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PR00647

Identifier
UROTENSIN2R  [View Relations]  [View Alignment]  
Accession
PR00647
No. of Motifs
9
Creation Date
10-DEC-1996  (UPDATE 31-MAY-2001)
Title
Urotensin II receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN

INTERPRO; IPR000670
GCRDB; GCR_1427; GCR_1443
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. TAL, M., AMMAR, D.A., KARPUJ, M., KRIZHANOVSKY, V., NAIM, M.
AND THOMPSON, D.A. 
A novel putative neuropeptide receptor expressed in neural tissue,
including sensory epithelia.
BIOCHEM.BIOPHYS.RES.COMMUN. 209 752-759 (1995).
 
7. AMES, R.S., SARAU, H.M., CHAMBERS, J.K., WILLETTE, R.N., AIYAR, N.V.,
ROMANIC, A.M., LOUDEN, C.S., FOLEY, J.J., SAUERMELCH, C.F., COATNEY, R.W.,
AO, Z., DISA, J., HOLMES, S.D., STADEL, J.M., MARTIN, J.D., LIU, W.S.,
GLOVER, G.I., WILSON, S., MCNULTY, D.E., ELLIS, C.E., ELSHOURBAGY, N.A.,
SHABON, U., TRILL, J.J., HAY, D.W., DOUGLAS, S.A. ET AL..
Human urotensin-II is a potent vasoconstrictor and agonist for the orphan
receptor GPR14.
NATURE 401 282-286 (1999).
 
8. OPGAARD, O.S., NOTHACKER, H.-P., EHLERT, F.J. AND KRAUSE, D.N.
Human urotensin II mediates vasoconstriction via an increase in inositol
phosphates.
EUR.J.PHARMACOL. 406 265-271 (2000).
 
9. DOUGLAS, S.A. AND OHLSTEIN, E.H.
Human urotensin-II, the most potent mammalian vasoconstrictor identified
to date, as a therapeutic target for the management of cardiovascular
disease.
TRENDS CARDIOVASC.MED. 10 229-237 (2000).

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]. 
 
Urotensin II is a vasoactive `somatostatin-like' peptide, first identified 
in fish spinal cord but later found in humans and other mammals [7]. A 
cyclic hexapeptide region of the molecule is responsible for the biological 
activity and is absolutely conserved between species [8]. Urotensin II is 
the most potent mammalian vasoconstrictor identified to date and causes 
contraction of arterial blood vessels, including the thoracic aorta [7,8]. 
The urotensin II receptor was originally isolated as an orphan receptor, 
expressed in neural and sensory tissues and named GPR14, or sensory 
epithelial neuropeptide-like receptor (SENR) [6]. The receptor has been 
found to be expressed in the CNS (cerebellum and spinal cord), skeletal 
muscle, pancreas, heart, endothelium and vascular smooth muscle [9]. It is 
likely to be involved in the pathophysiological control of cardiovascular 
function and may also influence CNS and endocrine functions [7,9]. Binding 
of urotensin II to the receptor leads to activation of phospholipase C, 
through coupling to Gq/11 family proteins [8]. The resulting increase in 
intracellular calcium may cause the contraction of vascular smooth muscle 
[8].
 
UROTENSIN2R is a 9-element fingerprint that provides a signature for the
urotensin II receptors. The fingerprint was derived from an initial 
alignment of 2 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 urotensin II receptors but 
distinguish them from the rest of the rhodopsin-like superfamily - motifs 
1-3 span the N-terminus; motif 4 spans the first external loop; motif 5 
spans the second cytoplasmic loop; motif 6 lies in the second external 
loop; motif 7 lies in the third cytoplasmic loop; motif 8 lies at the 
C-terminus of TM domain 7; and motif 9 resides at the C-terminus. A single
iteration on SPTR39_15f was required to reach convergence, no further 
sequences being identified beyond the starting set.
Summary Information
2 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
9222222222
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
GPRE_RAT      UR2R_HUMAN    
Sequence Titles
GPRE_RAT    PROBABLE G PROTEIN-COUPLED RECEPTOR GPR14. - RATTUS NORVEGICUS (RAT). 
UR2R_HUMAN Urotensin II receptor (UR-II-R) (G-protein coupled receptor 14) - Homo sapiens (Human).
Scan History
SPTR39_15f 1  80   NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MALTPESPSSFPGLAA UR2R_HUMAN 1 1 -
MALSLESTTSFHMLTV GPRE_RAT 1 1 -

