UniProt functional annotation for P12493



	UniProt functional annotation for P12493

UniProt code: P12493.

Organism: Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1).

Taxonomy: Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.

Function: [Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250|UniProtKB:P04591}.

Function: [Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (PubMed:16840558). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (PubMed:23552424). {ECO:0000250, ECO:0000269|PubMed:16840558, ECO:0000269|PubMed:23552424}.

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 disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5- alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (PubMed:24509437). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250, ECO:0000250|UniProtKB:P04591, ECO:0000269|PubMed:24509437}.

Function: [Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250|UniProtKB:P04591}.

Function: [p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000269|PubMed:11427703, ECO:0000269|PubMed:11595185, ECO:0000269|PubMed:19282983}.

Subunit: [Gag polyprotein]: Homotrimer; further assembles as hexamers of trimers (By similarity). Oligomerization possibly creates a central hole into which the cytoplasmic tail of the gp41 envelope protein may be inserted. Interacts with host TRIM22; this interaction seems to disrupt proper trafficking of Gag polyprotein and may interfere with budding (By similarity). Interacts with host PDZD8 (By similarity). When ubiquitinated, interacts (via p6-gag domain) with host PACSIN2; this interaction allows PACSIN2 recruitment to viral assembly sites and its subsequent incorporation into virions (By similarity). When ubiquitinated, interacts (via p6-gag domain) with host PACSIN2; this interaction allows PACSIN2 recruitment to viral assembly sites and its subsequent incorporation into virions (By similarity). {ECO:0000250|UniProtKB:P03349, ECO:0000250|UniProtKB:P04591}.

Subunit: [Matrix protein p17]: Homotrimer; further assembles as hexamers of trimers (By similarity). Interacts with gp41 (via C- terminus) (PubMed:8918455). Interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group (PubMed:21799007). Interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly (PubMed:15766529). Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase (By similarity). {ECO:0000250|UniProtKB:P04591, ECO:0000269|PubMed:15766529, ECO:0000269|PubMed:21799007, ECO:0000269|PubMed:8918455}.

Subunit: [Capsid protein p24]: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers (PubMed:24066695). Interacts with human PPIA/CYPA; this interaction stabilizes the capsid (PubMed:8980234). Interacts with human NUP153 (PubMed:24130490, PubMed:23523133, PubMed:29997211). Interacts with host PDZD8; this interaction stabilizes the capsid (By similarity). Interacts with monkey TRIM5; this interaction destabilizes the capsid (By similarity). Interacts with human CPSF6 (PubMed:23523133, PubMed:29997211). {ECO:0000250|UniProtKB:P04591, ECO:0000269|PubMed:23523133, ECO:0000269|PubMed:24066695, ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:29997211, ECO:0000269|PubMed:8980234}.

Subunit: [p6-gag]: Interacts with Vpr; this interaction allows Vpr incorporation into the virion (By similarity). Interacts with host TSG101 (PubMed:11427703, PubMed:11595185). Interacts with host PDCD6IP/AIP1(PubMed:19282983). {ECO:0000250|UniProtKB:P03348, ECO:0000269|PubMed:11427703, ECO:0000269|PubMed:19282983}.

Subcellular location: [Gag polyprotein]: Host cell membrane; Lipid- anchor {ECO:0000269|PubMed:14722309}. Host endosome, host multivesicular body. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000269|PubMed:14722309}.

Subcellular location: [Matrix protein p17]: Virion membrane; Lipid- anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.

Subcellular location: [Capsid protein p24]: Virion {ECO:0000305}.

Subcellular location: [Nucleocapsid protein p7]: Virion {ECO:0000305}.

Domain: Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. p6-gag contains two L domains: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a LYPX(n)L motif which interacts with PDCD6IP/AIP1. {ECO:0000269|PubMed:19282983}.

Ptm: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000269|PubMed:22334652}.

Ptm: [Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250|UniProtKB:P04591}.

Ptm: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000269|PubMed:24509437}.

Ptm: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250|UniProtKB:P03347}.

Miscellaneous: The infectious clone pNL4-3 is a chimeric provirus that consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).

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: [Isoform Gag polyprotein]: Produced by conventional translation.

Similarity: Belongs to the primate lentivirus group gag polyprotein family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1).
Taxonomy:		Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.



Function:		[Gag polyprotein]: Mediates, with Gag-Pol polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). {ECO:0000250\|UniProtKB:P04591}.



Function:		[Matrix protein p17]: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus (PubMed:16840558). Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA (PubMed:23552424). {ECO:0000250, ECO:0000269\|PubMed:16840558, ECO:0000269\|PubMed:23552424}.



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 disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5- alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating (PubMed:24509437). On the other hand, interactions with PDZD8 or CYPA stabilize the capsid. {ECO:0000250, ECO:0000250\|UniProtKB:P04591, ECO:0000269\|PubMed:24509437}.



