NDUFS1

Protein identityUniProt · HPA

UniProt accession

P28331

Gene

NDUFS1

Ensembl

ENSG00000023228

Chromosome

2

Canonical length

727 aa

Protein class

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

Subcellular location

Mitochondria

OverviewNCBI Gene

The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

Canonical amino-acid sequenceUniProt

727 residues, UniProt reviewed canonical sequence.

>P28331|NDUFS1
     1  MLRIPVRKAL VGLSKSPKGC VRTTATAASN LIEVFVDGQS VMVEPGTTVL QACEKVGMQI
    61  PRFCYHERLS VAGNCRMCLV EIEKAPKVVA ACAMPVMKGW NILTNSEKSK KAREGVMEFL
   121  LANHPLDCPI CDQGGECDLQ DQSMMFGNDR SRFLEGKRAV EDKNIGPLVK TIMTRCIQCT
   181  RCIRFASEIA GVDDLGTTGR GNDMQVGTYI EKMFMSELSG NIIDICPVGA LTSKPYAFTA
   241  RPWETRKTES IDVMDAVGSN IVVSTRTGEV MRILPRMHED INEEWISDKT RFAYDGLKRQ
   301  RLTEPMVRNE KGLLTYTSWE DALSRVAGML QSFQGKDVAA IAGGLVDAEA LVALKDLLNR
   361  VDSDTLCTEE VFPTAGAGTD LRSNYLLNTT IAGVEEADVV LLVGTNPRFE APLFNARIRK
   421  SWLHNDLKVA LIGSPVDLTY TYDHLGDSPK ILQDIASGSH PFSQVLKEAK KPMVVLGSSA
   481  LQRNDGAAIL AAVSSIAQKI RMTSGVTGDW KVMNILHRIA SQVAALDLGY KPGVEAIRKN
   541  PPKVLFLLGA DGGCITRQDL PKDCFIIYQG HHGDVGAPIA DVILPGAAYT EKSATYVNTE
   601  GRAQQTKVAV TPPGLAREDW KIIRALSEIA GMTLPYDTLD QVRNRLEEVS PNLVRYDDIE
   661  GANYFQQANE LSKLVNQQLL ADPLVPPQLT IKDFYMTDSI SRASQTMAKC VKAVTEGAQA
   721  VEEPSIC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NDUFS1 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)

0.23

Highest tissue expression

211 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NDUFS1.

Disease | AllUniProt

Conditions NDUFS1 is implicated in, by any mechanism.

• Mitochondrial complex I deficiency, nuclear type 5 (MC1DN5) MIM:618226

Disease | GeneticClinVar

51 pathogenic / likely-pathogenic of 515 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial complex I deficiency, nuclear type 5
• Leigh syndrome
• NDUFS1-related disorder
• Mitochondrial complex I deficiency, nuclear type 1
• 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)

0.81

gnomAD pLI

0

gnomAD missense Z

-0.08

DepMap mean gene effect

-0.45

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

Molecular functions

• 2 iron, 2 sulfur cluster binding
• 4 iron, 4 sulfur cluster binding
• electron transfer activity
• metal ion binding
• NADH dehydrogenase (ubiquinone) activity
• oxidoreductase activity, acting on NAD(P)H

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• 2Fe-2S ferredoxin-type iron-sulfur binding domain
• 2Fe-2S ferredoxin-like superfamily
• NADH:ubiquinone oxidoreductase, 75kDa subunit, conserved site
• Molybdopterin oxidoreductase
• Molybdopterin oxidoreductase, 4Fe-4S domain
• NADH:ubiquinone oxidoreductase, subunit G
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial-like
• NADH:ubiquinone oxidoreductase, subunit G, iron-sulphur binding
• NADH-ubiquinone oxidoreductase, ferredoxin-like domain
• Molybdopterin oxidoreductase
• NADH-ubiquinone oxidoreductase subunit G, C-terminal
• NADH-ubiquinone oxidoreductase-G iron-sulfur binding region
• 2Fe-2S iron-sulfur cluster binding domain
• NADH-quinone oxidoreductase subunit 3, ferredoxin-like domain
• NADH-ubiquinone oxidoreductase NDSU1/NuoG-like, 4Fe-4S domain

KeywordsUniProt

• 2Fe-2S
• 4Fe-4S
• Acetylation
• Electron transport
• Iron
• Iron-sulfur
• Membrane
• Metal-binding
• Mitochondrion
• Mitochondrion inner membrane
• NAD
• Oxidoreductase
• Primary mitochondrial disease
• Respiratory chain
• Transit peptide
• Translocase
• Transport
• Ubiquinone

InteractionsUniProt · HPA

Protein binding partners of NDUFS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AKAP1
• MDM2
• NDUFA9
• NDUFB3
• NDUFS5
• NDUFS6
• NDUFS7
• SOAT1