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704  structures 5684  species 0  interactions 45153  sequences 2301  architectures

Family: rve (PF00665)

Summary: Integrase core domain

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This is the Wikipedia entry entitled "Integrase". More...

Integrase Edit Wikipedia article

Integrase Zinc binding domain
PDB 1wjd EBI.jpg
solution structure of the n-terminal zn binding domain of hiv-1 integrase (e form), nmr, 38 structures
Integrase core domain
PDB 1c1a EBI.jpg
Crystal structure of the RSV two-domain integrase.
Pfam clanCL0219
Integrase DNA binding domain
PDB 1c1a EBI.jpg
Crystal structure of the RSV two-domain integrase.

Retroviral integrase (IN) is an enzyme produced by a retrovirus (such as HIV) that integrates—forms covalent links between—its DNA (genetic information) into that of the host cell it infects.[citation needed] Retroviral INs are distinct from phage integrases, such as λ phage integrase, as discussed in site-specific recombination.[not verified in body]

The macromolecular complex of an IN macromolecule bound to the ends of the viral DNA ends has been referred to as the intasome; IN is a key component in this and the retroviral pre-integration complex.[clarification needed][1]


All retroviral IN proteins contain three canonical domains, connected by flexible linkers:[2][non-primary source needed]

  • an N-terminal HH-CC zinc-binding domain (a three-helical bundle stabilised by coordination of a Zn(II) cation)
  • a catalytic core domain (RNaseH fold)
  • a C-terminal DNA-binding domain (SH3 fold).

Crystal and NMR structures of the individual domains and 2-domain constructs of integrases from HIV-1, HIV-2, SIV, and Rous Sarcoma Virus (RSV) have been reported, with the first structures determined in 1994.[citation needed] Biochemical data and structural data suggest that retroviral IN functions as a tetramer (dimer-of-dimers), with all three domains being important for multimerisation and viral DNA binding.[citation needed] In addition, several host cellular proteins have been shown to interact with IN to facilitate the integration process: e.g., the host factor, human chromatin-associated protein LEDGF, tightly binds HIV IN and directs the HIV pre-integration complex towards highly expressed genes for integration.[citation needed]

Human foamy virus (HFV), an agent harmless to humans, has an integrase similar to HIV IN and is therefore a model of HIV IN function; a 2010 crystal structure of the HFV integrase assembled on viral DNA ends has been determined.[3][non-primary source needed][4][5]

Function and mechanism

Integration occurs following production of the double-stranded viral DNA by the viral RNA/DNA-dependent DNA polymerase reverse transcriptase.[citation needed]

The main function of IN is to insert the viral DNA into the host chromosomal DNA, a step that is essential for HIV replication.[citation needed] Integration is a "point of no return"" for the cell,{{cite quote"" which becomes a permanent carrier of the viral genome (provirus).[citation needed] Integration is in part responsible for the persistence of retroviral infections.[citation needed] After integration, the viral gene expression and particle production may take place immediately or at some point in the future, the timing of which depends on the activity of the chromosomal locus hosting the provirus.[citation needed]

Vis-a-vis mechanism, known retroviral INs catalyzes two reactions:[citation needed]

  • 3'-processing, in which two or three nucleotides are removed from one or both 3' ends of the viral DNA to expose an invariant CA dinucleotide at both 3'-ends of the viral DNA.
  • the strand transfer reaction, in which the processed 3' ends of the viral DNA are covalently ligated to host chromosomal DNA.

Both reactions are catalysed in the same active site, and involve transesterification that does not involve a covalent protein-DNA intermediate[citation needed] (in contrast to Ser/Tyr recombinase-catalyzed reactions.[citation needed]


HIV Integrase shown in its full structure with its catalytic amino acids shown in ball and stick form.

HIV integrase is a 32 kDa protein produced from the C-terminal portion of the Pol gene product, and is an attractive target for new anti-HIV drugs.[citation needed]

In November 2005, data from a phase 2 study of an investigational HIV integrase inhibitor, MK-0518, demonstrated that the compound has potent antiviral activity.[6][7] On October 12, 2007, the Food and Drug Administration (U.S.) approved the integrase inhibitor Raltegravir (MK-0518, brand name Isentress).[8] The second integrase inhibitor, elvitegravir, was approved in the U.S. in August 2012.[9]

See also


  1. ^ Masuda, T. (January 1, 2011). "Non-Enzymatic Functions of Retroviral Integrase: The Next Target for Novel Anti-HIV Drug Development". Frontiers in Microbiology. 2: 210. doi:10.3389/fmicb.2011.00210. PMC 3192317. PMID 22016749.
  2. ^ Lodi PJ, Ernst JA, Kuszewski J, Hickman AB, Engelman A, Craigie R, Clore GM, Gronenborn AM (August 1995). "Solution structure of the DNA binding domain of HIV-1 integrase". Biochemistry. 34 (31): 9826–33. doi:10.1021/bi00031a002. PMID 7632683.
  3. ^ Hare S, Gupta SS, Valkov E, Engelman A, Cherepanov P (March 2010). "Retroviral intasome assembly and inhibition of DNA strand transfer". Nature. 464 (7286): 232–6. Bibcode:2010Natur.464..232H. doi:10.1038/nature08784. PMC 2837123. PMID 20118915.
  4. ^ See the PDB-101 link at the end of the article for the overall assembly.
  5. ^ "Scientists say crack HIV/AIDS puzzle for drugs". Reuters. January 31, 2010.
  6. ^ Morales-Ramirez JO, Teppler H, Kovacs C, et al. Antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, in ART-naïve HIV-1 infected patients. Program and abstracts of the 10th European AIDS Conference; November 17–20, 2005; Dublin, Ireland. Abstract LBPS1/6. Online summary:
  7. ^ Savarino A (December 2006). "A historical sketch of the discovery and development of HIV-1 integrase inhibitors". Expert Opin Investig Drugs. 15 (12): 1507–22. doi:10.1517/13543784.15.12.1507. PMID 17107277.
  8. ^ "FDA approves drug that fights HIV in new way -". CNN. October 12, 2007. Retrieved May 5, 2010.
  9. ^ Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K, White K, Kearney BP, Szwarcberg J, Quirk E, Cheng AK (June 2012). "Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks". Lancet. 379 (9835): 2439–48. doi:10.1016/S0140-6736(12)60917-9. PMID 22748591.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Integrase core domain Provide feedback

