ID   CTLA4_MOUSE             Reviewed;         223 AA.
AC   P09793; Q9QZZ7;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   08-NOV-2023, entry version 178.
DE   RecName: Full=Cytotoxic T-lymphocyte protein 4;
DE   AltName: Full=Cytotoxic T-lymphocyte-associated antigen 4;
DE            Short=CTLA-4;
DE   AltName: CD_antigen=CD152;
DE   Flags: Precursor;
GN   Name=Ctla4; Synonyms=Cd152;
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].
RX   PubMed=3496540; DOI=10.1038/328267a0;
RA   Brunet J.-F., Denizot F., Luciani M.-F., Roux-Dosseto M., Suzan M.,
RA   Mattei M.-G., Golstein P.;
RT   "A new member of the immunoglobulin superfamily -- CTLA-4.";
RL   Nature 328:267-270(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC   STRAIN=129/SvJ;
RX   PubMed=10493833; DOI=10.1006/geno.1999.5930;
RA   Ling V., Wu P.W., Finnerty H.F., Sharpe A.H., Gray G.S., Collins M.;
RT   "Complete sequence determination of the mouse and human CTLA4 gene loci:
RT   cross-species DNA sequence similarity beyond exon borders.";
RL   Genomics 60:341-355(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE OF 1-36.
RX   PubMed=1713603;
RA   Harper K., Balzano C., Rouvier E., Mattei M.-G., Luciani M.-F.,
RA   Golstein P.;
RT   "CTLA-4 and CD28 activated lymphocyte molecules are closely related in both
RT   mouse and human as to sequence, message expression, gene structure, and
RT   chromosomal location.";
RL   J. Immunol. 147:1037-1044(1991).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 38-154, AND DISULFIDE BONDS.
RX   PubMed=11052947; DOI=10.1126/science.290.5492.816;
RA   Ostrov D.A., Shi W., Schwartz J.-C., Almo S.C., Nathenson S.G.;
RT   "Structure of murine CTLA-4 and its role in modulating T cell
RT   responsiveness.";
RL   Science 290:816-819(2000).
CC   -!- FUNCTION: Inhibitory receptor acting as a major negative regulator of
CC       T-cell responses. The affinity of CTLA4 for its natural B7 family
CC       ligands, CD80 and CD86, is considerably stronger than the affinity of
CC       their cognate stimulatory coreceptor CD28.
CC       {ECO:0000250|UniProtKB:P16410}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2.
CC       Interacts with ICOSLG. {ECO:0000250|UniProtKB:P16410}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P16410};
CC       Single-pass type I membrane protein {ECO:0000250|UniProtKB:P16410}.
CC       Note=Exists primarily an intracellular antigen whose surface expression
CC       is tightly regulated by restricted trafficking to the cell surface and
CC       rapid internalization. {ECO:0000250|UniProtKB:P16410}.
CC   -!- TISSUE SPECIFICITY: Widely expressed with highest levels in lymphoid
CC       tissues. {ECO:0000269|PubMed:10493833}.
CC   -!- PTM: N-glycosylation is important for dimerization.
CC       {ECO:0000250|UniProtKB:P16410}.
CC   -!- PTM: Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter
CC       complex, blocks endocytosis, and leads to retention of CTLA4 on the
CC       cell surface. {ECO:0000250|UniProtKB:P16410}.
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DR   EMBL; X05719; CAA29191.1; -; mRNA.
DR   EMBL; AF142145; AAF01489.1; -; Genomic_DNA.
DR   EMBL; M74362; AAA37489.1; -; Genomic_DNA.
DR   CCDS; CCDS14993.1; -.
DR   PIR; A29063; A29063.
DR   RefSeq; NP_033973.2; NM_009843.4.
DR   PDB; 1DQT; X-ray; 2.00 A; A/B/C/D=38-154.
DR   PDB; 5E56; X-ray; 1.50 A; A=38-154.
DR   PDB; 5E5M; X-ray; 2.18 A; A/C/E/G=38-154.
DR   PDBsum; 1DQT; -.
DR   PDBsum; 5E56; -.
DR   PDBsum; 5E5M; -.
DR   AlphaFoldDB; P09793; -.
DR   SMR; P09793; -.
DR   BioGRID; 198575; 1.
DR   ELM; P09793; -.
DR   IntAct; P09793; 1.
DR   MINT; P09793; -.
DR   STRING; 10090.ENSMUSP00000027164; -.
DR   GlyCosmos; P09793; 3 sites, No reported glycans.
DR   GlyGen; P09793; 3 sites.
