CD8A_MOUSE
ID CD8A_MOUSE Reviewed; 247 AA.
AC P01731;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=T-cell surface glycoprotein CD8 alpha chain;
DE AltName: Full=T-cell surface glycoprotein Lyt-2;
DE AltName: CD_antigen=CD8a;
DE Flags: Precursor;
GN Name=Cd8a; Synonyms=Lyt-2, Lyt2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=3927298; DOI=10.1073/pnas.82.15.5126;
RA Nakauchi H., Nolan G.P., Hsu C., Huang H.S., Kavathas P., Herzenberg L.A.;
RT "Molecular cloning of Lyt-2, a membrane glycoprotein marking a subset of
RT mouse T lymphocytes: molecular homology to its human counterpart, Leu-2/T8,
RT and to immunoglobulin variable regions.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:5126-5130(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3935316; DOI=10.1016/0092-8674(85)90020-0;
RA Zamoyska R., Vollmer A.C., Sizer K.C., Liaw C.W., Parnes J.R.;
RT "Two Lyt-2 polypeptides arise from a single gene by alternative splicing
RT patterns of mRNA.";
RL Cell 43:153-163(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3495785; DOI=10.1093/nar/15.10.4337;
RA Nakauchi H., Tagawa M., Nolan G.P., Herzenberg L.A.;
RT "Isolation and characterization of the gene for the murine T cell
RT differentiation antigen and immunoglobulin-related molecule, Lyt-2.";
RL Nucleic Acids Res. 15:4337-4347(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C.AKR;
RX PubMed=3267233; DOI=10.1007/bf00364233;
RA Youn H.J., Harriss J.V., Gottlieb P.D.;
RT "Nucleotide sequence analysis of the C.AKR Lyt-2a gene: structural
RT polymorphism in alleles encoding the Lyt-2.1 T-cell surface alloantigen.";
RL Immunogenetics 28:345-352(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3487583;
RA Liaw C.W., Zamoyska R., Parnes J.R.;
RT "Structure, sequence, and polymorphism of the Lyt-2 T cell differentiation
RT antigen gene.";
RL J. Immunol. 137:1037-1043(1986).
RN [6]
RP PHOSPHORYLATION.
RX PubMed=2512251; DOI=10.1007/bf02421181;
RA DiSanto J.P., Klein J.S., Flomenberg N.;
RT "Phosphorylation and down-regulation of CD4 and CD8 in human CTLs and mouse
RT L cells.";
RL Immunogenetics 30:494-501(1989).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=1673361; DOI=10.1016/0092-8674(91)90462-8;
RA Fung-Leung W.P., Schilham M.W., Rahemtulla A., Kuendig T.M.,
RA Vollenweider M., Potter J., van Ewijk W., Mak T.W.;
RT "CD8 is needed for development of cytotoxic T cells but not helper T
RT cells.";
RL Cell 65:443-449(1991).
RN [8]
RP FUNCTION.
RX PubMed=15105501; DOI=10.1126/science.1092316;
RA Madakamutil L.T., Christen U., Lena C.J., Wang-Zhu Y., Attinger A.,
RA Sundarrajan M., Ellmeier W., von Herrath M.G., Jensen P., Littman D.R.,
RA Cheroutre H.;
RT "CD8alphaalpha-mediated survival and differentiation of CD8 memory T cell
RT precursors.";
RL Science 304:590-593(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-152 IN COMPLEX WITH H-2KB.
RX PubMed=9806638; DOI=10.1016/s1074-7613(00)80635-4;
RA Kern P.S., Teng M.K., Smolyar A., Liu J.H., Liu J., Hussey R.E., Spoerl R.,
RA Chang H.-C., Reinherz E.L., Wang J.-H.;
RT "Structural basis of CD8 coreceptor function revealed by crystallographic
RT analysis of a murine CD8alphaalpha ectodomain fragment in complex with H-
RT 2Kb.";
RL Immunity 9:519-530(1998).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 28-151 IN COMPLEX WITH CD8B AND
RP ANTIBODY, SUBUNIT, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-69.
RX PubMed=18929574; DOI=10.1016/j.jmb.2008.09.069;
RA Shore D.A., Issafras H., Landais E., Teyton L., Wilson I.A.;
RT "The crystal structure of CD8 in complex with YTS156.7.7 Fab and
RT interaction with other CD8 antibodies define the binding mode of CD8
RT alphabeta to MHC class I.";
RL J. Mol. Biol. 384:1190-1202(2008).
