This gene encodes a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigenes and is also a receptor for the human immunodeficiency virus.This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, and granulocytes. It is also expressed in specific regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified inThis gene. [provided by RefSeq, Aug 2010]
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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) . Down-regulated by HIV-1 Vpu . Acts as a receptor for Human Herpes virus 7/HHV-7 .
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Cellular Localization:
Cell membrane ; Single-pass type I membrane protein . 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.
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Tissue Expression:
Expressed in natural killer (NK) cells, CD8(+) alpha-beta and gamma-delta T-cells. Expressed on essentially all CD56+CD3- NK cells from freshly isolated PBMC. Expressed in interferon-producing killer dendritic cells (IKDCs).