NDUFAF1 is located on the q arm of chromosome 15 in position 15.1.[7] The NDUFAF1 gene produces a 37.8 kDa protein composed of 327 amino acids.[14][15] NDUFAF1 is associated to complexes of 600 and 700 kDa.[8] Complex I is structured in a bipartite L-shaped configuration, which is made up of a peripheral matrix arm, consisting of flavoproteins and iron-sulfur proteins involved in electron transfer, and a membrane arm, consisting of mtDNA-encoded subunits involved in ubiquinone reduction and proton pumping.[13] NDUFAF1 has been shown to interact with assembly intermediates and may play roles in the correct assembly and combination of the peripheral arm to the complete membrane arm as well as in the stabilization and scaffolding of those intermediates through those close interactions.[8]
Functionedit
NDUFAF1 is an assembly factor that is important for the correct assembly of NADH dehydrogenase (ubiquinone). It ensures the correct combination of complex intermediates and is necessary for the correct functioning of NADH dehydrogenase (ubiquinone). Specifically, NDUFAF1 binds to the large membrane arm intermediate and is involved in the combination of the small and large membrane arm intermediates of complex I. It has also been suggested that NDUFAF1 is involved in the stabilization and scaffolding of assembly intermediates and that this role may be more prominent than its part in intermediate combination.[8]
In a patient with missense mutations in NDUFAF1, fatal infantile hypertrophic cardiomyopathy was diagnosed. In this case, complex I disassembly resulted in a mitochondrial cardiomyopathy with marked lactic acidosis.[11] Another patient, a child with a compound heterozygous mutation (c.278A > G; c.247G > A) within exon 2 in the NDUFAF1 gene, was diagnosed with leukodystrophy associated with mitochondrial complex I deficiency. Signs and symptoms included regression of mental and motor development, white matter lesions, peripheral neuropathy with high muscle tension and hyperreflexia of limbs, and high levels of lactate and creatine kinase. The parents were found to be heterozygous carriers for the mutation.[12] A third patient was found to have a mutation in both alleles of the NDUFAF1 gene and was diagnosed with cardioencephalomyopathy and reduced levels and activity of complex I.[13]
Interactionsedit
In addition to co-complexes, NDUFAF1 has protein-protein interactions with PNLIPRP1,[17] TMEM97,[18] TMEM86B,[19]YIPF6,[20] SLC30A2,[21] ATIC,[22] and MAGEA11.[23]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000137806 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000027305 - 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.
^Janssen R, Smeitink J, Smeets R, van Den Heuvel L (March 2002). "CIA30 complex I assembly factor: a candidate for human complex I deficiency?". Human Genetics. 110 (3): 264–70. doi:10.1007/s00439-001-0673-3. PMID 11935339. S2CID 19502660.
^Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W (May 2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". Genome Research. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC310876. PMID 10810093.
^ abcdVogel RO, Janssen RJ, Ugalde C, Grovenstein M, Huijbens RJ, Visch HJ, van den Heuvel LP, Willems PH, Zeviani M, Smeitink JA, Nijtmans LG (October 2005). "Human mitochondrial complex I assembly is mediated by NDUFAF1". The FEBS Journal. 272 (20): 5317–26. doi:10.1111/j.1742-4658.2005.04928.x. PMID 16218961. S2CID 29896047.
^"NDUFAF1 - Complex I intermediate-associated protein 30, mitochondrial precursor - Homo sapiens (Human) - NDUFAF1 gene & protein". www.uniprot.org. Retrieved 2018-07-23.
^Donald., Voet (2013). Fundamentals of biochemistry : life at the molecular level. Voet, Judith G., Pratt, Charlotte W. (Fourth ed.). Hoboken, NJ: Wiley. ISBN9780470547847. OCLC 738349533.
^ abFassone E, Taanman JW, Hargreaves IP, Sebire NJ, Cleary MA, Burch M, Rahman S (October 2011). "Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy". Journal of Medical Genetics. 48 (10): 691–7. doi:10.1136/jmedgenet-2011-100340. PMID 21931170. S2CID 35411085.
