ID   CTLA4_RABIT             Reviewed;         223 AA.
AC   P42072;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   25-MAY-2022, entry version 117.
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;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=B/J X Chbb:HM;
RX   PubMed=7642234; DOI=10.1007/bf00191228;
RA   Isono T., Seto A.;
RT   "Cloning and sequencing of the rabbit gene encoding T-cell costimulatory
RT   molecules.";
RL   Immunogenetics 42:217-220(1995).
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   -!- 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; D49844; BAA08644.1; -; mRNA.
DR   PIR; I46696; I46696.
DR   RefSeq; NP_001076154.1; NM_001082685.2.
DR   AlphaFoldDB; P42072; -.
DR   SMR; P42072; -.
DR   STRING; 9986.ENSOCUP00000017677; -.
DR   GeneID; 100009412; -.
DR   KEGG; ocu:100009412; -.
DR   CTD; 1493; -.
DR   eggNOG; ENOG502RZVK; Eukaryota.
DR   InParanoid; P42072; -.
DR   OrthoDB; 1222373at2759; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:0042129; P:regulation of T cell proliferation; IEA:InterPro.
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   2: Evidence at transcript level;
KW   Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW   Immunoglobulin domain; Membrane; Phosphoprotein; Reference proteome;
KW   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_0000014737"
FT   TOPO_DOM        38..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        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:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        85..103
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        157
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:P16410"
SQ   SEQUENCE   223 AA;  24656 MW;  85A9269793B88160 CRC64;
     MARLGFQRQG TQLDLASRTW SCAALFSLLF LPVFSKALHV SQPAVVLASS RGVASFVCEY
     ASSHKATEVR VTVLRQANSQ MTEVCAMTYT VENELTFIDD STCTGISHGN KVNLTIQGLS
     AMDTGLYICK VELMYPPPYY VGMGNGTQIY VIEPEPCPDS DFLLWILAAI SSGLFFYSFL
     ITAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN