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PR00529

Identifier
GNADOTRPHINR  [View Relations]  [View Alignment]  
Accession
PR00529
No. of Motifs
8
Creation Date
01-JUN-1996  (UPDATE 10-JUN-1999)
Title
Gonadotrophin releasing hormone receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN

INTERPRO; IPR001658
GCRDB; GCR_0501; GCR_0562; GCR_0579; GCR_0673; GCR_0678; GCR_0744

GCRDB; GCR_0839
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. WATSON, S. AND ARKINSTALL, S.
Gonadotrophin-releasing hormone.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.150-151.

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]. 
 
Gonadotrophin-releasing hormone (GnRH) is an important hypothalamic
regulator of reproductive processes [6]. Its major site of action is in
the regulation of synthesis and release of gonadotrophins (FSH and LH)
from the anterior pituitary. GnRH agonists are of potential therapeutic
use in the suppression of prostate cancer and endometriosis [6]. GnRH
receptors are found in the anterior pituitary, placenta, ovary, testis,
prostate, breast, and in certain tumours and immortalised cell lines.
They are also present in the nervous system and gonads of certain species.
 
GNADOTRPHINR is an 8-element fingerprint that provides a signature for the
gonadotrophin-releasing hormone receptors. The fingerprint was derived
from an initial alignment of 9 sequences: the motifs were drawn from
conserved sections within either loop or TM regions, focusing on those
areas of the alignment that characterise the GnRH receptors but distinguish
them from the rest of the rhodopsin-like superfamily - motif 1 lies at the
N-terminus; motif 2 encodes part of TM domain 1; motif 3 spans the first
cytoplasmic loop; motif 4 spans the first external loop; motif 5 encodes
part of TM domain 4; motif 6 spans the second external loop; motif 7 spans
the third cytoplasmic loop; and motif 8 spans the third external loop. A
single iteration on OWL28.0 was required to reach convergence, no further
sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 6 sequences, and 2
partial matches.
Summary Information
   6 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
1 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
866666666
700000000
600000000
500000000
411110000
300010101
200000000
12345678
True Positives
GRHR_BOVIN    GRHR_HUMAN    GRHR_MOUSE    GRHR_PIG      
GRHR_RAT GRHR_SHEEP
True Positive Partials
Codes involving 4 elements
Q92644
Codes involving 3 elements
GRHR_CLAGA
Sequence Titles
GRHR_BOVIN  GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) - BOS TAURUS (BOVINE). 
GRHR_HUMAN GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) - HOMO SAPIENS (HUMAN).
GRHR_MOUSE GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) - MUS MUSCULUS (MOUSE).
GRHR_PIG GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) (LUTEINIZING HORMONE- RELEASING HORMONE RECEPTOR) (LHRH) - SUS SCROFA (PIG).
GRHR_RAT GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) - RATTUS NORVEGICUS (RAT).
GRHR_SHEEP GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) - OVIS ARIES (SHEEP).

Q92644 GONADOTROPIN-RELEASING HORMONE RECEPTOR - HOMO SAPIENS (HUMAN).

GRHR_CLAGA GONADOTROPIN-RELEASING HORMONE RECEPTOR (GNRH-R) - CLARIAS GARIEPINUS (SHARPTOOTH CATFISH) (AFRICAN CATFISH).
Scan History
OWL28_0    1  50   NSINGLE    
SPTR37_9f 2 8 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
HCSAINNSIPLMQGNLPTLT GRHR_HUMAN 13 13 -
HCSAINNSIPLIQGKLPTLT GRHR_MOUSE 13 13 -
HCSAINNSIPLTQGKLPTLT GRHR_RAT 13 13 -
HCSAINSSIPLTPGSLPTLT GRHR_BOVIN 13 13 -
HCSAINNSIPLTQGKLPTLT RNGNRH 13 13 -
HCSAINNSIPLTQGKLPTLT RATGNRHR 48 48 -
HCSAINSSILLTQGNLPTLT PIGLHRHR 13 13 -
HCSAINSSILLTPGRLPTLT OAGNRNREP 13 13 -
HCSAINSSILLTPGSLPTLT GRHR_SHEEP 13 13 -

Motif 2 width=19
Element Seqn Id St Int Rpt
SGKIRVTVTFFLFLLSTAF GRHR_MOUSE 34 1 -
SGKIRVTVTFFLFLLSTAF GRHR_RAT 34 1 -
SGKIRVTVTFFLFLLSTIF GRHR_BOVIN 34 1 -
SGKIRVTVTFFLFLLSATF GRHR_HUMAN 34 1 -
SGKIRVTVTFFLFLLSTAF RATGNRHR 69 1 -
SGKIRVTVTFFLFLLSTAF RNGNRH 34 1 -
SPNIRVTVTFFLFLLSTAF PIGLHRHR 34 1 -
SGKIRVTVTFFLFLLSTIF OAGNRNREP 34 1 -
SGKIRVTVTFFLFLLSTIF GRHR_SHEEP 34 1 -

