T-cell-specific surface glycoprotein CD28

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• protease binding Source: MGI
• protein homodimerization activity Source: MGI
• protein kinase binding Source: MGI <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling."
    Semple K., Nguyen A., Yu Y., Wang H., Anasetti C., Yu X.Z.
    Blood 117:3096-3103(2011) [PubMed] [Europe PMC] [Abstract]
• SH3/SH2 adaptor activity Source: MGI

GO - Biological processⁱ

• apoptotic signaling pathway Source: MGI <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Several different cell surface molecules control negative selection of medullary thymocytes."
    Kishimoto H., Sprent J.
    J. Exp. Med. 190:65-73(1999) [PubMed] [Europe PMC] [Abstract]
• immune response Source: InterPro
• immune system process Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of gene expression Source: MGI
• negative thymic T cell selection Source: MGI <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Several different cell surface molecules control negative selection of medullary thymocytes."
    Kishimoto H., Sprent J.
    J. Exp. Med. 190:65-73(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of alpha-beta T cell proliferation Source: MGIInferred from direct assayⁱ
  • "Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins."
    Heissmeyer V., Macian F., Im S.H., Varma R., Feske S., Venuprasad K., Gu H., Liu Y.C., Dustin M.L., Rao A.
    Nat. Immunol. 5:255-265(2004) [PubMed] [Europe PMC] [Abstract]
  • "Heat-stable antigen/CD24 on mouse T lymphocytes: evidence for a costimulatory function."
    Hubbe M., Altevogt P.
    Eur. J. Immunol. 24:731-737(1994) [PubMed] [Europe PMC] [Abstract]
  • "Homotypic interaction of the heat-stable antigen is not responsible for its co-stimulatory activity for T cell clonal expansion."
    Zhou Q., Wu Y., Nielsen P.J., Liu Y.
    Eur. J. Immunol. 27:2524-2528(1997) [PubMed] [Europe PMC] [Abstract]
• positive regulation of gene expression Source: MGI
• positive regulation of inflammatory response to antigenic stimulus Source: MGIInferred from mutant phenotypeⁱ
  • "The heat-stable antigen determines pathogenicity of self-reactive T cells in experimental autoimmune encephalomyelitis."
    Bai X.F., Liu J.Q., Liu X., Guo Y., Cox K., Wen J., Zheng P., Liu Y.
    J. Clin. Invest. 105:1227-1232(2000) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-10 production Source: UniProtKB
• positive regulation of interleukin-2 biosynthetic process Source: MGIInferred from mutant phenotypeⁱ
  • "Differential T cell costimulatory requirements in CD28-deficient mice."
    Shahinian A., Pfeffer K., Lee K.P., Kundig T.M., Kishihara K., Wakeham A., Kawai K., Ohashi P.S., Thompson C.B., Mak T.W.
    Science 261:609-612(1993) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-4 production Source: UniProtKB
• positive regulation of isotype switching to IgG isotypes Source: MGIInferred from mutant phenotypeⁱ
  • "Differential T cell costimulatory requirements in CD28-deficient mice."
    Shahinian A., Pfeffer K., Lee K.P., Kundig T.M., Kishihara K., Wakeham A., Kawai K., Ohashi P.S., Thompson C.B., Mak T.W.
    Science 261:609-612(1993) [PubMed] [Europe PMC] [Abstract]
• positive regulation of mitotic nuclear division Source: UniProtKB
• positive regulation of phosphatidylinositol 3-kinase signaling Source: MGIInferred from direct assayⁱ
  • "Butyrophilin Btn2a2 inhibits TCR activation and phosphatidylinositol 3-kinase/Akt pathway signaling and induces Foxp3 expression in T lymphocytes."
    Ammann J.U., Cooke A., Trowsdale J.
    J. Immunol. 190:5030-5036(2013) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein kinase B signaling Source: MGIInferred from direct assayⁱ
  • "Butyrophilin Btn2a2 inhibits TCR activation and phosphatidylinositol 3-kinase/Akt pathway signaling and induces Foxp3 expression in T lymphocytes."
    Ammann J.U., Cooke A., Trowsdale J.
    J. Immunol. 190:5030-5036(2013) [PubMed] [Europe PMC] [Abstract]
• positive regulation of T cell proliferation Source: MGIInferred from direct assayⁱ
  • "Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation."
    Egawa T., Albrecht B., Favier B., Sunshine M.J., Mirchandani K., O'Brien W., Thome M., Littman D.R.
    Curr. Biol. 13:1252-1258(2003) [PubMed] [Europe PMC] [Abstract]
  • "The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses."
    Suh W.-K., Gajewska B.U., Okada H., Gronski M.A., Bertram E.M., Dawicki W., Duncan G.S., Bukczynski J., Plyte S., Elia A., Wakeham A., Itie A., Chung S., Da Costa J., Arya S., Horan T., Campbell P., Gaida K.

