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PR01728

Identifier
KISS1RECEPTR  [View Relations]  [View Alignment]  
Accession
PR01728
No. of Motifs
10
Creation Date
15-APR-2002
Title
KiSS-1 peptide receptor 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. OHTAKI, T., SHINTANI, Y., HONDA, S., MATSUMOTO, H., HORI, A.,
KANEHASHI, K., TERAO, Y., KUMANO, S., TAKATSU, Y., MASUDA, Y., ISHIBASHI, Y.,
WATANABE, T., ASADA, M., YAMADA, T., SUENAGA, M., KITADA, C., USUKI, S., 
KUROKAWA, T., ONDA, H., NISHIMURA, O. AND FUJINO, M.
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a
G-protein-coupled receptor.
NATURE 411(6837) 613-617 (2001).
 
7. KOTANI, M., DETHEUX, M., VANDENBOGAERDE, A., COMMUNI, D., VANDERWINDEN,
J.M., LE POUL, E., BREZILLON, S., TYLDESLEY, R., SUAREZ-HUERTA, N.,
VANDEPUT, F., BLANPAIN, C., SCHIFFMANN, S.N., VASSART, G. AND PARMENTIER, M.
The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural
ligands of the orphan G protein-coupled receptor GPR54.
J.BIOL.CHEM. 276(37) 34631-34636 (2001).
 
8. CLEMENTS, M.K., MCDONALD, T.P., WANG, R., XIE, G., O'DOWD, B.F., 
GEORGE, S.R., AUSTIN, C.P. AND LIU, Q.
FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled
receptor GPR54.
BIOCHEM.BIOPHYS.RES.COMMUN. 284(5) 1189-1193 (2001).  

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]. 
 
The metastasis suppressor gene KiSS-1 encodes a number of RFamide-related 
peptides, the largest of which, metastin, contains 54 amino acids [6,7].
An orphan G protein-coupled receptor, GPR54, has been identified as a 
receptor for these peptides [6-8]. GPR54 is highly expressed in placenta, 
pituitary, pancreas and spinal cord [7]. Binding of KiSS-1-encoded peptides
to the receptor results in coupling to the Gq pathway, stimulating calcium
mobilisation, phosphatidylinositol hydrolysis, arachidonic acid release, 
ERK and p38 MAP kinase phosphorylation and stress fibre formation. It also
inhibits cell proliferation [7]. The distribution of GPR54, together with 
the finding that administration of KiSS-1 peptides in rat stimulates 
oxytocin secretion, suggests a role in regulation of endocrine function [7].
 
KISS1RECEPTR is a 10-element fingerprint that provides a signature for the
KiSS-1 peptide receptors. The fingerprint was derived from an initial 
alignment of 5 sequences: the motifs were drawn from conserved sections 
within N- and C-terminal and loop regions, focusing on those areas of the 
alignment that characterise the KiSS-1 peptide receptors but distinguish 
them from the rest of the rhodopsin-like superfamily - motifs 1 and 2 
encode the N-terminus; motif 3 spans the first cytoplasmic loop; motifs 4 
and 5 are located in the first external loop; motif 6 spans the second
cytoplasmic loop; motif 7 lies in the second external loop; motifs 8 and 9
encode the third cytoplasmic loop; and motif 10 lies in the C-terminus, 
immediately after TM domain 7. A single iteration on SPTR40_20f was 
required to reach convergence, no further sequences being identified beyond
the starting set.
Summary Information
5 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
0 codes involving 2 elements
Composite Feature Index
105555555555
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
Q91V45        Q924U1        Q969F8        Q96QG0        
Q9Z0T7
Sequence Titles
Q91V45      G-PROTEIN-COUPLED RECEPTOR GPR54 (G PROTEIN-COUPLED RECEPTOR 54) - Mus musculus (Mouse). 
Q924U1 G PROTEIN-COUPLED RECEPTOR - Rattus norvegicus (Rat).
Q969F8 G PROTEIN-COUPLED RECEPTOR (PUTATIVE G PROTEIN-COUPLED RECEPTOR) (G-PROTEIN-COUPLED RECEPTOR GPR54) - Homo sapiens (Human).
Q96QG0 G PROTEIN-COUPLED RECEPTOR - Homo sapiens (Human).
Q9Z0T7 ORPHAN G PROTEIN-COUPLED RECEPTOR GPR54 - Rattus norvegicus (Rat).
Scan History
SPTR40_20f 1  110  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
ATLGPNVSWWAPSNASGCPG Q924U1 5 5 -
ATLGPNVSWWAPSNASGCPG Q9Z0T7 5 5 -
ATLAPNVTWWAPSNASGCPG Q91V45 5 5 -
ATSGPNASWGAPANASGCPG Q969F8 5 5 -
ATSGPNASWGAPANASGCPG Q96QG0 5 5 -

