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

• coreceptor activity Source: UniProtKB <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "CD28/B7 costimulation: a review."
    Greenfield E.A., Nguyen K.A., Kuchroo V.K.
    Crit Rev Immunol 18:389-418(1998) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: UniProtKB <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • "Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen)."
    Hara T., Fu S.M., Hansen J.A.
    J Exp Med 161:1513-1524(1985) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: BHF-UCL <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%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23."
    Fourie A.M., Coles F., Moreno V., Karlsson L.
    J Biol Chem 278:30469-30477(2003) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: Ensembl

GO - Biological processⁱ

• apoptotic signaling pathway Source: Ensembl
• cell surface receptor signaling pathway Source: UniProtKBTraceable author statementⁱ
  • "CD28/B7 costimulation: a review."
    Greenfield E.A., Nguyen K.A., Kuchroo V.K.
    Crit Rev Immunol 18:389-418(1998) [PubMed] [Europe PMC] [Abstract]
• cytokine biosynthetic process Source: UniProtKBTraceable author statementⁱ
  • "CD28/B7 system of T cell costimulation."
    Lenschow D.J., Walunas T.L., Bluestone J.A.
    Annu Rev Immunol 14:233-258(1996) [PubMed] [Europe PMC] [Abstract]
• humoral immune response Source: UniProtKBTraceable author statementⁱ
  • "CD28/B7 system of T cell costimulation."
    Lenschow D.J., Walunas T.L., Bluestone J.A.
    Annu Rev Immunol 14:233-258(1996) [PubMed] [Europe PMC] [Abstract]
• 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%2Dgo%2Devidence%2Dcodes#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 Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of apoptotic process Source: UniProtKBTraceable author statementⁱ
  • "CD28/B7 system of T cell costimulation."
    Lenschow D.J., Walunas T.L., Bluestone J.A.
    Annu Rev Immunol 14:233-258(1996) [PubMed] [Europe PMC] [Abstract]
• negative regulation of gene expression Source: UniProtKB <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%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation."
    Gieseke F., Kruchen A., Tzaribachev N., Bentzien F., Dominici M., Muller I.
    Eur. J. Immunol. 43:2741-2749(2013) [PubMed] [Europe PMC] [Abstract]
• negative thymic T cell selection Source: Ensembl
• positive regulation of alpha-beta T cell proliferation Source: Ensembl
• positive regulation of gene expression Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation."
    Gieseke F., Kruchen A., Tzaribachev N., Bentzien F., Dominici M., Muller I.
    Eur. J. Immunol. 43:2741-2749(2013) [PubMed] [Europe PMC] [Abstract]
• positive regulation of inflammatory response to antigenic stimulus Source: Ensembl
• positive regulation of interleukin-10 production Source: UniProtKB <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%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.12

    "Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis."
    Blotta M.H., Marshall J.D., DeKruyff R.H., Umetsu D.T.
    J. Immunol. 156:3133-3140(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• positive regulation of interleukin-2 production Source: UniProtKBInferred from direct assayⁱ
  • "Involvement of T44 molecules in an antigen-independent pathway of T cell activation. Analysis of the correlations to the T cell antigen-receptor complex."
    Moretta A., Pantaleo G., Lopez-Botet M., Moretta L.
    J Exp Med 162:823-838(1985) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-4 production Source: UniProtKBInferred from direct assayⁱ
  • Ref.12

    "Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis."
    Blotta M.H., Marshall J.D., DeKruyff R.H., Umetsu D.T.
    J. Immunol. 156:3133-3140(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• positive regulation of isotype switching to IgG isotypes Source: Ensembl
• positive regulation of mitotic nuclear division Source: UniProtKBInferred from direct assayⁱ
  • "Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen)."
    Hara T., Fu S.M., Hansen J.A.
    J Exp Med 161:1513-1524(1985) [PubMed] [Europe PMC] [Abstract]
• positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
• positive regulation of protein kinase B signaling Source: Reactome
• positive regulation of T cell proliferation Source: UniProtKBInferred from direct assayⁱ
  • "Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen)."
    Hara T., Fu S.M., Hansen J.A.
    J Exp Med 161:1513-1524(1985) [PubMed] [Europe PMC] [Abstract]
  • Ref.12

