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

    Gene ID: 4719, updated on 28-Oct-2024

    Summary

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    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

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    See NDUFS1 in Genome Data Viewer
    Location:
    2q33.3
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (206114817..206159444, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (206596710..206641337, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (206979541..207024168, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene INO80 complex subunit D Neighboring gene ribosomal protein L27 pseudogene 8 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:206946709-206947498 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:206948195-206949016 Neighboring gene Sharpr-MPRA regulatory region 7917 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12263 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12264 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12265 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:206950661-206951480 Neighboring gene INO80D antisense RNA 1 Neighboring gene GCSH pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17026 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12266 Neighboring gene small nucleolar RNA, C/D box 51 Neighboring gene small nucleolar RNA, H/ACA box 41 Neighboring gene eukaryotic translation elongation factor 1 beta 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. Localization of the human 75-kDal Fe-S protein of NADH-coenzyme Q reductase gene (NDUFS1) to 2q33----q34. Duncan AM, et al. Cytogenet Cell Genet, 1992. PMID 1505218
    2. Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies. Hoefs SJ, et al. Mol Genet Metab, 2010 Jul. PMID 20382551
    3. Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer. Ni Y, et al. Cells, 2019 Sep 25. PMID 31557978, Free PMC Article
    4. Gamma oscillations in the hippocampus require high complex I gene expression and strong functional performance of mitochondria. Kann O, et al. Brain, 2011 Feb. PMID 21183487
    5. Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1. Ferreira M, et al. Neurogenetics, 2011 Feb. PMID 21203893

    See all (160) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Association between NDUFS1 from urinary extracellular vesicles and decreased differential renal function in children with ureteropelvic junction obstruction.
      Title: Association between NDUFS1 from urinary extracellular vesicles and decreased differential renal function in children with ureteropelvic junction obstruction.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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?
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    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
    		not available

    Variation

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    See Variation Viewer (GRCh37.p13)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC26839

    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 aerobic respiration NAS
    Non-traceable Author Statement
    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 proton 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
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of respiratory chain complex I IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of respiratory chain complex I IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    part_of respiratory chain complex I NAS
    Non-traceable Author Statement
    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
    NP_001186911.1
    NP_001186912.1
    NP_001186913.1
    NP_004997.4

    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

    1. NG_009248.2 RefSeqGene

      Range
      5000..49627
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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

    2. 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

    3. 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 ...

    4. 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

    5. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      206114817..206159444 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_015495299.1 Reference GRCh38.p14 PATCHES

      Range
      223835..268462 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      206596710..206641337 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P28331.3 GenPept UniProtKB/Swiss-Prot:P28331

    Gene LinkOut

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