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] See more...

Aliases for CD28 Gene

Aliases for CD28 Gene

  • CD28 Molecule 2 3 5
  • T-Cell-Specific Surface Glycoprotein CD28 3 4
  • CD28 Antigen 3 4
  • T-Cell-Specific Surface Glycoprotein 2
  • CD28 Antigen (Tp44) 2
  • Tp44 3
  • CD28 5
  • TP44 4

External Ids for CD28 Gene

Previous GeneCards Identifiers for CD28 Gene

  • GC02P202788
  • GC02P203295
  • GC02P204535
  • GC02P204773
  • GC02P204396
  • GC02P204279
  • GC02P196418

Summaries for CD28 Gene

Entrez Gene Summary for CD28 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]

GeneCards Summary for CD28 Gene

CD28 (CD28 Molecule) is a Protein Coding gene. Diseases associated with CD28 include Mycosis Fungoides and Sezary's Disease. Among its related pathways are Nur77 Signaling in T-Cell and RET signaling. Gene Ontology (GO) annotations related to this gene include identical protein binding and SH3/SH2 adaptor activity. An important paralog of this gene is CTLA4.

UniProtKB/Swiss-Prot Summary for CD28 Gene

  • Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation (PubMed:8617933). Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells (PubMed:15067037).

Gene Wiki entry for CD28 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CD28 Gene

Genomics for CD28 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CD28 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J203704 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 623.5 +1.6 1588 7.8 SP1 ZNF512 BACH1 TCF12 IKZF2 RELA POLR2A CEBPA ARID3A TCF7 CD28 ICOS CTLA4 RNU6-474P NBEAL1 KRT18P39 ENSG00000228513 HSALNG0021688
GH02J203737 Enhancer 0.8 FANTOM5 ENCODE dbSUPER 28.8 +34.9 34941 7.2 ZSCAN4 SOX6 CEBPB NR3C1 CD28 KRT18P39 ICOS RNU6-474P RAPH1 CTLA4 RF00017-3411 HSALNG0021688
GH02J203936 Promoter/Enhancer 1.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 13.1 +232.2 232226 5.4 POLR2A MLLT1 ICOS CD28 CTLA4 LOC101927840 PARD3B
GH02J203717 Enhancer 1.1 FANTOM5 ENCODE dbSUPER 15.1 +13.8 13762 6.2 GATAD2A RXRB SP1 YY1 CEBPA SOX13 RUNX3 FOXA2 ZBTB25 TEAD1 HSALNG0021688 CD28 ICOS RAPH1 RNU6-474P KRT18P39 CTLA4 CARF CYP20A1
GH02J203730 Enhancer 0.9 Ensembl ENCODE dbSUPER 18.1 +25.0 25026 7 FOXA2 USF1 NFIC POLR2A JUNB BATF NFIB FOXA1 JUND FOXA3 CD28 RAPH1 RNU6-474P KRT18P39 HSALNG0021688 RF00017-3411 CTLA4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CD28 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CD28

Top Transcription factor binding sites by QIAGEN in the CD28 gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA
  • Nkx2-5
  • p300
  • STAT3

Genomic Locations for CD28 Gene

Genomic Locations for CD28 Gene
chr2:203,706,475-203,739,756
(GRCh38/hg38)
Size:
33,282 bases
Orientation:
Plus strand
chr2:204,571,198-204,603,635
(GRCh37/hg19)
Size:
32,438 bases
Orientation:
Plus strand

Genomic View for CD28 Gene

Genes around CD28 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CD28 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CD28 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CD28 Gene

Proteins for CD28 Gene

  • Protein details for CD28 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P10747-CD28_HUMAN
    Recommended name:
    T-cell-specific surface glycoprotein CD28
    Protein Accession:
    P10747
    Secondary Accessions:
    • A8KAC1
    • Q13964
    • Q52M23
    • Q70WG0
    • Q8NI54
    • Q8NI55
    • Q8NI56
    • Q8WXJ2
    • Q9BYV0

    Protein attributes for CD28 Gene

    Size:
    220 amino acids
    Molecular mass:
    25066 Da
    Quaternary structure:
    • Homodimer; disulfide-linked. Interacts with DUSP14. Binds to CD80/B7-1 and CD86/B7-2/B70. Interacts with GRB2. Isoform 3 interacts with CD40LG (PubMed:15067037).