Motif 3 width=19
Element Seqn Id St Int Rpt
KLQRWTQKRKKGKKLSRMK RNGNRH 59 6 -
KLQRWTQKRKKGKKLSRMK RATGNRHR 94 6 -
KLQKWTQRKEKGKKLSRMK PIGLHRHR 59 6 -
KLQNWAQRKEKRKKLSKMK OAGNRNREP 59 6 -
KLQNWTQRKEKRKKLSRMK GRHR_BOVIN 59 6 -
KLQRWTQKRKKGKKLSRMK GRHR_RAT 59 6 -
KLQKWTQKRKKGKKLSRMK GRHR_MOUSE 59 6 -
KLQNWTQRKEKRKKLSKMK GRHR_SHEEP 59 6 -
KLQKWTQKKEKGKKLSRMK GRHR_HUMAN 59 6 -

Motif 4 width=16
Element Seqn Id St Int Rpt
PLDGMWNITVQWYAGE GRHR_RAT 96 18 -
PLDGMWNITVQWYAGE GRHR_BOVIN 96 18 -
PLDGMWNITVQWYAGE OAGNRNREP 96 18 -
PLDGMWNITVQWYAGE PIGLHRHR 96 18 -
PLDGMWNITVQWYAGE RNGNRH 96 18 -
PLDGMWNITVQWYAGE RATGNRHR 131 18 -
PLDGMWNITVQWYAGE GRHR_HUMAN 96 18 -
PLDGMWNITVQWYAGE GRHR_SHEEP 96 18 -
PLDGMWNITVQWYAGE GRHR_MOUSE 96 18 -

Motif 5 width=19
Element Seqn Id St Int Rpt
FAGPQLYIFRMIYLVDGSG RNGNRH 170 58 -
FAGPQLYIFRMIYLADGSG RATGNRHR 205 58 -
FAGPQLYIFGMIHLADDSG GRHR_SHEEP 170 58 -
FAGPQLYIFRMIYLADGSG GRHR_MOUSE 170 58 -
FAGPQLYIFRMIYLADGSG GRHR_RAT 170 58 -
FAGPQLYIFGMIHLADDSG GRHR_BOVIN 170 58 -
FAGPQLYIFRMIHLADSSG GRHR_HUMAN 170 58 -
FAGPQLYIFGMIHLADDSG OAGNRNREP 170 58 -
FAGPQLYIFRMIHLADSSG PIGLHRHR 170 58 -

Motif 6 width=15
Element Seqn Id St Int Rpt
FSQCVTHCSFPQWWH RNGNRH 192 3 -
FSQCVTHCSFPQWWH RATGNRHR 227 3 -
FSQCVTHCSFPQWWH GRHR_BOVIN 193 4 -
FSQCVTHCSFPQWWH GRHR_RAT 192 3 -
FSQCVTHCSFPQWWH GRHR_MOUSE 192 3 -
FSQCVTHCSFPQWWH GRHR_SHEEP 193 4 -
FSQCVTHCSFSQWWH GRHR_HUMAN 193 4 -
FSQCVTHGSFPQWWH PIGLHRHR 193 4 -
FSQCVTHCSFPQWWH OAGNRNREP 193 4 -

Motif 7 width=19
Element Seqn Id St Int Rpt
QDPRKLQLNQSKNNIPRAR GRHR_RAT 243 36 -
QDPRKLQLNQSKNNIPRAR GRHR_MOUSE 243 36 -
QDPHKLQLNQSKNNIPQAR GRHR_SHEEP 244 36 -
QDPHELQLNQSKNNIPRAR GRHR_HUMAN 244 36 -
QDPRKLQLNQSKNNIPRAR RNGNRH 243 36 -
QDPHNLQLNQSKNNIPRAR PIGLHRHR 244 36 -
QDPRKLQLNQSKNNIPRAR RATGNRHR 278 36 -
QDPHKLQLNQSKNNIPQAR OAGNRNREP 244 36 -
QDPHKLQLNQSKNNIPRAR GRHR_BOVIN 244 36 -

