CTLA4_MOUSE
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 25-MAY-2022, entry version 172.
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 GlyGen; P09793; 3 sites.
DR iPTMnet; P09793; -.
DR PhosphoSitePlus; P09793; -.
DR EPD; P09793; -.
DR PaxDb; P09793; -.
DR PRIDE; P09793; -.
DR ProteomicsDB; 285397; -.
DR ABCD; P09793; 1 sequenced antibody.
DR DNASU; 12477; -.
DR GeneID; 12477; -.
DR KEGG; mmu:12477; -.
DR CTD; 1493; -.
DR MGI; MGI:88556; Ctla4.
DR eggNOG; ENOG502RZVK; Eukaryota.
DR InParanoid; P09793; -.
DR OrthoDB; 1222373at2759; -.
DR PhylomeDB; P09793; -.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR BioGRID-ORCS; 12477; 1 hit in 77 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:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
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:cellular response to DNA damage stimulus; 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:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0042129; P:regulation of T cell proliferation; IEA:InterPro.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 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; PTHR11494; 1.
DR PANTHER; PTHR11494:SF8; PTHR11494:SF8; 1.
DR Pfam; PF07686; V-set; 1.
DR PRINTS; PR01720; CTLANTIGEN4.
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; 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
