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PR01105

Identifier
CXCCHMKINER6  [View Relations]  [View Alignment]  
Accession
PR01105
No. of Motifs
9
Creation Date
20-MAR-1999  (UPDATE 04-JUN-2001)
Title
C-X-C chemokine receptor type 6 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
INTERPRO; IPR002235
GCRDB; GCR_2411; GCR_1328; GCR_1330; GCR_2393; GCR_2409
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. LIAO, F., ALKHATIB, G., PEDEN, K.W., SHARMA, G., BERGER, E.A.
AND FARBER, J.M.
STRL33, A novel chemokine receptor-like protein, functions as a fusion
cofactor for both macrophage-tropic and T cell line-tropic HIV-1.
J.EXP.MED. 185 2015-2023 (1997). 
 
8. MATLOUBIAN, M., DAVID, A., ENGEL, S., RYAN, J.E. AND CYSTER, J.G.
A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo.
NAT.IMMUNOL. 1(4) 298-304 (2000).
 
9. WILBANKS, A., ZONDLO, S.C., MURPHY, K., MAK, S., SOLER, D., LANGDON, P.,
ANDREW, D.P., WU, L. AND BRISKIN, M.
Expression cloning of the STRL33/BONZO/TYMSTR ligand reveals elements of CC,
CXC, and CX3C chemokines.
J.IMMUNOL. 166(8) 5145-5154 (2001).

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).
 
A novel chemokine, CXCL16, has been identified that is a member of the C-X-C
family [8,9]. Despite possessing the CXC motif, however, it is distantly
related to the other family members and has greatest sequence similarity to
members of the C-C family [9]. CXCL16 also differs in structure from the
other family members (all of which are secreted proteins) and contains a
TM domain linked to the chemokine domain by a heavily glycosylated mucin
stalk. This structure is similar to that of the CX3C chemokine fractalkine,
the only other known chemokine with a TM domain [9]. CXCL16 has been found 
to be expressed in the spleen, lymph nodes, Peyer's patches and thymus. In
non-lymphoid tissues, CXCL16 is found in the lung, small intestine, kidney,
heart and liver [8]. The chemokine appears to be expressed as a membrane-
bound cell surface ligand on antigen presenting cells (APCs), such as 
B cells and macrophages [9]. CXCL16 can also be shed from the cell surface
in an active, soluble form [8,9]. These two forms may have different
functions. Expression of CXCL16 is upregulated by exposure to inflammatory
stimuli [8].
 
The receptor for CXCL16 has been identified as an orphan receptor, Bonzo,
which has now been renamed CXCR6 [8]. CXCL16 does not activate any other
known chemokine receptor, making this pairing highly specific [9]. CXCR6 is
expressed in lymphoid tissues and activated T cells and is induced in
peripheral blood leukocytes [7]. It has also been found on natural killer
cells [8]. Binding of CXCL16 to CXCR6 causes chemotactic migration in
activated T cells. This chemotactic response is sensitive to pertussis toxin
and CXCL16 also results in calcium mobilisation, suggesting coupling to a
Gi/o protein [8]. A number of roles have been suggested for CXCR6. Subset-
specific immune responses may be regulated by cell-cell contacts between 
activated subsets of T cells (expressing CXCR6) and APCs (expressing
CXCL16). CXCR6 may also be involved in cell-cell contacts during chronic
inflammation [9]. Additional roles for the receptor include T cell migration
in the splenic red pulp, thymocyte development and effector T cell
trafficking [8]. CXCR6 also acts as a coreceptor for T cell line-tropic and
macrophage-tropic HIV-1 strains, and may play a role in the establishment
and progression of HIV infection [7].
 
