GAG_HV1A2
ID GAG_HV1A2 Reviewed; 502 AA.
AC P03349;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Gag polyprotein;
DE AltName: Full=Pr55Gag;
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:P12493};
DE Short=SP1;
DE AltName: Full=p2;
DE Contains:
DE RecName: Full=Nucleocapsid protein p7;
DE Short=NC;
DE Contains:
DE RecName: Full=Spacer peptide 2 {ECO:0000250|UniProtKB:P12493};
DE Short=SP2;
DE AltName: Full=p1;
DE Contains:
DE RecName: Full=p6-gag;
GN Name=gag;
OS Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11685;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2578227; DOI=10.1126/science.2578227;
RA Sanchez-Pescador R., Power M.D., Barr P.J., Steimer K.S., Stempien M.M.,
RA Brown-Shimer S.L., Gee W.W., Renard A., Randolph A., Levy J.A., Dina D.,
RA Luciw P.A.;
RT "Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-
RT 2).";
RL Science 227:484-492(1985).
RN [2]
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).
RN [3]
RP INTERACTION WITH HOST PACSIN2, AND MUTAGENESIS OF THR-458; LEU-491; LEU-494
RP AND PHE-495.
RX PubMed=29891700; DOI=10.1073/pnas.1801849115;
RA Popov S., Popova E., Inoue M., Wu Y., Goettlinger H.;
RT "HIV-1 gag recruits PACSIN2 to promote virus spreading.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:7093-7098(2018).
CC -!- FUNCTION: [Gag polyprotein]: Mediates, with Gag-Pol 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). {ECO:0000250|UniProtKB:P04591}.
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 (By similarity). Matrix protein is part of the
CC pre-integration complex. Implicated in the release from host cell
CC mediated by Vpu. Binds to RNA (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P12493}.
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). The capsid promotes immune invasion by
CC cloaking viral DNA from CGAS detection (By similarity). Host
CC restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral
CC capsids and cause premature capsid disassembly, leading to blocks in
CC reverse transcription. Capsid restriction by TRIM5 is one of the
CC factors which restricts HIV-1 to the human species. Host PIN1
CC apparently facilitates the virion uncoating (By similarity). On the
CC other hand, interactions with PDZD8 or CYPA stabilize the capsid (By
CC similarity). {ECO:0000250|UniProtKB:P04591,
CC ECO:0000250|UniProtKB:P12493}.
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:P04591}.
CC -!- FUNCTION: [p6-gag]: Plays a role in budding of the assembled particle
CC by interacting with the host class E VPS proteins TSG101 and
CC PDCD6IP/AIP1. {ECO:0000250|UniProtKB:P12493}.
CC -!- SUBUNIT: [Gag polyprotein]: Homotrimer; further assembles as hexamers
CC of trimers (By similarity). Oligomerization possibly creates a central
CC hole into which the cytoplasmic tail of the gp41 envelope protein may
CC be inserted. Interacts with host TRIM22; this interaction seems to
CC disrupt proper trafficking of Gag polyprotein and may interfere with
CC budding (By similarity). Interacts with host PDZD8 (By similarity).
CC When ubiquitinated, interacts (via p6-gag domain) with host PACSIN2;
CC this interaction allows PACSIN2 recruitment to viral assembly sites and
CC its subsequent incorporation into virions (PubMed:29891700). Interacts
CC with MOV10 (By similarity). {ECO:0000250|UniProtKB:P04591,
CC ECO:0000269|PubMed:29891700}.
CC -!- SUBUNIT: [Matrix protein p17]: Homotrimer; further assembles as
CC hexamers of trimers. Interacts with gp41 (via C-terminus). Interacts
CC with host CALM1; this interaction induces a conformational change in
CC the Matrix protein, triggering exposure of the myristate group.
CC Interacts with host AP3D1; this interaction allows the polyprotein
CC trafficking to multivesicular bodies during virus assembly. Part of the
CC pre-integration complex (PIC) which is composed of viral genome, matrix
CC protein, Vpr and integrase. {ECO:0000250|UniProtKB:P04591,
CC ECO:0000250|UniProtKB:P12493}.
CC -!- SUBUNIT: [Capsid protein p24]: Homodimer; the homodimer further
CC multimerizes as homohexamers or homopentamers (By similarity).
CC Interacts with host NUP98 (By similarity). Interacts with host
CC PPIA/CYPA; this interaction stabilizes the capsid (By similarity).
CC Interacts with host NUP153 (By similarity). Interacts with host PDZD8;
CC this interaction stabilizes the capsid. Interacts with host TRIM5; this
CC interaction destabilizes the capsid (By similarity). Interacts with
CC host CPSF6 (By similarity). Interacts with host NONO; the interaction
CC is weak (By similarity). {ECO:0000250|UniProtKB:P04591,
CC ECO:0000250|UniProtKB:P12493}.
