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   27-MAR-2024, entry version 206.
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}.
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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   GlyCosmos; P01731; 3 sites, No reported glycans.
DR   GlyGen; P01731; 3 sites.
DR   iPTMnet; P01731; -.
DR   PhosphoSitePlus; P01731; -.
DR   EPD; P01731; -.
DR   MaxQB; P01731; -.
DR   PaxDb; 10090-ENSMUSP00000068123; -.
DR   ProteomicsDB; 281350; -. [P01731-1]
DR   ABCD; P01731; 12 sequenced antibodies.
DR   Antibodypedia; 3495; 5840 antibodies from 57 providers.
DR   DNASU; 12525; -.
DR   Ensembl; ENSMUST00000066747.14; ENSMUSP00000068123.8; ENSMUSG00000053977.14. [P01731-1]
DR   GeneID; 12525; -.
DR   KEGG; mmu:12525; -.
DR   UCSC; uc009cgr.1; mouse. [P01731-1]
DR   AGR; MGI:88346; -.
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; 5323965at2759; -.
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 79 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 58 other cell types or tissues.
DR   ExpressionAtlas; P01731; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
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; NAS: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   CDD; cd05720; IgV_CD8_alpha; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 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; CD8 ALPHA CHAIN; 1.
DR   PANTHER; PTHR10441:SF2; T-CELL SURFACE GLYCOPROTEIN CD8 ALPHA CHAIN; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00406; IGv; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   Genevisible; P01731; MM.
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
//