^ abWu L, Peng J, Ma Y, He F, Deng X, Wang G, Lifen Y, Yin F (2016). "Leukodystrophy associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFAF1 gene". Mitochondrial DNA Part A. 27 (2): 1034–7. doi:10.3109/19401736.2014.926543. PMID 24963768. S2CID 207677530.
^ abcDunning CJ, McKenzie M, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR, Ryan MT (July 2007). "Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease". The EMBO Journal. 26 (13): 3227–37. doi:10.1038/sj.emboj.7601748. PMC1914096. PMID 17557076.
^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. PMC4076475. PMID 23965338.
^Yao, Daniel. . amino.heartproteome.org. Archived from the original on 2018-07-23. Retrieved 2018-07-23.
^"Mitochondrial complex I deficiency". www.uniprot.org. Retrieved 2018-07-23.
Küffner R, Rohr A, Schmiede A, Krüll C, Schulte U (October 1998). "Involvement of two novel chaperones in the assembly of mitochondrial NADH:Ubiquinone oxidoreductase (complex I)". Journal of Molecular Biology. 283 (2): 409–17. doi:10.1006/jmbi.1998.2114. PMID 9769214.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Vogel RO, Janssen RJ, van den Brand MA, Dieteren CE, Verkaart S, Koopman WJ, Willems PH, Pluk W, van den Heuvel LP, Smeitink JA, Nijtmans LG (March 2007). "Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly". Genes & Development. 21 (5): 615–24. doi:10.1101/gad.408407. PMC1820902. PMID 17344420.
Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC1847948. PMID 17353931. S2CID 670227.
Vogel RO, van den Brand MA, Rodenburg RJ, van den Heuvel LP, Tsuneoka M, Smeitink JA, Nijtmans LG (June 2007). "Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients". Molecular Genetics and Metabolism. 91 (2): 176–82. doi:10.1016/j.ymgme.2007.02.007. PMID 17383918.
Dunning CJ, McKenzie M, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR, Ryan MT (July 2007). "Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease". The EMBO Journal. 26 (13): 3227–37. doi:10.1038/sj.emboj.7601748. PMC1914096. PMID 17557076.
ndufaf1, complex, intermediate, associated, protein, mitochondrial, cia30, nadh, dehydrogenase, ubiquinone, alpha, subcomplex, assembly, factor, protein, that, humans, encoded, cia30, gene, gene, encodes, human, homolog, neurospora, crassa, protein, involved, . Complex I intermediate associated protein 30 mitochondrial CIA30 or NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 NDUFAF1 is a protein that in humans is encoded by the NDUFAF1 or CIA30 gene 5 6 7 8 9 The NDUFAF1 gene encodes a human homolog of a Neurospora crassa protein involved in the assembly of complex I 7 The NDUFAF1 protein is an assembly factor 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 10 Variants of the NDUFAF1 gene are associated with hypertrophic cardiomyopathy leukodystrophy and cardioencephalomyopathy 11 12 13 NDUFAF1IdentifiersAliasesNDUFAF1 CGI65 CIA30 CGI 65 NADH ubiquinone oxidoreductase complex assembly factor 1 MC1DN11External IDsOMIM 606934 MGI 1916952 HomoloGene 32289 GeneCards NDUFAF1Gene location Human Chr Chromosome 15 human 1 Band15q15 1Start41 387 218 bp 1 End41 409 403 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 2 E5Start119 485 927 bp 2 End119 493 308 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed ingastrocnemius muscleright adrenal glandright ventricleleft adrenal glandleft ventriclespermdeltoid musclebiceps brachiivastus lateralis muscleprefrontal cortexTop expressed indigastric musclesternocleidomastoid muscletemporal musclesacculesoleus musclemyocardium of ventricleinterventricular septumvastus lateralis muscletriceps brachii muscletibialis anterior muscleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionunfolded protein binding protein bindingCellular componentmitochondrial inner membrane mitochondrial respiratory chain complex I mitochondrion cytosol mitochondrial matrixBiological