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CD28 CD28 molecule [ Homo sapiens (human) ]

Gene ID: 940, updated on 6-Sep-2020

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

Genomic context

See CD28 in Genome Data Viewer
Location:
2q33.2
Exon count:
5
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (203706509..203739756)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (204571198..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
coreceptor activity TAS
Traceable Author Statement
more info
PubMed 
identical protein binding NAS
Non-traceable Author Statement
more info
PubMed 
protease binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
T cell activation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
T cell activation IGI
Inferred from Genetic Interaction
more info
PubMed 
T cell costimulation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
T cell costimulation TAS
Traceable Author Statement
more info
PubMed 
T cell receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
 
cell surface receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
cytokine biosynthetic process TAS
Traceable Author Statement
more info
PubMed 
humoral immune response TAS
Traceable Author Statement
more info
PubMed 
immune system process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative thymic T cell selection IEA
Inferred from Electronic Annotation
more info
 
positive regulation of T cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell proliferation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of alpha-beta T cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of inflammatory response to antigenic stimulus IEA
Inferred from Electronic Annotation
more info
 
positive regulation of interleukin-10 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-2 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-4 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of isotype switching to IgG isotypes IEA
Inferred from Electronic Annotation
more info
 
positive regulation of mitotic nuclear division IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of phosphatidylinositol 3-kinase signaling IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein kinase B signaling TAS
Traceable Author Statement
more info
 
positive regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
positive regulation of translation NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of viral genome replication NAS
Non-traceable Author Statement
more info
PubMed 
regulation of defense response to virus by virus TAS
Traceable Author Statement
more info
 
regulation of regulatory T cell differentiation IEA
Inferred from Electronic Annotation
more info
 
regulatory T cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
external side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
external side of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
immunological synapse IEA
Inferred from Electronic Annotation
more info
 
integral component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
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)

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 109.20200815

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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