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PR01480

Identifier
NEUROTENSN1R  [View Relations]  [View Alignment]  
Accession
PR01480
No. of Motifs
6
Creation Date
12-MAR-2001
Title
Neurotensin type 1 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. TANAKA, K., MASU, M. AND NAKANISHI, S.
Structure and functional expression of the cloned rat neurotensin receptor.
NEURON 4(6) 847-854 (1990).

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 NT1 receptor was cloned in 1990 from rat brain and found to act as a
high affinity, levocabastine insensitive receptor for neurotensin [8]. The
affinity of neurotensin for the receptor could be decreased by both sodium
ions and guanosine triphosphate (GTP) [7]. The NT1 receptor is expressed
predominantly in the brain and intestine. In the brain, expression has been
found in the diagonal band of Broca, medial septal nucleus, nucleus basalis
magnocellularis, suprachiasmatic nucleus, supramammillary area, substantia
nigra and ventral tegmental area. The receptor is also expressed in the
dorsal root ganglion neurones of the spinal cord [7]. The predominant
response upon activation of the receptor by neurotensin is activation of
phospholipase C, causing an increase in intracellular calcium levels. The
receptor can also stimulate cAMP formation, MAP kinase activation and the
induction of growth related genes, such as krox-24 [7].
 
NEUROTENSN1R is a 6-element fingerprint that provides a signature for the
neurotensin type 1 receptors. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections
within the N and C-termini and loop regions, focusing on those areas of the 
alignment that characterise the neurotensin type 1 receptors but distinguish 
them from the rest of neurotensin receptor family - motif 1 resides within 
the N-terminus; motif 2 spans the first cytoplasmic loop; motifs 3 and 4 
span the second external loop; motif 5 is located in the third cytoplasmic 
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
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
NTR1_HUMAN    NTR1_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).
O88319 NEUROTENSIN RECEPTOR TYPE 1 - MUS MUSCULUS (MOUSE).
Scan History
SPTR39_15f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
NGSGNSSESI O88319 38 38 -
NGSGNTSESD NTR1_RAT 38 38 -
NASGNASERV NTR1_HUMAN 37 37 -

Motif 2 width=16
Element Seqn Id St Int Rpt
FTLARKKSLQSLQSTV O88319 86 38 -
FTLARKKSLQSLQSTV NTR1_RAT 87 39 -
FTLARKKSLQSLQSTV NTR1_HUMAN 86 39 -

Motif 3 width=13
Element Seqn Id St Int Rpt
QNRSADGQHPGGL O88319 210 108 -
QNRSGDGTHPGGL NTR1_RAT 211 108 -
QNRSADGQHAGGL NTR1_HUMAN 210 108 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PTVDTATVKVVI O88319 226 3 -
PIVDTATVKVVI NTR1_RAT 227 3 -
PTIHTATVKVVI NTR1_HUMAN 226 3 -

Motif 5 width=13
Element Seqn Id St Int Rpt
EHSTFNMSIEPGR O88319 287 49 -
EHSTFNMTIEPGR NTR1_RAT 287 48 -
EHSTFSMAIEPGR NTR1_HUMAN 282 44 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PTFSRKPNSMSSNHAFSTS O88319 399 99 -
PTFSRKPNSMSSNHAFSTS NTR1_RAT 399 99 -
PAFSRKADSVSSNHTLSSN NTR1_HUMAN 393 98 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
NGSGNSSESI O88319 38 38 -
NGSGNTSESD NTR1_RAT 38 38 -
NASGNASERV NTR1_HUMAN 37 37 -

Motif 2 width=16
Element Seqn Id St Int Rpt
FTLARKKSLQSLQSTV O88319 86 38 -
FTLARKKSLQSLQSTV NTR1_RAT 87 39 -
FTLARKKSLQSLQSTV NTR1_HUMAN 86 39 -

Motif 3 width=13
Element Seqn Id St Int Rpt
QNRSADGQHPGGL O88319 210 108 -
QNRSGDGTHPGGL NTR1_RAT 211 108 -
QNRSADGQHAGGL NTR1_HUMAN 210 108 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PTVDTATVKVVI O88319 226 3 -
PIVDTATVKVVI NTR1_RAT 227 3 -
PTIHTATVKVVI NTR1_HUMAN 226 3 -

Motif 5 width=13
Element Seqn Id St Int Rpt
EHSTFNMSIEPGR O88319 287 49 -
EHSTFNMTIEPGR NTR1_RAT 287 48 -
EHSTFSMAIEPGR NTR1_HUMAN 282 44 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PTFSRKPNSMSSNHAFSTS O88319 399 99 -
PTFSRKPNSMSSNHAFSTS NTR1_RAT 399 99 -
PAFSRKADSVSSNHTLSSN NTR1_HUMAN 393 98 -