Summary

Type I restriction enzyme R protein N terminus (HSDR_N)

This family consists of a number of N terminal regions found in type I restriction enzyme R (HSDR) proteins. Restriction and modification (R/M) systems are found in a wide variety of prokaryotes and are thought to protect the host bacterium from the uptake of foreign DNA [1]. Type I restriction and modification systems are encoded by three genes: hsdR, hsdM, and hsdS. The three polypeptides, HsdR, HsdM, and HsdS, often assemble to give an enzyme (R2M2S1) that modifies hemimethylated DNA and restricts unmethylated DNA [2].

Literature references

Piekarowicz A, Klyz A, Kwiatek A, Stein DC; , Mol Microbiol 2001;41:1199-1210.: Analysis of type I restriction modification systems in the Neisseriaceae: genetic organization and properties of the gene products. PUBMED:11555298
Makovets S, Doronina VA, Murray NE; , Proc Natl Acad Sci U S A 1999;96:9757-9762.: Regulation of endonuclease activity by proteolysis prevents breakage of unmodified bacterial chromosomes by type I restriction enzymes. PUBMED:10449767

InterPro entry IPR007409

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements PUBMED:15121719, PUBMED:12665693, as summarised below:

Type I enzymes () cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase () activities.
Type II enzymes () cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.
Type III enzymes () cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase ().
Type IV enzymes target methylated DNA.

Type I restriction endonucleases are components of prokaryotic DNA restriction-modification mechanisms that protects the organism against invading foreign DNA. Type I enzymes have three different subunits subunits - M (modification), S (specificity) and R (restriction) - that form multifunctional enzymes with restriction (), methylase () and ATPase activities PUBMED:15121719, PUBMED:12595133. The S subunit is required for both restriction and modification and is responsible for recognition of the DNA sequence specific for the system. The M subunit is necessary for modification, and the R subunit is required for restriction. These enzymes use S-Adenosyl-L-methionine (AdoMet) as the methyl group donor in the methylation reaction, and have a requirement for ATP. They recognise asymmetric DNA sequences split into two domains of specific sequence, one 3-4 bp long and another 4-5 bp long, separated by a nonspecific spacer 6-8 bp in length. Cleavage occurs a considerable distance from the recognition sites, rarely less than 400 bp away and up to 7000 bp away. Adenosyl residues are methylated, one on each strand of the recognition sequence. These enzymes are widespread in eubacteria and archaea. In enteric bacteria they have been subdivide into four families: types IA, IB, IC and ID.

Type III restriction endonucleases () are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. Type III enzymes are hetero-oligomeric, multifunctional proteins composed of two subunits, Res and Mod. The Mod subunit recognises the DNA sequence specific for the system and is a modification methyltransferase; as such it is functionally equivalent to the M and S subunits of type I restriction endonuclease. Res is required for restriction, although it has no enzymatic activity on its own. Type III enzymes recognise short 5-6 bp long asymmetric DNA sequences and cleave 25-27 bp downstream to leave short, single-stranded 5' protrusions. They require the presence of two inversely oriented unmethylated recognition sites for restriction to occur. These enzymes methylate only one strand of the DNA, at the N-6 position of adenosyl residues, so newly replicated DNA will have only one strand methylated, which is sufficient to protect against restriction. Type III enzymes belong to the beta-subfamily of N6 adenine methyltransferases, containing the nine motifs that characterise this family, including motif I, the AdoMet binding pocket (FXGXG), and motif IV, the catalytic region (S/D/N (PP) Y/F) PUBMED:15121719, PUBMED:12595133.

This entry represents the N-terminal domain found in both the R subunit (HsdR) of type I enzymes and the Res subunit of type III enzymes. The type I enzyme represented is EcoRI, which recognises the DNA sequence 5'-GAATTC; the R protein (HsdR) is required for both nuclease and ATPase activity PUBMED:, PUBMED:, PUBMED:10449767, PUBMED:11555298.

This domain is often found adjacent to a methylase domain () in restriction endonucleases or methylases. In one of the proteins, , it is adjacent to a helicase domain () in a putative restriction endonuclease.

Clan

This family is a member of clan PDDEXK (CL0236), which contains the following 44 members:

BamHI Cas_APE2256 Cas_Cas02710 Cas_Cas4 Cas_Csm6 Cas_NE0113 CoiA Dna2 DpnII DUF1016 DUF1052 DUF1064 DUF1626 DUF1703 DUF1887 DUF2034 DUF234 DUF2726 DUF2800 DUF506 DUF524 DUF559 DUF790 DUF820 DUF91 DUF911 EcoRII-C Endonuc-BglII Herpes_alk_exo Herpes_UL24 Hjc HSDR_N McrBC Mrr_cat NERD RAP RE_LlaJI RmuC SfsA Transposase_31 UPF0102 VRR_NUC Vsr YqaJ

Gene Ontology

Molecular function	DNA binding (GO:0003677)
Molecular function	endonuclease activity (GO:0004519)
Biological process	DNA modification (GO:0006304)

External database links

PANDIT:	PF04313
SYSTERS:	HSDR_N

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (78) Full (1699) NCBI (1836) Metagenomics (742)
Viewer:

Formatting options

Alignment:	Seed (78) Full (1699)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (78) Full (1699) NCBI (1836) Metagenomics (742)
Full length sequences	Full-sequences (1699)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

Seed source:

COG2810

Previous IDs:

DUF450;

Type:

Family

Author:

Kerrison ND, Finn RD, Yeats C

Number in seed:

78

Number in full:

1699

Average length of the domain:

159.10 aa

Average identity of full alignment:

16 %

Average coverage of the sequence by the domain:

18.29 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.2	8.6
Trusted cut-off	21.2	8.6
Noise cut-off	21.1	8.5

Model length:

185

Family (HMM) version:

7

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
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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 HSDR_N domain has been found.

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Family: HSDR_N (PF04313)

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