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PR01104

Identifier
ANPHYLATOXNR  [View Relations]  [View Alignment]  
Accession
PR01104
No. of Motifs
5
Creation Date
14-MAR-1999
Title
Anaphylatoxin chemotactic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01060 C3ANPHYLTXNR; PR00426 C5ANPHYLTXNR
INTERPRO; IPR002234
GCRDB; GCR_0464; GCR_0618; GCR_1052; GCR_1916; GCR_1994; GCR_1303

GCRDB; GCR_1304
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. WATSON, S. AND ARKINSTALL,
C5a anaphylatoxin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp71-73.
 
7. AMES, R.S., LI, Y., SARAU, H.M., NUTHULAGANTI, P., FOLEY, J.J., 
ELLIS, C., ZENG, Z., SU, K., JUREWICZ, A.J., HERTZBERG, R.P., BERGSMA, D.J.
AND KUMAR, C.
Molecular cloning and characterization of the human anaphylatoxin C3a receptor.
J.BIOL.CHEM. 271 20231-20234 (1996). 
 
8. CRASS, T., RAFFETSEDER, U., MARTIN, U., GROVE, M., KLOS, A., KOHL, J.
AND BAUTSCH, W.
Expression cloning of the human C3a anaphylatoxin receptor (C3aR) from
differentiated U-937 cells.
EUR.J.IMMUNOL. 26 1944-1950 (1996). 

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 accumulation of phagocytic cells at the site of injury or infection is
regulated by substances that stimulate chemotaxis, granule secretion,
superoxide generation and upregulation of cell surface adhesion molecules
in cells of the immune system [6]. The chemoattractant substances include
C5a, N-formylmethionyl-containing peptides, interleukin 8, leukotriene B4
and platelet activating factor, many of which participate in anaphylactoid
and septic shock [6]. The C5a receptor is found on cells of the immune
system (e.g., neutrophils, macrophages, mast cells and related cell lines),
and is also present in smooth muscle. The amino acid sequence of the
receptor contains several N-terminal acidic residues, which may be
involved in binding the basic C5a peptide.
 
An orphan GPCR with 37% nucleotide identity to the C5a receptor [6] has 
been identified [7]. By contrast with C5aR and other GPCRs, a novel feature
of the gene product is the presence of an unusually large predicted extra-
cellular loop, containing in excess of 160 amino acid residues, between
TM domains 4 and 5 [7]. In human tissues, expression of mRNA for this 
receptor is similar to, but distinct from C5aR expression [7]. Although
there are some differences, transcripts for both receptors are detected
in tissues throughout the body and the central nervous system [7]. This
novel gene has been shown to encode the human anaphylatoxin C3a receptor 
[7]. The C3aR appears to be widely expressed in different lymphoid tissues,
providing evidence for a central role of the C3a anaphylatoxin in 
inflammatory processes [8]. 
 
ANPHYLATOXNR is a 5-element fingerprint that provides a signature for the
anaphylatoxin receptors. The fingerprint was derived from an initial
alignment of 9 sequences: the motifs were drawn from conserved sections
within either loop or TM regions, focusing on those areas of the alignment
that characterise the anaphylatoxin receptors but distinguish them from the
rest of the rhodopsin-like superfamily - motif 1 lies in the second 
cytoplasmic loop; motif 2 resides at the C-terminus of TM domain 4, leading
into the second external loop; motif 3 spans the C-terminus of the second
external loop, leading into TM domain 5; motif 4 spans the C-terminus of 
TM domain 5 and part of the third cytoplasmic loop; and motif 5 lies at the
C-terminus of TM domain 7, leading into the C-terminal cytoplasmic domain.
Two iterations on SPTR37_9f were required to reach convergence, at which 
point a true set comprising 10 sequences was identified. 
Summary Information
10 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51010101010
400000
300000
200000
12345
True Positives
C3AR_HUMAN    C3AR_MOUSE    C5AR_CANFA    C5AR_HUMAN    
C5AR_MOUSE C5AR_RAT O43771 O55197
O70129 O88680
Sequence Titles
C3AR_HUMAN  C3a anaphylatoxin chemotactic receptor (C3a-R) (C3AR) - Homo sapiens (Human). 
C3AR_MOUSE C3a anaphylatoxin chemotactic receptor (C3a-R) (C3AR) (Complement component 3a receptor 1) - Mus musculus (Mouse).
C5AR_CANFA C5a anaphylatoxin chemotactic receptor (C5a-R) (C5aR) (CD88 antigen) - Canis familiaris (Dog).
C5AR_HUMAN C5a anaphylatoxin chemotactic receptor (C5a-R) (C5aR) (CD88 antigen) - Homo sapiens (Human).
C5AR_MOUSE C5a anaphylatoxin chemotactic receptor (C5a-R) (C5aR) (CD88 antigen) - Mus musculus (Mouse).
C5AR_RAT C5a anaphylatoxin chemotactic receptor (C5a-R) (C5aR) (CD88 antigen) - Rattus norvegicus (Rat).
O43771 C3A ANAPHYLATOXIN RECEPTOR - HOMO SAPIENS (HUMAN).
O55197 ANAPHYLATOXIN C3A RECEPTOR - RATTUS NORVEGICUS (RAT).
O70129 ANAPHYLATOXIN C5A RECEPTOR - CAVIA PORCELLUS (GUINEA PIG).
O88680 C3A RECEPTOR - CAVIA PORCELLUS (GUINEA PIG).
Scan History
SPTR37_9f  2  40   NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
RCLVVFKPIWCQ C3AR_HUMAN 120 120 -
RFLLVFKPIWCQ C5AR_MOUSE 130 130 -
RCLIVHKPIWCQ C3AR_MOUSE 120 120 -
RFLLVFKPIWCQ C5AR_HUMAN 134 134 -
RFVLVFNPIWCQ C5AR_CANFA 135 135 -

