WORKLIST ENTRIES (1):
PRPRECEPTOR View alignment View Structure Prolactin-releasing peptide receptor signature
Type of fingerprint: COMPOUND with 10 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
INTERPRO; IPR001402
Creation date 03-DEC-1998; UPDATE 03-JUN-2001
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
(PrRP) to GPR10, a novel G protein coupled receptor.
BR.J.PHARMACOL. 131(4) 683-688 (2000).
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 [1,2]. 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 FINGERPRINT INDEX
10| 3 3 3 3 3 3 3 3 3 3
9| 0 0 0 0 0 0 0 0 0 0
8| 0 0 0 0 0 0 0 0 0 0
7| 0 0 0 0 0 0 0 0 0 0
6| 0 0 0 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0 0 0 0
--+---------------------------------------------------
| 1 2 3 4 5 6 7 8 9 10
True positives..
GPRA_HUMAN O75194 GPRA_RAT
PROTEIN TITLES
GPRA_HUMAN PROBABLE G PROTEIN-COUPLED RECEPTOR GPR10 - Homo sapiens (Hu
O75194 HUMAN PROLACTIN-RELEASING PEPTIDE RECEPTOR - Homo sapiens (H
GPRA_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR GPR10 (UHR-1) - Rattus n
SCAN HISTORY
SPTR39_15f 2 100 NSINGLE
INITIAL MOTIF SETS
PRPRECEPTOR1 Length of motif = 19 Motif number = 1
Prolactin-releasing peptide receptor motif I - 1
PCODE ST INT
DLFSGPSPAGSTPANQSAE GPRA_RAT 13 13
DLFSGLPPAVTTPANQSAE GPRA_HUMAN 13 13
PRPRECEPTOR2 Length of motif = 18 Motif number = 2
Prolactin-releasing peptide receptor motif II - 1
PCODE ST INT
EASESNVSATVPRAAAVT GPRA_RAT 31 -1
EASAGNGSVAGADAPAVT GPRA_HUMAN 31 -1
PRPRECEPTOR3 Length of motif = 17 Motif number = 3
Prolactin-releasing peptide receptor motif III - 1
PCODE ST INT
TLAYAFEPRGWVFGGGL GPRA_RAT 117 68
TLAYAFEPRGWVFGGGL GPRA_HUMAN 117 68
PRPRECEPTOR4 Length of motif = 18 Motif number = 4
Prolactin-releasing peptide receptor motif IV - 1
PCODE ST INT
VFFLQPVTVYVSVFTLTT GPRA_RAT 137 3
VFFLQPVTVYVSVFTLTT GPRA_HUMAN 137 3
PRPRECEPTOR5 Length of motif = 18 Motif number = 5
Prolactin-releasing peptide receptor motif V - 1
PCODE ST INT
KPHDVRLCEEFWGSQERQ GPRA_RAT 204 49
KPHDVRLCEEFWGSQERQ GPRA_HUMAN 203 48
PRPRECEPTOR6 Length of motif = 15 Motif number = 6
Prolactin-releasing peptide receptor motif VI - 1
PCODE ST INT
ILLSYVRVSVKLRNR GPRA_RAT 241 19
ILLSYVRVSVKLRNR GPRA_HUMAN 240 19
PRPRECEPTOR7 Length of motif = 23 Motif number = 7
Prolactin-releasing peptide receptor motif VII - 1
PCODE ST INT
VVPGSVTQSQADWDRARRRRTFC GPRA_RAT 256 0
VVPGCVTQSQADWDRARRRRTFC GPRA_HUMAN 255 0
PRPRECEPTOR8 Length of motif = 22 Motif number = 8
Prolactin-releasing peptide receptor motif VIII - 1
PCODE ST INT
NLLRDLDPRAIDPYAFGLVQLL GPRA_RAT 298 19
NLLRDLDPHAIDPYAFGLVQLL GPRA_HUMAN 297 19
