ID POL_HV1Z6 Reviewed; 148 AA. AC P04586; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 13-AUG-1987, sequence version 1. DT 15-FEB-2017, entry version 130. DE RecName: Full=Gag-Pol polyprotein; DE AltName: Full=Pr160Gag-Pol; DE Contains: DE RecName: Full=Integrase; DE Short=IN; DE EC=2.7.7.- {ECO:0000250|UniProtKB:P04585}; DE EC=3.1.-.- {ECO:0000250|UniProtKB:P04585}; DE Flags: Fragment; GN Name=gag-pol; OS Human immunodeficiency virus type 1 group M subtype D (isolate Z6) OS (HIV-1). OC Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae; OC Lentivirus; Primate lentivirus group. OX NCBI_TaxID=11708; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=3036660; DOI=10.1016/0378-1119(87)90396-9; RA Srinivasan A., Anand R., York D., Ranganathan P., Feorino P., RA Schochetman G., Curran J., Kalyanaraman V.S., Luciw P.A., RA Sanchez-Pescador R.; RT "Molecular characterization of human immunodeficiency virus from RT Zaire: nucleotide sequence analysis identifies conserved and variable RT domains in the envelope gene."; RL Gene 52:71-82(1987). RN [2] RP STRUCTURE BY NMR OF 80-130. RX PubMed=7632683; DOI=10.1021/bi00031a002; RA Lodi P.J., Ernst J.A., Kuszewski J., Hickman A.B., Engelman A., RA Craigie R., Clore G.M., Gronenborn A.M.; RT "Solution structure of the DNA binding domain of HIV-1 integrase."; RL Biochemistry 34:9826-9833(1995). CC -!- FUNCTION: Integrase: Catalyzes viral DNA integration into the host CC chromosome, by performing a series of DNA cutting and joining CC reactions. This enzyme activity takes place after virion entry CC into a cell and reverse transcription of the RNA genome in dsDNA. CC The first step in the integration process is 3' processing. This CC step requires a complex comprising the viral genome, matrix CC protein, Vpr and integrase. This complex is called the pre- CC integration complex (PIC). The integrase protein removes 2 CC nucleotides from each 3' end of the viral DNA, leaving recessed CA CC OH's at the 3' ends. In the second step, the PIC enters cell CC nucleus. This process is mediated through integrase and Vpr CC proteins, and allows the virus to infect a non dividing cell. This CC ability to enter the nucleus is specific of lentiviruses, other CC retroviruses cannot and rely on cell division to access cell CC chromosomes. In the third step, termed strand transfer, the CC integrase protein joins the previously processed 3' ends to the 5' CC ends of strands of target cellular DNA at the site of integration. CC The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 CC bp apart. A Y-shaped, gapped, recombination intermediate results, CC with the 5'-ends of the viral DNA strands and the 3' ends of CC target DNA strands remaining unjoined, flanking a gap of 5 bp. The CC last step is viral DNA integration into host chromosome. This CC involves host DNA repair synthesis in which the 5 bp gaps between CC the unjoined strands are filled in and then ligated. Since this CC process occurs at both cuts flanking the HIV genome, a 5 bp CC duplication of host DNA is produced at the ends of HIV-1 CC integration. Alternatively, Integrase may catalyze the excision of CC viral DNA just after strand transfer, this is termed CC disintegration. {ECO:0000250|UniProtKB:P04585}. CC -!- SUBUNIT: Matrix protein p17: Homotrimer; further assembles as CC hexamers of trimers (By similarity). Matrix protein p17: Interacts CC with gp41 (via C-terminus) (By similarity). Matrix protein p17: CC interacts with host CALM1; this interaction induces a CC conformational change in the Matrix protein, triggering exposure CC of the myristate group (By similarity). Matrix protein p17: CC interacts with host AP3D1; this interaction allows the polyprotein CC trafficking to multivesicular bodies during virus assembly (By CC similarity). Matrix protein p17: Part of the pre-integration CC complex (PIC) which is composed of viral