    Three dimensional structures from OCA and Proteopedia for CD28 Gene

    Alternative splice isoforms for CD28 Gene

neXtProt entry for CD28 Gene

Post-translational modifications for CD28 Gene

  • CD40LG induces tyrosine phosphorylation of isoform 3.
  • Glycosylation at Asn37, Asn129, Asn71, Asn92, and Asn105
  • Modification sites at PhosphoSitePlus

Other Protein References for CD28 Gene

Antibody Products

  • Abcam antibodies for CD28

No data available for DME Specific Peptides for CD28 Gene

Domains & Families for CD28 Gene

Gene Families for CD28 Gene

Protein Domains for CD28 Gene

InterPro:
Blocks:
  • CD28 antigen signature
ProtoNet:

Suggested Antigen Peptide Sequences for CD28 Gene

GenScript: Design optimal peptide antigens:
  • TP44 (CD28_HUMAN)
genes like me logo Genes that share domains with CD28: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for CD28 Gene

Function for CD28 Gene

Molecular function for CD28 Gene

UniProtKB/Swiss-Prot Function:
Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation (PubMed:8617933). Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells (PubMed:15067037).
GENATLAS Biochemistry:
cell differentiation antigen CD28 (Tp44),44kDa,identified by monoclonal antibody 9.3,KOLT2,expressed in T lymphocyte,CD80,CD86 ligand,stimulating PDE7 for T cell activation,regulated by CBLB

Phenotypes From GWAS Catalog for CD28 Gene

Gene Ontology (GO) - Molecular Function for CD28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 12777399
GO:0005070 SH3/SH2 adaptor activity IDA --
GO:0005515 protein binding IPI 7568038
GO:0015026 coreceptor activity TAS 9784967
GO:0019901 protein kinase binding IEA --
genes like me logo Genes that share ontologies with CD28: view
genes like me logo Genes that share phenotypes with CD28: view

Human Phenotype Ontology for CD28 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CD28 Gene

MGI Knock Outs for CD28:
  • Cd28 Cd28<tm1Mak>
  • Cd28 Cd28<tm1a(EUCOMM)Hmgu>
  • Cd28 Cd28<tm1Pjl>
  • Cd28 Cd28<tm1Shr>

Animal Model Products

  • Taconic Biosciences Mouse Models for CD28

CRISPR Products

miRNA for CD28 Gene

miRTarBase miRNAs that target CD28

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CD28

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CD28 Gene

Localization for CD28 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CD28 Gene

Membrane. Single-pass type I membrane protein.
[Isoform 3]: Cell surface.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CD28 gene
Compartment Confidence
plasma membrane 5
cytosol 5
extracellular 3
nucleus 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for CD28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001772 immunological synapse IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA,TAS --
GO:0005887 integral component of plasma membrane TAS 9784967
GO:0009897 external side of plasma membrane IDA 11390434
genes like me logo Genes that share ontologies with CD28: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CD28 Gene

Pathways & Interactions for CD28 Gene

genes like me logo Genes that share pathways with CD28: view

Pathways by source for CD28 Gene

5 GeneGo (Thomson Reuters) pathways for CD28 Gene
  • Immune response CD28 signaling
  • Immune response ICOS pathway in T-helper cell
  • Immune response IL-22 signaling pathway
  • Immune response NFAT in immune response
  • Transcription_NF-kB signaling pathway
16 Qiagen pathways for CD28 Gene
  • Akt Signaling
  • Antioxidant Action of Vitamin-C
  • CD28 Signaling in T-Helper Cell
  • CTLA4 Signaling
  • ICos-ICosL Pathway in T-Helper Cell
1 Cell Signaling Technology pathway for CD28 Gene

SIGNOR curated interactions for CD28 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for CD28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IBA 21873635
GO:0002863 positive regulation of inflammatory response to antigenic stimulus IEA --
GO:0006955 immune response IEA --
GO:0006959 humoral immune response TAS 8717514
GO:0007166 cell surface receptor signaling pathway TAS 9784967
genes like me logo Genes that share ontologies with CD28: view

Drugs & Compounds for CD28 Gene

(31) Drugs for CD28 Gene - From: ClinicalTrials, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Fludarabine Approved Pharma DNA synthsis inhibitor 1533,1533
Cyclophosphamide Approved, Investigational Pharma Nitrogen mustard alkylating agent and prodrug. 3670
Alkylating Agents Pharma 5372
Antibodies Pharma 7499
Antirheumatic Agents Pharma 12236

(12) Additional Compounds for CD28 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CD28: view

Transcripts for CD28 Gene

mRNA/cDNA for CD28 Gene

3 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CD28

Alternative Splicing Database (ASD) splice patterns (SP) for CD28 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b · 4c
SP1: - -
SP2: -
SP3: - -
SP4:

Relevant External Links for CD28 Gene

GeneLoc Exon Structure for
CD28

Expression for CD28 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CD28 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CD28 Gene

This gene is overexpressed in Whole Blood (x11.4).

