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163  structures 99  species 0  interactions 972  sequences 212  architectures

Family: IN_DBD_C (PF00552)

Summary: Integrase DNA binding domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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

Integrase Edit Wikipedia article

HIV integrase is an 31 kd protein produced from the the C-terminal portion of the Pol gene product. The integrase protein contains three domains: an N-terminal HH-CC zinc finger domain believed to be partially responsible for multimerization, a central catalytic domain and an C-terminal DNA binding domain. Integrase is responsible for the integration of proviral DNA into the host genome, which is essential for HIV replication. Integrase, therefore, remains a promising potential target for new anti-HIV therapeutics

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 DNA binding 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. The central domain is the catalytic domain PF00665. This domain is the carboxyl terminal domain that is a non-specific DNA binding domain [1].

Literature references

  1. Lodi PJ, Ernst JA, Kuszewski J, Hickman AB, Engelman A, Craigie R, Clore GM, Gronenborn AM; , Biochemistry 1995;34:9826-9833.: Solution structure of the DNA binding domain of HIV-1 integrase. PUBMED:7632683 EPMC:7632683


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001037

Integrase comprises three domains capable of folding independently and whose three-dimensional structures are known. However, the manner in which the N-terminal, catalytic core, and C-terminal domains interact in the holoenzyme remains obscure. Numerous studies indicate that the enzyme functions as a multimer, minimally a dimer. The integrase proteins from Human immunodeficiency virus 1 (HIV-1) and Avian sarcoma virus (have been studied most carefully with respect to the structural basis of catalysis. Although the active site of avian virus integrase does not undergo significant conformational changes on binding the required metal cofactor, that of HIV-1 does. This active site-mediated conformational change in HIV-1 reorganises the catalytic core and C-terminal domains and appears to promote an interaction that is favourable for catalysis [ PUBMED:10384242 ].

Retroviral integrase is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. The presence of retrovirus integrase-related gene sequences in eukaryotes is known. Bacterial transposases involved in the transposition of the insertion sequence also belong to this group.

HIV-1 integrase catalyses the incorporation of virally derived DNA into the human genome. This unique step in the virus life cycle provides a variety of points for intervention and hence is an attractive target for the development of new therapeutics for the treatment of AIDS [ PUBMED:9161051 ]. Substrate recognition by the retroviral integrase enzyme is critical for retroviral integration. To catalyse this recombination event, integrase must recognise and act on two types of substrates, viral DNA and host DNA, yet the necessary interactions exhibit markedly different degrees of specificity [ PUBMED:10384243 ].

Gene Ontology

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

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan SH3 (CL0010), which has the following description:

Src homology-3 (SH3) domains are comprised of about 60 amino acids, performing either an assembly or regulatory role. For example, SH3 domains in the Grb2 adaptor protein are essential for protein-protein interactions and signal transduction in the p21 Ras-dependent growth factor signaling pathway. Alternatively, SH3 performs a regulatory role in the Src family of tyrosine kinases. SH3 domains bind a variety of peptide ligands, many of which contain a PxxP motif. This PxxP motif is flanked by different specificity elements [1]. Structures of SH3 domains, both free and ligand complexed, have provided insights into the mechanism of ligand recognition. The SH3 fold consists of two anti-parallel beta sheets that lie at right angles to each other. Within the fold, there are two variable loops, referred to as RT and n-Src loops. When SH3 binds to its ligand, the proline rich ligand adopts a PPII helix conformation, with the PPII helix structure recognised by a pair of grooves on the surface of the SH3 domain that bind turns of the helix. The SH3 grooves are formed by a series of nearly parallel, well-conserved aromatic residues [1].

The clan contains the following 47 members:

CAP_GLY DUF150_C DUF1541 DUF1653 DUF2642 DUF3104 DUF3148 DUF3247 DUF3601 DUF4222 DUF4314 DUF4453 DUF4926 DUF5397 DUF5776 DUF951 Gemin7 GW hSH3 IN_DBD_C KapB MLVIN_C MSSS Myosin_N NdhS NifZ SH3_1 SH3_10 SH3_11 SH3_12 SH3_13 SH3_14 SH3_15 SH3_16 SH3_17 SH3_18 SH3_19 SH3_2 SH3_3 SH3_4 SH3_5 SH3_6 SH3_9 SlpA Spore_GerQ Vexin YjdM

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(8)
Full
(972)
Representative proteomes UniProt
(64867)
RP15
(822)
RP35
(855)
RP55
(952)
RP75
(993)
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PP/heatmap 1 View           

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(8)
Full
(972)
Representative proteomes UniProt
(64867)
RP15
(822)
RP35
(855)
RP55
(952)
RP75
(993)
Alignment:
Format:
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Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(8)
Full
(972)
Representative proteomes UniProt
(64867)
RP15
(822)
RP35
(855)
RP55
(952)
RP75
(993)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

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: SCOP
Previous IDs: integrase; Integrase;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 8
Number in full: 972
Average length of the domain: 43.1 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 5.62 %

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 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 45
Family (HMM) version: 24
Download: download the raw HMM for this family

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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Structures

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 IN_DBD_C domain has been found. There are 163 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