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PR01559

Identifier
DUFFYANTIGEN  [View Relations]  [View Alignment]  
Accession
PR01559
No. of Motifs
7
Creation Date
23-SEP-2001
Title
Duffy antigen/chemokine receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
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, S.
Chemokines.
IN THE G-PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.83-88.
 
7. HADLEY, T.J. AND PEIPER, S.C.
From malaria to chemokine receptor: the emerging physiologic role of the
Duffy blood group antigen.
BLOOD 89(9) 3077-3091 (1997).

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].
 
Chemokines are proteins that have important physiological and patho-
physiological roles in a wide range of acute and chronic inflammatory
processes [6]. Their sequences are similar and are characterised by a
4-cysteine motif: the family can be divided according to whether the first 2
Cys residues are adjacent (the C-C family), or separated by an intervening
residue (the C-x-C family).
 
The Duffy antigen/chemokine receptor was originally identified as a blood
group antigen on the surface of red blood cells (RBCs). It has been found 
to act as a multispecific receptor for chemokines of both the C-C and C-X-C
families, including: Il-8, MGSA, RANTES and MCP-1 [7]. While the receptor
is predicted to have 7 TM domains, it shares only very low levels of 
sequence similarity with the other chemokine receptors (indeed, the 
characteristic rhodopsin-like signature is virtually absent) - it is
considered to be most similar to the interleukin-8B receptors. 
 
Duffy is expressed on RBCs (in Duffy-positive individuals), endothelial
cells of postcapillary venules and Purkinje cells of the cerebellum. On 
RBCs, the Duffy antigen acts as a receptor for invasion by the malarial
parasite, Plasmodium vivax; Duffy-negative individuals, whose RBCs do not
express the receptor are resistant to such infection [7]. The normal
physiological function of Duffy remains unclear. It is believed to play a 
more important role on endothelial cells, since expression on these cell
types is highly conserved, whereas the function on RBCs appears to be 
dispensable in order to confer resistance to malaria. The signalling
pathways activated by Duffy are also unknown and the receptor has not 
been shown to act through a G protein [7].
 
DUFFYANTIGEN is a 7-element fingerprint that provides a signature for the
Duffy antigen/chemokine receptors. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length - the motifs encode
each of the putative TM domains. Two iterations on SPTR39.22_17.3f were
required to reach convergence, at which point a true set comprising 7
sequences was identified. Note that no member of any GPCR superfamily 
matched, or partially matched, this 7TM signature.
Summary Information
7 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
77777777
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
DUFF_HUMAN    O35970        O75898        Q9GLX0        
Q9QUI6 Q9UJP0 Q9UQE1
Sequence Titles
DUFF_HUMAN  DUFFY ANTIGEN (FY GLYCOPROTEIN) (GLYCOPROTEIN D) (GPFY) - Homo sapiens (Human). 
O35970 CHEMOKINE RECEPTOR (DUFFY BLOOD GROUP) - Mus musculus (Mouse).
O75898 DUFFY ANTIGEN/CHEMOKINE RECEPTOR - Homo sapiens (Human).
Q9GLX0 DUFFY ANTIGEN/RECEPTOR FOR CHEMOKINE GLYCOPROTEIN - Bos taurus (Bovine).
Q9QUI6 DUFFY ANTIGEN/RECEPTOR FOR CHEMOKINE GLYCOPROTEIN - Mus musculus (Mouse).
Q9UJP0 BK134P22.2 (DUFFY BLOOD GROUP PROTEIN (DARC, GPFY, GLYCOPROTEIN D)) - Homo sapiens (Human).
Q9UQE1 DUFFY BLOOD GROUP ANTIGEN - Homo sapiens (Human).
Scan History
SPTR39.22_17.3f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
ALPFFILTSVLGILASSTVLFMLF Q9UJP0 61 61 -
ALPFFILTSVLGILASSTVLFMLF Q9UQE1 63 63 -
SLPFFILVSILGILASGTILYALL Q9GLX0 55 55 -
SLPFFMLTSVLGMLASGSILFAIL O35970 59 59 -

Motif 2 width=24
Element Seqn Id St Int Rpt
VLAQLAVGSALFSIVVPVLAPGLG Q9UJP0 98 13 -
VLTQLAVGSALFSIVVPVLAPGLG Q9UQE1 100 13 -
TLVQLAVGSALFSIVVPILARGLS Q9GLX0 92 13 -
ILAELAVGSALFSIAVPILAPGLH O35970 96 13 -

Motif 3 width=22
Element Seqn Id St Int Rpt
ALCSLGYCVWYGSAFAQALLLG Q9UJP0 127 5 -
ALCSLGYCVWYGSAFAQALLLG Q9UQE1 129 5 -
SLCHLAHLVAYGSAFAQALLIG Q9GLX0 121 5 -
ALCNLGYWVWYTSAFAQALLIG O35970 125 5 -

Motif 4 width=24
Element Seqn Id St Int Rpt
GLTLGLTVGIWGVAALLTLPVTLA Q9UJP0 164 15 -
GLTLGLTVGIWGVAALLTLPVTLA Q9UQE1 166 15 -
GLRLGVTVGLWGVAALLSLPVVLG Q9GLX0 158 15 -
GFTLGLSVGLWGAAALSGLPVALA O35970 162 15 -

Motif 5 width=21
Element Seqn Id St Int Rpt
TVACLAIFVLLPLGLFGAKGL Q9UJP0 211 23 -
TVACLAIFVLLPLGLFGAKGL Q9UQE1 213 23 -
AAACFAIFVLLPLGLLGTKGL Q9GLX0 205 23 -
YAICFTIFTVLPLTLLAAKGL O35970 209 23 -

