Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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DEXDc DEAD-like helicases superfamily

SMART accession number:	SM00487
Description:
Interpro abstract (IPR014001):	Helicases have been classified in 5 superfamilies (SF1-SF5). All of the proteins bind ATP and, consequently, all of them carry the classical Walker A (phosphate-binding loop or P-loop) and Walker B (Mg2+-binding aspartic acid) motifs. For the two largest groups, commonly referred to as SF1 and SF2, a total of seven characteristic motifs has been identified [(PUBMED:2546125)]. These two superfamilies encompass a large number of DNA and RNA helicases from archaea, eubacteria, eukaryotes and viruses that seem to be active as monomers or dimers. RNA and DNA helicases are considered to be enzymes that catalyse the separation of double-stranded nucleic acids in an energy-dependent manner [(PUBMED:11839499)]. The various structures of SF1 and SF2 helicases present a common core with two alpha-beta RecA-like domains [(PUBMED:11839499), (PUBMED:11087862)]. The structural homology with the RecA recombination protein covers the five contiguous parallel beta strands and the tandem alpha helices. ATP binds to the amino proximal alpha-beta domain, where the Walker A (motif I) and Walker B (motif II) are found. The N-terminal domain also contains motif III (S-A-T) which was proposed to participate in linking ATPase and helicase activities. The carboxy-terminal alpha-beta domain is structurally very similar to the proximal one even though it is bereft of an ATP-binding site, suggesting that it may have originally arisen through gene duplication of the first one. This entry represents the DNA-binding domain of classical SF1 and SF2 helicases.
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 43042 DEXDc domains in 42714 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a DEXDc domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with DEXDc domain is also avaliable.

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  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the DEXDc domain.

  Protein	Disease
  Bloom syndrome protein (P54132) (SMART)	OMIM:210900: Bloom syndrome OMIM:604610: Bloom syndrome OMIM:210900:
  DNA excision repair protein ERCC-6 (Q03468) (SMART)	OMIM:133540: Cockayne syndrome-2, type B ; Cerebrooculofacioskeletal syndrome OMIM:214150:
  Transcriptional regulator ATRX (P46100) (SMART)	OMIM:300032: Alpha-thalassemia/mental retardation syndrome OMIM:301040: Juberg-Marsidi syndrome OMIM:309590: Sutherland-Haan syndrome OMIM:309470: Smith-Fineman-Myers syndrome OMIM:309580:

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 42.61 map00500 Starch and sucrose metabolism 42.61 map00790 Folate biosynthesis 8.48 map00230 Purine metabolism 5.29 map03090 Type II secretion system 0.50 map04310 Wnt signaling pathway 0.20 map03060 Protein export 0.10 map00970 Aminoacyl-tRNA biosynthesis 0.10 map03020 RNA polymerase 0.10 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 DEXDc domain which could be assigned to a KEGG orthologous group, and not all proteins containing DEXDc 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 DEXDc domains in PDB

