NDUFS1 NADH:ubiquinone oxidoreductase core subunit S1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NDUFS1provided by HGNC
Official Full Name: NADH:ubiquinone oxidoreductase core subunit S1provided by HGNC
Primary source: HGNC:HGNC:7707
See related: Ensembl:ENSG00000023228 MIM:157655; AllianceGenome:HGNC:7707
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CI-75k; MC1DN5; CI-75Kd; PRO1304
Summary: 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]
Expression: Ubiquitous expression in heart (RPKM 52.2), kidney (RPKM 30.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q33.3

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (206114817..206159444, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (206596710..206641337, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (206979541..207024168, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation.
Title: PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation.
Down regulation of NDUFS1 is involved in the progression of parenteral-nutrition-associated liver disease by increasing Oxidative stress.
Title: Down regulation of NDUFS1 is involved in the progression of parenteral-nutrition-associated liver disease by increasing Oxidative stress.
The biallelic mutations in NDUFS1 led to a decreased stability of the entire N-module of electron transport complex I and disrupted the electron transfer between two iron-sulfur clusters.
Title: Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer.
MDM2 directly binds and sequesters NDUFS1, preventing its mitochondrial localization and ultimately causing complex I and supercomplex destabilization and inefficiency of oxidative phosphorylation.
Title: MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network.
Results show that NDUFS1 protein and mRNA levels are down-regulated in lung neoplasm and correlate with poor overall survival.
Title: The opposite prognostic effect of NDUFS1 and NDUFS8 in lung cancer reflects the oncojanus role of mitochondrial complex I.
High NDUFS1 expression is associated with cognitive impairment in lung cancer.
Title: The Effect on Cognition of Mitochondrial Respiratory System Proteins in Peripheral Blood Mononuclear Cells in the Course of Lung Cancer.
Results found nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction.
Title: Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations?
Loss of FOXRED1, coupled with protein, choline and/or folate-deficient diets results in the depletion of glutathione, the dysregulation of nitric oxide metabolism and the peroxynitrite-mediated inactivation of complex I.
Title: Glutathione metabolism links FOXRED1 to NADH:ubiquinone oxidoreductase (complex I) deficiency: A hypothesis.
NDUFS1 may confer susceptibility to schizophrenia in male subjects, acting as a causative factor for the severity of negative symptoms in schizophrenia.
Title: Genetic variant in NDUFS1 gene is associated with schizophrenia and negative symptoms in Han Chinese.
The presented clinical courses of NDUFV1 and NDUFS1 mutation-based complex I deficiencies are characterized by leukoencephalopathy or early death and expand the already heterogeneous phenotypic spectrum.
Title: Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mitochondrial complex 1 deficiency, nuclear type 5 MedGen: C4748754 OMIM: 618226 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70856 (e-PCR)
- UniSTS:67344

D2S1782 (e-PCR), detects polymorphism
- UniSTS:37964

RH48316 (e-PCR)
- UniSTS:41553

SHGC-11975 (e-PCR)
- UniSTS:82320

NDUFS1 (e-PCR)
- UniSTS:505495

NDUFS1__6223 (e-PCR)
- UniSTS:464082

MARC_14924-14925:1012937004:1 (e-PCR)
- UniSTS:267773

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 2 iron, 2 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables 4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
contributes_to NADH dehydrogenase (ubiquinone) activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to NADH dehydrogenase (ubiquinone) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADH dehydrogenase (ubiquinone) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NADH dehydrogenase (ubiquinone) activity	NAS Non-traceable Author Statement more info	PubMed
enables electron transfer activity	NAS Non-traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ATP metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in aerobic respiration	NAS Non-traceable Author Statement more info	PubMed
involved_in apoptotic mitochondrial changes	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular respiration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial electron transport, NADH to ubiquinone	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial electron transport, NADH to ubiquinone	NAS Non-traceable Author Statement more info	PubMed
involved_in mitochondrial respiratory chain complex I assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial respiratory chain complex I assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proton motive force-driven mitochondrial ATP synthesis	NAS Non-traceable Author Statement more info	PubMed
involved_in reactive oxygen species metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of mitochondrial membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial matrix	TAS Traceable Author Statement more info
part_of mitochondrial respiratory chain complex I	IDA Inferred from Direct Assay more info	PubMed
part_of mitochondrial respiratory chain complex I	IMP Inferred from Mutant Phenotype more info	PubMed
part_of mitochondrial respiratory chain complex I	IPI Inferred from Physical Interaction more info	PubMed
part_of mitochondrial respiratory chain complex I	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial

Names: NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase); complex I 75kDa subunit; complex I, mitochondrial respiratory chain, 75-kD subunit; mitochondrial NADH-ubiquinone oxidoreductase 75 kDa subunit

NP_001186910.1

EC 7.1.1.2

NP_001186911.1

EC 7.1.1.2

NP_001186912.1

EC 7.1.1.2

NP_001186913.1

EC 7.1.1.2

NP_004997.4

EC 7.1.1.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009248.2 RefSeqGene

Range

5000..49627

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001199981.2 → NP_001186910.1 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AA150435, AC007383, AK295705, AW074155, BC018900, CA419316, DC413278

