POL_HV1J3
ID POL_HV1J3 Reviewed; 532 AA.
AC P12498;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Gag-Pol polyprotein;
DE AltName: Full=Pr160Gag-Pol;
DE Contains:
DE RecName: Full=Matrix protein p17;
DE Short=MA;
DE Contains:
DE RecName: Full=Capsid protein p24;
DE Short=CA;
DE Contains:
DE RecName: Full=Spacer peptide 1 {ECO:0000250|UniProtKB:P12497};
DE Short=SP1;
DE AltName: Full=p2;
DE Contains:
DE RecName: Full=Nucleocapsid protein p7;
DE Short=NC;
DE Contains:
DE RecName: Full=Transframe peptide;
DE Short=TF;
DE Contains:
DE RecName: Full=p6-pol;
DE Short=p6*;
DE Contains:
DE RecName: Full=Protease;
DE EC=3.4.23.16;
DE AltName: Full=PR;
DE AltName: Full=Retropepsin;
DE Flags: Fragment;
GN Name=gag-pol;
OS Human immunodeficiency virus type 1 group M subtype B (isolate JH32)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11694;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2669897; DOI=10.1089/aid.1989.5.411;
RA Komiyama N., Hattori N., Inoue J., Sakuma S., Kurimura T., Yoshida M.;
RT "Nucleotide sequences of gag and env genes of a Japanese isolate of HIV-1
RT and their expression in bacteria.";
RL AIDS Res. Hum. Retroviruses 5:411-419(1989).
RN [2]
RP REVIEW.
RX PubMed=8791726; DOI=10.1007/978-3-642-80145-7_4;
RA Vogt V.M.;
RT "Proteolytic processing and particle maturation.";
RL Curr. Top. Microbiol. Immunol. 214:95-131(1996).
RN [3]
RP REVIEW.
RX PubMed=9878383; DOI=10.1006/jmbi.1998.2354;
RA Turner B.G., Summers M.F.;
RT "Structural biology of HIV.";
RL J. Mol. Biol. 285:1-32(1999).
RN [4]
RP REVIEW.
RX PubMed=11700285; DOI=10.1146/annurev.genet.35.102401.090551;
RA Negroni M., Buc H.;
RT "Mechanisms of retroviral recombination.";
RL Annu. Rev. Genet. 35:275-302(2001).
RN [5]
RP REVIEW.
RX PubMed=11983066; DOI=10.1186/gb-2002-3-4-reviews3006;
RA Dunn B.M., Goodenow M.M., Gustchina A., Wlodawer A.;
RT "Retroviral proteases.";
RL Genome Biol. 3:REVIEWS3006.1-REVIEWS3006.7(2002).
RN [6]
RP REVIEW.
RX PubMed=12873766; DOI=10.1016/s0005-2736(03)00163-9;
RA Scarlata S., Carter C.;
RT "Role of HIV-1 Gag domains in viral assembly.";
RL Biochim. Biophys. Acta 1614:62-72(2003).
CC -!- FUNCTION: [Gag-Pol polyprotein]: Mediates, with Gag polyprotein, the
CC essential events in virion assembly, including binding the plasma
CC membrane, making the protein-protein interactions necessary to create
CC spherical particles, recruiting the viral Env proteins, and packaging
CC the genomic RNA via direct interactions with the RNA packaging sequence
CC (Psi). Gag-Pol polyprotein may regulate its own translation, by the
CC binding genomic RNA in the 5'-UTR. At low concentration, the
CC polyprotein would promote translation, whereas at high concentration,
CC the polyprotein would encapsidate genomic RNA and then shut off
CC translation. {ECO:0000250}.
CC -!- FUNCTION: [Matrix protein p17]: Targets the polyprotein to the plasma
CC membrane via a multipartite membrane-binding signal, that includes its
CC myristoylated N-terminus. Matrix protein is part of the pre-integration
CC complex. Implicated in the release from host cell mediated by Vpu.
CC Binds to RNA. {ECO:0000250|UniProtKB:P12497}.