Protein differential expression in normal tissues from HIPED for CD28 Gene

This gene is overexpressed in CD8 Tcells (48.9) and CD4 Tcells (17.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CD28 Gene



Protein tissue co-expression partners for CD28 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CD28

SOURCE GeneReport for Unigene cluster for CD28 Gene:

Hs.443123

mRNA Expression by UniProt/SwissProt for CD28 Gene:

P10747-CD28_HUMAN
Tissue specificity: Expressed in T-cells and plasma cells, but not in less mature B-cells.

Evidence on tissue expression from TISSUES for CD28 Gene

  • Blood(4.8)
  • Spleen(4)
  • Lymph node(3.9)
  • Intestine(3.2)
  • Bone marrow(3.1)
  • Heart(2.9)
  • Lung(2.8)
  • Kidney(2.8)
  • Liver(2.7)
  • Skin(2.7)
  • Nervous system(2.5)
  • Pancreas(2.2)
  • Bone(2.2)
  • Muscle(2.2)
  • Stomach(2.1)
genes like me logo Genes that share expression patterns with CD28: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CD28 Gene

Orthologs for CD28 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CD28 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CD28 30 31
  • 99.7 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CD28 30 31
  • 84.55 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CD28 30 31
  • 81.43 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Cd28 30
  • 77.67 (n)
Mouse
(Mus musculus)
Mammalia Cd28 30 17 31
  • 77.02 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CD28 31
  • 56 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CD28 31
  • 52 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CD28 30 31
  • 62.32 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CD28 31
  • 31 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia cd28 30
  • 49.78 (n)
Species where no ortholog for CD28 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for CD28 Gene

ENSEMBL:
Gene Tree for CD28 (if available)
TreeFam:
Gene Tree for CD28 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CD28: view image

Paralogs for CD28 Gene

Paralogs for CD28 Gene

genes like me logo Genes that share paralogs with CD28: view

Variants for CD28 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CD28 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
774413 Benign: not provided 203,726,685(+) G/A SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for CD28 Gene

Structural Variations from Database of Genomic Variants (DGV) for CD28 Gene

Variant ID Type Subtype PubMed ID
nsv1001799 CNV gain 25217958

Variation tolerance for CD28 Gene

Residual Variation Intolerance Score: 62.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.45; 9.87% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CD28 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CD28

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CD28 Gene

Disorders for CD28 Gene

MalaCards: The human disease database

(55) MalaCards diseases for CD28 Gene - From: Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
mycosis fungoides
  • mycosis fungoides lymphoma
sezary's disease
  • sezary disease
paracoccidioidomycosis
  • mucocutaneous-lymphangitic paracoccidioidomycosis
graft-versus-host disease
  • graft-versus-host disease, susceptibility to
pars planitis
  • posterior cyclitis
- elite association - COSMIC cancer census association via MalaCards
Search CD28 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CD28

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with CD28: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CD28 Gene

Publications for CD28 Gene

  1. Association of genetic variation in inducible costimulator gene with outcome of kidney transplantation. (PMID: 19202444) Haimila K … Partanen J (Transplantation 2009) 3 23 41
  2. Asthma and genes encoding components of the vitamin D pathway. (PMID: 19852851) Bossé Y … Laprise C (Respiratory research 2009) 3 23 41
  3. Genetic polymorphisms of immunoregulatory proteins in acute renal allograft rejection. (PMID: 19857736) Krichen H … Gorgi Y (Transplantation proceedings 2009) 3 23 41
  4. Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus. (PMID: 18174230) Miyagawa H … Horiuchi T (Rheumatology (Oxford, England) 2008) 3 23 41
  5. Association of common T cell activation gene polymorphisms with multiple sclerosis in Australian patients. (PMID: 14975605) Teutsch SM … Stewart GJ (Journal of neuroimmunology 2004) 3 23 41

Products for CD28 Gene

  • Addgene plasmids for CD28

Sources for CD28 Gene