CC -!- SUBUNIT: [Nucleocapsid protein p7]: Interacts with host NUP98.
CC {ECO:0000250|UniProtKB:P12493}.
CC -!- SUBUNIT: [p6-gag]: Interacts with Vpr; this interaction allows Vpr
CC incorporation into the virion (By similarity). Interacts with host
CC TSG101 (By similarity). Interacts with host PDCD6IP/AIP1 (By
CC similarity). {ECO:0000250|UniProtKB:P03348,
CC ECO:0000250|UniProtKB:P12493}.
CC -!- SUBCELLULAR LOCATION: [Gag polyprotein]: Host cell membrane
CC {ECO:0000250|UniProtKB:P12493}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P12493}. Host endosome, host multivesicular body
CC {ECO:0000250|UniProtKB:P12493}. Note=These locations are probably
CC linked to virus assembly sites. The main location is the cell membrane,
CC but under some circumstances, late endosomal compartments can serve as
CC productive sites for virion assembly. {ECO:0000250|UniProtKB:P12493}.
CC -!- SUBCELLULAR LOCATION: [Matrix protein p17]: Virion membrane
CC {ECO:0000250|UniProtKB:P12493}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P12493}. Host nucleus {ECO:0000250}. Host
CC cytoplasm {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein p24]: Virion
CC {ECO:0000250|UniProtKB:P12493}.
CC -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p7]: Virion
CC {ECO:0000250|UniProtKB:P12493}.
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 polyprotein;
CC IsoId=P03349-1; Sequence=Displayed;
CC Name=Gag-Pol polyprotein;
CC IsoId=P03369-1; Sequence=External;
CC -!- DOMAIN: Late-budding domains (L domains) are short sequence motifs
CC essential for viral particle budding. They recruit proteins of the host
CC ESCRT machinery (Endosomal Sorting Complex Required for Transport) or
CC ESCRT-associated proteins. p6-gag contains two L domains: a PTAP/PSAP
CC motif, which interacts with the UEV domain of TSG101 and a LYPX(n)L
CC motif which interacts with PDCD6IP/AIP1.
CC {ECO:0000250|UniProtKB:P12493}.
CC -!- PTM: Gag-Pol polyprotein: Specific enzymatic cleavages by the viral
CC protease yield mature proteins. {ECO:0000250|UniProtKB:P12493}.
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:P04591}.
CC -!- PTM: Capsid protein p24 is 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 is 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: [Isoform Gag polyprotein]: Produced by conventional
CC translation.
CC -!- SIMILARITY: Belongs to the primate lentivirus group gag polyprotein
CC family. {ECO:0000305}.
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DR EMBL; K02007; AAB59875.1; -; Genomic_RNA.
DR PIR; A03947; FOVWA2.
DR PDB; 4OBD; X-ray; 1.90 A; E/F=446-455.
DR PDB; 4OBF; X-ray; 1.68 A; E/F=446-455.
DR PDB; 4OBG; X-ray; 1.78 A; E/F=446-455.
DR PDB; 4OBH; X-ray; 1.85 A; E/F=446-455.
DR PDB; 4OBJ; X-ray; 1.75 A; C=446-455.
DR PDB; 4OBK; X-ray; 1.65 A; C=446-455.
DR PDB; 4QJ2; X-ray; 2.13 A; F/G=446-455.
DR PDB; 4QJ6; X-ray; 1.50 A; E/F=446-455.
DR PDB; 4QJ7; X-ray; 1.67 A; F/G=446-453.
DR PDB; 4QJ8; X-ray; 2.00 A; E/F=446-454.
DR PDB; 4QJ9; X-ray; 1.83 A; G=446-453.
DR PDB; 4QJA; X-ray; 1.54 A; P=446-454.
DR PDBsum; 4OBD; -.
DR PDBsum; 4OBF; -.
DR PDBsum; 4OBG; -.
DR PDBsum; 4OBH; -.
DR PDBsum; 4OBJ; -.
DR PDBsum; 4OBK; -.
DR PDBsum; 4QJ2; -.
DR PDBsum; 4QJ6; -.
DR PDBsum; 4QJ7; -.
DR PDBsum; 4QJ8; -.
DR PDBsum; 4QJ9; -.
DR PDBsum; 4QJA; -.
DR BMRB; P03349; -.
DR SMR; P03349; -.
DR PRIDE; P03349; -.
DR PRO; PR:P03349; -.
DR Proteomes; UP000007688; Genome.
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: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:0039702; P:viral budding via host ESCRT complex; 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 InterPro; IPR045345; Gag_p24_C.
DR InterPro; IPR000721; Gag_p24_N.
DR InterPro; IPR014817; Gag_p6.
DR InterPro; IPR000071; Lentvrl_matrix_N.
DR InterPro; IPR012344; Matrix_HIV/RSV_N.