Motif 2 width=10
Element Seqn Id St Int Rpt
IPVFVYREIF C3AR_HUMAN 155 23 -
IPSFVYREAY C5AR_MOUSE 165 23 -
VPVFVYRDLF C3AR_MOUSE 155 23 -
IPSFLYRVVR C5AR_HUMAN 169 23 -
VPSFIFRGVH C5AR_CANFA 170 23 -

Motif 3 width=10
Element Seqn Id St Int Rpt
AITITRLVVG C3AR_HUMAN 335 170 -
AVAILRLMVG C5AR_MOUSE 198 23 -
AITITRLVVG C3AR_MOUSE 328 163 -
AVAIVRLVLG C5AR_HUMAN 201 22 -
GVAILRLLMG C5AR_CANFA 203 23 -

Motif 4 width=16
Element Seqn Id St Int Rpt
YSFIVFRMQRGRFAKS C3AR_HUMAN 356 11 -
YTFLLLRTWSRKATRS C5AR_MOUSE 219 11 -
YSLIVFRMRKTNFTKS C3AR_MOUSE 349 11 -
YTFILLRTWSRRATRS C5AR_HUMAN 222 11 -
YTFLLIRTWSRKATRS C5AR_CANFA 224 11 -

Motif 5 width=15
Element Seqn Id St Int Rpt
YALLGKDFRKKARQS C3AR_HUMAN 435 63 -
YVMAGQGFHGRLLRS C5AR_MOUSE 297 62 -
YALLGKDFRKKARQS C3AR_MOUSE 428 63 -
YVVAGQGFQGRLRKS C5AR_HUMAN 300 62 -
YVLAAQGFHSRFLKS C5AR_CANFA 302 62 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
RCLVVFKPIWCQ C3AR_HUMAN 120 120 -
RCLVVFKPIWCQ O43771 120 120 -
RFLLVFKPIWCQ C5AR_MOUSE 130 130 -
RFLLVFKPIWCQ C5AR_RAT 135 135 -
RCLIVHKPIWCQ C3AR_MOUSE 120 120 -
RCLMVHKPIWCQ O55197 120 120 -
RFLLVFKPIWCQ C5AR_HUMAN 134 134 -
RCLMVLKPIWCQ O88680 120 120 -
RLLLVLSPIWCQ O70129 129 129 -
RFVLVFNPIWCQ C5AR_CANFA 135 135 -

Motif 2 width=10
Element Seqn Id St Int Rpt
IPVFVYREIF C3AR_HUMAN 155 23 -
IPVFVYREIF O43771 155 23 -
IPSFVYREAY C5AR_MOUSE 165 23 -
IPSFVFRRIH C5AR_RAT 170 23 -
VPVFVYRDLF C3AR_MOUSE 155 23 -
IPVFVYRDLL O55197 155 23 -
IPSFLYRVVR C5AR_HUMAN 169 23 -
IPVFVYRETF O88680 155 23 -
SPSFLYRRTH O70129 164 23 -
VPSFIFRGVH C5AR_CANFA 170 23 -

Motif 3 width=10
Element Seqn Id St Int Rpt
AITITRLVVG C3AR_HUMAN 335 170 -
AITITRLVVG O43771 335 170 -
AVAILRLMVG C5AR_MOUSE 198 23 -
AIAILRLMVG C5AR_RAT 203 23 -
AITITRLVVG C3AR_MOUSE 328 163 -
AITISRLVVG O55197 324 159 -
AVAIVRLVLG C5AR_HUMAN 201 22 -
VITFTRLVVG O88680 326 161 -
AVALVRLLVG O70129 196 22 -
GVAILRLLMG C5AR_CANFA 203 23 -

Motif 4 width=16
Element Seqn Id St Int Rpt
YSFIVFRMQRGRFAKS C3AR_HUMAN 356 11 -
YSFIVFRMQRGRFAKS O43771 356 11 -
YTFLLLRTWSRKATRS C5AR_MOUSE 219 11 -
YTFLLIRTWSRKATRS C5AR_RAT 224 11 -
YSLIVFRMRKTNFTKS C3AR_MOUSE 349 11 -
YSLIVFRMRKTNLTKS O55197 345 11 -
YTFILLRTWSRRATRS C5AR_HUMAN 222 11 -
YTLIIFRMRRVRVVKS O88680 347 11 -
YTFLLLRTWSRKATRS O70129 217 11 -
YTFLLIRTWSRKATRS C5AR_CANFA 224 11 -

Motif 5 width=15
Element Seqn Id St Int Rpt
YALLGKDFRKKARQS C3AR_HUMAN 435 63 -
YALLGKDFRKKARQS O43771 435 63 -
YVMAGQGFHGRLLRS C5AR_MOUSE 297 62 -
YVMAGQGFHGRLRRS C5AR_RAT 302 62 -
YALLGKDFRKKARQS C3AR_MOUSE 428 63 -
YALLGKDFRKKARQS O55197 424 63 -
YVVAGQGFQGRLRKS C5AR_HUMAN 300 62 -
YALLGRDLRKRVRQS O88680 426 63 -
YVVAGHGFQGRLLKS O70129 295 62 -
YVLAAQGFHSRFLKS C5AR_CANFA 302 62 -