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PR01562

Identifier
FRACTALKINER  [View Relations]  [View Alignment]  
Accession
PR01562
No. of Motifs
9
Creation Date
23-AUG-2001
Title
Fractalkine 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. IMAI, T., HIESHIMA, K., HASKELL, C., BABA, M., NAGIRA, M., NISHIMURA, M.,
KAKIZAKI, M., TAKAGI, S., NOMIYAMA, H., SCHALL, T.J. AND YOSHIE, O.
Identification and molecular characterization of fractalkine receptor
CX3CR1, which mediates both leukocyte migration and adhesion.
CELL 91(4) 521-530 (1997).
 
8. COMBADIERE, C., SALZWEDEL, K., SMITH, E.D., TIFFANY, H.L., BERGER, E.A.
AND MURPHY, P.M.
Identification of CX3CR1. A chemotactic receptor for the human CX3C
chemokine fractalkine and a fusion coreceptor for HIV-1.
J.BIOL.CHEM. 273(37) 23799-23804 (1998).

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). 
 
Two additional chemokine families have also been identified, each containing
only one member. C chemokines have only one of the first two Cys residues,
while C-x3-C chemokines contain both cysteines, separated by three
intervening residues [7]. The only C-x3-C chemokine identified to date is
fractalkine, a TM molecule containing a chemokine domain on an extended
mucin-like stalk [7,8]. The membrane-bound form of fractalkine can be 
induced on endothelial cells in response to inflammation, and promotes
adhesion of monocytes and T lymphocytes. The chemokine can also be released
in a soluble form, which causes chemotaxis of monocytes and T cells [7,8].
 
Both the adhesive and chemotactic effects of fractalkine are mediated 
through a G protein-coupled receptor - CX3CR1. CX3CR1 is expressed 
specifically on T cells, natural killer cells and monocytes and has closest 
similarity to the C-C chemokine receptors. Coupling of the receptor to 
pertussis toxin-sensitive Gi proteins leads to calcium mobilisation and 
chemotaxis. In contrast, adhesion mediated by the receptor is insensitive to
pertussis toxin and does not appear to involve calcium mobilisation [7]. 
CX3CR1 has also been found to act as a weak fusion cofactor for some HIV-1 
strains, an interaction that can be potently and specifically blocked by 
fractalkine [8].
 
FRACTALKINER is a 9-element fingerprint that provides a signature for the
fractalkine 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 sections that
characterise the fractalkine receptors but distinguish them from the rest of
the chemokine receptor family - motif 1 resides at the N-terminus; motif 2
spans part of the N-terminus, leading into TM domain 1; motif 3 spans the
second cytoplasmic loop; motif 4 encodes the C-terminal portion of TM domain
4, leading into the second external loop; motif 5 lies in the second
external loop, leading into TM domain 5; motif 6 spans the third external
loop; and motifs 7-9 reside at the C-terminus. A single iteration on
SPTR39.22_17.3f was required to reach convergence, no further sequences 
being identified beyond the starting set.
Summary Information
3 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
9333333333
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
C3X1_MOUSE    GPRD_HUMAN    GPRD_RAT      
Sequence Titles
C3X1_MOUSE  CX3C CHEMOKINE RECEPTOR 1 (C-X3-C CKR-1) (CX3CR1) (FRACTALKINE RECEPTOR) - Mus musculus (Mouse). 
GPRD_HUMAN PROBABLE G PROTEIN-COUPLED RECEPTOR GPR13 (V28) (BETA CHEMOKINE RECEPTOR-LIKE 1) (CMK-BRL-1) (CMKBLR1) - HOMO SAPIENS (HUMAN).
GPRD_RAT PROBABLE G PROTEIN-COUPLED RECEPTOR GPR13 (RBS11) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR39.22_17.3f 1  130  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
FPELDLENFEYDDSAEA GPRD_RAT 5 5 -
FPELDLENFEYDDSAEA C3X1_MOUSE 5 5 -
FPESVTENFEYDDLAEA GPRD_HUMAN 4 4 -

