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PR01481

Identifier
NEUROTENSN2R  [View Relations]  [View Alignment]  
Accession
PR01481
No. of Motifs
6
Creation Date
12-MAR-2001
Title
Neurotensin type 2 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01479 NEUROTENSINR
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).
 
8. VITA, N., OURY-DONAT, F., CHALON, P., GUILLEMOT, M., KAGHAD, M., BACHY,
A., THURNEYSSEN, O., GARCIA, S., POINOT-CHAZEL, C., CASELLAS, P., KEANE, P., 
LE FUR, G., MAFFRAND, J.P., SOUBRIE, P., CAPUT, D. AND FERRARA, P.
Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed 
in Chinese hamster ovary cells.
EUR.J.PHARMACOL. 360(2-3) 265-272 (1998).
 
9. YAMADA, M., YAMADA, M., LOMBET, A., FORGEZ, P. AND ROSTENE, W.
Distinct functional characteristics of levocabastine sensitive rat
neurotensin NT2 receptor expressed in Chinese hamster ovary cells.
LIFE SCI. 62(23) PL 375-380 (1998).

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].
 
The NT2 receptor was cloned from rat, mouse and human brains based on its
similarity to the NT1 receptor. The receptor was found to be a low affinity,
levocabastine sensitive receptor for neurotensin. Unlike the high affinity,
NT1 receptor, NT2 is insensitive to guanosine triphosphate and has low
sensitivity to sodium ions [7]. Highest levels of expression of the receptor
are found in the brain, in regions including: the olfactory system, cerebral
and cerebellar cortices, hippocampus and hypothalamic nuclei. The
distribution is distinct from that of the NT1 receptor, with only a few
areas (diagonal band of Broca, medial septal nucleus and suprachiasmatic
nuclei) expressing both receptor subtypes [7]. The receptor has also been
found at lower levels in the kidney, uterus, heart and lung [8]. Activation
of the NT2 receptor by non-peptide agonists suggests that the receptor can
couple to phospholipase C, phospholipase A2 and MAP kinase. A functional
response to neurotensin, however, is weak [9] or absent, and neurotensin
appears to act as an antagonist of the receptor [8]. It has been suggested
that a substance other than neurotensin may act as the natural ligand for
this receptor [8].
 
NEUROTENSN2R is a 6-element fingerprint that provides a signature for the
neurotensin type 2 receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections
within the N-terminus and loop regions, focusing on those areas of the 
alignment that characterise the neurotensin type 2 receptors but distinguish
them from the rest of neurotensin receptor family - motifs 1 and 2 span the 
N-terminus; motifs 3 and 4 span the second external loop; and motifs 5 and 6
span the third cytoplasmic loop. A single iteration on SPTR39_15f was 
required to reach convergence, no further sequences being identified beyond
the starting set.
Summary Information
3 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
6333333
5000000
4000000
3000000
2000000
123456
True Positives
NTR2_HUMAN    NTR2_MOUSE    NTR2_RAT      
Sequence Titles
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).
Scan History
SPTR39_15f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
METSSPWPPRPSP NTR2_RAT 1 1 -
METSSLWPPRPSP NTR2_MOUSE 1 1 -
METSSPRPPRPSS NTR2_HUMAN 1 1 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SAGLSLEARLGVD NTR2_RAT 14 0 -
SAGLSLEARLGVD NTR2_MOUSE 14 0 -
NPGLSLDARLGVD NTR2_HUMAN 14 0 -

Motif 3 width=14
Element Seqn Id St Int Rpt
QKHEVESADGEPEP NTR2_RAT 176 149 -
QKHEMERADGEPEP NTR2_MOUSE 176 149 -
QKHELETADGEPEP NTR2_HUMAN 176 149 -

Motif 4 width=12
Element Seqn Id St Int Rpt
ASRVCTVLVSRA NTR2_RAT 190 0 -
ASRVCTVLVSRA NTR2_MOUSE 190 0 -
ASRVCTVLVSRT NTR2_HUMAN 190 0 -

Motif 5 width=22
Element Seqn Id St Int Rpt
VPSASAQVSSIPSRLELLSEEG NTR2_RAT 240 38 -
VPSASAQVNSIPSRLELLSEEG NTR2_MOUSE 241 39 -
VPSTSTPGSSTPSRLELLSEEG NTR2_HUMAN 240 38 -

Motif 6 width=24
Element Seqn Id St Int Rpt
LLGFITWRKTLSLGVQASLVRHKD NTR2_RAT 262 0 -
LLGFITWRKTLSLGVQASLVRHKD NTR2_MOUSE 263 0 -
LLSFIVWKKTFIQGGQVSLVRHKD NTR2_HUMAN 262 0 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
METSSPWPPRPSP NTR2_RAT 1 1 -
METSSLWPPRPSP NTR2_MOUSE 1 1 -
METSSPRPPRPSS NTR2_HUMAN 1 1 -

Motif 2 width=13
Element Seqn Id St Int Rpt
SAGLSLEARLGVD NTR2_RAT 14 0 -
SAGLSLEARLGVD NTR2_MOUSE 14 0 -
NPGLSLDARLGVD NTR2_HUMAN 14 0 -

Motif 3 width=14
Element Seqn Id St Int Rpt
QKHEVESADGEPEP NTR2_RAT 176 149 -
QKHEMERADGEPEP NTR2_MOUSE 176 149 -
QKHELETADGEPEP NTR2_HUMAN 176 149 -

Motif 4 width=12
Element Seqn Id St Int Rpt
ASRVCTVLVSRA NTR2_RAT 190 0 -
ASRVCTVLVSRA NTR2_MOUSE 190 0 -
ASRVCTVLVSRT NTR2_HUMAN 190 0 -

Motif 5 width=22
Element Seqn Id St Int Rpt
VPSASAQVSSIPSRLELLSEEG NTR2_RAT 240 38 -
VPSASAQVNSIPSRLELLSEEG NTR2_MOUSE 241 39 -
VPSTSTPGSSTPSRLELLSEEG NTR2_HUMAN 240 38 -

Motif 6 width=24
Element Seqn Id St Int Rpt
LLGFITWRKTLSLGVQASLVRHKD NTR2_RAT 262 0 -
LLGFITWRKTLSLGVQASLVRHKD NTR2_MOUSE 263 0 -
LLSFIVWKKTFIQGGQVSLVRHKD NTR2_HUMAN 262 0 -