CD4

CD4 (CD4 Molecule) is a Protein Coding gene. Diseases associated with CD4 include Okt4 Epitope Deficiency and Pilonidal Sinus. Among its related pathways are G-protein signaling N-RAS regulation pathway and PEDF Induced Signaling. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and enzyme binding.

CD4 Molecule

CD4 Molecule; T-Cell Surface Glycoprotein CD4; T-Cell Surface Antigen T4/Leu-3; CD4 Antigen (P55); CD4 Receptor; CD4 Antigen; CD4mut;

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.
(Microbial infection) Primary receptor for human immunodeficiency virus-1 (HIV-1) (PubMed:2214026, PubMed:16331979, PubMed:9641677, PubMed:12089508).
Down-regulated by HIV-1 Vpu (PubMed:17346169).
Acts as a receptor for Human Herpes virus 7/HHV-7 (PubMed:7909607).

Adaptive immune response Source: UniProtKB-KW
Cell adhesion Source: InterPro
Cell surface receptor signaling pathway Source: ProtInc
Cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: CAFA
Cytokine-mediated signaling pathway Source: Reactome
Defense response to Gram-negative bacterium Source: Ensembl
Entry into host Source: Reactome
Enzyme linked receptor protein signaling pathway Source: ProtInc
Fusion of virus membrane with host plasma membrane Source: Reactome
Helper T cell enhancement of adaptive immune response Source: Ensembl
Immune response Source: UniProtKB
Induction by virus of host cell-cell fusion Source: UniProtKB
Interleukin-15-mediated signaling pathway Source: CAFA
Macrophage differentiation Source: ARUK-UCL
Maintenance of protein location in cell Source: MGI
Membrane organization Source: Reactome
Positive regulation of calcium ion transport into cytosol Source: Ensembl
Positive regulation of calcium-mediated signaling Source: Ensembl
Positive regulation of ERK1 and ERK2 cascade Source: CAFA
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: CAFA
Positive regulation of interleukin-2 production Source: UniProtKB
Positive regulation of kinase activity Source: CAFA
Positive regulation of MAPK cascade Source: CAFA
Positive regulation of monocyte differentiation Source: CAFA
Positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
Positive regulation of protein kinase activity Source: UniProtKB
Positive regulation of protein phosphorylation Source: CAFA
Positive regulation of T cell proliferation Source: Ensembl
Positive regulation of transcription, DNA-templated Source: CAFA
Positive regulation of viral entry into host cell Source: CAFA
Regulation of calcium ion transport Source: CAFA
Regulation of defense response to virus by virus Source: Reactome
Regulation of T cell activation Source: UniProtKB
Response to estradiol Source: Ensembl
Response to vitamin D Source: Ensembl
Signal transduction Source: ProtInc
T cell activation Source: GO_Central
T cell differentiation Source: UniProtKB
T cell receptor signaling pathway Source: Reactome
T cell selection Source: UniProtKB
Transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB

Cell membrane. Localizes to lipid rafts (PubMed:12517957, PubMed:9168119). Removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Cell surface expression is also down-modulated by HIV-1 Envelope polyprotein gp160 that interacts with, and sequesters CD4 in the endoplasmic reticulum.

Extracellular: 26-396
Helical: 397-418
Cytoplasmic: 419-458

Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.
Phosphorylated by PKC; phosphorylation at Ser-433 plays an important role for CD4 internalization.