CC -!- FUNCTION: Integral membrane glycoprotein that plays an essential role
CC in the immune response and serves multiple functions in responses
CC against both external and internal offenses. In T-cells, functions
CC primarily as a coreceptor for MHC class I molecule:peptide complex. The
CC antigens presented by class I peptides are derived from cytosolic
CC proteins while class II derived from extracellular proteins. Interacts
CC simultaneously with the T-cell receptor (TCR) and the MHC class I
CC proteins presented by antigen presenting cells (APCs). In turn,
CC recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK
CC then initiates different intracellular signaling pathways by
CC phosphorylating various substrates ultimately leading to lymphokine
CC production, motility, adhesion and activation of cytotoxic T-
CC lymphocytes (CTLs). This mechanism enables CTLs to recognize and
CC eliminate infected cells and tumor cells. In NK-cells, the presence of
CC CD8A homodimers at the cell surface provides a survival mechanism
CC allowing conjugation and lysis of multiple target cells. CD8A homodimer
CC molecules also promote the survival and differentiation of activated
CC lymphocytes into memory CD8 T-cells. {ECO:0000250|UniProtKB:P01732,
CC ECO:0000269|PubMed:15105501, ECO:0000269|PubMed:1673361}.
CC -!- SUBUNIT: Forms disulfide-linked heterodimers with CD8B at the cell
CC surface. Forms also homodimers in several cell types including NK-cells
CC or peripheral blood T-lymphocytes. Interacts with the MHC class I HLA-
CC A/B2M dimer. Interacts with LCK in a zinc-dependent manner.
CC {ECO:0000250|UniProtKB:P01732, ECO:0000269|PubMed:18929574,
CC ECO:0000269|PubMed:9806638}.
CC -!- INTERACTION:
CC P01731; P06240: Lck; NbExp=2; IntAct=EBI-1433, EBI-1401;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01732};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01732}.
CC Note=Cd8a localizes to lipid rafts only when associated with its
CC partner Cd8b. {ECO:0000250|UniProtKB:P01732}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A number of isoforms are produced. Alternative splicing
CC involves excision of the transmembrane or cytoplasmic domains.;
CC Name=1;
CC IsoId=P01731-1; Sequence=Displayed;
CC -!- PTM: Palmitoylated, but association with CD8B seems to be more
CC important for the enrichment of CdD8A in lipid rafts.
CC {ECO:0000250|UniProtKB:P01732}.
CC -!- PTM: Phosphorylated in cytotoxic T-lymphocytes (CTLs) following
CC activation. {ECO:0000269|PubMed:2512251}.
CC -!- DISRUPTION PHENOTYPE: Cd8a-deficient mice prevent the development of
CC class I MHC restricted cytotoxic T-cells. However, maturation of class
CC II MHC restricted T-helper cells seems to be unaffected by the absence
CC of Cd8a. {ECO:0000269|PubMed:1673361}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M12825; AAA39476.1; -; mRNA.
DR EMBL; M16981; AAA39477.1; ALT_TERM; mRNA.
DR EMBL; M12052; AAA39478.1; -; mRNA.
DR EMBL; Y00157; CAA68352.2; -; Genomic_DNA.
DR EMBL; M22064; AAA39665.1; -; Genomic_DNA.
DR EMBL; M12977; AAA39475.1; -; Genomic_DNA.
DR EMBL; M12819; AAA39475.1; JOINED; Genomic_DNA.
DR EMBL; M12975; AAA39475.1; JOINED; Genomic_DNA.
DR EMBL; M12976; AAA39475.1; JOINED; Genomic_DNA.
DR CCDS; CCDS39507.1; -. [P01731-1]
DR PIR; A01998; RWMST2.
DR PIR; A29523; A29523.
DR PIR; A34954; A34954.
DR RefSeq; NP_001074579.1; NM_001081110.2. [P01731-1]
DR PDB; 1BQH; X-ray; 2.80 A; G/H/I/K=28-156.
DR PDB; 1NEZ; X-ray; 2.10 A; G/H=28-149.
DR PDB; 2ARJ; X-ray; 2.88 A; Q/R=28-150.
DR PDB; 2ATP; X-ray; 2.40 A; A/C=28-149.
DR PDB; 3B9K; X-ray; 2.70 A; A/E=28-151.
