NDUFAF7

NDUFAF7
Identifiers
Aliases	NDUFAF7 , C2orf56, MidA, PRO1853, NADH:ubiquinone oxidoreductase complex assembly factor 7
External IDs	OMIM: 615898 MGI: 1920944 HomoloGene: 12508 GeneCards: NDUFAF7
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	79,255,481 bp
Gene ontology
Molecular function	enzyme binding ; protein binding ; methyltransferase activity ; transferase activity ; protein-arginine omega-N symmetric methyltransferase activity ;
Cellular component	mitochondrial matrix ; mitochondrion ; extracellular space ;
Biological process	mitochondrial respiratory chain complex I assembly ; ATP metabolic process ; methylation ; peptidyl-arginine methylation, to symmetrical-dimethyl arginine ;
	Sources:Amigo / QuickGO
Orthologs
	55471
	73694
	ENSG00000003509
	ENSMUSG00000024082
	Q7L592
	Q9CWG8
	NM_001083946 ; NM_018607 ; NM_144736
	NM_028611 ; NM_144760
	NP_001077415 ; NP_653337 ; NP_001336953 ; NP_001336954 ; NP_001336956 Contents Structure ; Function ; Clinical significance ; Interactions ; References ; Further reading ;
	NP_082887
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated August 19, 2023

Protein arginine methyltransferase NDUFAF7, mitochondrial, also known as NADH:ubiquinone oxidoreductase complex assembly factor 7 (NDUFAF7),MidA, C2orf56, or PRO1853, is a protein that in humans is encoded by the NDUFAF7 gene. NDUFAF7 is a methyltransferase mitochondrial assembly enzyme involved in the assembly and stabilization of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.^[4]^[5]^[6] Mutations in NDUFAF7 have been associated with pathologic myopia and complex I deficiency.^[5]^[7]

Structure

NDUFAF7 is located on the p arm of chromosome 2 in position 22.2 and has 14 exons.^[4] The NDUFAF7 gene produces a 49.2 kDa protein composed of 441 amino acids.^[8]^[9] NDUFAF7 is believed to be a part of the S-adenosylmethionine-dependent methyltransferase family. This family has a characteristic seven-β-strand protein fold. NDUFAF7 is a type II arginine methyltransferase, meaning that its enzymatic activity produces a symmetrical ω-N^G,N^G′-dimethylarginine.^[10] It has a methyltransferase domain and an N-terminal sequence that corresponds to the recognized mitochondrial-targeting peptide.^[11] NDUFAF7's stoichometry is disputed with some findings indicating that it is a homodimer,^[11] while others denote it to be monomeric.^[12]^[5]

Function

The NDUFAF7 gene encodes an assembly factor protein that is localized in the mitochondria and which helps in the assembly and stabilization of complex I, a large multi-subunit enzyme in the mitochondrial respiratory chain.^[4]^[11] NADH:ubiquinone oxidoreductase (complex I) is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. Complex I catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane.^[13] The encoded protein of NDUFAF7 is a methyltransferase that symmetrically dimethylates the ω-N^G,N^G′ atoms of Arg85 of subunit NDUFS2 of complex I in the early stages of its assembly. This interaction between NDUFAF7 and NDUFS2 is believed to be transient and it is suggested that this methylation stabilizes a 400 kDa subcomplex primarily associated with the peripheral arm of complex I. Without this methylation, the amount of intact complex I is significantly reduced, illustrating NDUFAF7's importance to the mitochondrial respiratory chain. A pseudogene related to this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants.^[4]^[10]

Clinical significance

Defects in NDUFAF7 may be a cause of susceptibility to pathologic myopia, a genetically heterogeneous disorder characterized by extreme, familial, early-onset vision loss and described as myopia accompanied by severe deformation of the eye besides excessive elongation of the eye. This defect, a heterozygous D266E missense mutation, also resulted in reduced complex I activity.^[5]^[7] Due to is role in early assembly of complex I, it has been suggested that mutations affecting NDUFAF7 may be lethal.^[10]

