SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01018

Identifier
PRPRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01018
No. of Motifs
10
Creation Date
03-DEC-1998  (UPDATE 03-JUN-2001)
Title
Prolactin-releasing peptide receptor signature 
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN

INTERPRO; IPR001402
GCRDB; GCR_1973; GCR_2359
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. HINUMA, S., HABATA, Y., FUJII, R., KAWAMATA, Y., HOSOYA, M., FUKUSUMI, S.,
KITADA, C., MASUO, Y., ASANO, T., MATSUMOTO, H., SEKIGUCHI, M., KUROKAWA, T.,
NISHIMURA, O., ONDA, H. AND FUJINO, M.
A prolactin-releasing peptide in the brain.
NATURE 393 272-276 (1998).
 
7. FUJII, R., FUKUSUMI, S., HOSOYA, M., KAWAMATA, Y., HABATA, Y., HINUMA, S.,
SEKIGUCHI, M., KITADA, C., KUROKAWA, T., NISHIMURA, O., ONDA, H., SUMINO, Y.
AND FUJINO, M.
Tissue distribution of prolactin-releasing peptide (PrRP) and its receptor.
REGUL.PEPT. 83 1-10 (1999).
 
8. LANGMEAD, C.J., SZEKERES, P.G., CHAMBERS, J.K., RATCLIFFE, S.J., 
JONES, D.N., HIRST, W.D., PRICE, G.W. AND HERDON, H.J.
Characterization of the binding of [125I]-human prolactin releasing peptide
BR.J.PHARMACOL. 131(4) 683-688 (2000).

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]. 
 
Hypothalamic peptide hormones regulate secretion of anterior pituitary 
hormones, such as growth hormone, follicle stimulating hormone, luteinising
hormone and thyrotropin. A novel bioactive peptide has been identified from 
bovine hypothalamus and found to increase prolactin secretion from the 
anterior pituitary [6]. This peptide - prolactin-releasing peptide (PrRP) -
is a member of the structurally related RF-amide family, which includes 
neuropeptide FF [8]. The peptide exists in two forms: a 31-amino acid form
and a truncated 20-amino acid form [6]. PrRP has been found in the medulla
oblongata, hypothalamus and pituitary, as well as in a number of other 
tissues [7]. This distribution suggests the peptide may have other roles
in addition to prolactin release [7].
 
The receptor for PrRP was identified to be an orphan receptor, previously
known as GPR10 [6]. This receptor is expressed in the central nervous 
system with highest levels in the pituitary. Expression has also been 
detected in the cerebellum, brainstem, hypothalamus, thalamus and spinal
cord in rat [7]. Binding of PrRP to the receptor results in activation of 
extracellular signal-related kinase (ERK) in a mainly pertussis toxin
sensitive manner, suggesting coupling to Gi/o proteins [8]. PrRP can also
cause increases in intracellular calcium and activation of c-Jun 
N-terminal protein kinase (JNK) in a pertussis toxin insensitive manner,
indicating that the receptor can also couple to Gq proteins, depending on 
the cell type in which it is expressed [8].
 
PRPRECEPTOR is a 10-element fingerprint that provides a signature for
prolactin-releasing peptide receptor. The fingerprint was derived from an 
initial alignment of 2 sequences: the motifs were drawn from conserved 
sections within either loop or TM regions, focusing on those areas of the 
alignment that characterise the prolactin-releasing peptide receptors but 
distinguish them from the rest of the rhodopsin-like superfamily - motifs 1 
and 2 lie at the N-terminus; motif 3 spans the C-terminal portion of TM 
domain 2 and part of the first external loop; motif 4 encodes the 
N-terminal portion of TM domain 3; motif 5 spans the second external loop; 
motif 6 spans the C-terminal portion of TM domain 5, leading into the third 
cytoplasmic loop; motif 7 encodes the rest of the third cytoplasmic loop; 
motif 8 spans the third external loop, leading into TM domain 7; and motifs 
9 and 10 lie at the C-terminus. Two iterations on SPTR39_15f were required
to reach convergence, at which point a true set comprising 3 sequences was
identified.
Summary Information
3 codes involving 10 elements
0 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
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
103333333333
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
GPRA_HUMAN    GPRA_RAT      O75194        
Sequence Titles
GPRA_HUMAN  PROBABLE G PROTEIN-COUPLED RECEPTOR GPR10 - Homo sapiens (Human). 
GPRA_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR GPR10 (UHR-1) - Rattus norvegicus (Rat).
O75194 HUMAN PROLACTIN-RELEASING PEPTIDE RECEPTOR - Homo sapiens (Human).
Scan History
SPTR39_15f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
DLFSGLPPAVTTPANQSAE GPRA_HUMAN 13 13 -
DLFSGPSPAGSTPANQSAE GPRA_RAT 13 13 -

