ID CD4_MACFU Reviewed; 458 AA. AC P79184; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 03-AUG-2022, entry version 96. DE RecName: Full=T-cell surface glycoprotein CD4; DE AltName: Full=T-cell surface antigen T4/Leu-3; DE AltName: CD_antigen=CD4; DE Flags: Precursor; GN Name=CD4; OS Macaca fuscata fuscata (Japanese macaque). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; OC Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9543; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Hashimoto O., Tatsumi M.; RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases. 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 II molecule:peptide complex. CC The antigens presented by class II peptides are derived from CC extracellular proteins while class I peptides are derived from CC cytosolic proteins. Interacts simultaneously with the T-cell receptor CC (TCR) and the MHC class II presented by antigen presenting cells CC (APCs). In turn, recruits the Src kinase LCK to the vicinity of the CC TCR-CD3 complex. LCK then initiates different intracellular signaling CC pathways by phosphorylating various substrates ultimately leading to CC lymphokine production, motility, adhesion and activation of T-helper CC cells. In other cells such as macrophages or NK cells, plays a role in CC differentiation/activation, cytokine expression and cell migration in a CC TCR/LCK-independent pathway. Participates in the development of T- CC helper cells in the thymus and triggers the differentiation of CC monocytes into functional mature macrophages. CC {ECO:0000250|UniProtKB:P01730}. CC -!- SUBUNIT: Forms disulfide-linked homodimers at the cell surface. CC Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI. CC Interacts with IL16; this interaction induces a CD4-dependent signaling CC in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha CC chain (via alpha-2 domain) and beta chain (via beta-2 domain); this CC interaction increases the affinity of TCR for peptide-MHCII. CD4 CC oligomerization via Ig-like C2-type 2 and 3 domains appears to be CC required for stable binding to MHCII and adhesion between T cells and CC APCs. {ECO:0000250|UniProtKB:P01730}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01730}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01730}. CC Note=Localizes to lipid rafts. {ECO:0000250|UniProtKB:P01730}. CC -!- DOMAIN: The Ig-like V-type domain mediates the interaction with MHCII. CC {ECO:0000250|UniProtKB:P01730}. CC -!- PTM: Palmitoylation and association with LCK contribute to the CC enrichment of CD4 in lipid rafts. {ECO:0000250|UniProtKB:P01730}. CC -!- PTM: Phosphorylated by PKC; phosphorylation plays an important role for CC CD4 internalization. {ECO:0000250|UniProtKB:P01730}. 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; D63348; BAA09672.1; -; mRNA. DR AlphaFoldDB; P79184; -. DR SMR; P79184; -. DR GO; GO:0009986; C:cell surface; IEA:UniProt. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro. DR GO; GO:0023026; F:MHC class II protein complex binding; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0007155; P:cell adhesion; IEA:InterPro. DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB. DR GO; GO:0045058; P:T cell selection; ISS:UniProtKB. DR Gene3D; 2.60.40.10; -; 4. DR InterPro; IPR000973; CD4. DR InterPro; IPR015274; CD4-extracel. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR008424; Ig_C2-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR013106; Ig_V-set. DR InterPro; IPR013151; Immunoglobulin. DR InterPro; IPR021963; Tcell_CD4_Cterm. DR PANTHER; PTHR11422:SF0; PTHR11422:SF0; 1. DR Pfam; PF05790; C2-set; 2. DR Pfam; PF09191; CD4-extracel; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF12104; Tcell_CD4_C; 1. DR PRINTS; PR00692; CD4TCANTIGEN. DR SMART; SM00409; IG; 3. DR SMART; SM00406; IGv; 1. DR SUPFAM; SSF48726; SSF48726; 4. DR PROSITE; PS50835; IG_LIKE; 1. PE 2: Evidence at transcript level; KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity; KW Immunoglobulin domain; Lipoprotein; Membrane; Palmitate; Phosphoprotein; KW Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..25 FT /evidence="ECO:0000250" FT CHAIN 26..458 FT /note="T-cell surface glycoprotein CD4" FT /id="PRO_0000014623" FT TOPO_DOM 26..396 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 397..418 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 419..458 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 26..125 FT /note="Ig-like V-type" FT DOMAIN 126..203 FT /note="Ig-like C2-type 1" FT DOMAIN 204..317 FT /note="Ig-like C2-type 2" FT DOMAIN 318..374 FT /note="Ig-like C2-type 3" FT MOD_RES 433 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P01730" FT MOD_RES 440 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P01730" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P01730" FT LIPID 419 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 422 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT CARBOHYD 42 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 325 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT DISULFID 41..109 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 155..184 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 328..370 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" SQ SEQUENCE 458 AA; 50828 MW; 76B3E7EF08185535 CRC64; MNRGIPFRHL LLVLQLALLP AVTQGKKVVL GKKGDTVELT CNASQKKNTQ FHWKNSNQIK ILGIQGSFLT KGPSKLSDRA DSRKSLWDQG CFSMIIKNLK IEDSDTYICE VENKKEEVEL LVFGLTANSD THLLEGQSLT LTLESPPGSS PSVKCRSPGG KNIQGGRTIS VPQLERQDSG TWTCTVSQDQ KTVEFKIDIV VLAFQKASST VYKKEGEQVE FSFPLAFTLE KLTGSGELWW QAERASSSKS WITFDLKNKE VSVKRVTQDP KLQMGKKLPL HLTLPQALPQ YAGSGNLTLA LEAKTGKLHQ EVNLVVMRAA QFQENLTCEV WGPTSPKLTL SLKLENKGAT VSKQAKAVWV LNPEAGMWQC LLSDSGQVLL ESNIKVVPTW PTPVQPMALI VLGGVAGLLL FTGLGIFFCV RCRHRRRQAE RMSQIKRLLS EKKTCQCPHR FQKTCSPI //