PRPRECEPTOR9 Length of motif = 14 Motif number = 9
Prolactin-releasing peptide receptor motif IX - 1
PCODE ST INT
AWLHDSFREELRKM GPRA_RAT 336 16
AWLHDSFREELRKL GPRA_HUMAN 335 16
PRPRECEPTOR10 Length of motif = 21 Motif number = 10
Prolactin-releasing peptide receptor motif X - 1
PCODE ST INT
MLLSWPRKIVPHGQNMTVSVV GPRA_RAT 349 -1
LLVAWPRKIAPHGQNMTVSVV GPRA_HUMAN 348 -1
FINAL MOTIF SETS
PRPRECEPTOR1 Length of motif = 19 Motif number = 1
Prolactin-releasing peptide receptor motif I - 2
PCODE ST INT
DLFSGLPPAVTTPANQSAE GPRA_HUMAN 13 13
DLFSGLPPAVTTPANQSAE O75194 13 13
DLFSGPSPAGSTPANQSAE GPRA_RAT 13 13
PRPRECEPTOR2 Length of motif = 18 Motif number = 2
Prolactin-releasing peptide receptor motif II - 2
PCODE ST INT
EASAGNGSVAGADAPAVT GPRA_HUMAN 31 -1
EASAGNGSVAGADAPAVT O75194 31 -1
EASESNVSATVPRAAAVT GPRA_RAT 31 -1
PRPRECEPTOR3 Length of motif = 17 Motif number = 3
Prolactin-releasing peptide receptor motif III - 2
PCODE ST INT
TLAYAFEPRGWVFGGGL GPRA_HUMAN 117 68
TLAYAFEPRGWVFGGGL O75194 117 68
TLAYAFEPRGWVFGGGL GPRA_RAT 117 68
PRPRECEPTOR4 Length of motif = 18 Motif number = 4
Prolactin-releasing peptide receptor motif IV - 2
PCODE ST INT
VFFLQPVTVYVSVFTLTT GPRA_HUMAN 137 3
VFFLQPVTVYVSVFTLTT O75194 137 3
VFFLQPVTVYVSVFTLTT GPRA_RAT 137 3
PRPRECEPTOR5 Length of motif = 18 Motif number = 5
Prolactin-releasing peptide receptor motif V - 2
PCODE ST INT
KPHDVRLCEEFWGSQERQ GPRA_HUMAN 203 48
KPHDVRLCEEFWGSQERQ O75194 204 49
KPHDVRLCEEFWGSQERQ GPRA_RAT 204 49
PRPRECEPTOR6 Length of motif = 15 Motif number = 6
Prolactin-releasing peptide receptor motif VI - 2
PCODE ST INT
ILLSYVRVSVKLRNR GPRA_HUMAN 240 19
ILLSYVRVSVKLRNR O75194 241 19
ILLSYVRVSVKLRNR GPRA_RAT 241 19
PRPRECEPTOR7 Length of motif = 23 Motif number = 7
Prolactin-releasing peptide receptor motif VII - 2
PCODE ST INT
VVPGCVTQSQADWDRARRRRTFC GPRA_HUMAN 255 0
VVPGCVTQSQADWDRARRRRTFC O75194 256 0
VVPGSVTQSQADWDRARRRRTFC GPRA_RAT 256 0
PRPRECEPTOR8 Length of motif = 22 Motif number = 8
Prolactin-releasing peptide receptor motif VIII - 2
PCODE ST INT
NLLRDLDPHAIDPYAFGLVQLL GPRA_HUMAN 297 19
NLLRDLDPHAIDPYAFGLVQLL O75194 298 19
NLLRDLDPRAIDPYAFGLVQLL GPRA_RAT 298 19
PRPRECEPTOR9 Length of motif = 14 Motif number = 9
Prolactin-releasing peptide receptor motif IX - 2
PCODE ST INT
AWLHDSFREELRKL GPRA_HUMAN 335 16
AWLHDSFREELRKL O75194 336 16
AWLHDSFREELRKM GPRA_RAT 336 16
PRPRECEPTOR10 Length of motif = 21 Motif number = 10
Prolactin-releasing peptide receptor motif X - 2
PCODE ST INT
LLVAWPRKIAPHGQNMTVSVV GPRA_HUMAN 348 -1
LLVAWPRKIAPHGQNMTVSVV O75194 349 -1
MLLSWPRKIVPHGQNMTVSVV GPRA_RAT 349 -1
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