Motif 2 width=17
Element Seqn Id St Int Rpt
CYLGDIVAFGTIFLSIF GPRD_RAT 22 0 -
CYLGDIVAFGTIFLSVF C3X1_MOUSE 22 0 -
CYIGDIVVFGTVFLSIF GPRD_HUMAN 21 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
NSMNNRTVQHG GPRD_RAT 137 98 -
NSMNNRTVQHG C3X1_MOUSE 137 98 -
NSMNNRTVQHG GPRD_HUMAN 136 98 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PQFMFTKRKDNE GPRD_RAT 164 16 -
PQFMFTKRKDNE C3X1_MOUSE 164 16 -
PQFMFTKQKENE GPRD_HUMAN 163 16 -

Motif 5 width=19
Element Seqn Id St Int Rpt
LGDYPEVLQEIWPVLRNSE GPRD_RAT 177 1 -
LGDYPEVLQEMWPVLRNSE C3X1_MOUSE 177 1 -
LGDYPEVLQEIWPVLRNVE GPRD_HUMAN 176 1 -

Motif 6 width=14
Element Seqn Id St Int Rpt
FLETLKFYNFFPSC GPRD_RAT 253 57 -
FLETLKFYNFFPSC C3X1_MOUSE 253 57 -
FLETLKLYDFFPSC GPRD_HUMAN 252 57 -

Motif 7 width=16
Element Seqn Id St Int Rpt
KCLAVLCGRPVHAGFS GPRD_RAT 311 44 -
KCLAVLCGHPVHTGFS C3X1_MOUSE 311 44 -
KCLAVLCGRSVHVDFS GPRD_HUMAN 310 44 -

Motif 8 width=13
Element Seqn Id St Int Rpt
ESQRSRQDSILSS GPRD_RAT 328 1 -
ESQRSRQDSILSS C3X1_MOUSE 328 1 -
ESQRSRHGSVLSS GPRD_HUMAN 328 2 -

Motif 9 width=10
Element Seqn Id St Int Rpt
TSEGEGSLLL GPRD_RAT 345 4 -
TSEGDGSLLL C3X1_MOUSE 345 4 -
TSDGDALLLL GPRD_HUMAN 346 5 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
FPELDLENFEYDDSAEA GPRD_RAT 5 5 -
FPELDLENFEYDDSAEA C3X1_MOUSE 5 5 -
FPESVTENFEYDDLAEA GPRD_HUMAN 4 4 -

Motif 2 width=17
Element Seqn Id St Int Rpt
CYLGDIVAFGTIFLSIF GPRD_RAT 22 0 -
CYLGDIVAFGTIFLSVF C3X1_MOUSE 22 0 -
CYIGDIVVFGTVFLSIF GPRD_HUMAN 21 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
NSMNNRTVQHG GPRD_RAT 137 98 -
NSMNNRTVQHG C3X1_MOUSE 137 98 -
NSMNNRTVQHG GPRD_HUMAN 136 98 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PQFMFTKRKDNE GPRD_RAT 164 16 -
PQFMFTKRKDNE C3X1_MOUSE 164 16 -
PQFMFTKQKENE GPRD_HUMAN 163 16 -

Motif 5 width=19
Element Seqn Id St Int Rpt
LGDYPEVLQEIWPVLRNSE GPRD_RAT 177 1 -
LGDYPEVLQEMWPVLRNSE C3X1_MOUSE 177 1 -
LGDYPEVLQEIWPVLRNVE GPRD_HUMAN 176 1 -

Motif 6 width=14
Element Seqn Id St Int Rpt
FLETLKFYNFFPSC GPRD_RAT 253 57 -
FLETLKFYNFFPSC C3X1_MOUSE 253 57 -
FLETLKLYDFFPSC GPRD_HUMAN 252 57 -

Motif 7 width=16
Element Seqn Id St Int Rpt
KCLAVLCGRPVHAGFS GPRD_RAT 311 44 -
KCLAVLCGHPVHTGFS C3X1_MOUSE 311 44 -
KCLAVLCGRSVHVDFS GPRD_HUMAN 310 44 -

Motif 8 width=13
Element Seqn Id St Int Rpt
ESQRSRQDSILSS GPRD_RAT 328 1 -
ESQRSRQDSILSS C3X1_MOUSE 328 1 -
ESQRSRHGSVLSS GPRD_HUMAN 328 2 -

Motif 9 width=10
Element Seqn Id St Int Rpt
TSEGEGSLLL GPRD_RAT 345 4 -
TSEGDGSLLL C3X1_MOUSE 345 4 -
TSDGDALLLL GPRD_HUMAN 346 5 -