UniProtKB/Swiss-Prot entry P05960

• FUNCTION: Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation (By similarity).
• FUNCTION: Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to plays a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu (By similarity).
• FUNCTION: Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is dissassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species (By similarity).
• FUNCTION: Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity (By similarity).
• FUNCTION: The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles (By similarity).
• CATALYTIC ACTIVITY: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.
• ENZYME REGULATION: The viral protease is inhibited by many synthetic protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. Use of protease inhibitors in tritherapy regimens permit more ambitious therapeutic strategies (By similarity).
• SUBUNIT: Pre-integration complex interacts with human HMGA1. Matrix protein p17 is a trimer. Interacts with gp120 and human BAF. Capsid is a homodimer. Interacts with human PPIA/CYPA. The protease is a homodimer, whose active site consists of two apposed aspartic acid residues (By similarity).
• SUBCELLULAR LOCATION: Matrix protein p17: Virion (Potential). Nucleus (By similarity). Cytoplasm (By similarity). Cell membrane; Lipid-anchor (Potential). Note=Following virus entry, the nuclear localization signal (NLS) of the matrix protein participates with Vpr to the nuclear localization of the viral genome. During virus production, the nuclear export activity of the matrix protein counteracts the NLS to maintain the Gag and Gag-Pol polyproteins in the cytoplasm, thereby directing unspliced RNA to the plasma membrane (By similarity).
• SUBCELLULAR LOCATION: Capsid protein p24: Virion (Potential).
• SUBCELLULAR LOCATION: Nucleocapsid protein p7: Virion (Potential).
• ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by ribosomal frameshifting. Translation results in the formation of the Gag polyprotein most of the time. Ribosomal frameshifting at the gag-pol genes boundary occurs at low frequency and produces the Gag-Pol polyprotein. This strategy of translation probably allows the virus to modulate the quantity of each viral protein. Maintenance of a correct Gag to Gag-Pol ratio is essential for RNA dimerization and viral infectivity.

  Name Gag-Pol polyprotein Isoform ID P05960-1 Note: Produced by -1 ribosomal frameshifting. This is the isoform sequence displayed in this entry.

  Name Gag polyprotein Isoform ID P05887-1 Note: Produced by conventional translation. This isoform is stored in UniProtKB/Swiss-Prot entry P05887.

• PTM: Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry (By similarity).
• PTM: Capsid protein p24 is phosphorylated (By similarity).
• PTM: Matrix protein p17 is tyrosine phosphorylated presumably in the virion by a host kinase. This modification targets the matrix protein to the nucleus (By similarity).
• MISCELLANEOUS: Capsid protein p24 is able to bind macaque TRIM5-alpha or owl monkey TRIMCyp, preventing reverse transcription of the viral genome and succesfull infection of macaque or owl monkey by HIV-1 (By similarity).
• 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).
• MISCELLANEOUS: Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in the clade B representative isolate HXB2 (AC P04585).
• SIMILARITY: Contains 2 CCHC-type zinc fingers.
• SIMILARITY: Contains 1 peptidase A2 domain [view classification].
• WEB RESOURCE: Name=resdb; Note=HIV resistance database; URL="http://resdb.lanl.gov/Resist_DB/";.
• WEB RESOURCE: Name=HIV drug resistance mutations; URL="http://www.iasusa.org/resistance_mutations/index.html";.
• WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database; URL="http://hivdb.stanford.edu";.