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; PF08705; Gag_p6; 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; SSF57756; SSF57756; 1.
DR PROSITE; PS50158; ZF_CCHC; 2.
PE 1: Evidence at protein level;
KW 3D-structure; AIDS; Capsid protein; Host cell membrane; Host cytoplasm;
KW Host endosome; Host membrane; Host nucleus; Host-virus interaction;
KW Lipoprotein; Membrane; Metal-binding; Methylation; Myristate;
KW Phosphoprotein; Reference proteome; Repeat; Ribosomal frameshifting;
KW RNA-binding; Viral budding; Viral budding via the host ESCRT complexes;
KW Viral nucleoprotein; Viral release from host cell; Virion; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..502
FT /note="Gag polyprotein"
FT /id="PRO_0000261208"
FT CHAIN 2..134
FT /note="Matrix protein p17"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038505"
FT CHAIN 135..365
FT /note="Capsid protein p24"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038506"
FT PEPTIDE 366..379
FT /note="Spacer peptide 1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038507"
FT CHAIN 380..434
FT /note="Nucleocapsid protein p7"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038508"
FT PEPTIDE 435..450
FT /note="Spacer peptide 2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038509"
FT CHAIN 451..502
FT /note="p6-gag"
FT /evidence="ECO:0000250"
FT /id="PRO_0000038510"
FT ZN_FING 392..409
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 413..430
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:P12493"
FT REGION 8..43
FT /note="Interaction with host CALM1"
FT /evidence="ECO:0000250|UniProtKB:P04591"
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:P12493"
FT REGION 73..77
FT /note="Interaction with membrane phosphatidylinositol 4,5-
FT bisphosphate"
FT /evidence="ECO:0000250|UniProtKB:P12493"
FT REGION 106..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 191..229
FT /note="Interaction with host PPIA/CYPA and NUP153"
FT /evidence="ECO:0000250|UniProtKB:P12493"
FT REGION 219..227
FT /note="PPIA/CYPA-binding loop"
FT /evidence="ECO:0000250|UniProtKB:P04591"
FT REGION 279..365
FT /note="Dimerization/Multimerization of capsid protein p24"
FT /evidence="ECO:0000250|UniProtKB:P04591"
FT REGION 446..502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 MOTIF 457..460
FT /note="PTAP/PSAP motif"
FT MOTIF 485..494
FT /note="LYPX(n)L motif"
FT COMPBIAS 463..478
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 134..135
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 365..366
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 379..380
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 434..435
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT SITE 450..451
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000250"
FT MOD_RES 150
FT /note="Phosphoserine; by host MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P12493"
FT MOD_RES 389
FT /note="Asymmetric dimethylarginine; in Nucleocapsid protein
FT p7; by host PRMT6"
FT /evidence="ECO:0000250"
FT MOD_RES 411
FT /note="Asymmetric dimethylarginine; in Nucleocapsid protein
FT p7; by host PRMT6"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine; by host"
FT /evidence="ECO:0000250"
FT MUTAGEN 458
FT /note="T->G: No effect on host PACSIN2 incorporation into
FT virions."
FT /evidence="ECO:0000269|PubMed:29891700"
FT MUTAGEN 491
FT /note="L->A: No effect on host PACSIN2 incorporation into
FT virions."
FT /evidence="ECO:0000269|PubMed:29891700"
FT MUTAGEN 494
FT /note="L->P: Slight decrease in host PACSIN2 incorporation
FT into virions."
FT /evidence="ECO:0000269|PubMed:29891700"
FT MUTAGEN 495
FT /note="F->S: Slight decrease in host PACSIN2 incorporation
FT into virions."
FT /evidence="ECO:0000269|PubMed:29891700"
SQ SEQUENCE 502 AA; 56066 MW; EF36C928D5F816E7 CRC64;
MGARASVLSG GELDKWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPGL LETSEGCRQI
LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIDVKDTKEA LEKIEEEQNK SKKKAQQAAA
AAGTGNSSQV SQNYPIVQNL QGQMVHQAIS PRTLNAWVKV VEEKAFSPEV IPMFSALSEG
ATPQDLNTML NTVGGHQAAM QMLKETINEE AAEWDRVHPV HAGPIAPGQM REPRGSDIAG
TTSTLQEQIG WMTNNPPIPV GEIYKRWIIL GLNKIVRMYS PTSILDIRQG PKEPFRDYVD
RFYKTLRAEQ ASQDVKNWMT ETLLVQNANP DCKTILKALG PAATLEEMMT ACQGVGGPGH
KARVLAEAMS QVTNPANIMM QRGNFRNQRK TVKCFNCGKE GHIAKNCRAP RKKGCWRCGR
EGHQMKDCTE RQANFLGKIW PSYKGRPGNF LQSRPEPTAP PEESFRFGEE KTTPSQKQEP
IDKELYPLTS LRSLFGNDPS SQ
