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Protein

T-cell surface glycoprotein CD8 alpha chain

Gene

Cd8a

Organism
Mus musculus (Mouse)
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.By similarity2 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: MGI
  • protein kinase binding Source: Ensembl

GO - Biological processi

  • cell surface receptor signaling pathway Source: MGI
  • cytotoxic T cell differentiation Source: MGI
  • defense response to virus Source: MGI
  • positive regulation of calcium-mediated signaling Source: MGI
  • T cell mediated immunity Source: MGI

Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
T-cell surface glycoprotein CD8 alpha chain
Alternative name(s):
T-cell surface glycoprotein Lyt-2
CD_antigen: CD8a
Gene namesi
Name:Cd8a
Synonyms:Lyt-2, Lyt2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:88346. 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 domaini28 – 196ExtracellularSequence analysisAdd BLAST169
Transmembranei197 – 217HelicalSequence analysisAdd BLAST21
Topological domaini218 – 247CytoplasmicSequence analysisAdd BLAST30

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Cd8a-deficient mice prevent the development of class I MHC restricted cytotoxic T-cells. However, maturation of class II MHC restricted T-helper cells seems to be unaffected by the absence of Cd8a.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Add BLAST27
ChainiPRO_000001463928 – 247T-cell surface glycoprotein CD8 alpha chainAdd BLAST220

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 129PROSITE-ProRule annotation1 Publication
Glycosylationi69N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi97N-linked (GlcNAc...) asparagine1
Glycosylationi150N-linked (GlcNAc...) asparagine1

Post-translational modificationi

Palmitoylated, but association with CD8B seems to be more important for the enrichment of CdD8A in lipid rafts.By similarity
Phosphorylated in cytotoxic T-lymphocytes (CTLs) following activation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

EPDiP01731.
MaxQBiP01731.
PaxDbiP01731.
PRIDEiP01731.

PTM databases

iPTMnetiP01731.
PhosphoSitePlusiP01731.

Expressioni

Gene expression databases

BgeeiENSMUSG00000053977.
CleanExiMM_CD8A.
ExpressionAtlasiP01731. baseline and differential.
GenevisibleiP01731. MM.

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.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LckP062402EBI-1433,EBI-1401

GO - Molecular functioni

  • protein homodimerization activity Source: MGI
  • protein kinase binding Source: Ensembl

Protein-protein interaction databases

IntActiP01731. 4 interactors.
MINTiMINT-7895757.
STRINGi10090.ENSMUSP00000068123.

Structurei

Secondary structure

1247
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi33 – 39Combined sources7
Beta strandi41 – 43Combined sources3
Beta strandi49 – 57Combined sources9
Beta strandi63 – 71Combined sources9
Beta strandi78 – 83Combined sources6
Beta strandi85 – 87Combined sources3
Beta strandi90 – 92Combined sources3
Turni94 – 97Combined sources4
Helixi98 – 100Combined sources3
Beta strandi102 – 107Combined sources6
Turni108 – 110Combined sources3
Beta strandi111 – 118Combined sources8
Helixi121 – 123Combined sources3
Beta strandi125 – 133Combined sources9
Beta strandi136 – 139Combined sources4
Beta strandi143 – 147Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BQHX-ray2.80G/H/I/K28-156[»]
1NEZX-ray2.10G/H28-149[»]
2ARJX-ray2.88Q/R28-150[»]
2ATPX-ray2.40A/C28-149[»]
3B9KX-ray2.70A/E28-151[»]
3DMMX-ray2.60C23-188[»]
ProteinModelPortaliP01731.
SMRiP01731.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01731.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 139Ig-like V-typeAdd BLAST112

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IWN3. Eukaryota.
ENOG410Z6EI. LUCA.
GeneTreeiENSGT00510000048935.
HOGENOMiHOG000004794.
HOVERGENiHBG008488.
InParanoidiP01731.
KOiK06458.
OMAiRVCKCPR.
OrthoDBiEOG091G0YIT.
PhylomeDBiP01731.
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.

Sequencei

Sequence statusi: Complete.

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

This entry describes 1 isoform i produced by alternative splicing. AlignAdd to basket

Note: A number of isoforms are produced. Alternative splicing involves excision of the transmembrane or cytoplasmic domains.
Isoform 1 (identifier: P01731-1) [UniParc]FASTAAdd to basket

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
MASPLTRFLS LNLLLLGESI ILGSGEAKPQ APELRIFPKK MDAELGQKVD
60 70 80 90 100
LVCEVLGSVS QGCSWLFQNS SSKLPQPTFV VYMASSHNKI TWDEKLNSSK
110 120 130 140 150
LFSAMRDTNN KYVLTLNKFS KENEGYYFCS VISNSVMYFS SVVPVLQKVN
160 170 180 190 200
STTTKPVLRT PSPVHPTGTS QPQRPEDCRP RGSVKGTGLD FACDIYIWAP
210 220 230 240
LAGICVALLL SLIITLICYH RSRKRVCKCP RPLVRQEGKP RPSEKIV
Length:247
Mass (Da):27,456
Last modified:July 21, 1986 - v1
Checksum:i22D0D78ECEC3EA04
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti81Missing in AAA39477 (PubMed:3495785).Curated1
Sequence conflicti81Missing in CAA68352 (PubMed:3495785).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti105M → V in strain: C.AKR. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12825 mRNA. Translation: AAA39476.1.
M16981 mRNA. Translation: AAA39477.1. Different termination.
M12052 mRNA. Translation: AAA39478.1.
Y00157 Genomic DNA. Translation: CAA68352.2.
M22064 Genomic DNA. Translation: AAA39665.1.
M12977
, M12819, M12975, M12976 Genomic DNA. Translation: AAA39475.1.
CCDSiCCDS39507.1. [P01731-1]
PIRiA01998. RWMST2.
A29523.
A34954.
RefSeqiNP_001074579.1. NM_001081110.2. [P01731-1]
UniGeneiMm.1858.

Genome annotation databases

EnsembliENSMUST00000066747; ENSMUSP00000068123; ENSMUSG00000053977. [P01731-1]
GeneIDi12525.
KEGGimmu:12525.
UCSCiuc009cgr.1. mouse. [P01731-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCD8A_MOUSE
AccessioniPrimary (citable) accession number: P01731
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 22, 2017
This is version 171 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references