NDUFS8

Protein identityUniProt · HPA

UniProt accession

O00217

Gene

NDUFS8

Ensembl

ENSG00000110717

Chromosome

11

Canonical length

210 aa

Protein class

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

Subcellular location

Mitochondria

OverviewNCBI Gene

This gene encodes a subunit of mitochondrial NADH:ubiquinone oxidoreductase, or Complex I, a multimeric enzyme of the respiratory chain responsible for NADH oxidation, ubiquinone reduction, and the ejection of protons from mitochondria. The encoded protein is involved in the binding of two of the six to eight iron-sulfur clusters of Complex I and, as such, is required in the electron transfer process. Mutations in this gene have been associated with Leigh syndrome. [provided by RefSeq, Mar 2010]

Canonical amino-acid sequenceUniProt

210 residues, UniProt reviewed canonical sequence.

>O00217|NDUFS8
     1  MRCLTTPMLL RALAQAARAG PPGGRSLHSS AVAATYKYVN MQDPEMDMKS VTDRAARTLL
    61  WTELFRGLGM TLSYLFREPA TINYPFEKGP LSPRFRGEHA LRRYPSGEER CIACKLCEAI
   121  CPAQAITIEA EPRADGSRRT TRYDIDMTKC IYCGFCQEAC PVDAIVEGPN FEFSTETHEE
   181  LLYNKEKLLN NGDKWEAEIA ANIQADYLYR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NDUFS8 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)

0.41

Highest tissue expression

468 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NDUFS8.

Disease | AllUniProt

Conditions NDUFS8 is implicated in, by any mechanism.

• Mitochondrial complex I deficiency, nuclear type 2 (MC1DN2) MIM:618222

Disease | GeneticClinVar

18 pathogenic / likely-pathogenic of 169 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial complex I deficiency, nuclear type 2
• Leigh syndrome

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)

0.74

gnomAD pLI

0.17

gnomAD missense Z

0.74

DepMap mean gene effect

-0.45

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aerobic respiration
• mitochondrial electron transport, NADH to ubiquinone
• mitochondrial respiratory chain complex I assembly
• proton motive force-driven mitochondrial ATP synthesis

Molecular functions

• 4 iron, 4 sulfur cluster binding
• metal ion binding
• NADH dehydrogenase (ubiquinone) activity
• oxidoreductase activity, acting on NAD(P)H

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• 4Fe-4S ferredoxin-type, iron-sulphur binding domain
• 4Fe-4S ferredoxin, iron-sulphur binding, conserved site
• NADH-quinone oxidoreductase, chain I
• 4Fe-4S dicluster domain

KeywordsUniProt

• 4Fe-4S
• Electron transport
• Iron
• Iron-sulfur
• Membrane
• Metal-binding
• Mitochondrion
• Mitochondrion inner membrane
• NAD
• Oxidoreductase
• Primary mitochondrial disease
• Repeat
• Respiratory chain
• Transit peptide
• Translocase
• Transport
• Ubiquinone

InteractionsUniProt · HPA

Protein binding partners of NDUFS8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RAB5IF
• DNAJC30
• NDUFA13
• NDUFAF4
• NDUFB3
• NDUFB5
• NDUFS5
• NDUFS6
• NDUFS7