Motif 2 width=19
Element Seqn Id St Int Rpt
CGVNASDGPGSAPRPLDAW Q924U1 25 0 -
CGVNASDGPGSAPRPLDAW Q9Z0T7 25 0 -
CGVNASDDPGSAPRPLDAW Q91V45 25 0 -
CGANASDGPVPSPRAVDAW Q969F8 25 0 -
CGANASDGPVPSPRAVDAW Q96QG0 25 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
FVICRHKHMQT Q924U1 65 21 -
FVICRHKHMQT Q9Z0T7 65 21 -
YVICRHKHMQT Q91V45 65 21 -
YVICRHKPMRT Q969F8 65 21 -
YVICRHKPMRT Q96QG0 65 21 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PLPTWVLGDFMC Q924U1 104 28 -
PLPTWVLGDFMC Q9Z0T7 104 28 -
PLPAWVLGDFMC Q91V45 104 28 -
PLPGWVLGDFMC Q969F8 104 28 -
PLPGWVLGDFMC Q96QG0 104 28 -

Motif 5 width=15
Element Seqn Id St Int Rpt
FVNYIQQVSVQATCA Q924U1 117 1 -
FVNYIQQVSVQATCA Q9Z0T7 117 1 -
FVNYIQQVSVQATCA Q91V45 117 1 -
FVNYIQQVSVQATCA Q969F8 117 1 -
FVNYIQQVSVQATCA Q96QG0 117 1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
YVTVFPLRALHRR Q924U1 142 10 -
YVTVFPLRALHRR Q9Z0T7 142 10 -
YVTVFPLRALHRR Q91V45 142 10 -
YVTVFPLRALHRR Q969F8 142 10 -
YVTVFPLRALHRR Q96QG0 142 10 -

Motif 7 width=25
Element Seqn Id St Int Rpt
LHRLSPGPHTYCSEAFPSRALERAF Q924U1 180 25 -
LHRLSPGPHTYCSEAFPSRALERAF Q9Z0T7 180 25 -
LHRLSPGPRTYCSEAFPSRALERAF Q91V45 180 25 -
LHRLSPGPRAYCSEAFPSRALERAF Q969F8 180 25 -
LHRLSPGPRAYCSEAFPSRALERAF Q96QG0 180 25 -

Motif 8 width=12
Element Seqn Id St Int Rpt
RHLGRAAVRPAP Q924U1 229 24 -
RHLGRAAVRPAP Q9Z0T7 229 24 -
RHLGRAAVRPAP Q91V45 229 24 -
RHLGRVAVRPAP Q969F8 229 24 -
RHLGRVAVRPAP Q96QG0 229 24 -

Motif 9 width=19
Element Seqn Id St Int Rpt
LQGQLLAQRAGAVRTKVSR Q924U1 245 4 -
LQGQLLAQRAGAVRTKVSR Q9Z0T7 245 4 -
LQGQLLAQRAGAVRTKVSR Q91V45 245 4 -
LQGQVLAERAGAVRAKVSR Q969F8 245 4 -
LQGQVLAERAGAVRAKVSR Q96QG0 245 4 -

