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PR01568

Identifier
LYMPHOTACTNR  [View Relations]  [View Alignment]  
Accession
PR01568
No. of Motifs
8
Creation Date
23-AUG-2001
Title
Lymphotactin 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. KELNER, G.S., KENNEDY, J., BACON, K.B., KLEYENSTEUBER, S., LARGAESPADA,
D.A., JENKINS, N.A., COPELAND, N.G., BAZAN, J.F., MOORE, K.W., SCHALL, T.J.
AND ZLOTNIK, A.
Lymphotactin: a cytokine that represents a new class of chemokine.
SCIENCE 266 1395-1399 (1994).
 
8. YOSHIDA, T., IMAI, T., KAKIZAKI, M., NISHIMURA, M., TAKAGI, S. AND
YOSHIE, O.
Identification of single C motif-1/lymphotactin receptor XCR1.
J.BIOL.CHEM. 273(26) 16551-16554 (1998).
 
9. YOSHIDA, T., IZAWA, D., NAKAYAMA, T., NAKAHARA, K., KAKIZAKI, M., IMAI,
T., SUZUKI, R., MIYASAKA, M. AND YOSHIE, O.
Molecular cloning of nXCR1, the murine SCM-1/lymphotactin receptor.
FEBS LETT. 458(1) 37-40 (1999).

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 [8]. Lymphotactin is the only known member of the C
chemokine family. It has closest similarity to the C-C chemokines but
contains only the second and fourth of the conserved cysteine residues. The
chemokine is produced by certain subsets of T cells and natural killer cells
and is also chemotactic for these cell types [7,8].
 
An orphan receptor (GPR5) has been identified as a receptor for lymphotactin
and has been renamed XCR1 [8]. XCR1 is strongly expressed in placenta and at
lower levels in the spleen and thymus. It is detected only at very low
levels in peripheral blood leukocytes [8]. Within these tissues, expression
of XCR1 appears to be restricted to CD8+ T cells and natural killer cells
[9]. Binding of lymphotactin to XCR1 stimulates calcium mobilisation and
migration in a pertussis toxin-sensitive manner, indicating coupling of the
receptor to Gi type proteins [8]. The matching expression patterns of both
lymphotactin and its receptor suggest a role for the chemokine in self- 
recruitment of leukocytes [9].
 
LYMPHOTACTNR is an 8-element fingerprint that provides a signature for the
lymphotactin receptors. The fingerprint was derived from an initial 
alignment of 2 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections
that characterise the lymphotactin receptors but distinguish them from the
rest of the chemokine receptor family - motif 1 lies at the N-terminus, 
leading into TM domain 1; motif 2 encodes the first cytoplasmic loop, 
leading into TM domain 2; motif 3 spans the N-terminal portion of TM domain
3; motif 4 spans the second cytoplasmic loop; motif 5 lies at the C-terminus
of TM domain 4, leading into the second external loop; motif 6 resides in 
the second external loop, leading into TM domain 5; motif 7 encodes the 
third cytoplasmic loop; and motif 8 is located 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
2 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
822222222
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
CXC1_HUMAN    CXC1_MOUSE    
Sequence Titles
CXC1_HUMAN                                                
CXC1_MOUSE CHEMOKINE XC RECEPTOR 1 (XC CHEMOKINE RECEPTOR 1) (LYMPHOTACTIN RECEPTOR) (SCM1 RECEPTOR) (MXCR1) - Mus musculus (Mouse).
Scan History
SPTR39.22_17.3f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
CENQAWVFATLATTV CXC1_HUMAN 22 22 -
CENNVIFFSTISTIV CXC1_MOUSE 18 18 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VKYESLESLTNIFI CXC1_HUMAN 57 20 -
VKYENLESLTNIFI CXC1_MOUSE 53 20 -

Motif 3 width=11
Element Seqn Id St Int Rpt
NMIFSISLYSS CXC1_HUMAN 106 35 -
NMIFGISLYSS CXC1_MOUSE 101 34 -

Motif 4 width=17
Element Seqn Id St Int Rpt
SVVSPLSTLRVPTLRCR CXC1_HUMAN 130 13 -
SVVSPISTLGIHTLRCR CXC1_MOUSE 125 13 -

Motif 5 width=16
Element Seqn Id St Int Rpt
SILSSILDTIFHKVLS CXC1_HUMAN 157 10 -
SILFSIPDAVFHKVIS CXC1_MOUSE 152 10 -

Motif 6 width=17
Element Seqn Id St Int Rpt
SELTWYLTSVYQHNLFF CXC1_HUMAN 178 5 -
SEHHGFLASVYQHNIFF CXC1_MOUSE 173 5 -

Motif 7 width=11
Element Seqn Id St Int Rpt
FRSRSKRRHRT CXC1_HUMAN 213 18 -
FRTRSRQRHRT CXC1_MOUSE 208 18 -

Motif 8 width=13
Element Seqn Id St Int Rpt
SPGAFAYEGASFY CXC1_HUMAN 321 97 -
SPGTFTYEGPSFY CXC1_MOUSE 310 91 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
CENQAWVFATLATTV CXC1_HUMAN 22 22 -
CENNVIFFSTISTIV CXC1_MOUSE 18 18 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VKYESLESLTNIFI CXC1_HUMAN 57 20 -
VKYENLESLTNIFI CXC1_MOUSE 53 20 -

Motif 3 width=11
Element Seqn Id St Int Rpt
NMIFSISLYSS CXC1_HUMAN 106 35 -
NMIFGISLYSS CXC1_MOUSE 101 34 -

Motif 4 width=17
Element Seqn Id St Int Rpt
SVVSPLSTLRVPTLRCR CXC1_HUMAN 130 13 -
SVVSPISTLGIHTLRCR CXC1_MOUSE 125 13 -

Motif 5 width=16
Element Seqn Id St Int Rpt
SILSSILDTIFHKVLS CXC1_HUMAN 157 10 -
SILFSIPDAVFHKVIS CXC1_MOUSE 152 10 -

Motif 6 width=17
Element Seqn Id St Int Rpt
SELTWYLTSVYQHNLFF CXC1_HUMAN 178 5 -
SEHHGFLASVYQHNIFF CXC1_MOUSE 173 5 -

Motif 7 width=11
Element Seqn Id St Int Rpt
FRSRSKRRHRT CXC1_HUMAN 213 18 -
FRTRSRQRHRT CXC1_MOUSE 208 18 -

Motif 8 width=13
Element Seqn Id St Int Rpt
SPGAFAYEGASFY CXC1_HUMAN 321 97 -
SPGTFTYEGPSFY CXC1_MOUSE 310 91 -