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.
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.
(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).
Biological Process
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
Cellular Location
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.
Topology
Extracellular: 26-396
Helical: 397-418
Cytoplasmic: 419-458
PTM
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.
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Datasheet