CXCCHMKINER6 is a 9-element fingerprint that provides a signature for the
type 6 C-X-C chemokine receptor. The fingerprint was derived from an initial 
alignment of 3 sequences: the motifs were drawn from short conserved regions 
spanning the full alignment length, focusing on those sections that 
characterise the type 6 C-X-C chemokine receptors but distinguish them from 
the rest of the chemokine receptor family - motifs 1 and 2 reside at the 
N-terminus; motif 3 spans the second cytoplasmic loop; motif 4 lies in the 
second external loop; motif 5 spans the third cytoplasmic loop, leading into 
TM domain 6; motifs 6 and 7 span the third external loop, leading into TM 
domain 7; and motifs 8 and 9 reside at the C-terminus. Two iterations on 
SPTR39_15f were required to reach convergence, at which point a true set 
comprising 6 sequences was identified.
Summary Information
6 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
9666666666
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
BONZ_CERAE    BONZ_HUMAN    BONZ_MACMU    BONZ_MACNE    
Q9N0Z0 Q9TV16
Sequence Titles
BONZ_CERAE  G PROTEIN-COUPLED RECEPTOR BONZO - Cercopithecus aethiops (Green monkey) (Grivet). 
BONZ_HUMAN G PROTEIN-COUPLED RECEPTOR BONZO (G PROTEIN-COUPLED RECEPTOR STRL33) - Homo sapiens (Human).
BONZ_MACMU G PROTEIN-COUPLED RECEPTOR BONZO (G PROTEIN-COUPLED RECEPTOR STRL33) - Macaca mulatta (Rhesus macaque).
BONZ_MACNE G PROTEIN-COUPLED RECEPTOR BONZO - Macaca nemestrina (Pig-tailed macaque).
Q9N0Z0 STRL33 - Cercocebus torquatus atys (Red-crowned mangabey) (Sooty mangabey).
Q9TV16 G PROTEIN-COUPLED RECEPTOR STRL33 - Pan troglodytes (Chimpanzee).
Scan History
SPTR39_15f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
AEHDYHEDYGLNSFNDSSQ BONZ_MACNE 2 2 -
AEHDYHEDYGFSSFNDSSQ BONZ_HUMAN 2 2 -
AEYDHYEDNGFNSFNDSSQ BONZ_CERAE 2 2 -

Motif 2 width=13
Element Seqn Id St Int Rpt
QEEHQDFLQFRKV BONZ_MACNE 20 -1 -
QEEHQDFLQFSKV BONZ_HUMAN 20 -1 -
QEEHQDFLQFSKV BONZ_CERAE 20 -1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
IVVVKATKAYNQQAKRMTWG BONZ_MACNE 129 96 -
IVVVKATKAYNQQAKRMTWG BONZ_HUMAN 129 96 -
IVVVKATKAYNQQAKKMTWG BONZ_CERAE 129 96 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GNVFNLDKLICGYHD BONZ_MACNE 170 21 -
GNVFNLDKLICGYHD BONZ_HUMAN 170 21 -
GNVFNLDKLICGYHD BONZ_CERAE 170 21 -

Motif 5 width=16
Element Seqn Id St Int Rpt
LHAGGFQKHRSLKIIF BONZ_MACNE 219 34 -
LHAGGFQKHRSLKIIF BONZ_HUMAN 219 34 -
LHAGGFQKHRSLKIIF BONZ_CERAE 219 34 -

Motif 6 width=14
Element Seqn Id St Int Rpt
NLVKLIRSTHWEYY BONZ_MACNE 248 13 -
NLMKFIRSTHWEYY BONZ_HUMAN 248 13 -
NLVKLIRSTHWEYY BONZ_CERAE 248 13 -

Motif 7 width=16
Element Seqn Id St Int Rpt
YAMTSFHYTIIVTEAI BONZ_MACNE 261 -1 -
YAMTSFHYTIMVTEAI BONZ_HUMAN 261 -1 -
YAMTSFHYTIIVTEAI BONZ_CERAE 261 -1 -

Motif 8 width=16
Element Seqn Id St Int Rpt
CLPYLGVSHQWKSSED BONZ_MACNE 308 31 -
CLPYLGVSHQWKSSED BONZ_HUMAN 308 31 -
CLPYLGVSHQWKSSED BONZ_CERAE 308 31 -

Motif 9 width=17
Element Seqn Id St Int Rpt
DNSKTFSASHNVEATSM BONZ_MACNE 323 -1 -
DNSKTFSASHNVEATSM BONZ_HUMAN 323 -1 -
DNSKTFSASHNVEATSM BONZ_CERAE 323 -1 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
EYDHYEDDGFLNSFNDSSQ BONZ_MACMU 3 3 -
AEHDYHEDYGLNSFNDSSQ BONZ_MACNE 2 2 -
AEHDYHEDYGFSSFNDSSQ BONZ_HUMAN 2 2 -
AEHDYHEDYGFNSFNDSSQ Q9TV16 2 2 -
AEYDHYEDNGFNSFNDSSQ BONZ_CERAE 2 2 -
EYDHYEDDEFFNSFNDSSQ Q9N0Z0 3 3 -