Consensus CDS

CCDS56164.1

UniProtKB/TrEMBL

A0A291FIZ5

Related

ENSP00000409766.1, ENST00000440274.5

Conserved Domains (4) summary

smart00929
Location:77 → 117

NADH-G_4Fe-4S_3; NADH-ubiquinone oxidoreductase-G iron-sulfur binding region

PRK09130
Location:31 → 687

PRK09130; NADH dehydrogenase subunit G; Validated

cd02773
Location:213 → 594

MopB_Res-Cmplx1_Nad11; MopB_Res_Cmplx1_Nad11: The second domain of the Nad11/75-kDa subunit of the NADH-quinone oxidoreductase/respiratory complex I/NADH dehydrogenase-1(NDH-1) of eukaryotes and the Nqo3/G subunit of alphaproteobacteria NDH-1. The NADH-quinone oxidoreductase ...

pfam09326
Location:642 → 674

NADH_dhqG_C; NADH-ubiquinone oxidoreductase subunit G, C-terminal
NM_001199982.2 → NP_001186911.1 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial isoform 3

See identical proteins and their annotated locations for NP_001186911.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate coding segment compared to variant 1, that causes a frameshift. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AA150435, AC007383, AK298320, AW074155, BC018900, CA419316, DC413278

Consensus CDS

CCDS56163.1

UniProtKB/TrEMBL

B4DJ81

Related

ENSP00000409689.1, ENST00000432169.5

Conserved Domains (3) summary

smart00929
Location:3 → 42

NADH-G_4Fe-4S_3; NADH-ubiquinone oxidoreductase-G iron-sulfur binding region

cd02773
Location:138 → 519

MopB_Res-Cmplx1_Nad11; MopB_Res_Cmplx1_Nad11: The second domain of the Nad11/75-kDa subunit of the NADH-quinone oxidoreductase/respiratory complex I/NADH dehydrogenase-1(NDH-1) of eukaryotes and the Nqo3/G subunit of alphaproteobacteria NDH-1. The NADH-quinone oxidoreductase ...

pfam09326
Location:567 → 599

NADH_dhqG_C; NADH-ubiquinone oxidoreductase subunit G, C-terminal
NM_001199983.2 → NP_001186912.1 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial isoform 4

See identical proteins and their annotated locations for NP_001186912.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate coding exon compared to variant 1, that causes a frameshift. The resulting isoform (4) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AA150435, AC007383, AK300585, AW074155, BC018900, CA419316, DC413278

Consensus CDS

CCDS56162.1

UniProtKB/TrEMBL

B4DJ81

Related

ENSP00000397760.1, ENST00000423725.5

Conserved Domains (5) summary

smart00929
Location:56 → 96

NADH-G_4Fe-4S_3; NADH-ubiquinone oxidoreductase-G iron-sulfur binding region

PRK09130
Location:2 → 666

PRK09130; NADH dehydrogenase subunit G; Validated

cd02773
Location:192 → 573

MopB_Res-Cmplx1_Nad11; MopB_Res_Cmplx1_Nad11: The second domain of the Nad11/75-kDa subunit of the NADH-quinone oxidoreductase/respiratory complex I/NADH dehydrogenase-1(NDH-1) of eukaryotes and the Nqo3/G subunit of alphaproteobacteria NDH-1. The NADH-quinone oxidoreductase ...

pfam09326
Location:621 → 653

NADH_dhqG_C; NADH-ubiquinone oxidoreductase subunit G, C-terminal

cl00159
Location:3 → 50

fer2; 2Fe-2S iron-sulfur cluster binding domain. Iron-sulfur proteins play an important role in electron transfer processes and in various enzymatic reactions. The family includes plant and algal ferredoxins, which act as electron carriers in photosynthesis ...
NM_001199984.2 → NP_001186913.1 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial isoform 5

See identical proteins and their annotated locations for NP_001186913.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) has a longer and distinct N-terminus compared to isoform 1.

Source sequence(s)

AA150435, AC007383, AK295987, AW074155, BC018900, CA419316

Consensus CDS

CCDS56165.1

UniProtKB/TrEMBL

A0A291FIZ5

Conserved Domains (5) summary

smart00929
Location:127 → 167

NADH-G_4Fe-4S_3; NADH-ubiquinone oxidoreductase-G iron-sulfur binding region

PRK09130
Location:45 → 737

PRK09130; NADH dehydrogenase subunit G; Validated

cd02773
Location:263 → 644

MopB_Res-Cmplx1_Nad11; MopB_Res_Cmplx1_Nad11: The second domain of the Nad11/75-kDa subunit of the NADH-quinone oxidoreductase/respiratory complex I/NADH dehydrogenase-1(NDH-1) of eukaryotes and the Nqo3/G subunit of alphaproteobacteria NDH-1. The NADH-quinone oxidoreductase ...

pfam09326
Location:692 → 724

NADH_dhqG_C; NADH-ubiquinone oxidoreductase subunit G, C-terminal

pfam13510
Location:43 → 121

Fer2_4; 2Fe-2S iron-sulfur cluster binding domain
NM_005006.7 → NP_004997.4 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_004997.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest and predominant transcript. Variant 1 encodes isoform 1.

Source sequence(s)

AA150435, AC007383, AW074155, BC018900, CA419316, DC413278

Consensus CDS

CCDS2366.1

UniProtKB/Swiss-Prot

B4DIN9, B4DJA0, B4DPG1, B4DUC1, E7ENF3, P28331, Q53TR8, Q8N1C4, Q8TCC9

UniProtKB/TrEMBL

A0A291FIZ5, E5KRK5

Related

ENSP00000233190.5, ENST00000233190.11

Conserved Domains (1) summary

PRK09130
Location:31 → 723

PRK09130; NADH dehydrogenase subunit G; Validated