NDUFS1
Identifiers
AliasesNDUFS1, CI-75Kd, CI-75k, PRO1304, NADH:ubiquinone oxidoreductase core subunit S1, MC1DN5
External IDsOMIM: 157655 MGI: 2443241 HomoloGene: 3670 GeneCards: NDUFS1
Orthologs
SpeciesHumanMouse
Entrez

4719

227197

Ensembl

ENSG00000023228
ENSG00000283447

ENSMUSG00000025968

UniProt

P28331

Q91VD9

RefSeq (mRNA)

NM_005006
NM_001199981
NM_001199982
NM_001199983
NM_001199984

NM_001160038
NM_001160039
NM_001160040
NM_145518

RefSeq (protein)

NP_001186910
NP_001186911
NP_001186912
NP_001186913
NP_004997

NP_001153510
NP_001153511
NP_001153512
NP_663493

Location (UCSC)Chr 2: 206.11 – 206.16 MbChr 1: 63.18 – 63.22 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the NDUFS1 gene.[5] The encoded protein, NDUFS1, is the largest subunit of complex I, located on the inner mitochondrial membrane, and is important for mitochondrial oxidative phosphorylation. Mutations in this gene are associated with complex I deficiency.[6]

Structure

NDUFS1 is located on the q arm of chromosome 2 in position 33.3 and has 20 exons.[7] The NDUFS1 gene produces a 79.5 kDa protein composed of 727 amino acids.[8][9] NDUFS1, the protein encoded by this gene, is a member of the complex I 75 kDa subunit family. It contains a transit peptide, 10 turns, 19 beta strands, 27 alpha helixes, and cofactor binding sites for [2Fe-2S] and [4Fe-4S] clusters. The cluster domains consist of a 79 amino acid 2Fe-2S ferredoxin-type from positions 30–108, a 40 amino acid 4Fe-4S His(Cys)3-ligated-type from positions 108–147, and a 57 amino acid 4Fe-4S Mo/W bis-MGD-type from positions 245–301.[10][11] Several transcript variants encoding different isoforms have been found for this gene.[6]

Function

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.[6]

Clinical significance

Mutations in the NDUFS1 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders.[12][13] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype–phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible.[14] However, the majority of cases are caused by mutations in nuclear-encoded genes.[15][16] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[17]

Interactions

NDUFS1 has been shown to have 124 binary protein-protein interactions including 110 co-complex interactions. NDUFS1 appears to interact with SOAT1, NDUFA9, HLA-B, ECE2, C1QTNF9, GPAA1, STOM, GDI1, ACAP2, EHBP1, MBOAT7, PIGS.[18]

See also

References

  1. 1 2 3 ENSG00000283447 GRCh38: Ensembl release 89: ENSG00000023228, ENSG00000283447 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025968 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Chow W, Ragan I, Robinson BH (November 1991). "Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase". European Journal of Biochemistry. 201 (3): 547–50. doi:10.1111/j.1432-1033.1991.tb16313.x. PMID 1935949.
  6. 1 2 3 "Entrez Gene: NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase)".Public Domain This article incorporates text from this source, which is in the public domain.
  7. ↑ "Entrez Gene: Cytochrome c oxidase assembly factor 7 (putative)". Retrieved 2018-08-08.Public Domain This article incorporates text from this source, which is in the public domain.
  8. ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-27.
  9. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  10. ↑ "NDUFS1 - NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial precursor - Homo sapiens (Human) - NDUFS1 gene & protein". www.uniprot.org. Retrieved 2018-08-27. This article incorporates text available under the CC BY 4.0 license.
  11. ↑ "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  12. ↑ Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM, Kirk EP, Boneh A, Taylor RW, Dahl HH, Ryan MT, Thorburn DR (September 2004). "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation. 114 (6): 837–845. doi:10.1172/JCI20683. PMC 516258. PMID 15372108.
  13. ↑ McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ, Fletcher JM, Dixon JW, Collins FA, Turnbull DM, Taylor RW, Thorburn DR (January 2004). "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology. 55 (1): 58–64. doi:10.1002/ana.10787. PMID 14705112. S2CID 21076359.
  14. ↑ Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M, Strecker V, Graf E, Mayr JA, Herberg U, Hennermann JB, Klopstock T, Kuhn KA, Ahting U, Sperl W, Wilichowski E, Hoffmann GF, Tesarova M, Hansikova H, Zeman J, Plecko B, Zeviani M, Wittig I, Strom TM, Schuelke M, Freisinger P, Meitinger T, Prokisch H (April 2012). "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing" (PDF). Journal of Medical Genetics. 49 (4): 277–283. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. S2CID 3177674.
  15. ↑ Loeffen JL, Smeitink JA, Trijbels JM, Janssen AJ, Triepels RH, Sengers RC, van den Heuvel LP (2000). "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation. 15 (2): 123–134. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489. S2CID 35579133.
  16. ↑ Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA (2001). "Respiratory chain complex I deficiency". American Journal of Medical Genetics. 106 (1): 37–45. doi:10.1002/ajmg.1397. PMID 11579423.
  17. ↑ Robinson BH (May 1998). "Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1364 (2): 271–286. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.
  18. ↑ "124 binary interactions found for search term NDUFS1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.

Further reading

  • Overview of all the structural information available in the PDB for UniProt: P28331 (NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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