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PR01416

Identifier
APJRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01416
No. of Motifs
7
Creation Date
29-NOV-2000
Title
APJ receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN

GCRDB; GCR_0806
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. O'DOWD B.F., HEIBER, M., CHAN, A., HENG, H.H., TSUI, L.C., KENNEDY, J.L.,
SHI, X., PETRONIS, A., GEORGE, S.R. AND NGUYEN, T.
A human gene that shows identity with the gene encoding the angiotensin
receptor is located on chromosome 11.
GENE 136 355-360 (1993).
 
7. TATEMOTO, K., HOSOYA, M., HABATA, Y., FUJII, R., KAKEGAWA, T., ZOU, M-X,
KAWAMATA, Y., FUKUSUMI, S., HINUMA, S., KITADA, C., KUROKAWA, T., ONDA, H.
AND FUJINO, M.
Isolation and charaterization of a novel endogenous peptide ligand for the
human APJ receptor.
BIOCHEM.BIOPHYS.RES.COMMUN. 251 471-476 (1998).
 
8. LEE, D.K., CHENG, R., NGUYEN, T., FAN, T., KARIYAWASAM, A.P., LIU, Y.,
OSMOND, D.H., GEORGE, S.R. AND O'DOWD, B.F.
Characterization of apelin, the ligand for the APJ receptor.
J.NEUROCHEM. 74 34-41 (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].
 
The human APJ gene was originally cloned in 1993 using a set of primers
based on the 7 conserved TM domains. The putative sequence is closest in
terms of identity (40-50% in the TM regions) to the angiotensin receptor
(AT1); however, angiotensin II shows no affinity for the receptor [6]. The
endogenous ligand has recently been isolated from bovine stomach and
characterised as a 77 amino acid peptide, which was named apelin [7]. The
mature transcript encodes a preproprotein that yields a 13 amino acid active
peptide from the C-terminal end. Apelin has a similar mRNA distribution to
angiotensin II and the active peptides share some similarity. In vivo
administration of apelin to rats results in acute hypotensive and thirst-
promoting effects [8].
 
APJRECEPTOR is a 7-element fingerprint that provides a signature for APJ
receptors. The fingerprint was derived from an initial alignment of 3
sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those areas of the alignment that
characterise the APJ receptors but distinguish them from the related
angiotensin II receptors and the rest of the rhodopsin-like superfamily -
motifs 1 and 2 span the extracellular N-terminus; motif 3 lies in the second
external loop; motif 4 spans the C-terminus of the third external loop and 
the N-terminus of TM domain 7; and motifs 5-7 lie in the cytoplasmic
C-terminus. A single iteration on SPTR39_14f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Summary Information
3 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
73333333
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
APJ_HUMAN     O97666        Q9WV08        
Sequence Titles
APJ_HUMAN   Apelin receptor (G-protein coupled receptor APJ) (Angiotensin receptor-like 1) (HG11) - Homo sapiens (Human). 
O97666 PUTATIVE CHEMOKINE RECEPTOR - Macaca mulatta (Rhesus macaque).
Q9WV08 G PROTEIN-COUPLED RECEPTOR - Mus musculus (Mouse).
Scan History
SPTR39_14f 1  60   NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
DNYYGADNQSEC O97666 8 8 -
DNYYGADNQSEC APJ_HUMAN 8 8 -
YNYYGADNQSEC Q9WV08 6 6 -

Motif 2 width=10
Element Seqn Id St Int Rpt
EYTDWKSSGA O97666 20 0 -
EYTDWKSSGA APJ_HUMAN 20 0 -
DYADWKPSGA Q9WV08 18 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
TKVQCYMDYSMVATVSSDWAWE O97666 177 147 -
TKVQCYMDYSMVATVSSEWAWE APJ_HUMAN 177 147 -
TKIQCYMDYSMVATSNSEWAWE Q9WV08 175 147 -

Motif 4 width=13
Element Seqn Id St Int Rpt
HWPCDFDLFLMNV O97666 278 79 -
HWPCDFDLFLMNI APJ_HUMAN 278 79 -
HWPCDFDIFLMNV Q9WV08 276 79 -

Motif 5 width=9
Element Seqn Id St Int Rpt
TSMLCCGQS O97666 321 30 -
TSMLCCGQS APJ_HUMAN 321 30 -
TSMLCCDQS Q9WV08 319 30 -

Motif 6 width=15
Element Seqn Id St Int Rpt
GHSQGPGPNMGKGGE O97666 349 19 -
GHSQGPGPNMGKGGE APJ_HUMAN 349 19 -
GHSQGPGPNMGKGGE Q9WV08 347 19 -

Motif 7 width=14
Element Seqn Id St Int Rpt
QMHEKSIPYSQETL O97666 364 0 -
QMHEKSIPYSQETL APJ_HUMAN 364 0 -
QMHEKSIPYSQETL Q9WV08 362 0 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
DNYYGADNQSEC O97666 8 8 -
DNYYGADNQSEC APJ_HUMAN 8 8 -
YNYYGADNQSEC Q9WV08 6 6 -

Motif 2 width=10
Element Seqn Id St Int Rpt
EYTDWKSSGA O97666 20 0 -
EYTDWKSSGA APJ_HUMAN 20 0 -
DYADWKPSGA Q9WV08 18 0 -

Motif 3 width=22
Element Seqn Id St Int Rpt
TKVQCYMDYSMVATVSSDWAWE O97666 177 147 -
TKVQCYMDYSMVATVSSEWAWE APJ_HUMAN 177 147 -
TKIQCYMDYSMVATSNSEWAWE Q9WV08 175 147 -

Motif 4 width=13
Element Seqn Id St Int Rpt
HWPCDFDLFLMNV O97666 278 79 -
HWPCDFDLFLMNI APJ_HUMAN 278 79 -
HWPCDFDIFLMNV Q9WV08 276 79 -

Motif 5 width=9
Element Seqn Id St Int Rpt
TSMLCCGQS O97666 321 30 -
TSMLCCGQS APJ_HUMAN 321 30 -
TSMLCCDQS Q9WV08 319 30 -

Motif 6 width=15
Element Seqn Id St Int Rpt
GHSQGPGPNMGKGGE O97666 349 19 -
GHSQGPGPNMGKGGE APJ_HUMAN 349 19 -
GHSQGPGPNMGKGGE Q9WV08 347 19 -

Motif 7 width=14
Element Seqn Id St Int Rpt
QMHEKSIPYSQETL O97666 364 0 -
QMHEKSIPYSQETL APJ_HUMAN 364 0 -
QMHEKSIPYSQETL Q9WV08 362 0 -