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PR01026

Identifier
NEUROKININ3R  [View Relations]  [View Alignment]  
Accession
PR01026
No. of Motifs
9
Creation Date
29-NOV-1998  (UPDATE 03-JUL-1999)
Title
Neurokinin NK3 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00244 NEUROKININR
INTERPRO; IPR001013
GCRDB; GCR_0359; GCR_0385; GCR_0143
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. YOKOTA, Y., SASAI, Y., TANAKA, K., FUJIWARA, T, TSUCHIDA, K., 
SHIGEMOTO, R., KAKIZUKA, A., OHKUBO, H. AND NAKANISHI, S.
Molecular characterisation of a functional cDNA for rat substance P
receptor.
J.BIOL.CHEM. 264(30) 17649-17652 (1989).
 
7. WATSON, S. AND ARKINSTALL, S.
Tachykinins.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.261-70.

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]. 
 
Neuropeptide receptors are present in very small quantities in the cell
and are embedded tightly in the plasma membrane. The neuropeptides exhibit
a high degree of functional diversity through both regulation of peptide
production and through peptide-receptor interaction [6]. The mammalian
tachykinin system consists of 3 distinct peptides: substance P, substance
K and neuromedin K. All possess a common spectrum of biological activities,
including sensory transmission in the nervous system and contraction/
relaxation of peripheral smooth muscles, and each interacts with a 
specific receptor type.
 
NK3 receptors are distributed widely throughout the rat CNS, and are found
in high levels in cerebral cortex, basal ganglia and dorsal horn of the
spinal chord. They have limited distribution in peripheral tissues, and
are found in ganglia (e.g., myenteric plexus), kidney, and in a limited 
number of smooth muscles (e.g., rat portal vein) [7]. NK3 receptors
activate the phosphoinositide pathway through a pertussis-toxin-insensitive 
G protein, probably of the Gq/G11 class [7].
 
NEUROKININ3R is a 9-element fingerprint that provides a signature for the
neurokinin NK3 receptors. The fingerprint was derived from an initial 
alignment of 3 sequences: the motifs were drawn from conserved sections 
within either loop or TM regions, focusing on those areas of the alignment
that characterise the NK3 receptors but distinguish them from the rest of
the neurokinin family - motifs 1-3 reside within the N-terminus; motifs 4
and 5 span the second external loop, leading into TM domain 5; motif 6 lies
in the third cytoplasmic loop; motif 7 spans the C-terminus of TM domain 6
and the third external loop; and motifs 8 and 9 reside at the C-terminus.
Two iterations on OWL30.2 were required to reach convergence, at which point
at true set comprising 5 sequences was identified. Several partial matches 
were also found, all of which are homologues or fragments that fail to match
three or more motifs.
 
An update on SPTR37_9f identified a true set of 2 sequences, and 1
partial match.
Summary Information
   2 codes involving  9 elements
0 codes involving 8 elements
0 codes involving 7 elements
1 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
6000111111
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
NK3R_HUMAN    NK3R_RAT      
True Positive Partials
Codes involving 6 elements
NK4R_HUMAN
Sequence Titles
NK3R_HUMAN  Neuromedin-K receptor (NKR) (Neurokinin B receptor) (NK-3 receptor) (NK-3R) (Tachykinin receptor 3) - Homo sapiens (Human). 
NK3R_RAT Neuromedin-K receptor (NKR) (Neurokinin B receptor) (NK-3 receptor) (NK-3R) (Tachykinin receptor 3) - Rattus norvegicus (Rat).

