NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial

Function

Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.

Classification

Family (Pfam)

PF04800 NDUS4

InterPro

NADH_UbQ_FeS_4_mit-like, NDUFS4-like_sf

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 7

• 5XTB EM 3.40A
• 5XTD EM 3.70A
• 5XTH EM 3.90A
• 5XTI EM 17.40A
• 9CWT EM 3.44A
• 9I4I EM 2.63A
• 9TI4 EM 2.66A

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005743 mitochondrial inner membrane
• GO:0005739 mitochondrion
• GO:0045271 respiratory chain complex I
• GO:0008137 NADH dehydrogenase (ubiquinone) activity
• GO:0009060 aerobic respiration
• GO:0007420 brain development
• GO:0006120 mitochondrial electron transport, NADH to ubiquinone
• GO:0032981 mitochondrial respiratory chain complex I assembly
• GO:0042776 proton motive force-driven mitochondrial ATP synthesis
• GO:0072593 reactive oxygen species metabolic process
• GO:0001932 regulation of protein phosphorylation
• GO:0022904 respiratory electron transport chain
• GO:0051591 response to cAMP

Disease associations

• mitochondrial complex I deficiency, nuclear type 1 MONDO:0100224

Drugs targeting this protein · 2

• METFORMIN HYDROCHLORIDE inhibitor
• ME-344 inhibitor

Related proteins · sequence + function similarity

• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.99
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.99
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.97
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.97
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.97
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.96
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.63
• NADH-ubiquinone oxidoreductase 21 kDa subunit, mitochondrial 0.55
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 0.55
• Small ribosomal subunit protein uS10m 0.51

Co-cited proteins · studied together in the literature

• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial 2 shared papers
• Mitochondrial import receptor subunit TOM40 homolog 1 shared papers
• B-cell receptor-associated protein 31 1 shared papers
• Non-selective voltage-gated ion channel VDAC1 1 shared papers
• Apoptosis regulator Bcl-2 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 1 shared papers
• Distal membrane-arm assembly complex protein 1 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 1 shared papers

Literature · 14 cited papers

• BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites. Sci. Adv. · 2019
• Accessory subunits are integral for assembly and function of human mitochondrial complex I. Nature · 2016
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Phosphorylation pattern of the NDUFS4 subunit of complex I of the mammalian respiratory chain. Mitochondrion · 2010
• NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement. Mol. Genet. Metab. · 2009
• A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family. J. Inherit. Metab. Dis. · 2008
• Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of the splice variants. FEBS Lett. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome. Hum. Genet. · 2003
• The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J. Biol. Chem. · 2003
• A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome. Hum. Mol. Genet. · 2001
• … and 2 more in the literature graph