processmitochondrial electron transport NADH to ubiquinone mitochondrial respiratory chain complex I assembly protein containing complex assemblySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez5110369702EnsemblENSG00000137806ENSMUSG00000027305UniProtQ9Y375Q9CWX2RefSeq mRNA NM 016013NM 027175NM 001356467RefSeq protein NP 057097NP 081451NP 001343396NP 001393427NP 001393428NP 001393429NP 001393430NP 001393431NP 001393432Location UCSC Chr 15 41 39 41 41 MbChr 2 119 49 119 49 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseContents 1 Structure 2 Function 3 Clinical Significance 4 Interactions 5 References 6 Further readingStructure editNDUFAF1 is located on the q arm of chromosome 15 in position 15 1 7 The NDUFAF1 gene produces a 37 8 kDa protein composed of 327 amino acids 14 15 NDUFAF1 is associated to complexes of 600 and 700 kDa 8 Complex I is structured in a bipartite L shaped configuration which is made up of a peripheral matrix arm consisting of flavoproteins and iron sulfur proteins involved in electron transfer and a membrane arm consisting of mtDNA encoded subunits involved in ubiquinone reduction and proton pumping 13 NDUFAF1 has been shown to interact with assembly intermediates and may play roles in the correct assembly and combination of the peripheral arm to the complete membrane arm as well as in the stabilization and scaffolding of those intermediates through those close interactions 8 Function editNDUFAF1 is an assembly factor that is important for the correct assembly of NADH dehydrogenase ubiquinone It ensures the correct combination of complex intermediates and is necessary for the correct functioning of NADH dehydrogenase ubiquinone Specifically NDUFAF1 binds to the large membrane arm intermediate and is involved in the combination of the small and large membrane arm intermediates of complex I It has also been suggested that NDUFAF1 is involved in the stabilization and scaffolding of assembly intermediates and that this role may be more prominent than its part in intermediate combination 8 Clinical Significance editMutations in NDUFAF1 can result in mitochondrial deficiencies and associated disorders A disorder of the mitochondrial respiratory chain can cause a wide range of clinical manifestations from lethal neonatal disease to adult onset neurodegenerative disorders Phenotypes include macrocephaly with progressive leukodystrophy non specific encephalopathy cardiomyopathy myopathy liver disease Leigh syndrome Leber hereditary optic neuropathy and some forms of Parkinson disease 16 In a patient with missense mutations in NDUFAF1 fatal infantile hypertrophic cardiomyopathy was diagnosed In this case complex I disassembly resulted in a mitochondrial cardiomyopathy with marked lactic acidosis 11 Another patient a child with a compound heterozygous mutation c 278A gt G c 247G gt A within exon 2 in the NDUFAF1 gene was diagnosed with leukodystrophy associated with mitochondrial complex I deficiency Signs and symptoms included regression of mental and motor development white matter lesions peripheral neuropathy with high muscle tension and hyperreflexia of limbs and high levels of lactate and creatine kinase The parents were found to be heterozygous carriers for the mutation 12 A third patient was found to have a mutation in both alleles of the NDUFAF1 gene and was diagnosed with cardioencephalomyopathy and reduced levels and activity of complex I 13 Interactions editIn addition to co complexes NDUFAF1 has protein protein interactions with PNLIPRP1 17 TMEM97 18 TMEM86B 19 YIPF6 20 SLC30A2 21 ATIC 22 and MAGEA11 23 References edit a b c GRCh38 Ensembl release 89 ENSG00000137806 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000027305 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 Janssen R Smeitink J Smeets R van Den Heuvel L March 2002 CIA30 complex I assembly