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PR01720

Identifier
CTLANTIGEN4  [View Relations]  [View Alignment]  
Accession
PR01720
No. of Motifs
4
Creation Date
21-MAR-2002
Title
Cytotoxic T-lymphocyte antigen 4 signature
Database References

INTERPRO; IPR003596
PDB; 1AH1; 1DQT; 1I85; 1H6E
SCOP; 1AH1; 1DQT; 1I85
CATH; 1AH1; 1DQT
Literature References
1. LINSLEY, P.S., BRADY, W., URNES, M., GROSMAIRE, L,S., DAMLE, N.K. AND 
LEDBETTER, J.A.
CTLA-4 is a second receptor for the B cell activation antigen B7.
J.EXP.MED. 174 561-569 (1991).
 
2. ZHENG, P., WU, Y., GUO, Y., LEE, C. AND LIU, Y.
B7-CTLA-4 interaction enhances both production of antitumor cytotoxic T 
lymphocytes and resistance to tumor challenge. 
PROC.NATL.ACAD.SCI.U.S.A 95 6284-6289 (1998).
 
3. OSTROV, D.A., SHI, W., SCHWARTZ, J.C.D., ALMO, S.C. AND NATHENSON, S.G.
Structure of murine CTLA-4 and its role in modulating T cell responsiveness.
SCIENCE 290 816-819 (2000).
 
4. WANG, X.B., GISCOMBE, R., YAN, Z., HEIDEN, T., XU, D. AND LEFVERT, A.K.
Expression of CTLA-4 by human monocytes.
SCAND.J.IMMUNOL. 55 53-60 (2002).
 
5. GREENWALD, R.J., OOSTERWEGEL, M.A., WOUDE, D., KUBAL, A., MANDELBROT, D.A., 
BOUSSIOTIS, V.A. AND SHARPE, A.
CTLA-4 regulates cell cycle progression during a primary immune response.
EUR.J.IMMUNOL. 32 366-373 (2002).
 
6. MERWE, P.A., AND DAVIS, S.J
Immunology. The immunological synapse-a multitasking system
SCIENCE 295 5559 1479-1480 (2002).

Documentation
T cell-dependent immune processes require cell-surface interactions that
mediate the initiation, modulation and the ultimate course of the response.
The specificity of T cell recognition is determined by the engagement of the
T cell receptor (TCR) on T cells with cognate peptide-MHC complexes 
presented by antigen presenting cells (APCs). Additional signals are
required to sustain and enhance T cell activity, the most important of which
is provided by the engagement of CD28 on T cells with its ligands B7-1
(CD80) and B7-2 (CD86). By contrast, the interaction of B7 isoforms
with cytotoxic T lymphocyte-associated molecule-4 CTLA-4, a CD28 homologue 
receptor on T cells (31% identity), provides inhibitory signals required
for down-regulation of the response, while it may also prevent T cell 
activation by weak TCR signals [1-5].
 
Unlike CD28, which is not expressed on resting T cells, CTLA-4 is not 
detected on the cell surface until 24 hours after activation. In fact, T
cell activation leads to both increased CTLA4 gene expression and
trafficking of CTLA4 protein to the cell surface. In addition, CTLA-4
exhibits an affinity for the B7 isoforms that is 10 to 100 times that for
CD28. Covalent dimerisation of CTLA4 is required for its high binding
avidity, but each monomeric subunit also contains a binding site for CD80
and CD86. On the basis of these differences in expression patterns and
affinities, it is likely that CTLA-4 directly competes with CD28 for binding
B7 and also directs the assembly of inhibitory signalling complexes that
lead to quiescence or anergy. Thus the balance between the opposing signals 
elicited by CD28 and CTLA-4 is central to the regulation of T cell
responsiveness and homeostasis. One mechanism by which CTLA-4 may perform
this function is by regulating cell-cycle progression; by contrast with 
CD28, which down-regulates the cell-cycle inhibitor p27kip1, CTLA-4 
prevents this degradation [2,3,5].
 
Sequence comparison between human CTLA-4 and CD28 proteins suggests they are
homologous, with the highest of degree of similarity being in the juxta-
membrane and cytoplasmic regions. In addition, the cytoplasmic domains
of human and murine CTLA-4 are identical, suggesting that this region has
important functional properties [1].
   
