UniProt functional annotation for P05540

UniProt code: P05540.

Organism: Rattus norvegicus (Rat).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.
 
Function: Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T- helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. {ECO:0000250|UniProtKB:P01730}.
 
Subunit: Forms disulfide-linked homodimers at the cell surface. Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI. Interacts with IL16; this interaction induces a CD4-dependent signaling in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha chain (via alpha-2 domain) and beta chain (via beta-2 domain); this interaction increases the affinity of TCR for peptide-MHCII. CD4 oligomerization via Ig-like C2-type 2 and 3 domains appears to be required for stable binding to MHCII and adhesion between T cells and APCs. {ECO:0000250|UniProtKB:P01730}.
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P01730}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01730}. Note=Localizes to lipid rafts. {ECO:0000250|UniProtKB:P01730}.
Domain: The Ig-like V-type domain mediates the interaction with MHCII. {ECO:0000250|UniProtKB:P01730}.
Ptm: Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts. {ECO:0000250|UniProtKB:P01730}.
Ptm: Phosphorylated by PKC; phosphorylation plays an important role for CD4 internalization. {ECO:0000250|UniProtKB:P01730}.

Annotations taken from UniProtKB at the EBI.