Interactions

NDUFAF7 interacts transiently with NDUFS2, dimethylating Arg85 on the subunit.^[10] A correlation between the presence of MidA and NDUFS7 was also identified.^[11] In addition to co-complexes, NDUFAF4 has protein-protein interactions with LRRK2, q5nfq6_fratt, and q5ngw2_fratt.^[14]

Related Research Articles

Respiratory complex I, EC 7.1.1.2 is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes the transfer of electrons from NADH to coenzyme Q10 (CoQ10) and translocates protons across the inner mitochondrial membrane in eukaryotes or the plasma membrane of bacteria.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial (NDUFS4) also known as NADH-ubiquinone oxidoreductase 18 kDa subunit is an enzyme that in humans is encoded by the NDUFS4 gene. This gene encodes a nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase. Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial is an enzyme that in humans is encoded by the NDUFS3 gene on chromosome 11. This gene encodes one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone oxidoreductase. Mutations in this gene are associated with Leigh syndrome resulting from mitochondrial complex I deficiency.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial also known as NADH-ubiquinone oxidoreductase 23 kDa subunit, Complex I-23kD (CI-23kD), or TYKY subunit is an enzyme that in humans is encoded by the NDUFS8 gene. The NDUFS8 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with Leigh syndrome.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (NDUFS2) also known as NADH-ubiquinone oxidoreductase 49 kDa subunit is an enzyme that in humans is encoded by the NDUFS2 gene. The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase. Mutations in this gene are associated with mitochondrial complex I deficiency.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 is a protein that in humans is encoded by the NDUFA1 gene. The NDUFA1 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. Mutations in the NDUFA1 gene are associated with mitochondrial Complex I deficiency.

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the NDUFS1 gene. 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.

NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial (NDUFV2) is an enzyme that in humans is encoded by the NDUFV2 gene. The encoded protein, NDUFV2, is a subunit of complex I of the mitochondrial respiratory chain, which is located on the inner mitochondrial membrane and involved in oxidative phosphorylation. Mutations in this gene are implicated in Parkinson's disease, bipolar disorder, schizophrenia, and have been found in one case of early onset hypertrophic cardiomyopathy and encephalopathy.

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial, also knowns as NADH-ubiquinone oxidoreductase 20 kDa subunit, Complex I-20kD (CI-20kD), or PSST subunit is an enzyme that in humans is encoded by the NDUFS7 gene. The NDUFS7 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6, also known as complex I-B17, is a protein that in humans is encoded by the NDUFB6 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 6, is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 is a protein that in humans is encoded by the NDUFA2 gene. The NDUFA2 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. Mutations in the NDUFA2 gene are associated with Leigh's syndrome.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFA9 gene. The NDUFA9 protein is a subunit of NADH:ubiquinone oxidoreductase, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. In the case of NDUFA9, a mutation to the MT-ND3 gene might interrupt their interaction and formation of subcomplexes, compromising Complex I function and leading to disease.

FAD-dependent oxidoreductase domain-containing protein 1 (FOXRED1), also known as H17, or FP634 is an enzyme that in humans is encoded by the FOXRED1 gene. FOXRED1 is an oxidoreductase and complex I-specific molecular chaperone involved in the assembly and stabilization of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in FOXRED1 have been associated with Leigh syndrome and infantile-onset mitochondrial encephalopathy.

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3, also known as 2P1, E3-3, or C3orf60, is a protein that in humans is encoded by the NDUFAF3 gene. NDUFAF3 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with severe complex I deficiency and Leigh syndrome.

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7, also known as complex I-B18, is an enzyme that in humans is encoded by the NDUFB7 gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 7 is an accessory subunit of the NADH dehydrogenase (ubiquinone) complex, located in the mitochondrial inner membrane. It is also known as Complex I and is the largest of the five complexes of the electron transport chain.

NADH:ubiquinone oxidoreductase complex assembly factor 4, (NDUFAF4) also known as Hormone-regulated proliferation-associated protein of 20 kDa, (HRPAP20) or C6orf66 is a protein that in humans is encoded by the NDUFAF4 gene. NDUFAF4 is a mitochondrial assembly protein involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with complex I deficiency and infantile mitochondrial encephalomyopathy. Elevations in HRPAP20 have also been implicated in breast cancer.