Motif 2 width=18
Element Seqn Id St Int Rpt
EASAGNGSVAGADAPAVT GPRA_HUMAN 31 -1 -
EASESNVSATVPRAAAVT GPRA_RAT 31 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
TLAYAFEPRGWVFGGGL GPRA_HUMAN 117 68 -
TLAYAFEPRGWVFGGGL GPRA_RAT 117 68 -

Motif 4 width=18
Element Seqn Id St Int Rpt
VFFLQPVTVYVSVFTLTT GPRA_HUMAN 137 3 -
VFFLQPVTVYVSVFTLTT GPRA_RAT 137 3 -

Motif 5 width=18
Element Seqn Id St Int Rpt
KPHDVRLCEEFWGSQERQ GPRA_HUMAN 203 48 -
KPHDVRLCEEFWGSQERQ GPRA_RAT 204 49 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ILLSYVRVSVKLRNR GPRA_HUMAN 240 19 -
ILLSYVRVSVKLRNR GPRA_RAT 241 19 -

Motif 7 width=23
Element Seqn Id St Int Rpt
VVPGCVTQSQADWDRARRRRTFC GPRA_HUMAN 255 0 -
VVPGSVTQSQADWDRARRRRTFC GPRA_RAT 256 0 -

Motif 8 width=22
Element Seqn Id St Int Rpt
NLLRDLDPHAIDPYAFGLVQLL GPRA_HUMAN 297 19 -
NLLRDLDPRAIDPYAFGLVQLL GPRA_RAT 298 19 -

Motif 9 width=14
Element Seqn Id St Int Rpt
AWLHDSFREELRKL GPRA_HUMAN 335 16 -
AWLHDSFREELRKM GPRA_RAT 336 16 -

Motif 10 width=21
Element Seqn Id St Int Rpt
LLVAWPRKIAPHGQNMTVSVV GPRA_HUMAN 348 -1 -
MLLSWPRKIVPHGQNMTVSVV GPRA_RAT 349 -1 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
DLFSGLPPAVTTPANQSAE GPRA_HUMAN 13 13 -
DLFSGLPPAVTTPANQSAE O75194 13 13 -
DLFSGPSPAGSTPANQSAE GPRA_RAT 13 13 -

Motif 2 width=18
Element Seqn Id St Int Rpt
EASAGNGSVAGADAPAVT GPRA_HUMAN 31 -1 -
EASAGNGSVAGADAPAVT O75194 31 -1 -
EASESNVSATVPRAAAVT GPRA_RAT 31 -1 -

Motif 3 width=17
Element Seqn Id St Int Rpt
TLAYAFEPRGWVFGGGL GPRA_HUMAN 117 68 -
TLAYAFEPRGWVFGGGL O75194 117 68 -
TLAYAFEPRGWVFGGGL GPRA_RAT 117 68 -

Motif 4 width=18
Element Seqn Id St Int Rpt
VFFLQPVTVYVSVFTLTT GPRA_HUMAN 137 3 -
VFFLQPVTVYVSVFTLTT O75194 137 3 -
VFFLQPVTVYVSVFTLTT GPRA_RAT 137 3 -

Motif 5 width=18
Element Seqn Id St Int Rpt
KPHDVRLCEEFWGSQERQ GPRA_HUMAN 203 48 -
KPHDVRLCEEFWGSQERQ O75194 204 49 -
KPHDVRLCEEFWGSQERQ GPRA_RAT 204 49 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ILLSYVRVSVKLRNR GPRA_HUMAN 240 19 -
ILLSYVRVSVKLRNR O75194 241 19 -
ILLSYVRVSVKLRNR GPRA_RAT 241 19 -

Motif 7 width=23
Element Seqn Id St Int Rpt
VVPGCVTQSQADWDRARRRRTFC GPRA_HUMAN 255 0 -
VVPGCVTQSQADWDRARRRRTFC O75194 256 0 -
VVPGSVTQSQADWDRARRRRTFC GPRA_RAT 256 0 -

Motif 8 width=22
Element Seqn Id St Int Rpt
NLLRDLDPHAIDPYAFGLVQLL GPRA_HUMAN 297 19 -
NLLRDLDPHAIDPYAFGLVQLL O75194 298 19 -
NLLRDLDPRAIDPYAFGLVQLL GPRA_RAT 298 19 -

Motif 9 width=14
Element Seqn Id St Int Rpt
AWLHDSFREELRKL GPRA_HUMAN 335 16 -
AWLHDSFREELRKL O75194 336 16 -
AWLHDSFREELRKM GPRA_RAT 336 16 -

Motif 10 width=21
Element Seqn Id St Int Rpt
LLVAWPRKIAPHGQNMTVSVV GPRA_HUMAN 348 -1 -
LLVAWPRKIAPHGQNMTVSVV O75194 349 -1 -
MLLSWPRKIVPHGQNMTVSVV GPRA_RAT 349 -1 -