Protein-coding gene in the species Homo sapiens
NDUFAB1 |
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Available structures |
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PDB | Human UniProt search: PDBe RCSB |
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Identifiers |
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Aliases | NDUFAB1, ACP, FASN2A, SDAP, NADH:ubiquinone oxidoreductase subunit AB1, ACP1 |
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External IDs | OMIM: 603836; MGI: 4936891; HomoloGene: 80336; GeneCards: NDUFAB1; OMA:NDUFAB1 - orthologs |
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Gene location (Human) |
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![Chromosome 16 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/2/2d/Ideogram_human_chromosome_16.svg/300px-Ideogram_human_chromosome_16.svg.png) | Chr. | Chromosome 16 (human)[1] |
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| Band | 16p12.2 | Start | 23,581,014 bp[1] |
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End | 23,596,316 bp[1] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - right ventricle
- myocardium of left ventricle
- apex of heart
- biceps brachii
- atrium
- right auricle
- body of tongue
- Skeletal muscle tissue of biceps brachii
- triceps brachii muscle
- vastus lateralis muscle
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| | More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - calcium ion binding
- NADH dehydrogenase (ubiquinone) activity
- fatty acid binding
- acyl binding
- acyl carrier activity
- protein binding
- phosphopantetheine binding
| Cellular component | - mitochondrial membranes
- mitochondrial respiratory chain complex I
- mitochondrial matrix
- mitochondrial inner membrane
- respirasome
- nucleoplasm
- mitochondrion
- cytosol
- mitochondrial large ribosomal subunit
| Biological process | - lipid metabolism
- fatty acid metabolic process
- fatty acid biosynthetic process
- protein lipoylation
- lipid A biosynthetic process
- mitochondrial respiratory chain complex I assembly
- mitochondrial electron transport, NADH to ubiquinone
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (protein) | | |
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Location (UCSC) | Chr 16: 23.58 – 23.6 Mb | n/a |
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PubMed search | [2] | [3] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa is a protein that in humans is encoded by the NDUFAB1 gene.[4] The NDUFAB1 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[5]
Structure
The NDUFAB1 gene is located on the p arm of chromosome 16 at position 12.2 and it spans 15,327 base pairs.[4] The NDUFAB1 gene produces a 17.4 kDa protein composed of 156 amino acids.[6][7] NDUFAB1 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[5] NDUFAB1 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.[4]
Function
The human NDUFAB1 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[4] However, NDUFAB1 is an accessory subunit of the complex that is believed not to be involved in catalysis.[8] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[5]
Clinical Significance
In a genome-wide association study (GWAS) meta-analysis conducted across European and African American populations, the NDUFAB1 gene and two other genes (MFAP3L and PALB2) were identified as genetic loci significantly associated with anxiety disorders (ADs). Since the comorbidity of ADs arises from their shared genetic basis, these candidate genetic loci may become therapeutic targets for AD treatments.[9] Moreover, a study to identify small molecule drug targets for Tetralogy of Fallot (TOF), a congenital malformation of the heart, found the NDUFAB1 gene to be a major hub gene of differentially expressed genes in TOF.[10]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000004779 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "Entrez Gene: NDUFAB1 NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1, 8kDa".
- ^ a b c Voet D, Voet JG, Pratt CW (2013). "Chapter 18". Fundamentals of biochemistry: life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 978-0-470-54784-7.
- ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 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.
- ^ "NDUFAB1 - NADH dehydrogenase [ubiquinone] 1 alpha/beta subcomplex subunit 1". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ^ "NDUFAB1 - NADH dehydrogenase [ubiquinone] 1 alpha/beta subcomplex subunit 1". UniProt: a hub for protein information. The UniProt Consortium. Retrieved 24 March 2015.
- ^ Otowa T, Maher BS, Aggen SH, McClay JL, van den Oord EJ, Hettema JM (2014-11-12). "Genome-wide and gene-based association studies of anxiety disorders in European and African American samples". PLOS ONE. 9 (11): e112559. Bibcode:2014PLoSO...9k2559O. doi:10.1371/journal.pone.0112559. PMC 4229211. PMID 25390645.
- ^ Gu Q, Chen XT, Xiao YB, Chen L, Wang XF, Fang J, Chen BC, Hao J (June 2014). "Identification of differently expressed genes and small molecule drugs for Tetralogy of Fallot by bioinformatics strategy". Pediatric Cardiology. 35 (5): 863–9. doi:10.1007/s00246-014-0868-8. PMID 24463614. S2CID 24162298.