Motif 8 width=21
Element Seqn Id St Int Rpt
WYWFDPDMVNRVSDPVNHFFF OAGNRNREP 289 26 -
WYWFDPEMLNRVSEPVNHFFF RNGNRH 288 26 -
WYWFDPEMLNRVSEPVNHFFF RATGNRHR 323 26 -
WYWFDPEMLNRLSDPVNHFFF GRHR_HUMAN 289 26 -
WYWFDPDMVNRVSDPVNHFFF GRHR_SHEEP 289 26 -
WYWFDPEMLNRVSEPVNHFFF GRHR_MOUSE 288 26 -
WYWFDPEMLNRVSEPVNHFFF GRHR_RAT 288 26 -
WYWFDPDMVNRVSDPVNHFFF GRHR_BOVIN 289 26 -
WYWFDPEMVNRVSDPVNHFFF PIGLHRHR 289 26 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
HCSAINSSIPLTPGSLPTLT GRHR_BOVIN 13 13 -
HCSAINNSIPLTQGKLPTLT GRHR_RAT 13 13 -
HCSAINNSIPLIQGKLPTLT GRHR_MOUSE 13 13 -
HCSAINSSILLTQGNLPTLT GRHR_PIG 13 13 -
HCSAINSSILLTPGSLPTLT GRHR_SHEEP 13 13 -
HCSAINNSIPLMQGNLPTLT GRHR_HUMAN 13 13 -

Motif 2 width=19
Element Seqn Id St Int Rpt
SGKIRVTVTFFLFLLSTIF GRHR_BOVIN 34 1 -
SGKIRVTVTFFLFLLSTAF GRHR_RAT 34 1 -
SGKIRVTVTFFLFLLSTAF GRHR_MOUSE 34 1 -
SPNIRVTVTFFLFLLSTAF GRHR_PIG 34 1 -
SGKIRVTVTFFLFLLSTIF GRHR_SHEEP 34 1 -
SGKIRVTVTFFLFLLSATF GRHR_HUMAN 34 1 -

Motif 3 width=19
Element Seqn Id St Int Rpt
KLQNWTQRKEKRKKLSRMK GRHR_BOVIN 59 6 -
KLQRWTQKRKKGKKLSRMK GRHR_RAT 59 6 -
KLQKWTQKRKKGKKLSRMK GRHR_MOUSE 59 6 -
KLQKWTQRKEKGKKLSRMK GRHR_PIG 59 6 -
KLQNWTQRKEKRKKLSKMK GRHR_SHEEP 59 6 -
KLQKWTQKKEKGKKLSRMK GRHR_HUMAN 59 6 -

Motif 4 width=16
Element Seqn Id St Int Rpt
PLDGMWNITVQWYAGE GRHR_BOVIN 96 18 -
PLDGMWNITVQWYAGE GRHR_RAT 96 18 -
PLDGMWNITVQWYAGE GRHR_MOUSE 96 18 -
PLDGMWNITVQWYAGE GRHR_PIG 96 18 -
PLDGMWNITVQWYAGE GRHR_SHEEP 96 18 -
PLDGMWNITVQWYAGE GRHR_HUMAN 96 18 -

Motif 5 width=19
Element Seqn Id St Int Rpt
FAGPQLYIFGMIHLADDSG GRHR_BOVIN 170 58 -
FAGPQLYIFRMIYLADGSG GRHR_RAT 170 58 -
FAGPQLYIFRMIYLADGSG GRHR_MOUSE 170 58 -
FAGPQLYIFRMIHLADSSG GRHR_PIG 170 58 -
FAGPQLYIFGMIHLADDSG GRHR_SHEEP 170 58 -
FAGPQLYIFRMIHLADSSG GRHR_HUMAN 170 58 -

Motif 6 width=15
Element Seqn Id St Int Rpt
FSQCVTHCSFPQWWH GRHR_BOVIN 193 4 -
FSQCVTHCSFPQWWH GRHR_RAT 192 3 -
FSQCVTHCSFPQWWH GRHR_MOUSE 192 3 -
FSQCVTHGSFPQWWH GRHR_PIG 193 4 -
FSQCVTHCSFPQWWH GRHR_SHEEP 193 4 -
FSQCVTHCSFSQWWH GRHR_HUMAN 193 4 -

Motif 7 width=19
Element Seqn Id St Int Rpt
QDPHKLQLNQSKNNIPRAR GRHR_BOVIN 244 36 -
QDPRKLQLNQSKNNIPRAR GRHR_RAT 243 36 -
QDPRKLQLNQSKNNIPRAR GRHR_MOUSE 243 36 -
QDPHNLQLNQSKNNIPRAR GRHR_PIG 244 36 -
QDPHKLQLNQSKNNIPQAR GRHR_SHEEP 244 36 -
QDPHELQLNQSKNNIPRAR GRHR_HUMAN 244 36 -

Motif 8 width=21
Element Seqn Id St Int Rpt
WYWFDPDMVNRVSDPVNHFFF GRHR_BOVIN 289 26 -
WYWFDPEMLNRVSEPVNHFFF GRHR_RAT 288 26 -
WYWFDPEMLNRVSEPVNHFFF GRHR_MOUSE 288 26 -
WYWFDPEMVNRVSDPVNHFFF GRHR_PIG 289 26 -
WYWFDPDMVNRVSDPVNHFFF GRHR_SHEEP 289 26 -
WYWFDPEMLNRLSDPVNHFFF GRHR_HUMAN 289 26 -