CD28
T-cell-specific surface glycoprotein CD28
Also known as: CD28_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P10747
- Gene
- CD28
- Ensembl
- ENSG00000178562
- Chromosome
- 2
- Canonical length
- 220 aa
- Protein class
- CD markers, Predicted membrane proteins
- Subcellular location
- Plasma membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
220 residues, UniProt reviewed canonical sequence.
>P10747|CD28
1 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSC KYSYNLFSRE FRASLHKGLD
61 SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQ NLYVNQTDIY FCKIEVMYPP
121 PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVG GVLACYSLLV TVAFIIFWVR
181 SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CD28 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 29 nTPM
Expression across tissuesHPA
Tissue
- thymus: 29 nTPM
- lymph node: 26 nTPM
- tonsil: 17 nTPM
- appendix: 14 nTPM
- placenta: 14 nTPM
- spleen: 6.8 nTPM
Single-cell type
- t-cells: 147 nCPM
- hofbauer cells: 113 nCPM
- thymocytes: 51 nCPM
- macrophages: 16 nCPM
- innate lymphoid cells: 12 nCPM
- platelets: 8.4 nCPM
Immune cell
- T-reg: 102 nTPM
- memory CD4 T-cell: 55 nTPM
- MAIT T-cell: 51 nTPM
- naive CD4 T-cell: 48 nTPM
- memory CD8 T-cell: 26 nTPM
- naive CD8 T-cell: 19 nTPM
Brain region
- choroid plexus: 2.3 nTPM
- thalamus: 0.8 nTPM
- cerebral cortex: 0.6 nTPM
- medulla oblongata: 0.6 nTPM
- white matter: 0.6 nTPM
- amygdala: 0.5 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CD28.
Disease | AllUniProt
Conditions CD28 is implicated in, by any mechanism.
- Immunodeficiency 123 with HPV-related verrucosis (IMD123) MIM:620901
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 21 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Immunodeficiency 123 with HPV-related verrucosis
Disease | AutoantibodyPubMed
Conditions in which antibodies against CD28 are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for CD28 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
19 publications
- Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice.
2005 · J Immunol · RCR 3.7 · 208 citations - Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis.
2010 · J Biol Chem · RCR 1.7 · 79 citations - Ex vivo generated regulatory T cells modulate experimental autoimmune myasthenia gravis.
2008 · J Immunol · RCR 1.2 · 56 citations - Induction of T regulatory cells by the superagonistic anti-CD28 antibody D665 leads to decreased pathogenic IgG autoantibodies against desmoglein 3 in a HLA-transgenic mouse model of pemphigus vulgaris.
2016 · Exp Dermatol · RCR 1 · 24 citations - Effects of FK506 and other immunosuppressive anti-rheumatic agents on T cell activation mediated IL-6 and IgM production in vitro.
2001 · Int Immunopharmacol · RCR 0.9 · 36 citations
Show 14 more
- T cells recognize multiple GAD65 and proinsulin epitopes in human type 1 diabetes, suggesting determinant spreading.
2004 · J Clin Immunol · RCR 0.8 · 45 citations - Retinal self-antigen induces a predominantly Th1 effector response in Axl and Mertk double-knockout mice.
2011 · J Immunol · RCR 0.7 · 27 citations - Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm.
2021 · Cancer Immunol Immunother · RCR 0.7 · 13 citations - Prevention of lupus nephritis development in NZB/NZW mice by selective blockade of CD28.
2017 · Eur J Immunol · RCR 0.6 · 16 citations - Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death.
2016 · Photochem Photobiol Sci · RCR 0.5 · 11 citations - The outer surface lipoprotein OspA of Borrelia burgdorferi provides co-stimulatory signals to normal human peripheral CD4+ and CD8+ T lymphocytes.
1996 · Eur J Immunol · RCR 0.5 · 21 citations - Effect of CD28 antibody on T cells from patients with systemic lupus erythematosus.
1994 · J Autoimmun · RCR 0.4 · 18 citations - Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects.
2004 · J Autoimmun · RCR 0.3 · 16 citations - Evaluation of topoisomerase-1-specific CD8+ T-cell response in systemic sclerosis.
2005 · Ann N Y Acad Sci · RCR 0.2 · 12 citations - Autoantibodies against CD28 are associated with atopic diseases.
2006 · Clin Exp Immunol · RCR 0.2 · 12 citations - Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts.
2016 · J Immunother · RCR 0.2 · 8 citations - Autoantibodies against T-Cell costimulatory molecules are produced in canine autoimmune diseases.
2003 · J Immunother · RCR 0.2 · 5 citations - Serum antibodies against CD28-- a new potential marker of dismal prognosis in melanoma patients.
2013 · PLoS One - Sinomenine modulates autoantigen-specific immune responses by inhibiting dendritic cell activation in experimental arthritis.
2026 · Eur J Pharmacol
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.71
- gnomAD pLI
- 0.36
- gnomAD missense Z
- 0.8
- DepMap mean gene effect
- 0
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic signaling pathway
- CD4-positive, alpha-beta T cell proliferation
- cell surface receptor signaling pathway
- humoral immune response
- negative regulation of apoptotic process
- negative regulation of gene expression
- negative thymic T cell selection
- phosphatidylinositol 3-kinase/protein kinase B signal transduction
- positive regulation of CD4-positive, alpha-beta T cell proliferation
- positive regulation of cytokine production
- positive regulation of gene expression
- positive regulation of inflammatory response to antigenic stimulus
- positive regulation of interleukin-10 production
- positive regulation of interleukin-2 production
- positive regulation of interleukin-4 production
- positive regulation of isotype switching to IgG isotypes
- positive regulation of mitotic nuclear division
- positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- positive regulation of T cell proliferation
- positive regulation of T cell receptor signaling pathway
- positive regulation of transcription by RNA polymerase II
- positive regulation of translation
- positive regulation of viral genome replication
- regulation of regulatory T cell differentiation
- regulatory T cell differentiation
- T cell activation
- T cell costimulation
- T cell receptor signaling pathway
- transcription by RNA polymerase II
Molecular functions
- coreceptor activity
- identical protein binding
- protein kinase binding
- transmembrane signaling receptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CD28 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CD28 as an antibody target. Whether an autoantibody or antibody against CD28 could matter depends on whether native CD28 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CD28 is annotated at the cell surface, where native CD28 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label CD28 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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