Protein Nef

Name	Protein Nef
Synonyms	3'ORF F-protein Negative factor
Gene Name	nef
Organism	HIV-1
Amino acid sequence	>lcl\|BSEQ0017384\|Protein Nef MGGKWSKSSVVGWPAVRERMRRAEPAADGVGAASRDLEKHGAITSSNTAANNAACAWLEA QEEEKVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIHSQRRQDILDLWIYHTQGY FPDWQNYTPGPGIRYPLTFGWCYKLVPVEPEKLEEANKGENTSLLHPVSLHGMDDPEREV LEWRFDSRLAFHHVARELHPEYFKNC
Number of residues	None
Molecular Weight	23366.225
Theoretical pI	None
GO Classification	Functions thioesterase binding calmodulin binding ATPase binding protein kinase binding GTP binding MHC class I protein binding receptor binding SH3 domain binding CD4 receptor binding Processes negative regulation by symbiont of host T-cell mediated immune response negative regulation of CD4 biosynthetic process regulation of calcium-mediated signaling suppression by virus of host autophagy viral life cycle suppression by virus of host adaptive immune response pathogenesis suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II apoptotic process Components membrane extracellular region host cell Golgi membrane virion host cell plasma membrane
General Function	Thioesterase binding
Specific Function	Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocytes function and down-regulates immunity surface molecules in order to evade host defense and increase viral infectivity. Alters the functionality of other immunity cells, like dendritic cells, monocytes/macrophages and NK cells.In infected CD4(+) T-lymphocytes, down-regulates the surface MHC-I, mature MHC-II, CD4, CD28, CCR5 and CXCR4 molecules. Mediates internalization and degradation of host CD4 through the interaction of with the cytoplasmic tail of CD4, the recruitment of AP-2 (clathrin adapter protein complex 2), internalization through clathrin coated pits, and subsequent transport to endosomes and lysosomes for degradation. Diverts host MHC-I molecules to the trans-Golgi network-associated endosomal compartments by an endocytic pathway to finally target them for degradation. MHC-I down-regulation may involve AP-1 (clathrin adapter protein complex 1) or possibly Src family kinase-ZAP70/Syk-PI3K cascade recruited by PACS2. In consequence infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Decreasing the number of immune receptors also prevents reinfection by more HIV particles (superinfection).Bypasses host T-cell signaling by inducing a transcriptional program nearly identical to that of anti-CD3 cell activation. Interaction with TCR-zeta chain up-regulates the Fas ligand (FasL). Increasing surface FasL molecules and decreasing surface MHC-I molecules on infected CD4(+) cells send attacking cytotoxic CD8+ T-lymphocytes into apoptosis.Plays a role in optimizing the host cell environment for viral replication without causing cell death by apoptosis. Protects the infected cells from apoptosis in order to keep them alive until the next virus generation is ready to strike. Inhibits the Fas and TNFR-mediated death signals by blocking MAP3K5/ASK1. Decreases the half-life of TP53, protecting the infected cell against p53-mediated apoptosis. Inhibits the apoptotic signals regulated by the Bcl-2 family proteins through the formation of a Nef/PI3-kinase/PAK2 complex that leads to activation of PAK2 and induces phosphorylation of Bad.Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors.
Transmembrane Regions
GenBank Protein ID
UniProtKB ID	P04324
UniProtKB Entry Name
Cellular Location	Host cell membrane
Gene sequence	None
GenBank Gene ID
GeneCard ID	None
GenAtlas ID
HGNC ID
Chromosome Location	None
Locus	None
References	Arya SK, Gallo RC: Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2209-13. [3008154 ] Barnham KJ, Monks SA, Hinds MG, Azad AA, Norton RS: Solution structure of a polypeptide from the N terminus of the HIV protein Nef. Biochemistry. 1997 May 20;36(20):5970-80. [9166767 ]

From www.t3db.ca