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PR01024

Identifier
NEUROKININ1R  [View Relations]  [View Alignment]  
Accession
PR01024
No. of Motifs
9
Creation Date
29-NOV-1998  (UPDATE 21-JUN-1999)
Title
Neurokinin NK1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00244 NEUROKININR
INTERPRO; IPR000046
GCRDB; GCR_0244; GCR_0157; GCR_0241; GCR_0258; GCR_0259; GCR_0261
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.
 
In the brain, high concentrations of the NK1 receptor are found in striatum,
olfactory bulb, dendate gyrus, locus coeruleus and spinal chord [7]. In 
peripheral tissues NK1 receptors are found in smooth muscle (e.g., ileum 
and bladder), enteric neurons, secretory glands (e.g., parotid), cells of 
the immune system and vascular endothelium [7]. NK1 receptors activate the 
phosphoinositide pathway through a pertussis-toxin-insensitive G protein [7].
 
NEUROKININ1R is a 9-element fingerprint that provides a signature for the
neurokinin NK1 receptors. The fingerprint was derived from an initial 
alignment of 4 sequences: the motifs were drawn from conserved sections 
within either loop or TM regions, focusing on those areas of the alignment
that characterise the NK1 receptors but distinguish them from the rest of
the neurokinin family - motifs 1 and 2 reside at the N-terminus; motifs 3
and 4 span the second external loop; motif 5 spans the C-terminal portion of
TM domain 6 and the third external loop; and motifs 6-9 reside within the 
C-terminus. Two iterations on OWL30.2 were required to reach convergence,
at which point at true set comprising 5 sequences was identified. A single
partial match was also found, NK1R_RANCA, an NK1 receptor from bull frog 
that matches motifs 6, 8 and 9.
 
An update on SPTR37_9f identified a true set of 4 sequences, and 1
partial match.
Summary Information
   4 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
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
9444444444
8000000000
7000000000
6000000000
5000000000
4000000000
3000001011
2000000000
123456789
True Positives
NK1R_CAVPO    NK1R_HUMAN    NK1R_MOUSE    NK1R_RAT      
True Positive Partials
Codes involving 3 elements
NK1R_RANCA
Sequence Titles
NK1R_CAVPO  Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1) - Cavia porcellus (Guinea pig). 
NK1R_HUMAN Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1) - Homo sapiens (Human).
NK1R_MOUSE Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1) - Mus musculus (Mouse).
NK1R_RAT Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1) - Rattus norvegicus (Rat).

NK1R_RANCA Substance-P receptor (SPR) (NK-1 receptor) (NK-1R) (Tachykinin receptor 1) - Rana catesbeiana (Bull frog).
Scan History
OWL30_2    2  100  NSINGLE    
SPTR37_9f 1 75 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
DNVLPVDSDLSP NK1R_HUMAN 2 2 -
DNVLPMDSDLFP NK1R_RAT 2 2 -
DNVLPVDSDLFP NK1R_MOUSE 2 2 -
DNVLPVDSDLFP NK1R_CAVPO 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
PNISTNTSEPNQF NK1R_HUMAN 13 -1 -
PNISTNTSESNQF NK1R_RAT 13 -1 -
PNTSTNTSESNQF NK1R_MOUSE 13 -1 -
PNISTNTSEPNQF NK1R_CAVPO 13 -1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
QGYYSTTETMPSRVV NK1R_HUMAN 165 139 -
QGYYSTTETMPSRVV NK1R_RAT 165 139 -
QGYYSTTETMPSRVV NK1R_MOUSE 165 139 -
QGYYSTTETMPGRVV NK1R_CAVPO 165 139 -

Motif 4 width=16
Element Seqn Id St Int Rpt
MIEWPEHPNKIYEKVY NK1R_HUMAN 181 1 -
MIEWPEHPNRTYEKAY NK1R_RAT 181 1 -
MIEWPEHPNRTYEKAY NK1R_MOUSE 181 1 -
MIEWPSHPDKIYEKVY NK1R_CAVPO 181 1 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LPYINPDLYLK NK1R_HUMAN 270 73 -
LPYINPDLYLK NK1R_RAT 270 73 -
LPYINPDLYLK NK1R_MOUSE 270 73 -
LPYINPDLYLK NK1R_CAVPO 270 73 -

Motif 6 width=18
Element Seqn Id St Int Rpt
QTQGSVYKVSRLETTIST NK1R_HUMAN 343 62 -
QTQSSVYKVSRLETTIST NK1R_RAT 343 62 -
QTQSSVYKVSRLETTIST NK1R_MOUSE 343 62 -
QTQGSVYKVSRLETTIST NK1R_CAVPO 343 62 -