Integrase mediates integration of a DNA copy of the viral genome into the host chromosome. Integrase is composed of three domains. The amino-terminal domain is a zinc binding domain PF02022. This domain is the central catalytic domain. The carboxyl terminal domain that is a non-specific DNA binding domain PF00552. The catalytic domain acts as an endonuclease when two nucleotides are removed from the 3' ends of the blunt-ended viral DNA made by reverse transcription. This domain also catalyses the DNA strand transfer reaction of the 3' ends of the viral DNA to the 5' ends of the integration site [1].

Literature references

  1. Dyda F, Hickman AB, Jenkins TM, Engelman A, Craigie R, Davies DR; , Science 1994;266:1981-1986.: Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases [see comments] PUBMED:7801124 EPMC:7801124

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001584

The retroviral integrase is the enzyme responsible for the insertion of a DNA copy of the viral genome into host DNA, an essential step in the replication cycle of viruses [ PUBMED:9759480 ]. Integrases comprise three functional and structural domains: the central core domain, which contains the catalytic residues, an N-terminal zinc finger and a C-terminal DNA binding domain [ PUBMED:10384240 ].

The integrase catalytic domain catalyses a series of reactions to integrate the viral genome into a host chromosome. In the first step, it removes two 3' end nucleotides from each strand of the linear viral DNA, leaving overhanging CA-OH ends. In the second step, the processed 3' ends are covalently joined to the 5' ends of the target DNA. In the third step, which probably involves additional cellular enzymes, unpaired nucleotides at the viral 5' ends are removed and the ends are joined to the target site 3' ends, generating an integrated provirus flanked by five base-pair direct repeats of the target site DNA [ PUBMED:7526778 ].

The crystal structure of the catalytic domain shows a dimeric structure, with each monomer containing a five-stranded beta-sheet and six alpha-helices [ PUBMED:7801124 ]. This fold is characteristic of the polynucleotidyltransferase superfamily whose members include RNase H, the bacteriophage Mu transposase, and the E. coli Holliday junction resolving enzyme, RuvC [ PUBMED:8696976 ]. The catalytic domain of integrase contains the DD35E triad motif. As in other DNA-binding proteins containing this motif, these acidic residues coordinate a divalent Mg2+ in the resting enzyme. Substituting any one of these residues abolishes both processing and integration activities of integrase.

The integrase catalytic domain is also found in various transposase proteins.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_10 (release 2.1)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 69
Number in full: 45153
Average length of the domain: 99.70 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 16.48 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 32.6 32.6
Trusted cut-off 32.6 32.6
Noise cut-off 32.5 32.5
Model length: 102
Family (HMM) version: 29
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the rve domain has been found. There are 704 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0B7P3V8 View 3D Structure Click here
A0A0G2KYC1 View 3D Structure Click here
A0A0G2L7N4 View 3D Structure Click here
A0A0P0VRV1 View 3D Structure Click here
A0A0P0W8Q2 View 3D Structure Click here
A0A0P0XGV8 View 3D Structure Click here
A0A0P0Y8T5 View 3D Structure Click here
A0A1D6HJ01 View 3D Structure Click here
A0A1D6MYT9 View 3D Structure Click here
A0A1D8PI28 View 3D Structure Click here
A0A2R8PZC6 View 3D Structure Click here
A0A2R8Q3K5 View 3D Structure Click here
A0A2R8Q4Z3 View 3D Structure Click here
A0A2R8Q722 View 3D Structure Click here
A0A2R8Q7E1 View 3D Structure Click here
A0A2R8QA15 View 3D Structure Click here
A0A2R8QBY4 View 3D Structure Click here
A0A2R8QV54 View 3D Structure Click here
A0A2R8RNF4 View 3D Structure Click here
A0A2R8RP35 View 3D Structure Click here
A0A2R8RPI8 View 3D Structure Click here
E7F1X4 View 3D Structure Click here
I6X5T4 View 3D Structure Click here
I6YC39 View 3D Structure Click here
O13527 View 3D Structure Click here
O13535 View 3D Structure Click here
P03975 View 3D Structure Click here
P0C2I2 View 3D Structure Click here
P0C2I3 View 3D Structure Click here
P0C2I5 View 3D Structure Click here
P0C2I6 View 3D Structure Click here
P0C2I9 View 3D Structure Click here
P0C2J0 View 3D Structure Click here
P0C2J1 View 3D Structure Click here
P0C2J3 View 3D Structure Click here
P0C2J7 View 3D Structure Click here
P0CF53 View 3D Structure Click here
P0CF54 View 3D Structure Click here
P0CF55 View 3D Structure Click here
P0CF56 View 3D Structure Click here