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Details on Person UniProt:P12480 nef
| Class:Id | ReferenceGeneProduct:165290 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2- added on Fri February 6 2015;initiator methionine:1 for 165290 removed on Fri Nov 03 2023;initiator methionine: for 165290 added on Fri Nov 03 2023;initiator methionine: for 165290 removed on Fri Aug 15 2025;initiator methionine:1 for 165290 added on Fri Aug 15 2025 |
| _displayName | UniProt:P12480 nef |
| _timestamp | 2025-08-15 21:09:07 |
| chain | initiator methionine:1 chain:2-17 |
| checksum | 6E6B3F26EFEB921E |
| comment | FUNCTION Factor of infectivity and pathogenicity, required for optimal virus replication. Alters numerous pathways of T-lymphocyte 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. One of the earliest and most abundantly expressed viral proteins (By similarity).FUNCTION 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) (By similarity).FUNCTION 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 (By similarity).FUNCTION 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. Interacts and decreases the half-life of p53, 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 (By similarity).FUNCTION Extracellular Nef protein targets CD4(+) T-lymphocytes for apoptosis by interacting with CXCR4 surface receptors.SUBUNIT Homodimer (By similarity). Interacts with Nef associated p21-activated kinase (PAK2); this interaction activates PAK2. Associates with the Nef-MHC-I-AP1 complex; this complex is required for MHC-I internalization. Interacts (via C-terminus) with host PI3-kinase (via C-terminus). Interacts with host PACS1; this interaction seems to be weak. Interacts with host PACS2. Interacts with host LCK and MAPK3; these interactions inhibit the kinase activity of the latter. Interacts with host ATP6V1H; this interaction may play a role in CD4 endocytosis. Associates with the CD4-Nef-AP2 complex; this complex is required for CD4 internalization. Interacts with TCR-zeta chain; this interaction up-regulates the Fas ligand (FasL) surface expression. Interacts with various cellular proteins including MAP3K5, beta-COP, HCK, and PTE1. Interacts with human RACK1; this increases Nef phosphorylation by PKC (By similarity).SUBCELLULAR LOCATION Predominantly found in the paranuclear area, probably in the TGN. Correct localization requires PACS1. Also associates with the inner plasma membrane through its N-terminal domain. Nef stimulates its own export via the release of exosomes. Also incorporated in virions at a rate of about 10 molecules per virion, where it is cleaved (By similarity).DOMAIN The N-terminal domain is composed of the N-myristoyl glycine and of a cluster of positively charged amino acids. It is required for inner plasma membrane targeting of Nef and virion incorporation, and thereby for infectivity. This domain is also involved in binding to p53 (By similarity).DOMAIN The SH3-binding domain constituted of PxxP motifs mediates binding to several Src family proteins thereby regulating their tyrosine kinase activity. The same motifs also mediates the association with MAPK3, PI3-kinase and TCR-zeta (By similarity).DOMAIN The di-leucine internalization motif and a diacidic motif seem to be required for binding to AP-2.DOMAIN The acidic region may play a stabilizing role in the formation of a ternary complex between Nef, the MHC-I cytoplasmic domain, and AP1M1.PTM The virion-associated Nef proteins are cleaved by the viral protease to release the soluble C-terminal core protein. Nef is probably cleaved concomitantly with viral structural proteins on maturation of virus particles (By similarity).PTM Phosphorylated on serine residues, probably by host PKC.MISCELLANEOUS HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).SIMILARITY Belongs to the lentivirus primate group Nef protein family. |
| created | [InstanceEdit:165206] Schmidt, EE, 2005-08-03 04:18:22 |
| description | recommendedName: Protein Nef alternativeName: 3'ORF alternativeName: Negative factor shortName: F-protein |
| geneName | nef |
| identifier | P12480 |
| isSequenceChanged | FALSE |
| keyword | AIDS Apoptosis Early protein Host cell membrane Host cytoplasm Host membrane Host-virus interaction Lipoprotein Membrane Myristate Phosphoprotein Secreted Viral immunoevasion Virion Virulence |
| modified | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9773244] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | nef |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | NEF_HV1J3 |
| sequenceLength | 17 |
| species | [Species:164493] Human immunodeficiency virus 1 |
| (referenceEntity) | [EntityWithAccessionedSequence:165599] Nef Protein (UniProt:P12480) [cytosol] [Human immunodeficiency virus 1] [EntityWithAccessionedSequence:167594] Nef Protein (UniProt:P12480) [cytosol] [Human immunodeficiency virus 1] [EntityWithAccessionedSequence:175103] Nef Protein (UniProt:P12480) [Human immunodeficiency virus 1] [EntityWithAccessionedSequence:175275] Nef Protein (UniProt:P12480) [Human immunodeficiency virus 1] |
| (referenceSequence) | [ModifiedResidue:167534] N-myristoylglycine at 1 |
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No pathways have been reviewed or authored by UniProt:P12480 nef (165290)