Motif 7 width=18
Element Seqn Id St Int Rpt
TVVGAHEEEPEDGPKATP NK1R_HUMAN 360 -1 -
TVVGAHEEEPEEGPKATP NK1R_RAT 360 -1 -
TVVGAHEDEPEEGPKATP NK1R_MOUSE 360 -1 -
TVVGAHEEDPEEGPKATP NK1R_CAVPO 360 -1 -

Motif 8 width=14
Element Seqn Id St Int Rpt
PSSLDLTSNCSSRS NK1R_HUMAN 377 -1 -
PSSLDLTSNGSSRS NK1R_RAT 377 -1 -
PSSLDLTSNGSSRS NK1R_MOUSE 377 -1 -
PSSLDLTSNGSSRS NK1R_CAVPO 377 -1 -

Motif 9 width=17
Element Seqn Id St Int Rpt
SDSKTMTESFSFSSNVL NK1R_HUMAN 390 -1 -
SNSKTMTESSSFYSNML NK1R_RAT 390 -1 -
SNSKTMTESSSFYSNIL NK1R_MOUSE 390 -1 -
SNSKTVTESSSFYSNML NK1R_CAVPO 390 -1 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
DNVLPVDSDLSP NK1R_HUMAN 2 2 -
DNVLPMDSDLFP NK1R_RAT 2 2 -
DNVLPVDSDLFP NK1R_MOUSE 2 2 -
DNVLPVDSDLFP NK1R_CAVPO 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
PNISTNTSEPNQF NK1R_HUMAN 13 -1 -
PNISTNTSESNQF NK1R_RAT 13 -1 -
PNTSTNTSESNQF NK1R_MOUSE 13 -1 -
PNISTNTSEPNQF NK1R_CAVPO 13 -1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
QGYYSTTETMPSRVV NK1R_HUMAN 165 139 -
QGYYSTTETMPSRVV NK1R_RAT 165 139 -
QGYYSTTETMPSRVV NK1R_MOUSE 165 139 -
QGYYSTTETMPGRVV NK1R_CAVPO 165 139 -

Motif 4 width=16
Element Seqn Id St Int Rpt
MIEWPEHPNKIYEKVY NK1R_HUMAN 181 1 -
MIEWPEHPNRTYEKAY NK1R_RAT 181 1 -
MIEWPEHPNRTYEKAY NK1R_MOUSE 181 1 -
MIEWPSHPDKIYEKVY NK1R_CAVPO 181 1 -

Motif 5 width=11
Element Seqn Id St Int Rpt
LPYINPDLYLK NK1R_HUMAN 270 73 -
LPYINPDLYLK NK1R_RAT 270 73 -
LPYINPDLYLK NK1R_MOUSE 270 73 -
LPYINPDLYLK NK1R_CAVPO 270 73 -

Motif 6 width=18
Element Seqn Id St Int Rpt
QTQGSVYKVSRLETTIST NK1R_HUMAN 343 62 -
QTQSSVYKVSRLETTIST NK1R_RAT 343 62 -
QTQSSVYKVSRLETTIST NK1R_MOUSE 343 62 -
QTQGSVYKVSRLETTIST NK1R_CAVPO 343 62 -

Motif 7 width=18
Element Seqn Id St Int Rpt
TVVGAHEEEPEDGPKATP NK1R_HUMAN 360 -1 -
TVVGAHEEEPEEGPKATP NK1R_RAT 360 -1 -
TVVGAHEDEPEEGPKATP NK1R_MOUSE 360 -1 -
TVVGAHEEDPEEGPKATP NK1R_CAVPO 360 -1 -

Motif 8 width=14
Element Seqn Id St Int Rpt
PSSLDLTSNCSSRS NK1R_HUMAN 377 -1 -
PSSLDLTSNGSSRS NK1R_RAT 377 -1 -
PSSLDLTSNGSSRS NK1R_MOUSE 377 -1 -
PSSLDLTSNGSSRS NK1R_CAVPO 377 -1 -

Motif 9 width=17
Element Seqn Id St Int Rpt
SDSKTMTESFSFSSNVL NK1R_HUMAN 390 -1 -
SNSKTMTESSSFYSNML NK1R_RAT 390 -1 -
SNSKTMTESSSFYSNIL NK1R_MOUSE 390 -1 -
SNSKTVTESSSFYSNML NK1R_CAVPO 390 -1 -