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Protein

T-cell surface glycoprotein CD8 alpha chain

Gene

CD8A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

  • coreceptor activity Source: UniProtKB
  • MHC class I protein binding Source: UniProtKB
  • protein homodimerization activity Source: Ensembl
  • protein kinase binding Source: Ensembl

GO - Biological processi

  • antigen processing and presentation Source: UniProtKB
  • cell surface receptor signaling pathway Source: GO_Central
  • cytotoxic T cell differentiation Source: GO_Central
  • defense response to virus Source: Ensembl
  • immune response Source: UniProtKB
  • positive regulation of calcium-mediated signaling Source: Ensembl
  • regulation of immune response Source: Reactome
  • T cell activation Source: UniProtKB
  • T cell mediated immunity Source: GO_Central
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB

Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
SIGNORiP01732.

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD8 alpha chain
Alternative name(s):
T-lymphocyte differentiation antigen T8/Leu-2
CD_antigen: CD8a
Gene namesi
Name:CD8A
Synonyms:MAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000153563.15.
HGNCiHGNC:1706. CD8A.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 182ExtracellularSequence analysisAdd BLAST161
Transmembranei183 – 203HelicalSequence analysisAdd BLAST21
Topological domaini204 – 235CytoplasmicSequence analysisAdd BLAST32

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

CD8 deficiency, familial (CD8 deficiency)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.
See also OMIM:608957
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021020111G → S in CD8 deficiency; prevents CD8 expression. 1 PublicationCorresponds to variant dbSNP:rs121918660Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi111G → R: Prevents CD8 expression. 1 Publication1
Mutagenesisi206C → A: Complete loss of palmitoylation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi925.
MalaCardsiCD8A.
MIMi608957. phenotype.
OpenTargetsiENSG00000153563.
Orphaneti169085. Susceptibility to respiratory infections associated with CD8alpha chain mutation.
PharmGKBiPA26244.

Polymorphism and mutation databases

BioMutaiCD8A.
DMDMi116035.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000001463822 – 235T-cell surface glycoprotein CD8 alpha chainAdd BLAST214

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi43 ↔ 1152 Publications
Lipidationi206S-palmitoyl cysteine1 Publication1

Post-translational modificationi

Palmitoylated, but association with CD8B seems to be more important for the enrichment of CD8A in lipid rafts.1 Publication
O-glycosylated.1 Publication
Phosphorylated in cytotoxic T-lymphocytes (CTLs) following activation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP01732.
PeptideAtlasiP01732.
PRIDEiP01732.

PTM databases

iPTMnetiP01732.
PhosphoSitePlusiP01732.

Expressioni

Tissue specificityi

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 homo-dimers. Expressed at the cell surface of plasmacytoid dendritic cells upon herpes simplex virus-1 stimulation.3 Publications

Gene expression databases

BgeeiENSG00000153563.
CleanExiHS_CD8A.
HS_MAL.
ExpressionAtlasiP01732. baseline and differential.
GenevisibleiP01732. HS.

Organism-specific databases

HPAiCAB000012.
CAB075722.
HPA037756.

Interactioni

Subunit structurei

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. Interacts with LCK in a zinc-dependent manner.3 Publications

GO - Molecular functioni

  • MHC class I protein binding Source: UniProtKB
  • protein homodimerization activity Source: Ensembl
  • protein kinase binding Source: Ensembl

Protein-protein interaction databases

BioGridi107363. 14 interactors.
CORUMiP01732.
IntActiP01732. 4 interactors.
STRINGi9606.ENSP00000283635.

Structurei

Secondary structure

1235
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi24 – 27Combined sources4
Beta strandi39 – 45Combined sources7
Beta strandi54 – 64Combined sources11
Beta strandi68 – 77Combined sources10
Turni86 – 88Combined sources3
Beta strandi89 – 94Combined sources6
Beta strandi97 – 104Combined sources8
Helixi107 – 109Combined sources3
Beta strandi111 – 119Combined sources9
Beta strandi122 – 125Combined sources4
Beta strandi129 – 131Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AKJX-ray2.65D/E22-141[»]
1CD8X-ray2.60A22-135[»]
1Q69NMR-A209-227[»]
2HP4X-ray2.10A/B22-135[»]
3QZWX-ray2.80G/H/I/J22-135[»]
ProteinModelPortaliP01732.
SMRiP01732.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01732.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 135Ig-like V-typeAdd BLAST114

