IN - Integrase

HIV IN mediates the insertion of viral DNA into the host genome.





PDB-2ITG: HIV-1 (isolate UNKNOWN) Integrase - produced using SwissModel/SPDBV/POVray
[animated gif: 320x240 ]
ViralZone:HIV-1
PDB: 2ITG (HIV-1 Integrase)
SwissProt: P04585 (HIV-1 HXB2 POL)
Chime Tutorial: Online Macromolecular Museum
Los Alamos HIV structure DB: Integrase
EMBL: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Pol Protein Data Mining Tool


Isoforms:

  • p31 (288 amino acids)


Cleavage site:


Localization:

  • Virion
  • Cell nucleus


Function:

  • Viral enzyme
  • Catalyzes viral DNA integration into the host chromosome (Ref. #13)
  • exonuclease activity trims two nucleotides from each 3'-end of the linear DNA duplux (Ref. #4)
  • double-stranded endonuclease activity cleaves the host DNA at the integration site (Ref. #4)
  • ligase activity generates a single covalent linkage at each end of viral DNA (Ref. #4)

Additional Information:

  • after integration, cellular enzymes repair the integration site
  • no exogenous energy source (ie. ATP) is required for integration
  • accessibility of chromosomal DNA, not a specific DNA sequence, influences the site of integration (Ref. #5)
  • DNA kinking are "hot-spots" for integration in in vitro studies (Ref. #6)
  • integration into regions of open, transcriptionally active, chromatin may facilitate expression of viral proteins
  • non-integrated proviral DNA is expressed inefficiently (Ref. #7)

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2):

          10         20         30         40         50         60         70 
| | | | | | |
FLDGIDKAQD EHEKYHSNWR AMASDFNLPP VVAKEIVASC DKCQLKGEAM HGQVDCSPGI WQLDCTHLEG
80 90 100 110 120 130 140
| | | | | | |
KVILVAVHVA SGYIEAEVIP AETGQETAYF LLKLAGRWPV KTIHTDNGSN FTGATVRAAC WWAGIKQEFG
150 160 170 180 190 200 210
| | | | | | |
IPYNPQSQGV VESMNKELKK IIGQVRDQAE HLKTAVQMAV FIHNFKRKGG IGGYSAGERI VDIIATDIQT
220 230 240 250 260 270 280
| | | | | | |
KELQKQITKI QNFRVYYRDS RNPLWKGPAK LLWKGEGAVV IQDNSDIKVV PRRKAKIIRD YGKQMAGDDC
288
|
VASRQDED
[download in fasta format]

Length: 288 amino acids
Molecular Weight: 32166 Da
Theoretical pI: 8.16

Protein Domains/Folds/Motifs: [TOP]

InterPro signature for Retroviral Integrase, C-terminal - IPR001037

InterPro signature for Integrase, catalytic domain - IPR001584


Secondary Structure prediction:

Antigenic Sites - EMBOSS:





Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Protein-Protein Interactions: [TOP]

  • Host DNA
  • Viral DNA
  • Integrase binds to Ini1 for selective integration
  • Integrase binds to Reverse Transcriptase for initiation of reverse transcription
  • Integrase binds to UDG for its incorporation into virions
  • Integrase binds to Karyopherins for high MOI nuclear import


Primary and Secondary Database Entries: [TOP]

Identifiers:

ViralZone: HIV-1
PDB/MMDB: Search for HIV-1 & Integrase

SwissProt: P04585 (HIV-1 HXB2 POL)
EC: NONE
EMBL: K03455; AAB50259.1 [EMBL/GenBank/DDBJ]

PIR: UNKNOWN
HIV: K03455; UNKNOWN$HXB2
InterPro: IPR001037 / IPR001584
Pfam: PF00552 / PF00665 / PF02022
Prints: none
ProDom: PD000915 (1 - 55) / PD000348 (56 - 211) / PD000723 (219 - 270) / PD371748 (225 - 266)
SCOP: SSF46919 (N-terminus) Zn-binding domain / SSF53098 Ribonuclease H-like protein
SSF50122 (C-terminus) DNA-binding domain
BLOCKS: P04585
Prosite: P04585
ProtoNet: P04585
ProtoMap: P04585
PRESAGE: P04585
Database of Interacting Proteins: P04585
ModBase: P04585
Swiss-2DPAGE: 2D gel