CC -!- FUNCTION: [Capsid protein p24]: Forms the conical core that
CC encapsulates the genomic RNA-nucleocapsid complex in the virion. Most
CC core are conical, with only 7% tubular. The core is constituted by
CC capsid protein hexamer subunits. The core is disassembled soon after
CC virion entry (By similarity). Host restriction factors such as TRIM5-
CC alpha or TRIMCyp bind retroviral capsids and cause premature capsid
CC disassembly, leading to blocks in reverse transcription. Capsid
CC restriction by TRIM5 is one of the factors which restricts HIV-1 to the
CC human species. Host PIN1 apparently facilitates the virion uncoating.
CC On the other hand, interactions with PDZD8 or CYPA stabilize the
CC capsid. {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.
CC -!- FUNCTION: [Nucleocapsid protein p7]: Encapsulates and protects viral
CC dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc
CC fingers. Acts as a nucleic acid chaperone which is involved in
CC rearangement of nucleic acid secondary structure during gRNA
CC retrotranscription. Also facilitates template switch leading to
CC recombination. As part of the polyprotein, participates in gRNA
CC dimerization, packaging, tRNA incorporation and virion assembly.
CC {ECO:0000250|UniProtKB:P04585}.
CC -!- FUNCTION: [Protease]: Aspartyl protease that mediates proteolytic
CC cleavages of Gag and Gag-Pol polyproteins during or shortly after the
CC release of the virion from the plasma membrane. Cleavages take place as
CC an ordered, step-wise cascade to yield mature proteins. This process is
CC called maturation. Displays maximal activity during the budding process
CC just prior to particle release from the cell. Also cleaves Nef and Vif,
CC probably concomitantly with viral structural proteins on maturation of
CC virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off
CC the capped cellular mRNA translation. The resulting inhibition of
CC cellular protein synthesis serves to ensure maximal viral gene
CC expression and to evade host immune response. Also mediates cleavage of
CC host YTHDF3. Mediates cleavage of host CARD8, thereby activating the
CC CARD8 inflammasome, leading to the clearance of latent HIV-1 in patient
CC CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade
CC CARD8-sensing when its protease remains inactive in infected cells
CC prior to viral budding (By similarity). {ECO:0000250|UniProtKB:P04585,
CC ECO:0000255|PROSITE-ProRule:PRU00275}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specific for a P1 residue that is hydrophobic, and P1'
CC variable, but often Pro.; EC=3.4.23.16;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00275};
CC -!- ACTIVITY REGULATION: [Protease]: The viral protease is inhibited by
CC many synthetic protease inhibitors (PIs), such as amprenavir,
CC atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and
CC saquinavir. Use of protease inhibitors in tritherapy regimens permit
CC more ambitious therapeutic strategies. {ECO:0000250}.
CC -!- SUBUNIT: [Matrix protein p17]: Homotrimer; further assembles as
CC hexamers of trimers (By similarity). Interacts with gp41 (via C-
CC terminus) (By similarity). Interacts with host CALM1; this interaction
CC induces a conformational change in the Matrix protein, triggering
CC exposure of the myristate group (By similarity). Interacts with host
CC AP3D1; this interaction allows the polyprotein trafficking to
CC multivesicular bodies during virus assembly (By similarity). Part of
CC the pre-integration complex (PIC) which is composed of viral genome,
CC matrix protein, Vpr and integrase (By similarity).
CC {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.
CC -!- SUBUNIT: [Capsid protein p24]: Homodimer; the homodimer further
CC multimerizes as homohexamers or homopentamers. Interacts with human
CC PPIA/CYPA (By similarity); This interaction stabilizes the capsid.
CC Interacts with human NUP153 (By similarity). Interacts with host PDZD8;
CC this interaction stabilizes the capsid (By similarity). Interacts with
CC monkey TRIM5; this interaction destabilizes the capsid (By similarity).
CC {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}.
CC -!- SUBUNIT: [Protease]: Homodimer, whose active site consists of two
CC apposed aspartic acid residues. {ECO:0000250|UniProtKB:P04585,
CC ECO:0000250|UniProtKB:P12497}.
CC -!- SUBCELLULAR LOCATION: [Gag-Pol polyprotein]: Host cell membrane; Lipid-
CC anchor. Host endosome, host multivesicular body. Note=These locations
CC are linked to virus assembly sites. The main location is the cell
CC membrane, but under some circumstances, late endosomal compartments can
CC serve as productive sites for virion assembly.