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWN3. Eukaryota.
ENOG410Z6EI. LUCA.
GeneTreeiENSGT00510000048935.
HOGENOMiHOG000004794.
HOVERGENiHBG008488.
InParanoidiP01732.
KOiK06458.
OMAiRVCKCPR.
OrthoDBiEOG091G0YIT.
PhylomeDBiP01732.
TreeFamiTF336070.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiView protein in InterPro
IPR015468. CD8_asu.
IPR007110. Ig-like_dom.
IPR036179. Ig-like_dom_sf.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
PANTHERiPTHR10441. PTHR10441. 1 hit.
PfamiView protein in Pfam
PF07686. V-set. 1 hit.
SMARTiView protein in SMART
SM00409. IG. 1 hit.
SM00406. IGv. 1 hit.
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01732-1) [UniParc]FASTAAdd to basket
Also known as: membrane, mCD8alpha

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.

« Hide

        10         20         30         40         50
MALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP
60 70 80 90 100
TSGCSWLFQP RGAAASPTFL LYLSQNKPKA AEGLDTQRFS GKRLGDTFVL
110 120 130 140 150
TLSDFRRENE GYYFCSALSN SIMYFSHFVP VFLPAKPTTT PAPRPPTPAP
160 170 180 190 200
TIASQPLSLR PEACRPAAGG AVHTRGLDFA CDIYIWAPLA GTCGVLLLSL
210 220 230
VITLYCNHRN RRRVCKCPRP VVKSGDKPSL SARYV
Length:235
Mass (Da):25,729
Last modified:July 21, 1986 - v1
Checksum:iFCCA29BAA73726BB
GO
Isoform 2 (identifier: P01732-2) [UniParc]FASTAAdd to basket
Also known as: secreted, sCD8alpha

The sequence of this isoform differs from the canonical sequence as follows:
     172-209: VHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHR → G

Show »
Length:198
Mass (Da):21,585
Checksum:iBC89FA59F150598F
GO
Isoform 3 (identifier: P01732-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRNQAPGRPKGATFPPRRPTGSRAPPLAPELRAKQRPGERVM

Note: No experimental confirmation available.
Show »
Length:276
Mass (Da):30,214
Checksum:i0D75B1136A240ED4
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021020111G → S in CD8 deficiency; prevents CD8 expression. 1 PublicationCorresponds to variant dbSNP:rs121918660Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0544381M → MRNQAPGRPKGATFPPRRPT GSRAPPLAPELRAKQRPGER VM in isoform 3. 1 Publication1
Alternative sequenceiVSP_012653172 – 209VHTRG…YCNHR → G in isoform 2. CuratedAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M26315, M26313, M26314 Genomic DNA. Translation: AAA79217.1.
M26315, M26313, M26314 Genomic DNA. Translation: AAA79218.1.
M12824 mRNA. Translation: AAA61133.1.
M12828 mRNA. Translation: AAB04637.1.
M27161 Genomic DNA. Translation: AAA59674.1.
AK300089 mRNA. Translation: BAG61892.1.
AC064848 Genomic DNA. Translation: AAX88864.1.
AC112696 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAW99438.1.
CH471053 Genomic DNA. Translation: EAW99439.1.
CH471053 Genomic DNA. Translation: EAW99440.1.
CCDSiCCDS1992.1. [P01732-1]
CCDS1993.1. [P01732-2]
PIRiA30604. RWHUT8.
RefSeqiNP_001139345.1. NM_001145873.1. [P01732-1]
NP_001759.3. NM_001768.6. [P01732-1]
NP_741969.1. NM_171827.3. [P01732-2]
UniGeneiHs.85258.

Genome annotation databases

EnsembliENST00000283635; ENSP00000283635; ENSG00000153563. [P01732-1]
ENST00000352580; ENSP00000321631; ENSG00000153563. [P01732-2]
ENST00000409511; ENSP00000386559; ENSG00000153563. [P01732-1]
GeneIDi925.
KEGGihsa:925.
UCSCiuc002srt.4. human. [P01732-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCD8A_HUMAN
AccessioniPrimary (citable) accession number: P01732
Secondary accession number(s): B4DT80
, D6W5M8, Q13970, Q4ZG17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 25, 2017
This is version 191 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references