DR PDB; 3DMM; X-ray; 2.60 A; C=23-188.
DR PDBsum; 1BQH; -.
DR PDBsum; 1NEZ; -.
DR PDBsum; 2ARJ; -.
DR PDBsum; 2ATP; -.
DR PDBsum; 3B9K; -.
DR PDBsum; 3DMM; -.
DR AlphaFoldDB; P01731; -.
DR SMR; P01731; -.
DR ComplexPortal; CPX-6702; CD8alpha-beta complex.
DR ComplexPortal; CPX-6742; CD8alpha-alpha complex.
DR IntAct; P01731; 4.
DR MINT; P01731; -.
DR STRING; 10090.ENSMUSP00000068123; -.
DR GlyGen; P01731; 3 sites.
DR iPTMnet; P01731; -.
DR PhosphoSitePlus; P01731; -.
DR EPD; P01731; -.
DR MaxQB; P01731; -.
DR PaxDb; P01731; -.
DR PRIDE; P01731; -.
DR ProteomicsDB; 281350; -. [P01731-1]
DR ABCD; P01731; 12 sequenced antibodies.
DR Antibodypedia; 3495; 5216 antibodies from 57 providers.
DR DNASU; 12525; -.
DR Ensembl; ENSMUST00000066747; ENSMUSP00000068123; ENSMUSG00000053977. [P01731-1]
DR GeneID; 12525; -.
DR KEGG; mmu:12525; -.
DR UCSC; uc009cgr.1; mouse. [P01731-1]
DR CTD; 925; -.
DR MGI; MGI:88346; Cd8a.
DR VEuPathDB; HostDB:ENSMUSG00000053977; -.
DR eggNOG; ENOG502SAZN; Eukaryota.
DR GeneTree; ENSGT00940000156588; -.
DR HOGENOM; CLU_085753_0_0_1; -.
DR InParanoid; P01731; -.
DR OMA; FRMSPTQ; -.
DR OrthoDB; 1448152at2759; -.
DR PhylomeDB; P01731; -.
DR TreeFam; TF336070; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR BioGRID-ORCS; 12525; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Cd8a; mouse.
DR EvolutionaryTrace; P01731; -.
DR PRO; PR:P01731; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P01731; protein.
DR Bgee; ENSMUSG00000053977; Expressed in thymus and 57 other tissues.
DR ExpressionAtlas; P01731; baseline and differential.
DR Genevisible; P01731; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:ComplexPortal.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IPI:ComplexPortal.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0023024; F:MHC class I protein complex binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IC:ComplexPortal.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:MGI.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0045065; P:cytotoxic T cell differentiation; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; IDA:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IDA:MGI.
DR GO; GO:0042110; P:T cell activation; ISO:MGI.
DR GO; GO:0002456; P:T cell mediated immunity; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR015468; CD8_asu.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR PANTHER; PTHR10441; PTHR10441; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00406; IGv; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Lipoprotein;
KW Membrane; Palmitate; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..27
FT CHAIN 28..247
FT /note="T-cell surface glycoprotein CD8 alpha chain"
FT /id="PRO_0000014639"
FT TOPO_DOM 28..196
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..217
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 218..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..139
FT /note="Ig-like V-type"
FT REGION 156..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..176
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18929574"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 53..129
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18929574"
FT VARIANT 105
FT /note="M -> V (in strain: C.AKR)"
FT CONFLICT 81
FT /note="Missing (in Ref. 3; AAA39477/CAA68352)"
FT /evidence="ECO:0000305"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:1NEZ"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:1NEZ"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:1NEZ"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 111..118
FT /evidence="ECO:0007829|PDB:1NEZ"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1NEZ"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:1NEZ"
SQ SEQUENCE 247 AA; 27456 MW; 22D0D78ECEC3EA04 CRC64;
MASPLTRFLS LNLLLLGESI ILGSGEAKPQ APELRIFPKK MDAELGQKVD LVCEVLGSVS
QGCSWLFQNS SSKLPQPTFV VYMASSHNKI TWDEKLNSSK LFSAMRDTNN KYVLTLNKFS
KENEGYYFCS VISNSVMYFS SVVPVLQKVN STTTKPVLRT PSPVHPTGTS QPQRPEDCRP
RGSVKGTGLD FACDIYIWAP LAGICVALLL SLIITLICYH RSRKRVCKCP RPLVRQEGKP
RPSEKIV
