NDUFS2

Protein identityUniProt · HPA

UniProt accession

O75306

Gene

NDUFS2

Ensembl

ENSG00000158864

Chromosome

1

Canonical length

463 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Mitochondria,Calyx,Connecting piece

OverviewNCBI Gene

The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

463 residues, UniProt reviewed canonical sequence.

>O75306|NDUFS2
     1  MAALRALCGF RGVAAQVLRP GAGVRLPIQP SRGVRQWQPD VEWAQQFGGA VMYPSKETAH
    61  WKPPPWNDVD PPKDTIVKNI TLNFGPQHPA AHGVLRLVME LSGEMVRKCD PHIGLLHRGT
   121  EKLIEYKTYL QALPYFDRLD YVSMMCNEQA YSLAVEKLLN IRPPPRAQWI RVLFGEITRL
   181  LNHIMAVTTH ALDLGAMTPF FWLFEEREKM FEFYERVSGA RMHAAYIRPG GVHQDLPLGL
   241  MDDIYQFSKN FSLRLDELEE LLTNNRIWRN RTIDIGVVTA EEALNYGFSG VMLRGSGIQW
   301  DLRKTQPYDV YDQVEFDVPV GSRGDCYDRY LCRVEEMRQS LRIIAQCLNK MPPGEIKVDD
   361  AKVSPPKRAE MKTSMESLIH HFKLYTEGYQ VPPGATYTAI EAPKGEFGVY LVSDGSSRPY
   421  RCKIKAPGFA HLAGLDKMSK GHMLADVVAI IGTQDIVFGE VDR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NDUFS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

592 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NDUFS2.

Disease | AllUniProt

Conditions NDUFS2 is implicated in, by any mechanism.

• Mitochondrial complex I deficiency, nuclear type 6 (MC1DN6) MIM:618228
• Leber-like hereditary optic neuropathy, autosomal recessive 2 (LHONAR2) MIM:620569

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 280 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial complex I deficiency, nuclear type 6
• Leber optic atrophy
• Leber-like hereditary optic neuropathy, autosomal recessive 2
• Malignant tumor of esophagus
• Gastric cancer

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0

gnomAD missense Z

1.47

DepMap mean gene effect

-0.46

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 14% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aerobic respiration
• cellular response to oxygen levels
• gliogenesis
• mitochondrial ATP synthesis coupled electron transport
• mitochondrial electron transport, NADH to ubiquinone
• mitochondrial respiratory chain complex I assembly
• neural precursor cell proliferation
• neurogenesis
• proton motive force-driven mitochondrial ATP synthesis

Molecular functions

• 4 iron, 4 sulfur cluster binding
• electron transfer activity
• metal ion binding
• NAD binding
• NADH dehydrogenase (ubiquinone) activity
• oxidoreductase activity, acting on NAD(P)H
• oxygen sensor activity
• quinone binding
• ubiquitin protein ligase binding

Cellular components

• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion
• respiratory chain complex I

Protein domainsUniProt · Pfam · InterPro

• NADH-quinone oxidoreductase, subunit D
• NADH:ubiquinone oxidoreductase, 49kDa subunit, conserved site
• NAD(P)H-quinone oxidoreductase subunit D/H
• [NiFe]-hydrogenase, large subunit
• Respiratory-chain NADH dehydrogenase, 49 Kd subunit

KeywordsUniProt

• 4Fe-4S
• Acetylation
• Electron transport
• Iron
• Iron-sulfur
• Leber hereditary optic neuropathy
• Membrane
• Metal-binding
• Methylation
• Mitochondrion
• Mitochondrion inner membrane
• NAD
• Oxidoreductase
• Primary mitochondrial disease
• Respiratory chain
• Transit peptide
• Translocase
• Transport
• Ubiquinone

InteractionsUniProt · HPA

Protein binding partners of NDUFS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CERS2
• NDUFAF3
• NDUFAF7
• DNAJC30
• NDUFA13
• NDUFA7
• NDUFA9
• NDUFAF4
• NDUFB3
• NDUFB5
• NDUFS3
• NDUFS5
• NDUFS6
• NDUFS7