HRDC

Helicase and RNase D C-terminal

• SMART accession number: SM00341
• Description: Hypothetical role in nucleic acid binding. Mutations in the HRDC domain cause human disease.
• Interpro abstract (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)].
• GO component: intracellular (GO:0005622)
• GO function: nucleic acid binding (GO:0003676)

There are 1443 HRDC domains in 1360 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Liu Z et al.
• The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins.
• Structure Fold Des. 1999; 7: 1557-66

BACKGROUND: The HRDC (helicase and RNaseD C-terminal) domain is found at the C terminus of many RecQ helicases, including the human Werner and Bloom syndrome proteins. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. However, the specific functional roles of these proteins in DNA recombination and replication are not known. An HRDC domain exists in both of the human RecQ homologues that are implicated in human disease and may have an important role in their function. RESULTS: We have determined the three-dimensional structure of the HRDC domain in the Saccharomyces cerevisiae RecQ helicase Sgs1p by nuclear magnetic resonance (NMR) spectroscopy. The structure resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. We show that a positively charged region on the surface of the Sgs1p HRDC domain can interact with DNA. Structural similarities to bacterial DNA helicases suggest that the HRDC domain functions as an auxiliary domain in RecQ helicases. Homology models of the Werner and Bloom HRDC domains show different surface properties when compared with Sgs1p. CONCLUSIONS: The HRDC domain represents a structural scaffold that resembles auxiliary domains in proteins that are involved in nucleic acid metabolism. In Sgs1p, the HRDC domain could modulate the helicase function via auxiliary contacts to DNA. However, in the Werner and Bloom syndrome helicases the HRDC domain may have a role in their functional differences by mediating diverse molecular interactions.

• Morozov V, Mushegian AR, Koonin EV, Bork P
• A putative nucleic acid-binding domain in Bloom's and Werner's syndrome helicases.
• Trends Biochem Sci. 1997; 22: 417-8

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
48.44	map00500	Starch and sucrose metabolism
48.44	map00790	Folate biosynthesis
1.56	map00970	Aminoacyl-tRNA biosynthesis
1.56	map00330	Arginine and proline metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with HRDC domain which could be assigned to a KEGG orthologous group, and not all proteins containing HRDC domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of HRDC domains in PDB

PDB code	Title
1d8b	Nmr structure of the hrdc domain from saccharomyces cerevisiae recq helicase
1wud	E. coli recq hrdc domain
1yt3	Crystal structure of escherichia coli rnase d, an exoribonuclease involved in structured rna processing
2cpr	Solution structure of the hrdc domain of human exosome component 10
2dgz	Solution structure of the helicase and rnase d c-terminal domain in werner syndrome atp-dependent helicase
2e1e	Crystal structure of the hrdc domain of human werner syndrome protein, wrn
2e1f	Crystal structure of the hrdc domain of human werner syndrome protein, wrn
2hbj	Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain
2hbk	Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain; protein in complex with mn
2hbl	Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain; protein in complex with mn, zn, and amp
2hbm	Structure of the yeast nuclear exosome component, rrp6p, reveals an interplay between the active site and the hrdc domain; protein in complex with mn, zn, and ump
2rhf	D. radiodurans recq hrdc domain 3
3cym	Crystal structure of protein bad_0989 from bifidobacterium adolescentis

Links (links to other resources describing this domain)

• PFAM: HRDC
• INTERPRO: IPR002121