    "Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis."
    Blotta M.H., Marshall J.D., DeKruyff R.H., Umetsu D.T.
    J. Immunol. 156:3133-3140(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• positive regulation of transcription by RNA polymerase II Source: Ensembl
• positive regulation of translation Source: UniProtKBNon-traceable author statementⁱ
  • "The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes."
    Kleijn M., Proud C.G.
    BMC Biochem 3:11-11(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of viral genome replication Source: UniProtKBNon-traceable author statementⁱ
  • "Costimulation of CD4+ T cells via CD28 modulates human immunodeficiency virus type 1 infection and replication in vitro."
    Smithgall M.D., Wong J.G., Linsley P.S., Haffar O.K.
    AIDS Res Hum Retroviruses 11:885-892(1995) [PubMed] [Europe PMC] [Abstract]
• regulation of defense response to virus by virus Source: Reactome
• regulation of regulatory T cell differentiation Source: Ensembl
• regulatory T cell differentiation Source: BHF-UCLInferred from direct assayⁱ
  • "Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3."
    Zheng Y., Manzotti C.N., Burke F., Dussably L., Qureshi O., Walker L.S., Sansom D.M.
    J Immunol 181:1683-1691(2008) [PubMed] [Europe PMC] [Abstract]
• T cell activation Source: BHF-UCL <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%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1."
    Murooka T.T., Rahbar R., Platanias L.C., Fish E.N.
    Blood 111:4892-4901(2008) [PubMed] [Europe PMC] [Abstract]
• T cell costimulation Source: GO_CentralInferred 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 Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• T cell receptor signaling pathway Source: GO_CentralInferred 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 Bioinform 12:449-462(2011) [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 provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

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

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

Organism-specific 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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• identical protein binding Source: UniProtKBNon-traceable author statementⁱ
  • "Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen)."
    Hara T., Fu S.M., Hansen J.A.
    J Exp Med 161:1513-1524(1985) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23."
    Fourie A.M., Coles F., Moreno V., Karlsson L.
    J Biol Chem 278:30469-30477(2003) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: Ensembl

Protein-protein interaction databases

Miscellaneous 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

Miscellaneous 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%5Flength">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>Sequences (7)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE 
        60         70         80         90        100
FRASLHKGLD SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ 
       110        120        130        140        150
NLYVNQTDIY FCKIEVMYPP PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS 
       160        170        180        190        200
KPFWVLVVVG GVLACYSLLV TVAFIIFWVR SKRSRLLHSD YMNMTPRRPG 
       210        220
PTRKHYQPYA PPRDFAAYRS                                  

        10         20         30         40         50
MLRLLLALNL FPSIQVTGKH LCPSPLFPGP SKPFWVLVVV GGVLACYSLL 
        60         70         80         90        100
VTVAFIIFWV RSKRSRLLHS DYMNMTPRRP GPTRKHYQPY APPRDFAAYR 

S                                                      

        10         20         30         40         50
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSY NEKSNGTIIH 
        60         70         80         90        100
VKGKHLCPSP LFPGPSKPFW VLVVVGGVLA CYSLLVTVAF IIFWVRSKRS 
       110        120        130 
RLLHSDYMNM TPRRPGPTRK HYQPYAPPRD FAAYRS                

        10         20         30         40         50
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSW KHLCPSPLFP 
        60         70         80         90        100
GPSKPFWVLV VVGGVLACYS LLVTVAFIIF WVRSKRSRLL HSDYMNMTPR 
       110        120 
RPGPTRKHYQ PYAPPRDFAA YRS                              

        10         20         30         40         50
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSY NEKSNGTIIH 

VKGEE                                                  

        10         20         30         40         50
MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSY NEKSNGTIIH 
        60         70         80
VKGKHLCPSP LFPGPSKPYA PPRDFAAYRS                       

        10         20         30         40         50
MPCGLSALIM CPKGMVAVVV AVDDGDSQAL AGNKILVKQS PMLVAYDNAV 
        60         70         80         90        100
NLSCKYSYNL FSREFRASLH KGLDSAVEVC VVYGNYSQQL QVYSKTGFNC 
       110        120        130        140        150
DGKLGNESVT FYLQNLYVNQ TDIYFCKIEV MYPPPYLDNE KSNGTIIHVK 
       160        170        180        190        200
GKHLCPSPLF PGPSKPFWVL VVVGGVLACY SLLVTVAFII FWVRSKRSRL 
       210        220        230 
LHSDYMNMTP RRPGPTRKHY QPYAPPRDFA AYRS                  

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<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

• 100% Identity
• 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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials 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. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
2. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
3. Human chromosome 2
   Human chromosome 2: entries, gene names and cross-references to MIM
4. Human cell differentiation molecules
   CD nomenclature of surface proteins of human leucocytes and list of entries