NDUFS4

Protein identityUniProt · HPA

UniProt accession

O43181

Gene

NDUFS4

Ensembl

ENSG00000164258

Chromosome

5

Canonical length

175 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Mitochondria,Equatorial segment,Perinuclear theca,Calyx

OverviewNCBI Gene

This gene encodes an nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Canonical amino-acid sequenceUniProt

175 residues, UniProt reviewed canonical sequence.

>O43181|NDUFS4
     1  MAAVSMSVVL RQTLWRRRAV AVAALSVSRV PTRSLRTSTW RLAQDQTQDT QLITVDEKLD
    61  ITTLTGVPEE HIKTRKVRIF VPARNNMQSG VNNTKKWKME FDTRERWENP LMGWASTADP
   121  LSNMVLTFST KEDAVSFAEK NGWSYDIEER KVPKPKSKSY GANFSWNKRT RVSTK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NDUFS4 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)

0.53

Highest tissue expression

370 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NDUFS4.

Disease | AllUniProt

Conditions NDUFS4 is implicated in, by any mechanism.

• Mitochondrial complex I deficiency, nuclear type 1 (MC1DN1) MIM:252010

Disease | GeneticClinVar

48 pathogenic / likely-pathogenic of 252 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial complex I deficiency, nuclear type 1
• Leigh syndrome
• Mitochondrial complex I deficiency
• Inborn genetic diseases
• See cases

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)

1.16

gnomAD pLI

0

gnomAD missense Z

-0.84

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aerobic respiration
• brain development
• mitochondrial electron transport, NADH to ubiquinone
• mitochondrial respiratory chain complex I assembly
• proton motive force-driven mitochondrial ATP synthesis
• reactive oxygen species metabolic process
• regulation of protein phosphorylation
• response to cAMP

Molecular functions

• NADH dehydrogenase (ubiquinone) activity

Cellular components

• mitochondrial inner membrane
• mitochondrion
• perinuclear theca
• respiratory chain complex I
• sperm glycocalyx

Protein domainsUniProt · Pfam · InterPro

• NADH dehydrogenase ubiquinone Fe-S protein 4 mitochondrial-like
• NADH dehydrogenase ubiquinone Fe-S protein 4-like superfamily
• NADH dehydrogenase ubiquinone Fe-S protein 4

KeywordsUniProt

• Electron transport
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Phosphoprotein
• Primary mitochondrial disease
• Respiratory chain
• Transit peptide
• Transport

InteractionsUniProt · HPA

Protein binding partners of NDUFS4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BCAP31
• TOMM40
• NDUFA13
• NDUFA2
• NDUFA9
• NDUFB3
• NDUFS6