genome, matrix protein, CC Vpr and integrase (By similarity). Capsid protein p24: Homodimer; CC the homodimer further multimerizes as homohexamers or CC homopentamers. Capsid protein p24: Interacts with human PPIA/CYPA CC (By similarity); This interaction stabilizes the capsid. Capsid CC protein p24: Interacts with human NUP153 (By similarity). Capsid CC protein p24: Interacts with host PDZD8; this interaction CC stabilizes the capsid (By similarity). Capsid protein p24: CC Interacts with monkey TRIM5; this interaction destabilizes the CC capsid (By similarity).Protease: Homodimer, whose active site CC consists of two apposed aspartic acid residues. Reverse CC transcriptase/ribonuclease H: Heterodimer of p66 RT and p51 RT (RT CC p66/p51). Heterodimerization of RT is essential for DNA polymerase CC activity. Despite the sequence identities, p66 RT and p51 RT have CC distinct folding. Integrase: Homodimer; possibly can form CC homotetramer. Integrase: Part of the pre-integration complex (PIC) CC which is composed of viral genome, matrix protein, Vpr and CC integrase. Integrase: Interacts with human SMARCB1/INI1 and human CC PSIP1/LEDGF isoform 1. Integrase: Interacts with human KPNA3; this CC interaction might play a role in nuclear import of the pre- CC integration complex (By similarity). Integrase: Interacts with CC human NUP153; this interaction might play a role in nuclear import CC of the pre-integration complex (By similarity). CC {ECO:0000250|UniProtKB:P04585, ECO:0000250|UniProtKB:P12497}. CC -!- PTM: Specific enzymatic cleavages by the viral protease yield CC mature proteins. {ECO:0000250}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; K03458; AAA45376.1; -; Genomic_RNA. DR PIR; A26192; A26192. DR PDB; 1IHV; NMR; -; A/B=80-130. DR PDB; 1IHW; NMR; -; A/B=80-130. DR PDBsum; 1IHV; -. DR PDBsum; 1IHW; -. DR ProteinModelPortal; P04586; -. DR SMR; P04586; -. DR MEROPS; A02.001; -. DR EvolutionaryTrace; P04586; -. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0015074; P:DNA integration; IEA:UniProtKB-KW. DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW. DR GO; GO:0075713; P:establishment of integrated proviral latency; IEA:UniProtKB-KW. DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW. DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW. DR Gene3D; 2.30.30.10; -; 1. DR Gene3D; 3.30.420.10; -; 1. DR InterPro; IPR001037; Integrase_C_retrovir. DR InterPro; IPR001584; Integrase_cat-core. DR InterPro; IPR012337; RNaseH-like_dom. DR Pfam; PF00552; IN_DBD_C; 1. DR SUPFAM; SSF50122; SSF50122; 1. DR SUPFAM; SSF53098; SSF53098; 1. DR PROSITE; PS50994; INTEGRASE; 1. DR PROSITE; PS51027; INTEGRASE_DBD; 1. PE 1: Evidence at protein level; KW 3D-structure; AIDS; DNA integration; DNA recombination; DNA-binding; KW Endonuclease; Eukaryotic host gene expression shutoff by virus; KW Eukaryotic host translation shutoff by virus; KW Host gene expression shutoff by virus; Host-virus interaction; KW Hydrolase; Lipid-binding; Metal-binding; Nuclease; KW Viral genome integration; Virus entry into host cell. FT CHAIN <1 148 Gag-Pol polyprotein. FT /FTId=PRO_0000261289. FT CHAIN <1 148 Integrase. {ECO:0000250}. FT /FTId=PRO_0000042448. FT DOMAIN <1 64 Integrase catalytic. FT {ECO:0000255|PROSITE-ProRule:PRU00457}. FT DNA_BIND 83 130 Integrase-type. {ECO:0000255|PROSITE- FT ProRule:PRU00506}. FT METAL 12 12 Magnesium; catalytic; for integrase FT activity. {ECO:0000250|UniProtKB:P04585}. FT NON_TER 1 1 FT STRAND 82 88 {ECO:0000244|PDB:1IHV}. FT STRAND 93 115 {ECO:0000244|PDB:1IHV}. FT STRAND 117 121 {ECO:0000244|PDB:1IHV}. FT HELIX 122 124 {ECO:0000244|PDB:1IHV}. FT STRAND 125 129 {ECO:0000244|PDB:1IHV}. SQ SEQUENCE 148 AA; 16840 MW; A0DD31618CF0FC0E CRC64; IPYNPQSQGV VESMNKELKK IIGQVRDQAE HLKTAVQMAV FIHNFKRKGG IGGYSAGERI IDIIATDIQT KELQKQITKI QNFRVYYRDS RDPIWKGPAK LLWKGEGAVV IQDNSDIKVV PRRKVKIIRD YGKQMAGDDC VASRQDED //