DR   iPTMnet; P09793; -.
DR   PhosphoSitePlus; P09793; -.
DR   EPD; P09793; -.
DR   PaxDb; 10090-ENSMUSP00000027164; -.
DR   ProteomicsDB; 285397; -.
DR   ABCD; P09793; 1 sequenced antibody.
DR   DNASU; 12477; -.
DR   GeneID; 12477; -.
DR   KEGG; mmu:12477; -.
DR   AGR; MGI:88556; -.
DR   CTD; 1493; -.
DR   MGI; MGI:88556; Ctla4.
DR   eggNOG; ENOG502RZVK; Eukaryota.
DR   InParanoid; P09793; -.
DR   OrthoDB; 4108912at2759; -.
DR   PhylomeDB; P09793; -.
DR   Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR   BioGRID-ORCS; 12477; 1 hit in 82 CRISPR screens.
DR   ChiTaRS; Ctla4; mouse.
DR   EvolutionaryTrace; P09793; -.
DR   PRO; PR:P09793; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; P09793; Protein.
DR   GO; GO:0045334; C:clathrin-coated endocytic vesicle; ISO:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098636; C:protein complex involved in cell adhesion; ISO:MGI.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0050853; P:B cell receptor signaling pathway; ISO:MGI.
DR   GO; GO:0006974; P:DNA damage response; ISO:MGI.
DR   GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:MGI.
DR   GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISO:MGI.
DR   GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:MGI.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR   CDD; cd05721; IgV_CTLA-4; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   InterPro; IPR008096; CTLA4.
DR   InterPro; IPR040216; CTLA4/CD28.
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; PTHR11494; CYTOTOXIC T-LYMPHOCYTE PROTEIN; 1.
DR   PANTHER; PTHR11494:SF8; CYTOTOXIC T-LYMPHOCYTE PROTEIN 4; 1.
DR   Pfam; PF07686; V-set; 1.
DR   PRINTS; PR01720; CTLANTIGEN4.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00406; IGv; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW   Glycoprotein; Immunity; Immunoglobulin domain; Membrane; Phosphoprotein;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..35
FT                   /evidence="ECO:0000255"
FT   CHAIN           36..223
FT                   /note="Cytotoxic T-lymphocyte protein 4"
FT                   /id="PRO_0000014735"
FT   TOPO_DOM        36..161
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        162..182
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        183..223
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          36..145
FT                   /note="Ig-like V-type"
FT   REGION          46..50
FT                   /note="Homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:P16410"
FT   REGION          134..139
FT                   /note="Important for interaction with CD80 and CD86"
FT                   /evidence="ECO:0000250|UniProtKB:P16410"
FT   REGION          150..155
FT                   /note="Homodimerization"
FT                   /evidence="ECO:0000250|UniProtKB:P16410"
FT   MOD_RES         201
FT                   /note="Phosphotyrosine; by TXK and JAK2"
FT                   /evidence="ECO:0000250|UniProtKB:P16410"
FT   CARBOHYD        108
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        113
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        58..129
FT                   /evidence="ECO:0000269|PubMed:11052947,
FT                   ECO:0007744|PDB:1DQT"
FT   DISULFID        85..103
FT                   /evidence="ECO:0000269|PubMed:11052947,
FT                   ECO:0007744|PDB:1DQT"
FT   DISULFID        157
FT                   /note="Interchain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   CONFLICT        182
FT                   /note="S -> T (in Ref. 2; AAF01489)"
FT                   /evidence="ECO:0000305"
FT   STRAND          39..41
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          44..47
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          54..62
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          68..79
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          81..89
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          91..96
FT                   /evidence="ECO:0007829|PDB:1DQT"
FT   STRAND          103..108
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          111..116
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   HELIX           121..123
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          125..138
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          140..143
FT                   /evidence="ECO:0007829|PDB:5E56"
FT   STRAND          147..150
FT                   /evidence="ECO:0007829|PDB:5E56"
SQ   SEQUENCE   223 AA;  24993 MW;  5318FAAF416F4685 CRC64;
     MACLGLRRYK AQLQLPSRTW PFVALLTLLF IPVFSEAIQV TQPSVVLASS HGVASFPCEY
     SPSHNTDEVR VTVLRQTNDQ MTEVCATTFT EKNTVGFLDY PFCSGTFNES RVNLTIQGLR
     AVDTGLYLCK VELMYPPPYF VGMGNGTQIY VIDPEPCPDS DFLLWILVAV SLGLFFYSFL
     VSAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN
//