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PR00564

Identifier
CXCCHMKINER5  [View Relations]  [View Alignment]  
Accession
PR00564
No. of Motifs
8
Creation Date
13-SEP-1996  (UPDATE 04-JUN-2001)
Title
C-X-C chemokine receptor type 5 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
INTERPRO; IPR001053
GCRDB; GCR_0832; GCR_0648; GCR_0453
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. DOBNER, T., WOLF, I., EMRICH, T. AND LIPP, M.
Differentiation-specific expression of a novel G protein-coupled receptor
from Burkitt's lymphoma.
EUR.J.IMMUNOL. 22 2795-9 (1992).
 
8. LEGLER, D.F., LOETSCHER, M., ROOS, R.S., CLARK-LEWIS, I., BAGGIOLINI, M.
AND MOSER, B.
B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid
tissues, selectively attracts B lymphocytes via BLR1/CXCR5.
J.EXP.MED. 187(4) 655-660 (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).
 
A novel C-X-C chemokine, named B cell-attracting chemokine 1 (BCA-1), was
identified through screening of expressed sequence tag data [8]. The
chemokine was found to be expressed at highest levels in the liver, spleen,
lymph nodes, appendix and stomach. Lower levels of BCA-1 were also found in
the salivary and mammary glands. Expression appears to be constitutive in
lymphoid tissues [8].
 
The receptor for BCA-1 was found to be a previously identified orphan
receptor, expressed on B lymphocytes and Burkitt's lymphoma cells. This
receptor, originally named BLR1 (Burkitt's lymphoma receptor 1), has now
been renamed CXCR5 (C-X-C chemokine receptor type 5)[8]. B lymphocytes 
expressing CXCR5 migrate in a concentration dependent manner in response to
BCA-1. BCA-1 does not induce chemotaxis in T lymphocytes, monocytes or 
neutrophils. This selectivity for B lymphocytes is unique among the
chemokines [8]. BCA-l/CXCR5 may be important for the development of B 
cell areas of secondary lymphoid tissue; deletion of the CXCR5 gene in 
mice results in animals lacking inguinal lymph nodes and having defective 
formation of primary follicles and germinal centres of the spleen and Peyer's 
patches. Receptor-deficient B cells enter T cell areas but do not migrate 
into B cell areas [8]. The expression of CXCR5 in Burkitt's lymphoma cells 
also suggests a role for the receptor in lymphomagenesis [7].
 
CXCCHMKINER5 is an 8-element fingerprint that provides a signature for
type 5 C-X-C chemokine receptor. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the type 5 C-X-C chemokine receptors but
distinguish them from the rest of the chemokine receptor family - motifs 1
and 2 lie at the N-terminus; motif 3 spans the first cytoplasmic loop; motif
4 spans the second cytoplasmic loop; motif 5 lies in the second external
loop; motif 6 spans the third cytoplasmic loop; and motifs 7 and 8 lie at
the C-terminus. A single iteration on SPTR39_15f was required to reach
convergence, no further sequences being identified beyond the starting set.
A single partial match was found, O93281, a closely related receptor from
chicken that matches motifs 3, 4 and 6.
Summary Information
   3 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
833333333
700000000
600000000
500000000
400000000
300110100
200000000
12345678
True Positives
BLR1_HUMAN    BLR1_MOUSE    BLR1_RAT      
True Positive Partials
Codes involving 3 elements
O93281
Sequence Titles
BLR1_HUMAN  BURKITT'S LYMPHOMA RECEPTOR 1 (MONOCYTE-DERIVED RECEPTOR 15) (MDR15) - HOMO SAPIENS (HUMAN). 
BLR1_MOUSE BURKITT'S LYMPHOMA RECEPTOR 1 HOMOLOG - MUS MUSCULUS (MOUSE).
BLR1_RAT BURKITT'S LYMPHOMA RECEPTOR 1 HOMOLOG (NEUROLYMPHATIC RECEPTOR) (NLR) - RATTUS NORVEGICUS (RAT).

