CD28 CD28 molecule [Homo sapiens (human)] - Gene

Summary

Official Symbol: CD28provided by HGNC
Official Full Name: CD28 moleculeprovided by HGNC
Primary source: HGNC:HGNC:1653
See related: Ensembl:ENSG00000178562 MIM:186760; AllianceGenome:HGNC:1653
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; IMD123
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: mouse all
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Genomic context

Location:: 2q33.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (203706482..203738912)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (204188401..204220837)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (204571205..204603635)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

c-Kit signaling potentiates CAR T cell efficacy in solid tumors by CD28- and IL-2-independent co-stimulation.
Title: c-Kit signaling potentiates CAR T cell efficacy in solid tumors by CD28- and IL-2-independent co-stimulation.
Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies.
Title: Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies.
Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.
Title: Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.
Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.
Title: Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk.
[Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock].
Title: [Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock].
Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naive CD4(+) T cells.
Title: Specific transcriptional programs differentiate ICOS from CD28 costimulatory signaling in human Naïve CD4(+) T cells.
COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways.
Title: COPD is associated with increased pro-inflammatory CD28null CD8 T and NKT-like cells in the small airways.
Mice transgenic for human CTLA4-CD28 fusion gene show proliferation and transformation of ATLL-like and AITL-like T cells.
Title: Mice transgenic for human CTLA4-CD28 fusion gene show proliferation and transformation of ATLL-like and AITL-like T cells.
Cryptic association of B7-2 molecules and its implication for clustering.
Title: Cryptic association of B7-2 molecules and its implication for clustering.
Transcription factor activation and protein phosphorylation patterns are distinct for CD28 and ICAM-1 co-stimulatory molecules.
Title: Transcription factor activation and protein phosphorylation patterns are distinct for CD28 and ICAM-1 co-stimulatory molecules.

Submit: New GeneRIF Correction See all GeneRIFs (274)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies two new risk loci for Graves' disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

RH68962 (e-PCR)
- UniSTS:68487

NoName (e-PCR)
- UniSTS:483499

D2S2596 (e-PCR)
- UniSTS:36547

CD28_86 (e-PCR)
- UniSTS:276173

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 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 CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in T cell activation	IDA Inferred from Direct Assay 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
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
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 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
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 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/protein kinase B signal transduction	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
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info

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
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 plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
part_of protein complex involved in cell adhesion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: T-cell-specific surface glycoprotein CD28

NCBI Reference Sequences (RefSeq)

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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

NG_029618.1 RefSeqGene

Range

5165..37438

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001243077.2 → NP_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
NM_001243078.2 → NP_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, ENST00000374481.8
NM_001410981.1 → NP_001397910.1 T-cell-specific surface glycoprotein CD28 isoform 4

Status: REVIEWED

Source sequence(s)

AC125238

Consensus CDS

CCDS92935.1

Related

ENSP00000393648.2, ENST00000458610.6
NM_006139.4 → NP_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

A8KAC1, P10747, Q13964, Q52M23, Q70WG0, Q8NI54, Q8NI55, Q8NI56, Q8WXJ2, Q9BYV0

Related

ENSP00000324890.7, ENST00000324106.9

Conserved Domains (1) summary

cd05721
Location:21 → 136

IgV_CTLA-4; Immunoglobulin (Ig) domain of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)