  PDB code	Main view	Title
  1a1v		Hepatitis c virus ns3 helicase domain complexed with single stranded sdna
  1c4o		Crystal structure of the dna nucleotide excision repair enzyme uvrb from thermus thermophilus
  1cu1		Crystal structure of an enzyme complex from hepatitis c virus
  1d2m		Uvrb protein of thermus thermophilus hb8; a nucleotide excision repair enzyme
  1d9x		Crystal structure of the dna repair protein uvrb
  1d9z		Crystal structure of the dna repair protein uvrb in complex with atp
  1fuu		Yeast initiation factor 4a
  1gku		Reverse gyrase from archaeoglobus fulgidus
  1gl9		Archaeoglobus fulgidus reverse gyrase complexed with adpnp
  1gm5		Structure of recg bound to three-way dna junction
  1hei		Structure of the hepatitis c virus rna helicase domain
  1hv8		Crystal structure of a dead box protein from the hyperthermophile methanococcus jannaschii
  1oyw		Structure of the recq catalytic core
  1oyy		Structure of the recq catalytic core bound to atp-gamma-s
  1q0u		Crystal structure of the bstdead n-terminal domain
  1qde		Crystal structure of the atpase domain of translation initiation factor 4a from saccharomyces cerevisiae-the prototype of the dead box protein family
  1qva		Yeast initiation factor 4a n-terminal domain
  1rif		Crystal structure of the uvsw helicase from bacteriophage t4
  1s2m		Crystal structure of the dead box protein dhh1p
  1t5l		Crystal structure of the dna repair protein uvrb point mutant y96a revealing a novel fold for domain 2
  1t6n		Crystal structure of the n-terminal domain of human uap56
  1vec		Crystal structure of the n-terminal domain of rck/p54, a human dead-box protein
  1wp9		Crystal structure of pyrococcus furiosus hef helicase domain
  1wrb		Crystal structure of the n-terminal reca-like domain of djvlgb, a pranarian vasa-like rna helicase
  1xti		Structure of wildtype human uap56
  1xtj		Structure of human uap56 in complex with adp
  1xtk		Structure of decd to dead mutation of human uap56
  1yks		Crystal structure of yellow fever virus ns3 helicase
  1ymf		Crystal structure of yellow fever virus ns3 helicase complexed with adp
  1z3i		Structure of the swi2/snf2 chromatin remodeling domain of eukaryotic rad54
  1z63		Sulfolobus solfataricus swi2/snf2 atpase core in complex with dsdna
  1z6a		Sulfolobus solfataricus swi2/snf2 atpase core domain
  2bhr		Dengue virus rna helicase
  2bmf		Dengue virus rna helicase at 2.4a
  2d7d		Structural insights into the cryptic dna dependent atp-ase activity of uvrb
  2db3		Structural basis for rna unwinding by the dead-box protein drosophila vasa
  2eyq		Crystal structure of escherichia coli transcription-repair coupling factor
  2f55		Two hepatitis c virus ns3 helicase domains complexed with the same strand of dna
  2fdc		Structural basis of dna damage recognition and processing by uvrb: crystal structure of a uvrb/dna complex
  2fwr		Structure of archaeoglobus fulgidis xpb
  2fz4		Crystal structure of the n-terminal half of archaeoglobus fulgidus xpb
  2g9n		Structure of the dead domain of human eukaryotic initiation factor 4a, eif4a
  2gxq		Hera n-terminal domain in complex with amp, crystal form 1
  2gxs		Hera n-terminal domain in complex with amp, crystal form 2
  2gxu		Hera n-terminal domain in complex with orthophosphate, crystal form 1
  2hxy		Crystal structure of human apo-eif4aiii
  2hyi		Structure of the human exon junction complex with a trapped dead-box helicase bound to rna
  2i4i		Crystal structure of human dead-box rna helicase ddx3x
  2j0q		The crystal structure of the exon junction complex at 3.2 a resolution
  2j0s		The crystal structure of the exon junction complex at 2.2 a resolution
  2j0u		The crystal structure of eif4aiii-barentsz complex at 3.0 a resolution
  2jlq		Dengue virus 4 ns3 helicase structure, apo enzyme.
  2jlr		Dengue virus 4 ns3 helicase in complex with amppnp
  2jls		Dengue virus 4 ns3 helicase in complex with adp
  2jlu		Dengue virus 4 ns3 helicase in complex with ssrna
  2jlv		Dengue virus 4 ns3 helicase in complex with ssrna and amppnp