CC {ECO:0000250|UniProtKB:P12497}.
CC -!- SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane; Lipid-
CC anchor {ECO:0000305}. Host nucleus {ECO:0000250}. Host cytoplasm
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein p24]: Virion {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Ribosomal frameshifting; Named isoforms=2;
CC Comment=Translation results in the formation of the Gag polyprotein
CC most of the time. Ribosomal frameshifting at the gag-pol genes
CC boundary occurs at low frequency and produces the Gag-Pol
CC polyprotein. This strategy of translation probably allows the virus
CC to modulate the quantity of each viral protein. Maintenance of a
CC correct Gag to Gag-Pol ratio is essential for RNA dimerization and
CC viral infectivity.;
CC Name=Gag-Pol polyprotein;
CC IsoId=P12498-1; Sequence=Displayed;
CC Name=Gag polyprotein;
CC IsoId=P12494-1; Sequence=External;
CC -!- PTM: Specific enzymatic cleavages by the viral protease yield mature
CC proteins. The protease is released by autocatalytic cleavage. The
CC polyprotein is cleaved during and after budding, this process is termed
CC maturation. Proteolytic cleavage of p66 RT removes the RNase H domain
CC to yield the p51 RT subunit. Nucleocapsid protein p7 might be further
CC cleaved after virus entry (By similarity). {ECO:0000250}.
CC -!- PTM: [Matrix protein p17]: Tyrosine phosphorylated presumably in the
CC virion by a host kinase. Phosphorylation is apparently not a major
CC regulator of membrane association. {ECO:0000250|UniProtKB:P04585}.
CC -!- PTM: [Capsid protein p24]: Phosphorylated possibly by host MAPK1; this
CC phosphorylation is necessary for Pin1-mediated virion uncoating.
CC {ECO:0000250|UniProtKB:P12493}.
CC -!- PTM: [Nucleocapsid protein p7]: Methylated by host PRMT6, impairing its
CC function by reducing RNA annealing and the initiation of reverse
CC transcription. {ECO:0000250|UniProtKB:P03347}.
CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC majority of strains found worldwide belong to the group M. Group O
CC seems to be endemic to and largely confined to Cameroon and neighboring
CC countries in West Central Africa, where these viruses represent a small
CC minority of HIV-1 strains. The group N is represented by a limited
CC number of isolates from Cameroonian persons. The group M is further
CC subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC -!- MISCELLANEOUS: Resistance to inhibitors associated with mutations are
CC observed both in viral protease and in reverse transcriptase. Most of
CC the time, single mutations confer only a modest reduction in drug
CC susceptibility. Combination of several mutations is usually required to
CC develop a high-level drug resistance. These mutations are predominantly
CC found in clade B viruses and not in other genotypes. They are listed in
CC the clade B representative isolate HXB2 (AC P04585).
CC -!- MISCELLANEOUS: [Isoform Gag-Pol polyprotein]: Produced by -1 ribosomal
CC frameshifting.
CC -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC URL="https://hivdb.stanford.edu";
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DR EMBL; M21137; AAB03523.1; ALT_SEQ; Genomic_RNA.
DR SMR; P12498; -.
DR MEROPS; A02.001; -.
DR PRO; PR:P12498; -.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.30; -; 1.
DR Gene3D; 1.10.150.90; -; 1.
DR Gene3D; 1.10.375.10; -; 1.
DR Gene3D; 2.40.70.10; -; 1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR045345; Gag_p24_C.
DR InterPro; IPR000721; Gag_p24_N.
DR InterPro; IPR000071; Lentvrl_matrix_N.
DR InterPro; IPR012344; Matrix_HIV/RSV_N.
DR InterPro; IPR001995; Peptidase_A2_cat.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR018061; Retropepsins.
DR InterPro; IPR008916; Retrov_capsid_C.
DR InterPro; IPR008919; Retrov_capsid_N.
DR InterPro; IPR010999; Retrovr_matrix.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR Pfam; PF00540; Gag_p17; 1.
DR Pfam; PF00607; Gag_p24; 1.
DR Pfam; PF19317; Gag_p24_C; 1.
DR Pfam; PF00077; RVP; 1.
DR Pfam; PF00098; zf-CCHC; 2.
DR PRINTS; PR00234; HIV1MATRIX.