Typically, activation of T cells by TCR-engaging peptide-MHC is dramatically 
enhanced by interaction of the CD28 co-stimulatory receptor with its ligands 
CD80 (B7-1) and CD86 (B7-2) on the APC surface. Interestingly, CTLA-4 is 
transported from intracellular stores toward the region of the cell surface 
receiving activation signals. This suggests that binding of CD28 to its 
ligand may occur primarily at the centre of the mature immunological synapse, 
and that CTLA-4 may be transported to this site under certain circumstances 
to block or reverse this effect [6].
 
CTLANTIGEN4 is a 6-element fingerprint that provides a signature for the
cytotoxic T-lymphocyte antigen 4 proteins. The fingerprint was derived from 
an initial alignment of 6 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length - motif 2 spans the
first beta-strand; motif 3 encodes the third strand, which contains ligand-
binding residues; motif 4 encompasses strand 4; motif 5 spans strand 6,
which contains a glycosylation site; and motif 6 encodes strand 7. Two 
iterations on SPTR39_17f were required to reach convergence, at which point
a true set comprising 19 sequences was identified.
Summary Information
19 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
419191919
30000
20000
1234
True Positives
CTL4_HUMAN    CTL4_MOUSE    CTL4_PIG      CTL4_RABIT    
O97631 Q28090 Q62859 Q9BDC4
Q9BDN7 Q9BDP1 Q9GKP2 Q9JLV3
Q9N186 Q9QZZ7 Q9TT02 Q9XSI1
Q9XSY7 Q9XTA1 Q9Z1A7
Sequence Titles
CTL4_HUMAN  CYTOTOXIC T-LYMPHOCYTE PROTEIN 4 PRECURSOR (CYTOTOXIC T-LYMPHOCYTE- ASSOCIATED ANTIGEN 4) (CTLA-4) (CD152 ANTIGEN) - Homo sapiens (Human). 
CTL4_MOUSE CYTOTOXIC T-LYMPHOCYTE PROTEIN 4 PRECURSOR (CYTOTOXIC T-LYMPHOCYTE- ASSOCIATED ANTIGEN 4) (CTLA-4) - Mus musculus (Mouse).
CTL4_PIG CYTOTOXIC T-LYMPHOCYTE PROTEIN 4 PRECURSOR (CYTOTOXIC T-LYMPHOCYTE- ASSOCIATED ANTIGEN 4) (CTLA-4) - Sus scrofa (Pig).
CTL4_RABIT CYTOTOXIC T-LYMPHOCYTE PROTEIN 4 PRECURSOR (CYTOTOXIC T-LYMPHOCYTE- ASSOCIATED ANTIGEN 4) (CTLA-4) - Oryctolagus cuniculus (Rabbit).
O97631 CYTOTOXIC T-LYMPHOCYTE-ASSOCIATED PROTEIN 4 PRECURSOR - Ovis aries (Sheep).
Q28090 CTLA-4 PROTEIN PRECURSOR - Bos taurus (Bovine).
Q62859 CYTOTOXIC T-LYMPHOCYTE ASSOCIATED PROTEIN-4 PRECURSOR (CTLA4) - Rattus norvegicus (Rat).
Q9BDC4 CD152 PROTEIN PRECURSOR - Macaca mulatta (Rhesus macaque), Macaca nemestrina (Pig-tailed macaque), and Cercocebus torquatus atys (Red-crowned mangabey) (Sooty mangabey).
Q9BDN7 CD152 PROTEIN PRECURSOR - Papio anubis (Olive baboon).
Q9BDP1 CD152 PROTEIN PRECURSOR - Aotus trivirgatus (Night monkey) (Douroucouli).
Q9GKP2 COSTIMULATORY MOLECULE B7 RECEPTOR CD152 - Canis familiaris (Dog).
Q9JLV3 CYTOTOXIC T-LYMPHOCYTE ASSOCIATED ANTIGEN 4 - Marmota monax (Woodchuck).
Q9N186 CYTOTOXIC T LYMPHOCYTE-ASSOCIATED PROTEIN 4 PRECURSOR - Sus scrofa (Pig).
Q9QZZ7 CYTOTOXIC T-LYMPHOCYTE ASSOCIATED MOLECULE 4 - Mus musculus (Mouse).
Q9TT02 CYTOTOXIC T-LYMPHOCYTE ANTIGEN 4 - Canis familiaris (Dog).
Q9XSI1 T-CELL COSTIMULATORY MOLECULE - Canis familiaris (Dog).
Q9XSY7 CYTOTOXIC T LYMPHOCYTE-ASSOCIATED ANTIGEN 4 - Felis silvestris catus (Cat).
Q9XTA1 CYTOTOXIC T-LYMPHOCYTE-ASSOCIATED 4 (COSTIMULATORY MOLECULE B7 RECEPTOR CD152) - Felis silvestris catus (Cat).
Q9Z1A7 CTLA-4 (SCTLA4) - Rattus norvegicus (Rat).
Scan History
SPTR39_17f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
SRTWPCTALFSLLFIPVF Q9GKP2 17 17 -
SRTWPCTALFSLLFIPVF Q9XTA1 17 17 -
SRTWPCTALFSLLFIPVF Q9TT02 17 17 -
SRTWPCTALFSLLFIPVF Q9XSI1 17 17 -
SRTWPCTALFSLLFIPVF Q9XSY7 17 17 -
SRTWPCTALFSLLFIPVF Q9N186 17 17 -