BioAfrica Tools:
- Pol Protein Data Mining Tool provides real-time analysis of HIV-1 Pol isolates
- HIV Structure BLAST searches for similar HIV sequences that have known structures
- HIV Proteomics Resource contains protein sequence and structure analysis tools

Reviews and References: [TOP]


Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - Molecular Characteristics of HIV-1 Subtype C Viruses from KwaZulu-Natal, South Africa:
Implications for Vaccine and Antiretroviral Control Strategies.
Gordon M, De Oliveira T, Bishop K, Coovadia HM, Madurai L, Engelbrecht S, Janse van Rensburg E, Mosam A, Smith A, Cassol S.
Journal of Virology 77(4): 2587-2599 (2003) [pubmed: 12551997]
4 - Retroviral DNA integration directed by HIV integration protein in vitro.
Bushman FD, Fujiwara T, Craigie R.
Science 249: 1555-1558 (1990) [pubmed: 2171144]
5 - Nucleosomes, DNA-binding proteins, and DNA sequence modulate retroviral integration target
site selection.
Pryciak PM, Varmus HE.
Cell 69: 769-780 (1992) [pubmed: 1317268]
6 - Human immunodeficiency virus integrase directs integration to sites of severe DNA distortion
within the nucleosome core.
Pruss D, Bushman FD, Wolffe AP.
Proc Natl Acad Sci USA 91: 5913-5917 (1994) [pubmed: 8016088]
7 - Human immunodeficiency virus type 1 integrase: Effects of mutations on viral ability to integrate,
direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells.
Wiskerchen M, Muesing MA.
J Virol 69: 376-386 (1995) [pubmed: 7983732]
8 - [HIV Integrase Review - pdb:1K6Y] Structure of a two-domain fragment of HIV-1 integrase:
implications for domain organization in the intact protein.
Wang JY, Ling H, Yang W, Craigie R.
EMBO J 20(24): 7333-7343 (2001) [pubmed: 11743009]
9 - [Drug Resistant Mutations] Molecular Dynamics Studies of the Wild-Type and Double Mutant HIV-1
Integrase Complexed with the 5CITEP Inhibitor: Mechanism for Inhibition and Drug Resistance.
Barreca ML, Lee KW, Chimirri A, Briggs JM.
Biophys J 84(3): 1450-1463 (2003) [pubmed: 12609852]
10 - [Integrase forms multimers] HIV-1 integrase forms stable tetramers and associates with
LEDGF/p75 protein in human cells.
Cherepanov P, Maertens G, Proost P, Devreese B, Van Beeumen J, Engelborghs Y, De Clercq E, Debyser Z.
J Biol Chem 278(1): 372-81 (2003) [pubmed: 12407101]
11 - [EBR28 - peptide inhibitor of Integrase] A novel short peptide is a specific inhibitor of the
human immunodeficiency virus type 1 integrase.
de Soultrait VR, Caumont A, Parissi V, Morellet N, Ventura M, Lenoir C, Litvak S, Fournier M, Roques B.
J Mol Biol 318(1): 45-58 (2002) [pubmed: 12054767]
 12 - [Human Rad18 DNA damage/repair enzyme - stabilizes Integrase]
Interaction of HIV-1 integrase with DNA repair protein hRad18.
Mulder LC, Chakrabarti LA, Muesing MA.
J Biol Chem 277(30): 27489-27493 (2002) [pubmed: 12016221]
13 - Integrase and integration: biochemical activities of HIV-1 integrase.
Delelis O, Carayon K, Sab A, Deprez E, Mouscadet JF.
Retrovirology 17;5:114 (2008). [pubmed: 19091057]



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