DR SMART; SM00343; ZnF_C2HC; 2.
DR SUPFAM; SSF47836; SSF47836; 1.
DR SUPFAM; SSF47943; SSF47943; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS50175; ASP_PROT_RETROV; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS50158; ZF_CCHC; 2.
PE 3: Inferred from homology;
KW AIDS; Aspartyl protease; Capsid protein;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Host cell membrane;
KW Host cytoplasm; Host endosome; Host gene expression shutoff by virus;
KW Host membrane; Host nucleus; Host-virus interaction; Hydrolase;
KW Lipid-binding; Lipoprotein; Membrane; Metal-binding; Myristate;
KW Phosphoprotein; Protease; Repeat; Ribosomal frameshifting; RNA-binding;
KW Viral nucleoprotein; Viral release from host cell; Virion;
KW Virion maturation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..>532
FT /note="Gag-Pol polyprotein"
FT /id="PRO_0000261268"
FT CHAIN 2..132
FT /note="Matrix protein p17"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042362"
FT CHAIN 133..363
FT /note="Capsid protein p24"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042363"
FT PEPTIDE 364..377
FT /note="Spacer peptide 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042364"
FT CHAIN 378..432
FT /note="Nucleocapsid protein p7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042365"
FT PEPTIDE 433..440
FT /note="Transframe peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000246717"
FT CHAIN 441..488
FT /note="p6-pol"
FT /evidence="ECO:0000255"
FT /id="PRO_0000042366"
FT CHAIN 489..>532
FT /note="Protease"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038656"
FT DOMAIN 508..>532
FT /note="Peptidase A2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00275"
FT ZN_FING 390..407
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 411..428
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 7..31
FT /note="Interaction with Gp41"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 8..43
FT /note="Interaction with host CALM1"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 12..19
FT /note="Interaction with host AP3D1"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 14..33
FT /note="Interaction with membrane phosphatidylinositol 4,5-
FT bisphosphate and RNA"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 73..77
FT /note="Interaction with membrane phosphatidylinositol 4,5-
FT bisphosphate"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 106..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 189..227
FT /note="Interaction with human PPIA/CYPA and NUP153"
FT /evidence="ECO:0000250|UniProtKB:P12497"
FT REGION 277..363
FT /note="Dimerization/Multimerization of capsid protein p24"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT REGION 447..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..493
FT /note="Dimerization of protease"
FT /evidence="ECO:0000250|UniProtKB:P04585"
FT MOTIF 16..22
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 26..32
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 447..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 513
FT /note="For protease activity; shared with dimeric partner"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT SITE 132..133
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 221..222
FT /note="Cis/trans isomerization of proline peptide bond; by
FT human PPIA/CYPA"
FT /evidence="ECO:0000250"
FT SITE 363..364
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 377..378
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 432..433
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000255"
FT SITE 440..441
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 488..489
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT MOD_RES 132
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250"
FT NON_TER 532
SQ SEQUENCE 532 AA; 59412 MW; C47419992DFC78D6 CRC64;
MGARASVLSG GELDRWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPSL LETSEGCRQI
LGQLQPSLQT GSEELKSLFN TVATLYCVHQ RIEVKDTKEA LEKIEEEQNK SKKKAQQAAA
DTGNSSKVSQ NYPIVQNIQG QMVHQAISPR TLNAWVKVVE EKAFSPEVIP MFSALSEGAT
PQDLNTMLNT VGGHQAAMQM LKETINEEAA EWDRLHPAQA GPIAPGQMRE PRGSDIAGTT
STLQEQIGWM TSNPPIPVGE IYKRWIILGL NKIVRMYSPS SILDIRQGPK EPFRDYVDRF
YKTLRAEQAS QEVKNWMTET LLVQNANPDC KTILKALGPA ATLEEMMTAC QGVGGPGHKA
RVLAEAMSQV TNSTTIMMQR GNFRNQRKII KCFNCGKEGH LARNCRAPRK KGCWKCGKEG
HQMKDCNERQ ANFLREDLAF LQGKAREFSS EQTRANSPSR GELQVWGRDN NPLSEAGAER
QGTVSFSFPQ ITLWQRPLVT LKIGGQLKEA LLDTGADDTV LEEMNSPGRW KP