Function:		[Nucleocapsid protein p7]: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates in gRNA dimerization, packaging, tRNA incorporation and virion assembly. {ECO:0000250\|UniProtKB:P04591}.



Function:		[p6-gag]: Plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1. {ECO:0000269\|PubMed:11427703, ECO:0000269\|PubMed:11595185, ECO:0000269\|PubMed:19282983}.


Subunit:		[Gag polyprotein]: Homotrimer; further assembles as hexamers of trimers (By similarity). Oligomerization possibly creates a central hole into which the cytoplasmic tail of the gp41 envelope protein may be inserted. Interacts with host TRIM22; this interaction seems to disrupt proper trafficking of Gag polyprotein and may interfere with budding (By similarity). Interacts with host PDZD8 (By similarity). When ubiquitinated, interacts (via p6-gag domain) with host PACSIN2; this interaction allows PACSIN2 recruitment to viral assembly sites and its subsequent incorporation into virions (By similarity). When ubiquitinated, interacts (via p6-gag domain) with host PACSIN2; this interaction allows PACSIN2 recruitment to viral assembly sites and its subsequent incorporation into virions (By similarity). {ECO:0000250\|UniProtKB:P03349, ECO:0000250\|UniProtKB:P04591}.
Subunit:		[Matrix protein p17]: Homotrimer; further assembles as hexamers of trimers (By similarity). Interacts with gp41 (via C- terminus) (PubMed:8918455). Interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group (PubMed:21799007). Interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly (PubMed:15766529). Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase (By similarity). {ECO:0000250\|UniProtKB:P04591, ECO:0000269\|PubMed:15766529, ECO:0000269\|PubMed:21799007, ECO:0000269\|PubMed:8918455}.
Subunit:		[Capsid protein p24]: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers (PubMed:24066695). Interacts with human PPIA/CYPA; this interaction stabilizes the capsid (PubMed:8980234). Interacts with human NUP153 (PubMed:24130490, PubMed:23523133, PubMed:29997211). Interacts with host PDZD8; this interaction stabilizes the capsid (By similarity). Interacts with monkey TRIM5; this interaction destabilizes the capsid (By similarity). Interacts with human CPSF6 (PubMed:23523133, PubMed:29997211). {ECO:0000250\|UniProtKB:P04591, ECO:0000269\|PubMed:23523133, ECO:0000269\|PubMed:24066695, ECO:0000269\|PubMed:24130490, ECO:0000269\|PubMed:29997211, ECO:0000269\|PubMed:8980234}.
Subunit:		[p6-gag]: Interacts with Vpr; this interaction allows Vpr incorporation into the virion (By similarity). Interacts with host TSG101 (PubMed:11427703, PubMed:11595185). Interacts with host PDCD6IP/AIP1(PubMed:19282983). {ECO:0000250\|UniProtKB:P03348, ECO:0000269\|PubMed:11427703, ECO:0000269\|PubMed:19282983}.
Subcellular location:		[Gag polyprotein]: Host cell membrane; Lipid- anchor {ECO:0000269\|PubMed:14722309}. Host endosome, host multivesicular body. Note=These locations are probably linked to virus assembly sites. The main location is the cell membrane, but under some circumstances, late endosomal compartments can serve as productive sites for virion assembly. {ECO:0000269\|PubMed:14722309}.
Subcellular location:		[Matrix protein p17]: Virion membrane; Lipid- anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm {ECO:0000250}.
Subcellular location:		[Capsid protein p24]: Virion {ECO:0000305}.
Subcellular location:		[Nucleocapsid protein p7]: Virion {ECO:0000305}.
Domain:		Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. p6-gag contains two L domains: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a LYPX(n)L motif which interacts with PDCD6IP/AIP1. {ECO:0000269\|PubMed:19282983}.
Ptm:		Gag-Pol polyprotein: Specific enzymatic cleavages by the viral protease yield mature proteins. {ECO:0000269\|PubMed:22334652}.
Ptm:		[Matrix protein p17]: Tyrosine phosphorylated presumably in the virion by a host kinase. Phosphorylation is apparently not a major regulator of membrane association. {ECO:0000250\|UniProtKB:P04591}.
Ptm:		[Capsid protein p24]: Phosphorylated possibly by host MAPK1; this phosphorylation is necessary for Pin1-mediated virion uncoating. {ECO:0000269\|PubMed:24509437}.
Ptm:		[Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its function by reducing RNA annealing and the initiation of reverse transcription. {ECO:0000250\|UniProtKB:P03347}.
Miscellaneous:		The infectious clone pNL4-3 is a chimeric provirus that consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
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:		[Isoform Gag polyprotein]: Produced by conventional translation.
Similarity:		Belongs to the primate lentivirus group gag polyprotein family. {ECO:0000305}.