P01732 · CD8A_HUMAN
- ProteinT-cell surface glycoprotein CD8 alpha chain
- GeneCD8A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids235 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | external side of plasma membrane | |
Cellular Component | extracellular region | |
Cellular Component | plasma membrane | |
Cellular Component | plasma membrane raft | |
Cellular Component | receptor complex | |
Cellular Component | T cell receptor complex | |
Molecular Function | coreceptor activity | |
Molecular Function | MHC class I protein binding | |
Molecular Function | MHC class I protein complex binding | |
Biological Process | adaptive immune response | |
Biological Process | antigen processing and presentation | |
Biological Process | cell surface receptor protein tyrosine kinase signaling pathway | |
Biological Process | cell surface receptor signaling pathway | |
Biological Process | cytotoxic T cell differentiation | |
Biological Process | immune response | |
Biological Process | T cell activation | |
Biological Process | T cell mediated immunity | |
Biological Process | T cell receptor signaling pathway |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameT-cell surface glycoprotein CD8 alpha chain
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP01732
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
Cell membrane ; Single-pass type I membrane protein
Note: CD8A localizes to lipid rafts only when associated with its partner CD8B.
Isoform 2
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Topological domain | 22-182 | Extracellular | |||
Transmembrane | 183-203 | Helical | |||
Topological domain | 204-235 | Cytoplasmic | |||
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Immunodeficiency 116 (IMD116)
- Note
- DescriptionAn autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.
- See alsoMIM:608957
Natural variants in IMD116
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_021020 | 111 | G>S | in IMD116; prevents CD8 expression; dbSNP:rs121918660 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Natural variant | VAR_021020 | 111 | in IMD116; prevents CD8 expression; dbSNP:rs121918660 | ||
Mutagenesis | 111 | Prevents CD8 expression. | |||
Mutagenesis | 206 | Complete loss of palmitoylation. | |||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 342 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, lipidation.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Signal | 1-21 | ||||
Chain | PRO_0000014638 | 22-235 | T-cell surface glycoprotein CD8 alpha chain | ||
Disulfide bond | 43↔115 | ||||
Lipidation | 206 | S-palmitoyl cysteine | |||
Post-translational modification
Palmitoylated, but association with CD8B seems to be more important for the enrichment of CD8A in lipid rafts.
O-glycosylated.
Phosphorylated in cytotoxic T-lymphocytes (CTLs) following activation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
CD8 on thymus-derived T-cells usually consists of a disulfide-linked alpha/CD8A and a beta/CD8B chain. Less frequently, CD8 can be expressed as a CD8A homodimer. A subset of natural killer cells, memory T-cells, intraepithelial lymphocytes, monocytes and dendritic cells expresses CD8A homodimers. Expressed at the cell surface of plasmacytoid dendritic cells upon herpes simplex virus-1 stimulation.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms disulfide-linked heterodimers with CD8B at the cell surface. Forms also homodimers in several cell types including NK-cells or peripheral blood T-lymphocytes. Interacts with the MHC class I HLA-A/B2M dimer. One HLA-A molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop) (PubMed:2784196, PubMed:9177355).
Interacts with LCK in a zinc-dependent manner. Interacts with HLA-G; this interaction is direct and might down-regulate T cell receptor signaling
Interacts with LCK in a zinc-dependent manner. Interacts with HLA-G; this interaction is direct and might down-regulate T cell receptor signaling
Complex viewer
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
P01732-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Synonymsmembrane, mCD8alpha
- Length235
- Mass (Da)25,729
- Last updated1986-07-21 v1
- MD5 Checksum7E74731A8583EB61055862C16F8DDAF9
P01732-2
- Name2
- Synonymssecreted, sCD8alpha
- Differences from canonical
- 172-209: VHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHR → G
P01732-3
- Name3
- Differences from canonical
- 1-1: M → MRNQAPGRPKGATFPPRRPTGSRAPPLAPELRAKQRPGERVM
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B8ZZZ4 | B8ZZZ4_HUMAN | CD8A | 198 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Alternative sequence | VSP_054438 | 1 | in isoform 3 | ||
Alternative sequence | VSP_012653 | 172-209 | in isoform 2 | ||
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M26315 EMBL· GenBank· DDBJ | AAA79217.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M26313 EMBL· GenBank· DDBJ | AAA79217.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M26314 EMBL· GenBank· DDBJ | AAA79217.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M26315 EMBL· GenBank· DDBJ | AAA79218.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M26313 EMBL· GenBank· DDBJ | AAA79218.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M26314 EMBL· GenBank· DDBJ | AAA79218.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M12824 EMBL· GenBank· DDBJ | AAA61133.1 EMBL· GenBank· DDBJ | mRNA | ||
M12828 EMBL· GenBank· DDBJ | AAB04637.1 EMBL· GenBank· DDBJ | mRNA | ||
M27161 EMBL· GenBank· DDBJ | AAA59674.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK300089 EMBL· GenBank· DDBJ | BAG61892.1 EMBL· GenBank· DDBJ | mRNA | ||
AC064848 EMBL· GenBank· DDBJ | AAX88864.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC112696 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471053 EMBL· GenBank· DDBJ | EAW99438.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAW99439.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAW99440.1 EMBL· GenBank· DDBJ | Genomic DNA |