NADH:ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2), also known as B17.2L or NDUFA12L is a protein that in humans is encoded by the NDUFAF2, or B17.2L, gene. The NDUFAF2 protein is a chaperone involved in the assembly of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial complex I deficiency.

NADH:ubiquinone oxidoreductase complex assembly factor 6 is a protein that in humans is encoded by the NDUFAF6 gene. The protein is involved in the assembly of complex I in the mitochondrial electron transport chain. Mutations in the NDUFAF6 gene have been shown to cause Complex I deficiency, Leigh syndrome, and Acadian variant Fanconi Syndrome.

NADH:ubiquinone oxidoreductase complex assembly factor 5, also known as Arginine-hydroxylase NDUFAF5, or Putative methyltransferase NDUFAF5, is a protein that in humans is encoded by the NDUFAF5 gene. The NADH-ubiquinone oxidoreductase complex of the mitochondrial respiratory chain catalyzes the transfer of electrons from NADH to ubiquinone, and consists of at least 43 subunits. The complex is located in the inner mitochondrial membrane. This gene encodes a mitochondrial protein that is associated with the matrix face of the mitochondrial inner membrane and is required for complex I assembly. A mutation in this gene results in mitochondrial complex I deficiency. Multiple transcript variants encoding different isoforms have been found for this gene.

NADH:ubiquinone oxidoreductase complex assembly factor 8 is a protein that in humans is encoded by the NDUFAF8 gene. This protein stabilizes NDUFAF5 during assembly of mitochondrial Complex I.

References

1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024082 - 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.
1 2 3 4 "Entrez Gene: NADH:ubiquinone oxidoreductase complex assembly factor 7" . Retrieved 2018-07-26.
1 2 3 4 "NDUFAF7 - Protein arginine methyltransferase NDUFAF7, mitochondrial precursor - Homo sapiens (Human) - NDUFAF7 gene & protein". www.uniprot.org. Retrieved 2018-07-27.
↑ Donald Voet; Judith G. Voet; Charlotte W. Pratt (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.
1 2 Wang B, Liu Y, Chen S, Wu Y, Lin S, Duan Y, Zheng K, Zhang L, Gu X, Hong W, Shao H, Zeng X, Sun B, Duan S (August 2017). "A Novel Potentially Causative Variant of NDUFAF7 Revealed by Mutation Screening in a Chinese Family With Pathologic Myopia". Investigative Ophthalmology & Visual Science. 58 (10): 4182–4192. doi: 10.1167/iovs.16-20941 . PMID 28837730.
↑ 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 (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.
↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-07-27.
1 2 3 4 Rhein VF, Carroll J, Ding S, Fearnley IM, Walker JE (November 2013). "NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I". The Journal of Biological Chemistry. 288 (46): 33016–26. doi: 10.1074/jbc.M113.518803 . PMC 3829151 . PMID 24089531.
1 2 3 4 Carilla-Latorre S, Gallardo ME, Annesley SJ, Calvo-Garrido J, Graña O, Accari SL, Smith PK, Valencia A, Garesse R, Fisher PR, Escalante R (May 2010). "MidA is a putative methyltransferase that is required for mitochondrial complex I function". Journal of Cell Science. 123 (Pt 10): 1674–83. doi:10.1242/jcs.066076. PMID 20406883.
↑ Zurita Rendón O, Silva Neiva L, Sasarman F, Shoubridge EA (October 2014). "The arginine methyltransferase NDUFAF7 is essential for complex I assembly and early vertebrate embryogenesis". Human Molecular Genetics. 23 (19): 5159–70. doi:10.1093/hmg/ddu239. PMC 4159157 . PMID 24838397.
↑ Reference, Genetics Home. "NDUFAF1 gene". Genetics Home Reference. Retrieved 2018-07-27.
↑ "9 binary interactions found for search term NDUFAF7". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.