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22  structures 3520  species 2  interactions 6087  sequences 73  architectures

Family: HRDC (PF00570)

Summary: HRDC 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 "RecQ helicase". More...

RecQ helicase Edit Wikipedia article

Bloom syndrome
Identifiers
Symbol BLM
Entrez 641
HUGO 1058
OMIM 604610
RefSeq NM_000057
UniProt P54132
Other data
Locus Chr. 15 [1]
RecQ protein-like 4
Identifiers
Symbol RECQL4
Entrez 9401
HUGO 9949
OMIM 603780
RefSeq NM_004260
UniProt O94761
Other data
Locus Chr. 8 q24.3
RecQ protein-like 5
Identifiers
Symbol RECQL5
Entrez 9400
HUGO 9950
OMIM 603781
RefSeq NM_004259
UniProt O94762
Other data
Locus Chr. 17 q25
RMI1, RecQ mediated genome instability 1
Identifiers
Symbol RMI1
Alt. symbols C9orf76
Entrez 80010
HUGO 25764
OMIM 610404
RefSeq NM_024945
UniProt Q9H9A7
Other data
Locus Chr. 9 q22.1
Werner syndrome
Identifiers
Symbol WRN
Entrez 7486
HUGO 12791
OMIM 604611
RefSeq NM_000553
UniProt Q14191
Other data
Locus Chr. 8 p

RecQ helicase is a family of helicase enzymes initially found in Escherichia coli[1] that has been shown to be important in genome maintenance.[2][3][4] They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H2O → NDP + P to drive the unwinding of either DNA or RNA.

Function[edit]

In prokaryotes RecQ is necessary for plasmid recombination and DNA repair from UV-light, free radicals, and alkylating agents. This protein can also reverse damage from replication errors. In eukaryotes, replication does not proceed normally in the absence of RecQ proteins, which also function in aging, silencing, recombination and DNA repair.

Structure[edit]

RecQ family members share three regions of conserved protein sequence referred to as the:

  • N-terminal – Helicase
  • middle – RecQ-conserved (RecQ-Ct) and
  • C-terminal – Helicase-and-RNase-D C-terminal (HRDC) domains.

The removal of the N-terminal residues (Helicase and, RecQ-Ct domains) impairs both helicase and ATPase activity but has no effect on the binding ability of RecQ implying that the N-terminus functions as the catalytic end. Truncations of the C-terminus (HRDC domain) compromise the binding ability of RecQ but not the catalytic function. The importance of RecQ in cellular functions is exemplified by human diseases, which all lead to genomic instability and a predisposition to cancer.

Clinical significance[edit]

There are at least five human RecQ genes; and mutations in three human RecQ genes are implicated in heritable human diseases: WRN gene in Werner syndrome (WS), BLM gene in Bloom syndrome (BS), and RECQ4 in Rothmund-Thomson syndrome.[5] These syndromes are characterized by premature aging, and can give rise to the diseases of cancer, type 2 diabetes, osteoporosis, and atherosclerosis, which are commonly found in old age. These diseases are associated with high incidence of chromosomal abnormalities, including chromosome breaks, complex rearrangements, deletions and translocations, site specific mutations, and in particular sister chromatid exchanges (more common in BS) that are believed to be caused by a high level of somatic recombination.

Mechanism[edit]

The proper function of RecQ helicases requires the specific interaction with topoisomerase III (Top 3). Top 3 changes the topological status of DNA by binding and cleaving single stranded DNA and passing either a single stranded or a double stranded DNA segment through the transient break and finally religating the break. The interaction of RecQ helicase with topoisomerase III at the N-terminal region is involved in the suppression of spontaneous and damage induced recombination and the absence of this interaction results in a lethal or very severe phenotype. The emerging picture clearly is that RecQ helicases in concert with Top 3 are involved in maintaining genomic stability and integrity by controlling recombination events, and repairing DNA damage in the G2-phase of the cell cycle. The importance of RecQ for genomic integrity is exemplified by the diseases that arise as a consequence of mutations or malfunctions in RecQ helicases; thus it is crucial that RecQ is present and functional to ensure proper human growth and development.