O93281 PUTATIVE CHEMOKINE RECEPTOR - Gallus gallus (Chicken).
Scan History
SPTR39_15f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
NMDDLYKELAFYSNSTE BLR1_MOUSE 15 15 -
NMDDLYKELAIYSNSTE BLR1_RAT 15 15 -
NLEDLFWELDRLDNYND BLR1_HUMAN 13 13 -

Motif 2 width=17
Element Seqn Id St Int Rpt
DSNFCSTVEGPLLTSFK BLR1_MOUSE 36 4 -
DSIFCSTEEGPLLTSFK BLR1_RAT 36 4 -
ENHLCPATEGPLMASFK BLR1_HUMAN 34 4 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ERHRHTRSSTETFLFH BLR1_MOUSE 79 26 -
ERHRHTRSSTETFLFH BLR1_RAT 79 26 -
ERHRQTRSSTETFLFH BLR1_HUMAN 77 26 -

Motif 4 width=15
Element Seqn Id St Int Rpt
HAYRRRRLLSIHITC BLR1_MOUSE 158 63 -
HAYRRRRLLSIHITC BLR1_RAT 158 63 -
HAYRHRRLLSIHITC BLR1_HUMAN 156 63 -

Motif 5 width=18
Element Seqn Id St Int Rpt
SLPQCTFSQENEAETRAW BLR1_MOUSE 200 27 -
SLPQCIFSQENEAETRAW BLR1_RAT 200 27 -
SLPRCTFSQENQAETHAW BLR1_HUMAN 198 27 -

Motif 6 width=17
Element Seqn Id St Int Rpt
HRLLQAQRRPQRQKAVR BLR1_MOUSE 245 27 -
HRLLQAQRRPQRQKAVR BLR1_RAT 245 27 -
HRLRQAQRRPQRQKAVR BLR1_HUMAN 243 27 -

Motif 7 width=18
Element Seqn Id St Int Rpt
RLLTKLGCAGPASLCQLF BLR1_MOUSE 337 75 -
RLLTKLGCAGPASLCQLF BLR1_RAT 337 75 -
RLLTKLGCTGPASLCQLF BLR1_HUMAN 335 75 -

Motif 8 width=19
Element Seqn Id St Int Rpt
FPNWRKSSLSESENATSLT BLR1_MOUSE 354 -1 -
FPGWRKSSLSESENATSLT BLR1_RAT 354 -1 -
FPSWRRSSLSESENATSLT BLR1_HUMAN 352 -1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
NMDDLYKELAFYSNSTE BLR1_MOUSE 15 15 -
NMDDLYKELAIYSNSTE BLR1_RAT 15 15 -
NLEDLFWELDRLDNYND BLR1_HUMAN 13 13 -

Motif 2 width=17
Element Seqn Id St Int Rpt
DSNFCSTVEGPLLTSFK BLR1_MOUSE 36 4 -
DSIFCSTEEGPLLTSFK BLR1_RAT 36 4 -
ENHLCPATEGPLMASFK BLR1_HUMAN 34 4 -

Motif 3 width=16
Element Seqn Id St Int Rpt
ERHRHTRSSTETFLFH BLR1_MOUSE 79 26 -
ERHRHTRSSTETFLFH BLR1_RAT 79 26 -
ERHRQTRSSTETFLFH BLR1_HUMAN 77 26 -

Motif 4 width=15
Element Seqn Id St Int Rpt
HAYRRRRLLSIHITC BLR1_MOUSE 158 63 -
HAYRRRRLLSIHITC BLR1_RAT 158 63 -
HAYRHRRLLSIHITC BLR1_HUMAN 156 63 -

Motif 5 width=18
Element Seqn Id St Int Rpt
SLPQCTFSQENEAETRAW BLR1_MOUSE 200 27 -
SLPQCIFSQENEAETRAW BLR1_RAT 200 27 -
SLPRCTFSQENQAETHAW BLR1_HUMAN 198 27 -

Motif 6 width=17
Element Seqn Id St Int Rpt
HRLLQAQRRPQRQKAVR BLR1_MOUSE 245 27 -
HRLLQAQRRPQRQKAVR BLR1_RAT 245 27 -
HRLRQAQRRPQRQKAVR BLR1_HUMAN 243 27 -

Motif 7 width=18
Element Seqn Id St Int Rpt
RLLTKLGCAGPASLCQLF BLR1_MOUSE 337 75 -
RLLTKLGCAGPASLCQLF BLR1_RAT 337 75 -
RLLTKLGCTGPASLCQLF BLR1_HUMAN 335 75 -

Motif 8 width=19
Element Seqn Id St Int Rpt
FPNWRKSSLSESENATSLT BLR1_MOUSE 354 -1 -
FPGWRKSSLSESENATSLT BLR1_RAT 354 -1 -
FPSWRRSSLSESENATSLT BLR1_HUMAN 352 -1 -