Motif 2 width=27
Element Seqn Id St Int Rpt
KGMHVAQPAVVLASSRGVASFVCEYGS Q9GKP2 36 1 -
KGMHVAQPAVVLASSRGVASFVCEYGS Q9XTA1 36 1 -
KGMHVAQPAVVLASSRGVASFVCEYGS Q9TT02 36 1 -
KGMHAAQPAVVLASSRGVASFVCEYGS Q9XSI1 36 1 -
KGMHVAQPAVVLASSRGVASFVCEYGS Q9XSY7 36 1 -
KGMHVAQPAVVLANSRGVASFVCEYGS Q9N186 36 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
GSQMTEVCAATYTVE Q9GKP2 78 15 -
GSQMTEVCAATYTVE Q9XTA1 78 15 -
GSQMTEVCAATYTVE Q9TT02 78 15 -
GSQMTEVCAATYTVE Q9XSI1 78 15 -
GSQMTEVCAVTYTVE Q9XSY7 78 15 -
GSQMTEVCAATYTVE Q9N186 78 15 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NKVNLTIQGLRAM Q9GKP2 110 17 -
NKVNLTIQGLRAM Q9XTA1 110 17 -
NKVNLTIQGLRAM Q9TT02 110 17 -
NKVNLTIQGLRAM Q9XSI1 110 17 -
NKVNLTIQGLRAM Q9XSY7 110 17 -
NKVNLTIQGLRAV Q9N186 110 17 -
Final Motifs
Motif 1  width=18
Element Seqn Id St Int Rpt
SRTWPCTALFSLLFIPVF Q9GKP2 17 17 -
SRTWPCTALFSLLFIPVF Q9XTA1 17 17 -
SRTWPCTALFSLLFIPVF Q9TT02 17 17 -
SRTWPCTALFSLLFIPVF Q9XSI1 17 17 -
SRTWPCTALFSLLFIPVF Q9XSY7 17 17 -
SRTWPCTALFSLLFIPVF CTL4_PIG 17 17 -
SRTWPCTALFSLLFIPVF Q9N186 17 17 -
SRTWPCTALFFLVFIPVF Q28090 15 15 -
SRTWPCTALFFLLFIPVF O97631 15 15 -
SRTWSCAALFSLLFLPVF CTL4_RABIT 17 17 -
TRTWPCTFLFSLLFILVF Q9BDP1 17 17 -
TRTWPCTLLFFLLFIPVF CTL4_HUMAN 17 17 -
TRTRPYTLLFSLLFIPVF Q9BDC4 17 17 -
TRTRPYTLLFSLLFIPVF Q9BDN7 17 17 -
PRAWSCTALLSLLFIPIF Q9JLV3 17 17 -
SRTWPFVALLTLLFIPVF CTL4_MOUSE 17 17 -
SRTWPFVALLTLLFIPVF Q9QZZ7 17 17 -
SRTWPFGVLLSLLFIPIF Q62859 17 17 -
SRTWPFGVLLSLLFIPIF Q9Z1A7 17 17 -

