Protein Nef

Details

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
206
Molecular Weight
23366.225
Theoretical pI
Not Available
GO Classification
Functions
ATPase binding / calmodulin binding / CD4 receptor binding / GTP binding / MHC class I protein binding / protein kinase binding / receptor binding / SH3 domain binding / thioesterase binding
Processes
apoptotic process / negative regulation by symbiont of host T-cell mediated immune response / negative regulation of CD4 biosynthetic process / pathogenesis / regulation of calcium-mediated signaling / suppression by virus of host adaptive immune response / 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 / suppression by virus of host autophagy / viral life cycle
Components
extracellular region / host cell Golgi membrane / host cell plasma membrane / membrane / virion
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Host cell membrane
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP04324
UniProtKB Entry NameNEF_HV112
General References
  1. 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. [Article]
  2. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08231Myristic acidexperimentalunknownDetails