element Seqn Id St Int Rpt
PHVRICMPSTDGISS Q91ZZ5 377 3 -
PHVRICMPLTDGISS Q8WXD0 394 3 -
PHVRSCKPNTDGISS Q9HBX9 384 3 -

Motif 5 width=11
Element Seqn Id St Int Rpt
GVFDIKYRGQY Q91ZZ5 455 63 -
GIFDIKYRGQY Q8WXD0 472 63 -
GGFDLKFRGEY Q9HBX9 462 63 -

Motif 6 width=14
Element Seqn Id St Int Rpt
FGNFYGKNGVCFPL Q91ZZ5 546 80 -
FGNFYGKNGVCFPL Q8WXD0 563 80 -
FKNYYGTNGVCFPL Q9HBX9 553 80 -

Motif 7 width=15
Element Seqn Id St Int Rpt
LSLLQVEIPGTITSW Q91ZZ5 643 83 -
LSLFRVEIPDTMTSW Q8WXD0 660 83 -
LSLLQVEIPGTITSW Q9HBX9 650 83 -