Motif 10 width=14
Element Seqn Id St Int Rpt
GSHFRQAFCRVCPC Q924U1 327 63 -
GSHFRQAFCRVCPC Q9Z0T7 326 62 -
GSHFRQAFCRVCPC Q91V45 327 63 -
GSHFRQAFRRVCPC Q969F8 327 63 -
GSHFRQAFRRVCPC Q96QG0 327 63 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
ATLGPNVSWWAPSNASGCPG Q924U1 5 5 -
ATLGPNVSWWAPSNASGCPG Q9Z0T7 5 5 -
ATLAPNVTWWAPSNASGCPG Q91V45 5 5 -
ATSGPNASWGAPANASGCPG Q969F8 5 5 -
ATSGPNASWGAPANASGCPG Q96QG0 5 5 -

Motif 2 width=19
Element Seqn Id St Int Rpt
CGVNASDGPGSAPRPLDAW Q924U1 25 0 -
CGVNASDGPGSAPRPLDAW Q9Z0T7 25 0 -
CGVNASDDPGSAPRPLDAW Q91V45 25 0 -
CGANASDGPVPSPRAVDAW Q969F8 25 0 -
CGANASDGPVPSPRAVDAW Q96QG0 25 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
FVICRHKHMQT Q924U1 65 21 -
FVICRHKHMQT Q9Z0T7 65 21 -
YVICRHKHMQT Q91V45 65 21 -
YVICRHKPMRT Q969F8 65 21 -
YVICRHKPMRT Q96QG0 65 21 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PLPTWVLGDFMC Q924U1 104 28 -
PLPTWVLGDFMC Q9Z0T7 104 28 -
PLPAWVLGDFMC Q91V45 104 28 -
PLPGWVLGDFMC Q969F8 104 28 -
PLPGWVLGDFMC Q96QG0 104 28 -

Motif 5 width=15
Element Seqn Id St Int Rpt
FVNYIQQVSVQATCA Q924U1 117 1 -
FVNYIQQVSVQATCA Q9Z0T7 117 1 -
FVNYIQQVSVQATCA Q91V45 117 1 -
FVNYIQQVSVQATCA Q969F8 117 1 -
FVNYIQQVSVQATCA Q96QG0 117 1 -

Motif 6 width=13
Element Seqn Id St Int Rpt
YVTVFPLRALHRR Q924U1 142 10 -
YVTVFPLRALHRR Q9Z0T7 142 10 -
YVTVFPLRALHRR Q91V45 142 10 -
YVTVFPLRALHRR Q969F8 142 10 -
YVTVFPLRALHRR Q96QG0 142 10 -

Motif 7 width=25
Element Seqn Id St Int Rpt
LHRLSPGPHTYCSEAFPSRALERAF Q924U1 180 25 -
LHRLSPGPHTYCSEAFPSRALERAF Q9Z0T7 180 25 -
LHRLSPGPRTYCSEAFPSRALERAF Q91V45 180 25 -
LHRLSPGPRAYCSEAFPSRALERAF Q969F8 180 25 -
LHRLSPGPRAYCSEAFPSRALERAF Q96QG0 180 25 -

Motif 8 width=12
Element Seqn Id St Int Rpt
RHLGRAAVRPAP Q924U1 229 24 -
RHLGRAAVRPAP Q9Z0T7 229 24 -
RHLGRAAVRPAP Q91V45 229 24 -
RHLGRVAVRPAP Q969F8 229 24 -
RHLGRVAVRPAP Q96QG0 229 24 -

Motif 9 width=19
Element Seqn Id St Int Rpt
LQGQLLAQRAGAVRTKVSR Q924U1 245 4 -
LQGQLLAQRAGAVRTKVSR Q9Z0T7 245 4 -
LQGQLLAQRAGAVRTKVSR Q91V45 245 4 -
LQGQVLAERAGAVRAKVSR Q969F8 245 4 -
LQGQVLAERAGAVRAKVSR Q96QG0 245 4 -

Motif 10 width=14
Element Seqn Id St Int Rpt
GSHFRQAFCRVCPC Q924U1 327 63 -
GSHFRQAFCRVCPC Q9Z0T7 326 62 -
GSHFRQAFCRVCPC Q91V45 327 63 -
GSHFRQAFRRVCPC Q969F8 327 63 -
GSHFRQAFRRVCPC Q96QG0 327 63 -