References[edit]

  1. ^ Bernstein DA, Keck JL (June 2003). "Domain mapping of Escherichia coli RecQ defines the roles of conserved N- and C-terminal regions in the RecQ family". Nucleic Acids Res. 31 (11): 2778–85. doi:10.1093/nar/gkg376. PMC 156711. PMID 12771204. 
  2. ^ Cobb JA, Bjergbaek L, Gasser SM (October 2002). "RecQ helicases: at the heart of genetic stability". FEBS Lett. 529 (1): 43–8. doi:10.1016/S0014-5793(02)03269-6. PMID 12354611. 
  3. ^ Kaneko H, Fukao T, Kondo N (2004). "The function of RecQ helicase gene family (especially BLM) in DNA recombination and joining". Adv. Biophys. 38: 45–64. doi:10.1016/S0065-227X(04)80061-3. PMID 15493327. 
  4. ^ Ouyang KJ, Woo LL, Ellis NA (2008). "Homologous recombination and maintenance of genome integrity: cancer and aging through the prism of human RecQ helicases". Mech. Ageing Dev. 129 (7-8): 425–40. doi:10.1016/j.mad.2008.03.003. PMID 18430459. 
  5. ^ Hanada K, Hickson ID (September 2007). "Molecular genetics of RecQ helicase disorders". Cell. Mol. Life Sci. 64 (17): 2306–22. doi:10.1007/s00018-007-7121-z. PMID 17571213. 

Further reading[edit]

  • Skouboe C, Bjergbaek L, Andersen AH (2005). "Genome instability as a cause of ageing and cancer: Implications of RecQ helicases". Signal Transduction 5 (3): 142–151. doi:10.1002/sita.200400052. 
  • Laursen LV, Bjergbaek L, Murray JM, Andersen AH (2003). "RecQ helicases and topoisomerase III in cancer and aging". Biogerontology 4 (5): 275–87. doi:10.1023/A:1026218513772. PMID 14618025. 

External links[edit]

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.

HRDC domain Provide feedback

The HRDC (Helicase and RNase D C-terminal) domain has a putative role in nucleic acid binding. Mutations in the HRDC domain cause human disease. It is interesting to note that the RecQ helicase in Deinococcus radiodurans has three tandem HRDC domains [4].

Literature references

  1. Morozov V, Mushegian AR, Koonin EV, Bork P; , Trends Biochem Sci 1997;22:417-418.: A putative nucleic acid-binding domain in Bloom's and Werner's syndrome helicases PUBMED:9397680 EPMC:9397680

  2. Wu L, Chan KL, Ralf C, Bernstein DA, Garcia PL, Bohr VA, Vindigni A, Janscak P, Keck JL, Hickson ID; , EMBO J. 2005;24:2679-2687.: The HRDC domain of BLM is required for the dissolution of double Holliday junctions. PUBMED:15990871 EPMC:15990871

  3. Liu Z, Macias MJ, Bottomley MJ, Stier G, Linge JP, Nilges M, Bork P, Sattler M; , Structure. 1999;7:1557-1566.: The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins. PUBMED:10647186 EPMC:10647186

  4. Huang L, Hua X, Lu H, Gao G, Tian B, Shen B, Hua Y; , DNA Repair (Amst). 2006; [Epub ahead of print]: Three tandem HRDC domains have synergistic effect on the RecQ functions in Deinococcus radiodurans. PUBMED:17085080 EPMC:17085080


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002121

The HRDC (Helicase and RNase D C-terminal) domain has a putative role in nucleic acid binding. Mutations in the HRDC domain associated with the human BLM gene result in Bloom Syndrome (BS), an autosomal recessive disorder characterised by proportionate pre- and postnatal growth deficiency; sun-sensitive, telangiectatic, hypo- and hyperpigmented skin; predisposition to malignancy; and chromosomal instability [PUBMED:9397680].

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 HRDC-like (CL0426), which has the following description:

Superfamily includes HRDC domain from helicases, RNA polymerase II subunit RBP4, RNase D C-terminal domains, and EXOSC10 HRDC domain-like families.

The clan contains the following 3 members:

Helicase_Sgs1 HRDC RNA_pol_Rpb4

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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
(147)
Full
(6087)
Representative proteomes NCBI
(4778)
Meta
(961)
RP15
(541)
RP35
(1053)
RP55
(1412)
RP75
(1677)
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Format an alignment

  Seed
(147)
Full
(6087)
Representative proteomes NCBI
(4778)
Meta
(961)
RP15
(541)
RP35
(1053)
RP55
(1412)
RP75
(1677)
Alignment:
Format:
Order:
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
(147)
Full
(6087)
Representative proteomes NCBI
(4778)
Meta
(961)
RP15
(541)
RP35
(1053)
RP55
(1412)
RP75
(1677)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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 HMMER3.

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: Medline:98060076
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 147
Number in full: 6087
Average length of the domain: 67.30 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 11.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.4 20.4
Trusted cut-off 20.4 20.4
Noise cut-off 20.3 20.3
Model length: 68
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

HRDC DNA_pol_A_exo1

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 HRDC domain has been found. There are 22 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 seqence.

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