Molecule Information

General Information of the Molecule (ID: Mol04054)

• Name: NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUFS2) ,Homo sapiens
• Synonyms: Complex I-49kD; NADH-ubiquinone oxidoreductase 49 kDa subunit
• Molecule Type: Protein
• Gene Name: NDUFS2
• Gene ID: 4720
• Location: chr1:161197104-161214723[+]
• Sequence:
  MAALRALCGFRGVAAQVLRPGAGVRLPIQPSRGVRQWQPDVEWAQQFGGAVMYPSKETAH
  WKPPPWNDVDPPKDTIVKNITLNFGPQHPAAHGVLRLVMELSGEMVRKCDPHIGLLHRGT
  EKLIEYKTYLQALPYFDRLDYVSMMCNEQAYSLAVEKLLNIRPPPRAQWIRVLFGEITRL
  LNHIMAVTTHALDLGAMTPFFWLFEEREKMFEFYERVSGARMHAAYIRPGGVHQDLPLGL
  MDDIYQFSKNFSLRLDELEELLTNNRIWRNRTIDIGVVTAEEALNYGFSGVMLRGSGIQW
  DLRKTQPYDVYDQVEFDVPVGSRGDCYDRYLCRVEEMRQSLRIIAQCLNKMPPGEIKVDD
  AKVSPPKRAEMKTSMESLIHHFKLYTEGYQVPPGATYTAIEAPKGEFGVYLVSDGSSRPY
  RCKIKAPGFAHLAGLDKMSKGHMLADVVAIIGTQDIVFGEVDR
• 3D-structure: PDB ID: 5XTD; Classification: Oxidoreductase/electron transport; Method: Electron microscopy; Resolution: 3.70 Å
• Function: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:22036843, PubMed:28031252, PubMed:30922174). Essential for the catalytic activity of complex I (PubMed:22036843, PubMed:30922174). Essential for the assembly of complex I (By similarity). Redox-sensitive, critical component of the oxygen-sensing pathway in the pulmonary vasculature which plays a key role in acute pulmonary oxygen-sensing and hypoxic pulmonary vasoconstriction (PubMed:30922174). Plays an important role in carotid body sensing of hypoxia (By similarity). Essential for glia-like neural stem and progenitor cell proliferation, differentiation and subsequent oligodendrocyte or neuronal maturation (By similarity). .
• Uniprot ID: NDUS2_HUMAN
• Ensembl ID: ENSG00000158864
• HGNC ID: HGNC:7708

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Trastuzumab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Breast Cancer patients; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: The analysis of differentially expressed proteins exhibited the deregulation of energetic metabolism and mitochondrial pathways. A down-regulation of carbohydrate metabolism and up-regulation of mitochondria organization proteins, the tricarboxylic acid cycle, and oxidative phosphorylation, were observed in nRSs. Of note, Complex I-related proteins were increased in this condition and the inhibition by metformin highlighted that their activity is necessary for nRS survival. Furthermore, a correlation analysis showed that overexpression of Complex I proteins NDUFA10 and NDUFS2 was associated with high clinical risk and worse survival for HER2+ BC patients

References

• Ref 1: Proteomic Characterization of a 3D HER2+ Breast Cancer Model Reveals the Role of Mitochondrial Complex I in Acquired Resistance to Trastuzumab. Int J Mol Sci. 2024 Jul 5;25(13):7397.