Motif 6 width=22
Element Seqn Id St Int Rpt
PWMNILWAWFIFWWPHGVVLGL Q9UJP0 241 9 -
PWMNILWAWFIFWWPHGVVLGL Q9UQE1 243 9 -
PWVDVLWVWFIFWWPQGMTLGL Q9GLX0 235 9 -
PWVSVLWIWFIFWWPHGMVLIF O35970 239 9 -

Motif 7 width=27
Element Seqn Id St Int Rpt
ALDLLLNLAEALAILHCVATPLLLALF Q9UJP0 281 18 -
ALDLLLNLAEALAILHCVATPLLLALF Q9UQE1 283 18 -
ALDMLLDVAEALAILHCVATPLLLAWV Q9GLX0 275 18 -
ILDAMLNVTEALSMLHCVATPLLLALF O35970 279 18 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
ALPFFILTSVLGILASSTVLFMLF DUFF_HUMAN 63 63 -
ALPFFILTSVLGILASSTVLFMLF Q9UJP0 61 61 -
ALPFFILTSVLGILASSTVLFMLF O75898 61 61 -
ALPFFILTSVLGILASSTVLFMLF Q9UQE1 63 63 -
SLPFFILVSILGILASGTILYALL Q9GLX0 55 55 -
SLPFFMLTSVLGMLASGSILFAIL Q9QUI6 59 59 -
SLPFFMLTSVLGMLASGSILFAIL O35970 59 59 -

Motif 2 width=24
Element Seqn Id St Int Rpt
VLAQLAVGSALFSIVVPVLAPGLG DUFF_HUMAN 100 13 -
VLAQLAVGSALFSIVVPVLAPGLG Q9UJP0 98 13 -
VLTQLAVGSALFSIVVPVLAPGLG O75898 98 13 -
VLTQLAVGSALFSIVVPVLAPGLG Q9UQE1 100 13 -
TLVQLAVGSALFSIVVPILARGLS Q9GLX0 92 13 -
ILAELAVGSALFSIAVPILAPGLH Q9QUI6 96 13 -
ILAELAVGSALFSIAVPILAPGLH O35970 96 13 -

Motif 3 width=22
Element Seqn Id St Int Rpt
ALCSLGYCVWYGSAFAQALLLG DUFF_HUMAN 129 5 -
ALCSLGYCVWYGSAFAQALLLG Q9UJP0 127 5 -
ALCSLGYCVWYGSAFAQALLLG O75898 127 5 -
ALCSLGYCVWYGSAFAQALLLG Q9UQE1 129 5 -
SLCHLAHLVAYGSAFAQALLIG Q9GLX0 121 5 -
ALCNLGYWVWYTSAFAQALLIG Q9QUI6 125 5 -
ALCNLGYWVWYTSAFAQALLIG O35970 125 5 -

Motif 4 width=24
Element Seqn Id St Int Rpt
GLTLGLTVGIWGVAALLTLPVTLA DUFF_HUMAN 166 15 -
GLTLGLTVGIWGVAALLTLPVTLA Q9UJP0 164 15 -
GLTLGLTVGIWGVAALLTLPVTLA O75898 164 15 -
GLTLGLTVGIWGVAALLTLPVTLA Q9UQE1 166 15 -
GLRLGVTVGLWGVAALLSLPVVLG Q9GLX0 158 15 -
GFTLGLSVGLWGAAALLGLPVALA Q9QUI6 162 15 -
GFTLGLSVGLWGAAALSGLPVALA O35970 162 15 -

Motif 5 width=21
Element Seqn Id St Int Rpt
TVACLAIFVLLPLGLFGAKGL DUFF_HUMAN 213 23 -
TVACLAIFVLLPLGLFGAKGL Q9UJP0 211 23 -
TVACLAIFVLLPLGLFGAKGL O75898 211 23 -
TVACLAIFVLLPLGLFGAKGL Q9UQE1 213 23 -
AAACFAIFVLLPLGLLGTKGL Q9GLX0 205 23 -
YAICFTIFTVLPLTLLAAKGL Q9QUI6 209 23 -
YAICFTIFTVLPLTLLAAKGL O35970 209 23 -

Motif 6 width=22
Element Seqn Id St Int Rpt
PWMNILWAWFIFWWPHGVVLGL DUFF_HUMAN 243 9 -
PWMNILWAWFIFWWPHGVVLGL Q9UJP0 241 9 -
PWMNILWAWFIFWWPHGVVLGL O75898 241 9 -
PWMNILWAWFIFWWPHGVVLGL Q9UQE1 243 9 -
PWVDVLWVWFIFWWPQGMTLGL Q9GLX0 235 9 -
PWVSVLWIWFIFWWPHGMVLIF Q9QUI6 239 9 -
PWVSVLWIWFIFWWPHGMVLIF O35970 239 9 -

Motif 7 width=27
Element Seqn Id St Int Rpt
ALDLLLNLAEALAILHCVATPLLLALF DUFF_HUMAN 283 18 -
ALDLLLNLAEALAILHCVATPLLLALF Q9UJP0 281 18 -
ALDLLLNLAEALAILHCVATPLLLALF O75898 281 18 -
ALDLLLNLAEALAILHCVATPLLLALF Q9UQE1 283 18 -
ALDMLLDVAEALAILHCVATPLLLAWV Q9GLX0 275 18 -
ILDAMLNVTEALSMLHCVATPLLLALF Q9QUI6 279 18 -
ILDAMLNVTEALSMLHCVATPLLLALF O35970 279 18 -