  2jlw		Dengue virus 4 ns3 helicase in complex with ssrna2
  2jlx		Dengue virus 4 ns3 helicase in complex with ssrna and adp- vanadate
  2jly		Dengue virus 4 ns3 helicase in complex with ssrna and adp- phosphate
  2jlz		Dengue virus 4 ns3 helicase in complex with ssrna and adp
  2kbe		Solution structure of amino-terminal domain of dbp5p
  2nmv		Damage detection by the uvrabc pathway: crystal structure of uvrb bound to fluorescein-adducted dna
  2oca		The crystal structure of t4 uvsw
  2oxc		Human dead-box rna helicase ddx20, dead domain in complex with adp
  2p6r		Crystal structure of superfamily 2 helicase hel308 in complex with unwound dna
  2p6u		Apo structure of the hel308 superfamily 2 helicase
  2pl3		Human dead-box rna helicase ddx10, dead domain in complex with adp
  2qeq		Crystal structure of kunjin virus ns3 helicase
  2v1x		Crystal structure of human recq-like dna helicase
  2v8o		Structure of the murray valley encephalitis virus rna helicase to 1.9a resolution
  2va8		Dna repair helicase hel308
  2vbc		Crystal structure of the ns3 protease-helicase from dengue virus
  2vl7		Structure of s. tokodaii xpd4
  2vso		Crystal structure of a translation initiation complex
  2vsx		Crystal structure of a translation initiation complex
  2w00		Crystal structure of the hsdr subunit of the ecor124i restriction enzyme in complex with atp
  2z0m		Crystal structure of hypothetical atp-dependent rna helicase from sulfolobus tokodaii
  2z83		Crystal structure of catalytic domain of japanese encephalitis virus ns3 helicase/nucleoside triphosphatase at a resolution 1.8
  2zj2		Archaeal dna helicase hjm apo state in form 1
  2zj5		Archaeal dna helicase hjm complexed with adp in form 1
  2zj8		Archaeal dna helicase hjm apo state in form 2
  2zja		Archaeal dna helicase hjm complexed with amppcp in form 2
  2zjo		Crystal structure of hepatitis c virus ns3 helicase with a novel inhibitor
  2zu6		Crystal structure of the eif4a-pdcd4 complex
  3b6e		Crystal structure of human dech-box rna helicase mda5 (melanoma differentiation-associated protein 5), dech- domain
  3b7g		Human dead-box rna helicase ddx20, conserved domain i (dead) in complex with amppnp (adenosine-(beta,gamma)- imidotriphosphate)
  3ber		Human dead-box rna-helicase ddx47, conserved domain i in complex with amp
  3bor		Crystal structure of the deadc domain of human translation initiation factor 4a-2
  3dkp		Human dead-box rna-helicase ddx52, conserved domain i in complex with adp
  3dmq		Crystal structure of rapa, a swi2/snf2 protein that recycles rna polymerase during transcription
  3eiq		Crystal structure of pdcd4-eif4a
  3ews		Human dead-box rna-helicase ddx19 in complex with adp
  3ex7		The crystal structure of ejc in its transition state
  3fe2		Human dead-box rna helicase ddx5 (p68), conserved domain i in complex with adp
  3fhc		Crystal structure of human dbp5 in complex with nup214
  3fho		Structure of s. pombe dbp5
  3fht		Crystal structure of human dbp5 in complex with amppnp and rna
  3fmo		Crystal structure of the nucleoporin nup214 in complex with the dead-box helicase ddx19
  3fmp		Crystal structure of the nucleoporin nup214 in complex with the dead-box helicase ddx19
  3g0h		Human dead-box rna helicase ddx19, in complex with an atp- analogue and rna
  3h1t		The fragment structure of a putative hsdr subunit of a type i restriction enzyme from vibrio vulnificus yj016
  3i5x		Structure of mss116p bound to ssrna and amp-pnp
  3i5y		Structure of mss116p bound to ssrna containing a single 5- bru and amp-pnp
  3i61		Structure of mss116p bound to ssrna and adp-beryllium fluoride
  3i62		Structure of mss116p bound to ssrna and adp-aluminum fluoride
  3iuy		Crystal structure of ddx53 dead-box domain
  8ohm		Crystal structure of rna helicase from genotype 1b hepatitis c virus: mechanism of unwinding duplex rna

• Links (links to other resources describing this domain)

• PFAM	SNF2_N
  INTERPRO	IPR014001
  PROSITE	DEAH_ATP_HELICASE

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