DHX40

Model summary

An ATP-driven RNA-remodeling enzyme that assembles and remodels nuclear ribonucleoprotein complexes. Its helicase core and accessory modules cooperate to unwind and refold RNA and RNA–protein assemblies, positioning it as a remodeling factor within late-stage spliceosomal assemblies. By sustaining efficient nuclear RNA processing and splicing, it indirectly supports pathways that elevate cellular oxidoreductase activity. The protein operates in the nucleus, where it binds partner proteins and RNA to drive conformational transitions essential for RNA maturation.

Predicted Gene Ontology terms

1. 01

   I begin by dissecting the InterPro architecture and its order along the polypeptide.

   The N-terminal two-thirds are encompassed by IPR027417 (P-loop containing nucleoside triphosphate hydrolase homologous superfamily, residues 7–594), establishing a RecA-like NTPase core that powers conformational work. Within this core, IPR014001 (Helicase superfamily 1/2, ATP-binding domain, residues 47–240) and IPR011545 (DEAD/DEAH-box helicase domain, residues 60–216) define the NTP-binding and hydrolysis machinery that drives duplex remodeling. The presence of IPR002464 (DEAH-box type conserved site, residues 168–177) specifies the catalytic signature of DEAH-box RNA helicases, which couple ATP hydrolysis to RNA/protein complex rearrangements. Downstream, IPR001650 (Helicase, C-terminal domain-like, residues 263–442) provides the second RecA-like lobe that coordinates nucleic acid engagement and transduces ATPase cycles into mechanical motion. The mid-to-C-terminal region is reinforced by IPR007502 (Helicase-associated domain, residues 462–557) and its refined form IPR048333 (HA2 winged-helix domain, residues 463–491), which stabilize RNA/protein assemblies and tune substrate specificity. Finally, IPR011709 (DEAD-box helicase, OB fold, residues 619–698) caps the architecture with an OB-fold module that binds single-stranded nucleic acids and organizes terminal interactions. This ordered ensemble—ATPase core (N-terminus), helicase C-lobe, HA2/winged-helix accessory clamp, and OB-fold tail—creates a processive RNA-remodeling machine.

2. 02

   This architecture causes ATP-dependent RNA helicase activity: the P-loop NTPase superfamily (IPR027417) and DEAH-box catalytic site (IPR002464) supply ATP hydrolysis; the paired helicase lobes (IPR014001, IPR001650) and HA2/winged-helix clamp (IPR007502, IPR048333) convert chemical energy into remodeling of ribonucleoprotein assemblies.

   Such machines typically exhibit high-affinity protein binding surfaces and multivalent RNA/protein contacts, aligning with GO:0005515 protein binding as a core molecular function.

3. 03

   From this molecular function, I infer the biological role.

   DEAH-box helicases commonly drive spliceosome dynamics and RNP maturation. The explicit association with late-stage spliceosomal assemblies is supported by the cellular component label GO:0071013 catalytic step 2 spliceosome and by the accessory domains that specialize in RNP remodeling. Remodeling of pre-mRNA splicing complexes in the nucleus naturally explains a nuclear localization. The same remodeling capacity can modulate RNA processing pathways that influence mitochondrial redox enzyme expression. This provides a mechanistic route to GO:0051353 positive regulation of oxidoreductase activity: by ensuring efficient nuclear RNA processing and splicing of transcripts encoding mitochondrial oxidoreductases, the helicase indirectly elevates their cellular activity.

4. 04

   Cellular location follows directly from function and partners.

   The spliceosome operates in the nucleus, and the presence of spliceosomal association (GO:0071013) anchors the protein to nuclear RNP assemblies. Thus, I deduce a nuclear residence consistent with the stated subcellular location.

5. 05

   Mechanistically, I hypothesize that the helicase binds and remodels RNA–protein assemblies at catalytic step 2 of the spliceosome, using its HA2/winged-helix clamp and OB-fold tail to stabilize transient intermediates while the ATPase core executes directional remodeling.

   Likely interaction partners include spliceosomal proteins and auxiliary RNA chaperones that coordinate exon ligation and RNP recycling. Through these assemblies, the helicase tunes RNA maturation pathways that ultimately enhance the production and activity of cellular oxidoreductases.