    , Ohashi P.S., Watts T.H., Yoshinaga S.K., Bray M.R., Jordana M., Mak T.W.
    Nat. Immunol. 4:899-906(2003) [PubMed] [Europe PMC] [Abstract]
  • "B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells."
    Ng L.G., Sutherland A.P., Newton R., Qian F., Cachero T.G., Scott M.L., Thompson J.S., Wheway J., Chtanova T., Groom J., Sutton I.J., Xin C., Tangye S.G., Kalled S.L., Mackay F., Mackay C.R.
    J. Immunol. 173:807-817(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: MGI <p>Inferred from Genetic Interaction</p> <p>Used to describe “traditional” genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes."
    Cismasiu V.B., Ghanta S., Duque J., Albu D.I., Chen H.M., Kasturi R., Avram D.
    Blood 108:2695-2702(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of regulatory T cell differentiation Source: MGIInferred from genetic interactionⁱ
  • "Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling."
    Semple K., Nguyen A., Yu Y., Wang H., Anasetti C., Yu X.Z.
    Blood 117:3096-3103(2011) [PubMed] [Europe PMC] [Abstract]
• regulatory T cell differentiation Source: MGI
• T cell activation Source: MGI
• T cell costimulation Source: MGIInferred from direct assayⁱ
  • "Several different cell surface molecules control negative selection of medullary thymocytes."
    Kishimoto H., Sprent J.
    J. Exp. Med. 190:65-73(1999) [PubMed] [Europe PMC] [Abstract]
  • "The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses."
    Suh W.-K., Gajewska B.U., Okada H., Gronski M.A., Bertram E.M., Dawicki W., Duncan G.S., Bukczynski J., Plyte S., Elia A., Wakeham A., Itie A., Chung S., Da Costa J., Arya S., Horan T., Campbell P., Gaida K.

    , Ohashi P.S., Watts T.H., Yoshinaga S.K., Bray M.R., Jordana M., Mak T.W.
    Nat. Immunol. 4:899-906(2003) [PubMed] [Europe PMC] [Abstract]
  • "B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells."
    Ng L.G., Sutherland A.P., Newton R., Qian F., Cachero T.G., Scott M.L., Thompson J.S., Wheway J., Chtanova T., Groom J., Sutton I.J., Xin C., Tangye S.G., Kalled S.L., Mackay F., Mackay C.R.
    J. Immunol. 173:807-817(2004) [PubMed] [Europe PMC] [Abstract]
  • "Heat-stable antigen/CD24 on mouse T lymphocytes: evidence for a costimulatory function."
    Hubbe M., Altevogt P.
    Eur. J. Immunol. 24:731-737(1994) [PubMed] [Europe PMC] [Abstract]
  • "Homotypic interaction of the heat-stable antigen is not responsible for its co-stimulatory activity for T cell clonal expansion."
    Zhou Q., Wu Y., Nielsen P.J., Liu Y.
    Eur. J. Immunol. 27:2524-2528(1997) [PubMed] [Europe PMC] [Abstract]
• T cell receptor signaling pathway Source: MGIInferred from mutant phenotypeⁱ
  • "The lymphoid lineage-specific actin-uncapping protein Rltpr is essential for costimulation via CD28 and the development of regulatory T cells."
    Liang Y., Cucchetti M., Roncagalli R., Yokosuka T., Malzac A., Bertosio E., Imbert J., Nijman I.J., Suchanek M., Saito T., Wulfing C., Malissen B., Malissen M.
    Nat. Immunol. 14:858-866(2013) [PubMed] [Europe PMC] [Abstract]

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Topology

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywords - Cellular componentⁱ

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

GO - Molecular functionⁱ

• protease binding Source: MGI
• protein homodimerization activity Source: MGI
• protein kinase binding Source: MGIInferred from physical interactionⁱ
  • "Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling."
    Semple K., Nguyen A., Yu Y., Wang H., Anasetti C., Yu X.Z.
    Blood 117:3096-3103(2011) [PubMed] [Europe PMC] [Abstract]
• SH3/SH2 adaptor activity Source: MGI

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

        10         20         30         40         50
MTLRLLFLAL NFFSVQVTEN KILVKQSPLL VVDSNEVSLS CRYSYNLLAK 
        60         70         80         90        100
EFRASLYKGV NSDVEVCVGN GNFTYQPQFR SNAEFNCDGD FDNETVTFRL 
       110        120        130        140        150
WNLHVNHTDI YFCKIEFMYP PPYLDNERSN GTIIHIKEKH LCHTQSSPKL 
       160        170        180        190        200
FWALVVVAGV LFCYGLLVTV ALCVIWTNSR RNRLLQSDYM NMTPRRPGLT 
       210 
RKPYQPYAPA RDFAAYRP                                    

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
2. MGD cross-references
   Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot