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PR01479

Identifier
NEUROTENSINR  [View Relations]  [View Alignment]  
Accession
PR01479
No. of Motifs
6
Creation Date
12-MAR-2001
Title
Neurotensin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01480 NEUROTENSN1R; PR01481 NEUROTENSN2R
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.
Neurotensin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994,
PP.199-201.
 
7. VINCENT, J-P., MAZELLA, J. AND KITABGI, P.
Neurotensin and neurotensin receptors.
TRENDS PHARMACOL.SCI. 20(7) 302-309 (1999).

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].
 
Neurotensin is a 13-residue peptide transmitter, sharing significant
similarity in its 6 C-terminal amino acids with several other neuropeptides,
including neuromedin N. This region is responsible for the biological 
activity, the N-terminal portion having a modulatory role. Neurotensin is
distributed throughout the central nervous system, with highest levels in 
the hypothalamus, amygdala and nucleus accumbens. It induces a variety of
effects, including: analgesia, hypothermia and increased locomotor activity.
It is also involved in regulation of dopamine pathways. In the periphery,
neurotensin is found in endocrine cells of the small intestine, where it
leads to secretion and smooth muscle contraction [6].
 
The existence of 2 neurotensin receptor subtypes, with differing affinities
for neurotensin and differing sensitivities to the antihistamine
levocabastine, was originally demonstrated by binding studies in rodent
brain. Two neurotensin receptors (NT1 and NT2) with such properties have
since been cloned and have been found to be G protein-coupled receptor
family members [7].
 
NEUROTENSINR is a 6-element fingerprint that provides a signature for the
neurotensin receptors. The fingerprint was derived from an initial alignment
of 6 sequences: the motifs were drawn from conserved sections within the N-
and C-termini and external loop regions, focusing on those areas of the
alignment that characterise the neurotensin receptors but distinguish them
from the rest of the rhodopsin-like superfamily - motif 1 resides at the 
N-terminus, leading into TM domain 1; motifs 2 and 3 span the first external 
loop; motifs 4 and 5 span the third external loop; and motif 6 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
6 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
6666666
5000000
4000000
3000000
2000000
123456
True Positives
NTR1_HUMAN    NTR1_RAT      NTR2_HUMAN    NTR2_MOUSE    
NTR2_RAT O88319
Sequence Titles
NTR1_HUMAN  Neurotensin receptor type 1 (NT-R-1) (High-affinity levocabastine- insensitive neurotensin receptor) (NTRH) - Homo sapiens (Human). 
NTR1_RAT Neurotensin receptor type 1 (NT-R-1) (High-affinity levocabastine- insensitive neurotensin receptor) (NTRH) - Rattus norvegicus (Rat).
NTR2_HUMAN Neurotensin receptor type 2 (NT-R-2) (Levocabastine-sensitive neurotensin receptor) (NTR2 receptor) - Homo sapiens (Human).
NTR2_MOUSE Neurotensin receptor type 2 (NT-R-2) (Low-affinity levocabastine- sensitive neurotensin receptor) (NTRL) - Mus musculus (Mouse).
NTR2_RAT Neurotensin receptor type 2 (NT-R-2) (High-affinity levocabastine- sensitive neurotensin receptor) - Rattus norvegicus (Rat).
O88319 NEUROTENSIN RECEPTOR TYPE 1 - MUS MUSCULUS (MOUSE).
Scan History
SPTR39_15f 1  180  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
IYSKVLVTAVY O88319 60 60 -
IYSKVLVTAIY NTR1_RAT 61 61 -
IYSKVLVTAVY NTR1_HUMAN 60 60 -
LWAKVLFTALY NTR2_MOUSE 29 29 -
LWAKVLFTALY NTR2_RAT 29 29 -
LWAKVLFTALY NTR2_HUMAN 29 29 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VELYNFIWVHHPW O88319 122 51 -
VELYNFIWVHHPW NTR1_RAT 123 51 -
VELYNFIWVHHPW NTR1_HUMAN 122 51 -
MELYNFVWSHYPW NTR2_MOUSE 89 49 -
MELYNFVWSHYPW NTR2_RAT 89 49 -
VELYSFVWFHYPW NTR2_HUMAN 89 49 -

Motif 3 width=14
Element Seqn Id St Int Rpt
AFGDAGCRGYYFLR O88319 135 0 -
AFGDAGCRGYYFLR NTR1_RAT 136 0 -
AFGDAGCRGYYFLR NTR1_HUMAN 135 0 -
VFGDLGCRGYYFVR NTR2_MOUSE 102 0 -
VFGDLGCRGYYFVR NTR2_RAT 102 0 -
VFGDLGCRGYYFVH NTR2_HUMAN 102 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
FCYISDEQWTT O88319 331 182 -
FCYISDEQWTT NTR1_RAT 331 181 -
FCYISDEQWTP NTR1_HUMAN 326 177 -
YCYIPDDGWTD NTR2_MOUSE 321 205 -
YCYIPDDGWTN NTR2_RAT 320 204 -
YCYVPDDAWTD NTR2_HUMAN 320 204 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FLFDFYHYFYM O88319 342 0 -
FLFDFYHYFYM NTR1_RAT 342 0 -
FLYDFYHYFYM NTR1_HUMAN 337 0 -
ELYDFYHYFYM NTR2_MOUSE 332 0 -
ELYDFYHYFYM NTR2_RAT 331 0 -
PLYNFYHYFYM NTR2_HUMAN 331 0 -

Motif 6 width=11
Element Seqn Id St Int Rpt
VFLSTLACLCP O88319 379 26 -
VFLSTLACLCP NTR1_RAT 379 26 -
IFLATLACLCP NTR1_HUMAN 374 26 -
LFLESLSSLCG NTR2_MOUSE 369 26 -
LFLESLGSLCG NTR2_RAT 368 26 -
LFLEAVSSLCG NTR2_HUMAN 368 26 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
IYSKVLVTAVY O88319 60 60 -
IYSKVLVTAIY NTR1_RAT 61 61 -
IYSKVLVTAVY NTR1_HUMAN 60 60 -
LWAKVLFTALY NTR2_MOUSE 29 29 -
LWAKVLFTALY NTR2_RAT 29 29 -
LWAKVLFTALY NTR2_HUMAN 29 29 -

Motif 2 width=13
Element Seqn Id St Int Rpt
VELYNFIWVHHPW O88319 122 51 -
VELYNFIWVHHPW NTR1_RAT 123 51 -
VELYNFIWVHHPW NTR1_HUMAN 122 51 -
MELYNFVWSHYPW NTR2_MOUSE 89 49 -
MELYNFVWSHYPW NTR2_RAT 89 49 -
VELYSFVWFHYPW NTR2_HUMAN 89 49 -

Motif 3 width=14
Element Seqn Id St Int Rpt
AFGDAGCRGYYFLR O88319 135 0 -
AFGDAGCRGYYFLR NTR1_RAT 136 0 -
AFGDAGCRGYYFLR NTR1_HUMAN 135 0 -
VFGDLGCRGYYFVR NTR2_MOUSE 102 0 -
VFGDLGCRGYYFVR NTR2_RAT 102 0 -
VFGDLGCRGYYFVH NTR2_HUMAN 102 0 -

Motif 4 width=11
Element Seqn Id St Int Rpt
FCYISDEQWTT O88319 331 182 -
FCYISDEQWTT NTR1_RAT 331 181 -
FCYISDEQWTP NTR1_HUMAN 326 177 -
YCYIPDDGWTD NTR2_MOUSE 321 205 -
YCYIPDDGWTN NTR2_RAT 320 204 -
YCYVPDDAWTD NTR2_HUMAN 320 204 -

Motif 5 width=11
Element Seqn Id St Int Rpt
FLFDFYHYFYM O88319 342 0 -
FLFDFYHYFYM NTR1_RAT 342 0 -
FLYDFYHYFYM NTR1_HUMAN 337 0 -
ELYDFYHYFYM NTR2_MOUSE 332 0 -
ELYDFYHYFYM NTR2_RAT 331 0 -
PLYNFYHYFYM NTR2_HUMAN 331 0 -

Motif 6 width=11
Element Seqn Id St Int Rpt
VFLSTLACLCP O88319 379 26 -
VFLSTLACLCP NTR1_RAT 379 26 -
IFLATLACLCP NTR1_HUMAN 374 26 -
LFLESLSSLCG NTR2_MOUSE 369 26 -
LFLESLGSLCG NTR2_RAT 368 26 -
LFLEAVSSLCG NTR2_HUMAN 368 26 -