NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Function

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity of complex I. Essential for the assembly of complex I (By similarity). Redox-sensitive, critical component of the oxygen-sensing pathway in the pulmonary vasculature which plays a key role in acute pulmonary oxygen-sensing and hypoxic pulmonary vasoconstriction. Plays an important role in carotid body sensing of hypoxia (By similarity). Essential for glia-like neural stem and progenitor cell proliferation, differentiation and subsequent oligodendrocyte or neuronal maturation (By similarity).

Classification

Family (Pfam)

PF00346 Complex1_49kDa

InterPro

NADH_Q_OxRdtase_suD, NADH_UbQ_OxRdtase_49kDa_CS, NDH1_su_D/H, NiFe-Hase_large

Functional cluster

Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 8

• 5XTB EM 3.40A
• 5XTC EM 3.70A
• 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 · 22

• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix
• GO:0005739 mitochondrion
• GO:0045271 respiratory chain complex I
• GO:0051539 4 iron, 4 sulfur cluster binding
• GO:0009055 electron transfer activity
• GO:0046872 metal ion binding
• GO:0051287 NAD binding
• GO:0008137 NADH dehydrogenase (ubiquinone) activity
• GO:0016651 oxidoreductase activity, acting on NAD(P)H
• GO:0019826 oxygen sensor activity
• GO:0048038 quinone binding
• GO:0031625 ubiquitin protein ligase binding
• GO:0009060 aerobic respiration
• GO:0071453 cellular response to oxygen levels
• GO:0042063 gliogenesis
• GO:0042775 mitochondrial ATP synthesis coupled electron transport
• GO:0006120 mitochondrial electron transport, NADH to ubiquinone
• GO:0032981 mitochondrial respiratory chain complex I assembly
• GO:0061351 neural precursor cell proliferation
• GO:0022008 neurogenesis
• GO:0042776 proton motive force-driven mitochondrial ATP synthesis

Disease associations

• mitochondrial complex I deficiency, nuclear type 6 MONDO:0032611
• Leber-like hereditary optic neuropathy, autosomal recessive 2 MONDO:0958197

Drugs targeting this protein · 2

• METFORMIN HYDROCHLORIDE inhibitor
• ME-344 inhibitor

Related proteins · sequence + function similarity

• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1.00
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1.00
• NADH-ubiquinone oxidoreductase 49 kDa subunit, mitochondrial 0.96
• Probable NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 0.95
• NADH-quinone oxidoreductase subunit D 0.93
• NADH-quinone oxidoreductase subunit D 0.93
• NADH-quinone oxidoreductase subunit D 0.93
• NADH-quinone oxidoreductase subunit D 0.93

Co-cited proteins · studied together in the literature

• Protein arginine methyltransferase NDUFAF7, mitochondrial 3 shared papers
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial 2 shared papers
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3 1 shared papers
• Protein arginine methyltransferase NDUFAF7, mitochondrial 1 shared papers
• Protein arginine methyltransferase NDUFAF7, mitochondrial 1 shared papers
• Complex I assembly factor ACAD9, mitochondrial 1 shared papers
• Protein arginine methyltransferase NDUFAF7 homolog, mitochondrial 1 shared papers
• NADH-ubiquinone oxidoreductase 49 kDa subunit 1 shared papers
• NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4 1 shared papers

Literature · 18 cited papers

• Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction. Circ. Res. · 2019
• Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy. J. Med. Genet. · 2017
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• The arginine methyltransferase NDUFAF7 is essential for complex I assembly and early vertebrate embryogenesis. Hum. Mol. Genet. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I. J. Biol. Chem. · 2013
• A catalytic defect in mitochondrial respiratory chain complex I due to a mutation in NDUFS2 in a patient with Leigh syndrome. Biochim. Biophys. Acta · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nat. Genet. · 2010
• MidA is a putative methyltransferase that is required for mitochondrial complex I function. J. Cell Sci. · 2010
• Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease. Am. J. Hum. Genet. · 2009
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• … and 6 more in the literature graph