Motif 2 width=27
Element Seqn Id St Int Rpt
KGMHVAQPAVVLASSRGVASFVCEYGS Q9GKP2 36 1 -
KGMHVAQPAVVLASSRGVASFVCEYGS Q9XTA1 36 1 -
KGMHVAQPAVVLASSRGVASFVCEYGS Q9TT02 36 1 -
KGMHAAQPAVVLASSRGVASFVCEYGS Q9XSI1 36 1 -
KGMHVAQPAVVLASSRGVASFVCEYGS Q9XSY7 36 1 -
KGMHVAQPAVVLANSRGVASFVCEYGS CTL4_PIG 36 1 -
KGMHVAQPAVVLANSRGVASFVCEYGS Q9N186 36 1 -
KGMNVTQPPVVLASSRGVASFSCEYES Q28090 34 1 -
KGMNVTQPPVVLASSRGVASFTCEYES O97631 34 1 -
KALHVSQPAVVLASSRGVASFVCEYAS CTL4_RABIT 36 1 -
NAMHVAQPAVVLASSRGIASFVCEYAS Q9BDP1 36 1 -
KAMHVAQPAVVLASSRGIASFVCEYAS CTL4_HUMAN 36 1 -
KAMHVAQPAVVLANSRGIASFVCEYAS Q9BDC4 36 1 -
KAMHVAQPAVVLANSRGIASFVCEYAS Q9BDN7 36 1 -
KAMHVAQPAVVLASSRGVASFVCEYAA Q9JLV3 36 1 -
EAIQVTQPSVVLASSHGVASFPCEYSP CTL4_MOUSE 36 1 -
EAIQVTQPSVVLASSHGVASFPCEYSP Q9QZZ7 36 1 -
EAIQVTQPSVVLASSHGVASFPCEYAS Q62859 36 1 -
EAIQVTQPSVVLASSHGVASFPCEYAS Q9Z1A7 36 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
GSQMTEVCAATYTVE Q9GKP2 78 15 -
GSQMTEVCAATYTVE Q9XTA1 78 15 -
GSQMTEVCAATYTVE Q9TT02 78 15 -
GSQMTEVCAATYTVE Q9XSI1 78 15 -
GSQMTEVCAVTYTVE Q9XSY7 78 15 -
GSQMTEVCAATYTVE CTL4_PIG 78 15 -
GSQMTEVCAATYTVE Q9N186 78 15 -
GSQVTEVCAGTYMVE Q28090 76 15 -
GIQVTEVCAGTYMVE O97631 76 15 -
NSQMTEVCAMTYTVE CTL4_RABIT 78 15 -
DSQVTEVCAGTYIMG Q9BDP1 78 15 -
DSQVTEVCAATYMMG CTL4_HUMAN 78 15 -
DSQVTEVCAATYMMG Q9BDC4 78 15 -
DSQVTEVCAATYMMG Q9BDN7 78 15 -
ASQVTEVCATTYTVE Q9JLV3 78 15 -
NDQMTEVCATTFTEK CTL4_MOUSE 78 15 -
NDQMTEVCATTFTEK Q9QZZ7 78 15 -
NDQVTEVCATTFTVK Q62859 78 15 -
NDQVTEVCATTFTVK Q9Z1A7 78 15 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NKVNLTIQGLRAM Q9GKP2 110 17 -
NKVNLTIQGLRAM Q9XTA1 110 17 -
NKVNLTIQGLRAM Q9TT02 110 17 -
NKVNLTIQGLRAM Q9XSI1 110 17 -
NKVNLTIQGLRAM Q9XSY7 110 17 -
NKVNLTIQGLRAV CTL4_PIG 110 17 -
NKVNLTIQGLRAV Q9N186 110 17 -
NKVNLTIQGLRAM Q28090 108 17 -
NKVNLTIQGLRAM O97631 108 17 -
NKVNLTIQGLSAM CTL4_RABIT 110 17 -
NKVNLTIQGLRAM Q9BDP1 110 17 -
NQVNLTIQGLRAM CTL4_HUMAN 110 17 -
NQVNLTIQGLRAM Q9BDC4 110 17 -
NQVNLTIQGLRAM Q9BDN7 110 17 -
NQVNLTIQGLRTA Q9JLV3 110 17 -
SRVNLTIQGLRAV CTL4_MOUSE 110 17 -
SRVNLTIQGLRAV Q9QZZ7 110 17 -
SRVNLTIQGLRAA Q62859 110 17 -
SRVNLTIQGLRAA Q9Z1A7 110 17 -