Motif 2 width=13
Element Seqn Id St Int Rpt
QEEHQDFLQFRKV BONZ_MACNE 20 -1 -
QEEHQDFLQFSKV BONZ_HUMAN 20 -1 -
QEEHQDFLQFSKV BONZ_CERAE 20 -1 -
QKEHQDFLQFSKV Q9N0Z0 21 -1 -
QEEHQDFLQFRKV BONZ_MACMU 21 -1 -
QEEHQDFLQFSKV Q9TV16 20 -1 -

Motif 3 width=20
Element Seqn Id St Int Rpt
IVVVKATKAYNQQAKRMTWG BONZ_HUMAN 129 96 -
IVVVKATKAYNQQAKKMTWG BONZ_CERAE 129 96 -
IVVVKATKAYNQQAKRMTWG Q9N0Z0 130 96 -
IVVVKATKAYNQQAKRMTWG BONZ_MACMU 130 96 -
IVVVKATKAYNQQAKRMTWG Q9TV16 129 96 -
IVVVKATKAYNQQAKRMTWG BONZ_MACNE 129 96 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GNVFNLDKLICGYHD BONZ_CERAE 170 21 -
GNVFNLDKLICRYHD Q9N0Z0 171 21 -
GNVFNLDKLICGYHD BONZ_MACMU 171 21 -
GNVFNLDKLICGYHD Q9TV16 170 21 -
GNVFNLDKLICGYHD BONZ_MACNE 170 21 -
GNVFNLDKLICGYHD BONZ_HUMAN 170 21 -

Motif 5 width=16
Element Seqn Id St Int Rpt
LHAGGFQKHRSLKIIF Q9N0Z0 220 34 -
LHAGGFQKHRSLKIIF BONZ_MACMU 220 34 -
LHAGGFQKHRSLKIIF Q9TV16 219 34 -
LHAGGFQKHRSLKIIF BONZ_MACNE 219 34 -
LHAGGFQKHRSLKIIF BONZ_HUMAN 219 34 -
LHAGGFQKHRSLKIIF BONZ_CERAE 219 34 -

Motif 6 width=14
Element Seqn Id St Int Rpt
NLMKFIRSTHWEYY BONZ_HUMAN 248 13 -
NLMKLIRSTHWEYY Q9TV16 248 13 -
NLVKLIRSTHWEYY BONZ_MACNE 248 13 -
NLVKLIRSTHWEYY BONZ_CERAE 248 13 -
NLVKLIRSTHWEYY Q9N0Z0 249 13 -
NLVKLIRSTHWEYY BONZ_MACMU 249 13 -

Motif 7 width=16
Element Seqn Id St Int Rpt
YAMTSFHYTIIVTEAI BONZ_CERAE 261 -1 -
YAMTSFHYTIIVTEAI Q9N0Z0 262 -1 -
YAMTSFHYTIMVTEAI Q9TV16 261 -1 -
YAMTSFHYTIIVTEAI BONZ_MACMU 262 -1 -
YAMTSFHYTIIVTEAI BONZ_MACNE 261 -1 -
YAMTSFHYTIMVTEAI BONZ_HUMAN 261 -1 -

Motif 8 width=16
Element Seqn Id St Int Rpt
CLPYLGVSHQWKSSED BONZ_MACNE 308 31 -
CLPYLGVSHQWKSSED BONZ_HUMAN 308 31 -
CLPYLGVSHQWKSSED BONZ_CERAE 308 31 -
CLPYLGVSHQWKSSED Q9N0Z0 309 31 -
CLPYLGVSHQWKSSED BONZ_MACMU 309 31 -
CLPYLGVSHQWKSSED Q9TV16 308 31 -

Motif 9 width=17
Element Seqn Id St Int Rpt
DNSKTFSASHNVEATSM Q9N0Z0 324 -1 -
DNSKTFSASHNVEATSM BONZ_CERAE 323 -1 -
DNSKTFSASHNVEATSM BONZ_HUMAN 323 -1 -
DNSKTFSASHNVEATSM BONZ_MACNE 323 -1 -
DNSKTFSASHNVEATSM Q9TV16 323 -1 -
DNSKTFSASHNVEATSM BONZ_MACMU 324 -1 -