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    CD28 CD28 molecule [ Homo sapiens (human) ]

    Gene ID: 940, updated on 8-Jul-2021

    Summary

    Official Symbol
    CD28provided by HGNC
    Official Full Name
    CD28 moleculeprovided by HGNC
    Primary source
    HGNC:HGNC:1653
    See related
    Ensembl:ENSG00000178562 MIM:186760
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    Tp44
    Summary
    The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]
    Expression
    Biased expression in lymph node (RPKM 11.2), appendix (RPKM 7.3) and 7 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CD28 in Genome Data Viewer
    Location:
    2q33.2
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (203706509..203739756)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (204571362..204603635)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene zinc finger protein 207 pseudogene Neighboring gene NDUFA4, mitochondrial complex associated pseudogene Neighboring gene keratin 18 pseudogene 39 Neighboring gene nucleophosmin 1 pseudogene 33

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    A genome-wide association study identifies two new risk loci for Graves' disease.
    GeneReviews: Not available
    A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus.
    GeneReviews: Not available
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    GeneReviews: Not available
    Multiple common variants for celiac disease influencing immune gene expression.
    GeneReviews: Not available

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of CD28 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env In the presence of HIV-1 gp120, stimulation through the CD28 pathway partially restores IL-2 and IFN-gamma production by T cell lines in response to anti-CD3 antibodies PubMed
    env Molecular interactions of CD2 with LFA-3 and CD28 with B7-1 in conjunction with TCR occupancy prevent T cells from programmed apoptosis mediated by binding of CD4 to HIV-1 gp120, resulting in increased levels of IL-2 and IL-4 secretion from the T cells PubMed
    env The binding of HIV-1 gp120 to CD4 molecules on T cells interrupts the sequential cascade of intercellular interactions involving antigen/MHC class II-TCR/CD4, CD40L-CD40, and B71-CD28 PubMed
    Envelope surface glycoprotein gp160, precursor env CD3/28-treated resting CD4+ T cells produce more Env protein than untreated cells PubMed
    env Antibodies against cell surface molecules LFA-1, ICAM-1, HLA-DR, and CD28 inhibit the HIV-1 gp160-induced B cell differentiation response; gp160 also induces IL-6R and CD23 molecule expression on B cells PubMed
    Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 peptide (amino acids 581-597) inhibits lymphoproliferation stimulated via the T-cell-activation molecules CD3, CD2, and CD28, as well as via direct stimulation mediated by phorbol ester combined with ionomycin PubMed
    Nef nef HIV-1 Nef downregulates CD28, a major co-stimulatory receptor that mediates effective T-cell activation, by accelerating CD28 endocytosis via the AP-2 pathway PubMed
    nef HIV-1 Nef utilizes beta-COP in CD28 downregulation PubMed
    nef CD28 co-localizes with the AP-2 clathrin adaptor and an HIV-1 Nef-GFP fusion protein PubMed
    nef HIV-1 group N and group O Nef alleles only weakly downregulate CD4, CD28, and class I and II MHC molecules PubMed
    nef HIV-1 Nef directly interacts with clathrin adaptor complexes (AP) to downregulate numerous cellular proteins, including CD4, MHC-I, LIGHT, DC-SIGN, CD28 and MHC-II, by misrouting them to the endosomal degradation compartment or the trans Golgi-network PubMed
    nef HIV-1 Nef upregulates IL-2 secretion and HIV-1 transcription in T cells stimulated via CD3 or CD28 PubMed
    nef Amino acid residues 57-59 in HIV-1 Nef interact with the cytoplasmic domain at positions 185-193 of CD28, resulting in CD28 downregulation by endocytosis via the AP-2 pathway PubMed
    Pr55(Gag) gag CD3/28-treated resting CD4+ T cells produce more HIV-1 Gag protein than untreated cells PubMed
    Tat tat Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV-1 Tat-mediated transcription PubMed
    tat HIV-1 Tat interacts with CD3 and CD28 to co-stimulate IL-2 and IL-8 expression PubMed
    Vpr vpr HIV-1 Vpr significantly downregulates CD28 expression in infected T cells PubMed
    matrix gag IL-2-induced down modulation of CD28 is completely prevented by p17 MA, and cells derived from p17-stimulated cultures show a strong Tc1 polarization PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC138290

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables coreceptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables identical protein binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in T cell activation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in T cell activation IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in T cell costimulation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in T cell costimulation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in T cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in humoral immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative thymic T cell selection IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of T cell proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in positive regulation of T cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of T cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of alpha-beta T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of cytokine production TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of inflammatory response to antigenic stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of interleukin-10 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of interleukin-2 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of interleukin-4 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of isotype switching to IgG isotypes IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of mitotic nuclear division IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of protein kinase B signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of translation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of viral genome replication NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of regulatory T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulatory T cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in immunological synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    part_of protein complex involved in cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    T-cell-specific surface glycoprotein CD28

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029618.1 RefSeqGene

      Range
      5165..37438
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243077.2NP_001230006.1  T-cell-specific surface glycoprotein CD28 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001230006.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate, in-frame donor splice site at one of the coding exons compared to variant 1. This results in a shorter isoform (2) missing an internal protein segment compared to isoform 1.
      Source sequence(s)
      AA311148, AC125238, AF222341, AK303421, AW241446, BF509568, DA939711, J02988
      UniProtKB/Swiss-Prot
      P10747
      UniProtKB/TrEMBL
      B4E0L1
    2. NM_001243078.2NP_001230007.1  T-cell-specific surface glycoprotein CD28 isoform 3 precursor

      See identical proteins and their annotated locations for NP_001230007.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame coding exon compared to variant 1. This results in a shorter isoform (3) missing an internal protein segment compared to isoform 1.
      Source sequence(s)
      AA311148, AC125238, AF222342, AK303421, AW241446, BF509568, DA939711, J02988
      Consensus CDS
      CCDS58749.1
      UniProtKB/Swiss-Prot
      P10747
      UniProtKB/TrEMBL
      B4E0L1
      Related
      ENSP00000363605.4, ENST00000374481.7
    3. NM_006139.4NP_006130.1  T-cell-specific surface glycoprotein CD28 isoform 1 precursor

      See identical proteins and their annotated locations for NP_006130.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longest isoform (1).
      Source sequence(s)
      AA311148, AC125238, AK292986, AW241446, BF509568, DA939711, J02988
      Consensus CDS
      CCDS2361.1
      UniProtKB/Swiss-Prot
      P10747
      Related
      ENSP00000324890.7, ENST00000324106.9
      Conserved Domains (1) summary
      cd05721
      Location:21136
      IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

      Range
      203706509..203739756
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011512194.2XP_011510496.1  T-cell-specific surface glycoprotein CD28 isoform X1

      See identical proteins and their annotated locations for XP_011510496.1

      UniProtKB/Swiss-Prot
      P10747
      Related
      ENSP00000393648.2, ENST00000458610.6
      Conserved Domains (1) summary
      cd05721
      Location:35150
      IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
    2. XM_011512195.3XP_011510497.1  T-cell-specific surface glycoprotein CD28 isoform X2

      Conserved Domains (1) summary
      cl11960
      Location:3561
      Ig; Immunoglobulin domain
    3. XM_011512197.2XP_011510499.1  T-cell-specific surface glycoprotein CD28 isoform X3

      See identical proteins and their annotated locations for XP_011510499.1

      UniProtKB/Swiss-Prot
      P10747
      Conserved Domains (1) summary
      cl11960
      Location:2147
      Ig; Immunoglobulin domain
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