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Protein

Gag-Pol polyprotein

Gene

gag-pol

Organism
Human immunodeficiency virus type 1 group M subtype D (isolate Z6) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi12 – 121Magnesium; catalytic; for integrase activityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi83 – 13048Integrase-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA integration, DNA recombination, Eukaryotic host gene expression shutoff by virus, Eukaryotic host translation shutoff by virus, Host gene expression shutoff by virus, Host-virus interaction, Viral genome integration, Virus entry into host cell

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding

Protein family/group databases

MEROPSiA02.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Gag-Pol polyprotein
Alternative name(s):
Pr160Gag-Pol
Cleaved into the following chain:
Integrase (EC:2.7.7.-By similarity, EC:3.1.-.-By similarity)
Short name:
IN
Gene namesi
Name:gag-pol
OrganismiHuman immunodeficiency virus type 1 group M subtype D (isolate Z6) (HIV-1)
Taxonomic identifieri11708 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 148›148Gag-Pol polyproteinPRO_0000261289Add
BLAST
Chaini‹1 – 148›148IntegraseBy similarityPRO_0000042448Add
BLAST

Post-translational modificationi

Specific enzymatic cleavages by the viral protease yield mature proteins.By similarity

Interactioni

Subunit structurei

Matrix protein p17: Homotrimer; further assembles as hexamers of trimers (By similarity). Matrix protein p17: Interacts with gp41 (via C-terminus) (By similarity). Matrix protein p17: interacts with host CALM1; this interaction induces a conformational change in the Matrix protein, triggering exposure of the myristate group (By similarity). Matrix protein p17: interacts with host AP3D1; this interaction allows the polyprotein trafficking to multivesicular bodies during virus assembly (By similarity). Matrix protein p17: Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase (By similarity). Capsid protein p24: Homodimer; the homodimer further multimerizes as homohexamers or homopentamers. Capsid protein p24: Interacts with human PPIA/CYPA (By similarity); This interaction stabilizes the capsid. Capsid protein p24: Interacts with human NUP153 (By similarity). Capsid protein p24: Interacts with host PDZD8; this interaction stabilizes the capsid (By similarity). Capsid protein p24: Interacts with monkey TRIM5; this interaction destabilizes the capsid (By similarity).Protease: Homodimer, whose active site consists of two apposed aspartic acid residues. Reverse transcriptase/ribonuclease H: Heterodimer of p66 RT and p51 RT (RT p66/p51). Heterodimerization of RT is essential for DNA polymerase activity. Despite the sequence identities, p66 RT and p51 RT have distinct folding. Integrase: Homodimer; possibly can form homotetramer. Integrase: Part of the pre-integration complex (PIC) which is composed of viral genome, matrix protein, Vpr and integrase. Integrase: Interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1. Integrase: Interacts with human KPNA3; this interaction might play a role in nuclear import of the pre-integration complex (By similarity). Integrase: Interacts with human NUP153; this interaction might play a role in nuclear import of the pre-integration complex (By similarity).By similarity

Structurei

Secondary structure

1
148
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi82 – 887Combined sources
Beta strandi93 – 11523Combined sources
Beta strandi117 – 1215Combined sources
Helixi122 – 1243Combined sources
Beta strandi125 – 1295Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IHVNMR-A/B80-130[»]
1IHWNMR-A/B80-130[»]
ProteinModelPortaliP04586.
SMRiP04586. Positions 5-130.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04586.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini‹1 – 64›64Integrase catalyticPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 integrase catalytic domain.PROSITE-ProRule annotation
Contains 1 integrase-type DNA-binding domain.PROSITE-ProRule annotation

Family and domain databases

Gene3Di2.30.30.10. 1 hit.
3.30.420.10. 1 hit.
InterProiIPR001037. Integrase_C_retrovir.
IPR001584. Integrase_cat-core.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF00552. IN_DBD_C. 1 hit.
[Graphical view]
SUPFAMiSSF50122. SSF50122. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiPS50994. INTEGRASE. 1 hit.
PS51027. INTEGRASE_DBD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04586-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
IPYNPQSQGV VESMNKELKK IIGQVRDQAE HLKTAVQMAV FIHNFKRKGG
60 70 80 90 100
IGGYSAGERI IDIIATDIQT KELQKQITKI QNFRVYYRDS RDPIWKGPAK
110 120 130 140
LLWKGEGAVV IQDNSDIKVV PRRKVKIIRD YGKQMAGDDC VASRQDED
Length:148
Mass (Da):16,840
Last modified:August 13, 1987 - v1
Checksum:iA0DD31618CF0FC0E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03458 Genomic RNA. Translation: AAA45376.1.
PIRiA26192.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03458 Genomic RNA. Translation: AAA45376.1.
PIRiA26192.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IHVNMR-A/B80-130[»]
1IHWNMR-A/B80-130[»]
ProteinModelPortaliP04586.
SMRiP04586. Positions 5-130.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiA02.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP04586.

Family and domain databases

Gene3Di2.30.30.10. 1 hit.
3.30.420.10. 1 hit.
InterProiIPR001037. Integrase_C_retrovir.
IPR001584. Integrase_cat-core.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF00552. IN_DBD_C. 1 hit.
[Graphical view]
SUPFAMiSSF50122. SSF50122. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiPS50994. INTEGRASE. 1 hit.
PS51027. INTEGRASE_DBD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular characterization of human immunodeficiency virus from Zaire: nucleotide sequence analysis identifies conserved and variable domains in the envelope gene."
    Srinivasan A., Anand R., York D., Ranganathan P., Feorino P., Schochetman G., Curran J., Kalyanaraman V.S., Luciw P.A., Sanchez-Pescador R.
    Gene 52:71-82(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: STRUCTURE BY NMR OF 80-130.

Entry informationi

Entry nameiPOL_HV1Z6
AccessioniPrimary (citable) accession number: P04586
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: November 11, 2015
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.