Motif 2 width=16
Element Seqn Id St Int Rpt
VSGSTVTELPGDSNVS GPRE_RAT 16 -1 -
ATGSSVPEPPGGPNAT UR2R_HUMAN 16 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
TLNSSWASPTEPSSLED UR2R_HUMAN 31 -1 -
SLNSSWSGPTDPSSLKD GPRE_RAT 31 -1 -

Motif 4 width=21
Element Seqn Id St Int Rpt
IVATYVTKEWHFGDVGCRVLF UR2R_HUMAN 107 59 -
IIATYVTKDWHFGDVGCRVLF GPRE_RAT 107 59 -

Motif 5 width=14
Element Seqn Id St Int Rpt
PLDTVQRSKGYRKL GPRE_RAT 155 27 -
PLDTVQRPKGYRKL UR2R_HUMAN 155 27 -

Motif 6 width=19
Element Seqn Id St Int Rpt
LVRRGPKSLCLPAWGPRAH UR2R_HUMAN 190 21 -
LVRRGSKSLCLPAWGPRAH GPRE_RAT 190 21 -

Motif 7 width=21
Element Seqn Id St Int Rpt
YARLARAYRRSQRASFKRARR UR2R_HUMAN 231 22 -
YVRLARAYWLSQQASFKQTRR GPRE_RAT 231 22 -

Motif 8 width=15
Element Seqn Id St Int Rpt
NYREYLRGRQRSLGS GPRE_RAT 323 71 -
NYRDHLRGRVRGPGS UR2R_HUMAN 321 69 -

Motif 9 width=14
Element Seqn Id St Int Rpt
RVHLQQDSGRSLSS GPRE_RAT 352 14 -
RARFQRCSGRSLSS UR2R_HUMAN 348 12 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MALTPESPSSFPGLAA UR2R_HUMAN 1 1 -
MALSLESTTSFHMLTV GPRE_RAT 1 1 -

Motif 2 width=16
Element Seqn Id St Int Rpt
VSGSTVTELPGDSNVS GPRE_RAT 16 -1 -
ATGSSVPEPPGGPNAT UR2R_HUMAN 16 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
TLNSSWASPTEPSSLED UR2R_HUMAN 31 -1 -
SLNSSWSGPTDPSSLKD GPRE_RAT 31 -1 -

Motif 4 width=21
Element Seqn Id St Int Rpt
IVATYVTKEWHFGDVGCRVLF UR2R_HUMAN 107 59 -
IIATYVTKDWHFGDVGCRVLF GPRE_RAT 107 59 -

Motif 5 width=14
Element Seqn Id St Int Rpt
PLDTVQRSKGYRKL GPRE_RAT 155 27 -
PLDTVQRPKGYRKL UR2R_HUMAN 155 27 -

Motif 6 width=19
Element Seqn Id St Int Rpt
LVRRGPKSLCLPAWGPRAH UR2R_HUMAN 190 21 -
LVRRGSKSLCLPAWGPRAH GPRE_RAT 190 21 -

Motif 7 width=21
Element Seqn Id St Int Rpt
YARLARAYRRSQRASFKRARR UR2R_HUMAN 231 22 -
YVRLARAYWLSQQASFKQTRR GPRE_RAT 231 22 -

Motif 8 width=15
Element Seqn Id St Int Rpt
NYREYLRGRQRSLGS GPRE_RAT 323 71 -
NYRDHLRGRVRGPGS UR2R_HUMAN 321 69 -

Motif 9 width=14
Element Seqn Id St Int Rpt
RVHLQQDSGRSLSS GPRE_RAT 352 14 -
RARFQRCSGRSLSS UR2R_HUMAN 348 12 -