NK4R_HUMAN NEUROMEDIN K RECEPTOR (NKR) (NEUROKININ B RECEPTOR) (NK-4 RECEPTOR) (NK-4R) (K1R) (NEUROKININ 4 RECEPTOR) (NK4) - HOMO SAPIENS (HUMAN).
Scan History
OWL30_2    2  100  NSINGLE    
SPTR37_9f 2 35 NSINGLE
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ASVPRGENWTDGT NK3R_RAT 2 2 -
ATLPAAETWIDGG NK3R_HUMAN 2 2 -
ASVPTGENWTDGT NK3R_MOUSE 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
GVGSHTGNLSAAL NK3R_MOUSE 16 1 -
EVGTHTGNLSSAL NK3R_RAT 16 1 -
GVGADAVNLTASL NK3R_HUMAN 16 1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
SALGLPVASPAPSQPWANLT NK3R_HUMAN 56 27 -
SALGLPVTSQAPSQVRDNLT NK3R_MOUSE 43 14 -
SALGLPATTQAPSQVRANLT NK3R_RAT 43 14 -

Motif 4 width=14
Element Seqn Id St Int Rpt
CLYSKTKVMPGRTL NK3R_HUMAN 219 143 -
CLYSKIKVMPGRTL NK3R_RAT 206 143 -
CLYSKIKVMPGRTL NK3R_MOUSE 206 143 -

Motif 5 width=17
Element Seqn Id St Int Rpt
YVQWPEGPKQHFTYHII NK3R_RAT 221 1 -
YVQWPEGPKQHFTYHII NK3R_MOUSE 221 1 -
FVQWPEGPKQHFTYHII NK3R_HUMAN 234 1 -

Motif 6 width=10
Element Seqn Id St Int Rpt
GGEIPGDTCD NK3R_RAT 263 25 -
GGEILGDTCD NK3R_MOUSE 263 25 -
GGEIPGDTCD NK3R_HUMAN 276 25 -

Motif 7 width=14
Element Seqn Id St Int Rpt
LTAIYQQLNRWKYI NK3R_MOUSE 308 35 -
LTAIYQQLNRWKYI NK3R_HUMAN 321 35 -
LTAIYQQLNRWKYI NK3R_RAT 308 35 -

Motif 8 width=11
Element Seqn Id St Int Rpt
FIQVSSYDELE NK3R_MOUSE 363 41 -
FIKVSSYDELE NK3R_HUMAN 376 41 -
FIQVSSYDELE NK3R_RAT 363 41 -

Motif 9 width=12
Element Seqn Id St Int Rpt
ELKTTRFHPTRQ NK3R_MOUSE 373 -1 -
ELKTTRFHPTRQ NK3R_RAT 373 -1 -
ELKTTRFHPNRQ NK3R_HUMAN 386 -1 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ATLPAAETWIDGG NK3R_HUMAN 2 2 -
ASVPRGENWTDGT NK3R_RAT 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
GVGADAVNLTASL NK3R_HUMAN 16 1 -
EVGTHTGNLSSAL NK3R_RAT 16 1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
SALGLPVASPAPSQPWANLT NK3R_HUMAN 56 27 -
SALGLPATTQAPSQVRANLT NK3R_RAT 43 14 -

Motif 4 width=14
Element Seqn Id St Int Rpt
CLYSKTKVMPGRTL NK3R_HUMAN 219 143 -
CLYSKIKVMPGRTL NK3R_RAT 206 143 -

Motif 5 width=17
Element Seqn Id St Int Rpt
FVQWPEGPKQHFTYHII NK3R_HUMAN 234 1 -
YVQWPEGPKQHFTYHII NK3R_RAT 221 1 -

Motif 6 width=10
Element Seqn Id St Int Rpt
GGEIPGDTCD NK3R_HUMAN 276 25 -
GGEIPGDTCD NK3R_RAT 263 25 -

Motif 7 width=14
Element Seqn Id St Int Rpt
LTAIYQQLNRWKYI NK3R_HUMAN 321 35 -
LTAIYQQLNRWKYI NK3R_RAT 308 35 -

Motif 8 width=11
Element Seqn Id St Int Rpt
FIKVSSYDELE NK3R_HUMAN 376 41 -
FIQVSSYDELE NK3R_RAT 363 41 -

Motif 9 width=12
Element Seqn Id St Int Rpt
ELKTTRFHPNRQ NK3R_HUMAN 386 -1 -
ELKTTRFHPTRQ NK3R_RAT 373 -1 -