IN - Integrase
HIV IN mediates the insertion of viral DNA into the host genome.
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[animated gif: 320x240 ]
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Isoforms:
Cleavage site:
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Localization:
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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)
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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)
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Genomic Location: [TOP]
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Reference
Sequences:
HIV-1
(HXB2):
10 20 30 40 50 60 70
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FLDGIDKAQD EHEKYHSNWR AMASDFNLPP VVAKEIVASC DKCQLKGEAM HGQVDCSPGI WQLDCTHLEG
80 90 100 110 120 130 140
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KVILVAVHVA SGYIEAEVIP AETGQETAYF LLKLAGRWPV KTIHTDNGSN FTGATVRAAC WWAGIKQEFG
150 160 170 180 190 200 210
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IPYNPQSQGV VESMNKELKK IIGQVRDQAE HLKTAVQMAV FIHNFKRKGG IGGYSAGERI VDIIATDIQT
220 230 240 250 260 270 280
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KELQKQITKI QNFRVYYRDS RNPLWKGPAK LLWKGEGAVV IQDNSDIKVV PRRKAKIIRD YGKQMAGDDC
288
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VASRQDED
[download in fasta format]
Length:
288 amino acids
Molecular Weight: 32166 Da
Theoretical pI: 8.16
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Protein Domains/Folds/Motifs: [TOP]
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InterPro signature for Retroviral Integrase, C-terminal - IPR001037
InterPro signature for Integrase, catalytic domain - IPR001584
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Secondary Structure prediction:
Antigenic Sites - EMBOSS:
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N-glycosylation:
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N-myristoylation:
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Amidation:
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Protein kinase C:
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Casein kinase II:
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Tyrosine kinase:
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cAMP / cGMP kinase:
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Cell attachment motif:
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Asp Protease motif:
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Asp Prot Retro motif:
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Cysteine-rich Region:
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Tryptophan-rich Region:
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Zinc-finger CCHC motif:
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Leucine Zipper motif:
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Protein-Protein Interactions: [TOP]
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- 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
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Primary and Secondary Database Entries: [TOP]
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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
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Reviews and References: [TOP]
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- 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, Saïb A, Deprez E, Mouscadet JF.
- Retrovirology 17;5:114 (2008). [pubmed: 19091057]
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