factor a candidate for human complex I deficiency Human Genetics 110 3 264 70 doi 10 1007 s00439 001 0673 3 PMID 11935339 S2CID 19502660 Lai CH Chou CY Ch ang LY Liu CS Lin W May 2000 Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics Genome Research 10 5 703 13 doi 10 1101 gr 10 5 703 PMC 310876 PMID 10810093 a b c Entrez Gene NDUFAF1 NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 a b c d Vogel RO Janssen RJ Ugalde C Grovenstein M Huijbens RJ Visch HJ van den Heuvel LP Willems PH Zeviani M Smeitink JA Nijtmans LG October 2005 Human mitochondrial complex I assembly is mediated by NDUFAF1 The FEBS Journal 272 20 5317 26 doi 10 1111 j 1742 4658 2005 04928 x PMID 16218961 S2CID 29896047 NDUFAF1 Complex I intermediate associated protein 30 mitochondrial precursor Homo sapiens Human NDUFAF1 gene amp protein www uniprot org Retrieved 2018 07 23 Donald Voet 2013 Fundamentals of biochemistry life at the molecular level Voet Judith G Pratt Charlotte W Fourth ed Hoboken NJ Wiley ISBN 9780470547847 OCLC 738349533 a b Fassone E Taanman JW Hargreaves IP Sebire NJ Cleary MA Burch M Rahman S October 2011 Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy Journal of Medical Genetics 48 10 691 7 doi 10 1136 jmedgenet 2011 100340 PMID 21931170 S2CID 35411085 a b Wu L Peng J Ma Y He F Deng X Wang G Lifen Y Yin F 2016 Leukodystrophy associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFAF1 gene Mitochondrial DNA Part A 27 2 1034 7 doi 10 3109 19401736 2014 926543 PMID 24963768 S2CID 207677530 a b c Dunning CJ McKenzie M Sugiana C Lazarou M Silke J Connelly A Fletcher JM Kirby DM Thorburn DR Ryan MT July 2007 Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease The EMBO Journal 26 13 3227 37 doi 10 1038 sj emboj 7601748 PMC 1914096 PMID 17557076 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 Archived from the original on 2018 07 23 Retrieved 2018 07 23 Mitochondrial complex I deficiency www uniprot org Retrieved 2018 07 23 pnliprp1 ndufaf1 1 IntAct Retrieved 2018 07 23 tmem97 ndufaf1 1 IntAct Retrieved 2018 07 23 tmem86b ndufaf1 1 IntAct Retrieved 2018 07 23 yipf6 ndufaf1 1 IntAct Retrieved 2018 07 23 slc30a2 ndufaf1 1 IntAct Retrieved 2018 07 23 atic ndufaf1 IntAct Retrieved 2018 07 23 magea11 ndufaf1 IntAct Retrieved 2018 07 23 Further reading editKuffner R Rohr A Schmiede A Krull C Schulte U October 1998 Involvement of two novel chaperones in the assembly of mitochondrial NADH Ubiquinone oxidoreductase complex I Journal of Molecular Biology 283 2 409 17 doi 10 1006 jmbi 1998 2114 PMID 9769214 Rual JF Venkatesan K Hao T Hirozane Kishikawa T Dricot A Li N Berriz GF Gibbons FD Dreze M Ayivi Guedehoussou N Klitgord N Simon C Boxem M Milstein S Rosenberg J Goldberg DS Zhang LV Wong SL Franklin G Li S Albala JS Lim J Fraughton C Llamosas E Cevik S Bex C Lamesch P Sikorski RS Vandenhaute J Zoghbi HY Smolyar A Bosak S Sequerra R Doucette Stamm L Cusick ME Hill DE Roth FP Vidal M October 2005 Towards a proteome scale map of the human protein protein interaction network Nature 437 7062 1173 8 Bibcode 2005Natur 437 1173R doi 10 1038 nature04209 PMID 16189514 S2CID 4427026 Vogel RO Janssen RJ van den Brand MA Dieteren CE Verkaart S Koopman WJ Willems PH Pluk W van den Heuvel LP Smeitink JA Nijtmans LG March 2007 Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly Genes amp Development 21 5 615 24 doi 10 1101 gad 408407 PMC 1820902 PMID 17344420 Ewing RM Chu P Elisma F Li H Taylor P Climie S McBroom Cerajewski L Robinson MD O Connor L Li M Taylor R Dharsee M Ho Y Heilbut A Moore L Zhang S Ornatsky O Bukhman YV Ethier M Sheng Y Vasilescu J Abu Farha M Lambert JP Duewel HS Stewart II Kuehl B Hogue K Colwill K Gladwish K Muskat B Kinach R Adams SL Moran MF Morin GB Topaloglou T Figeys D 2007 Large scale mapping of human protein protein interactions by mass spectrometry Molecular Systems Biology 3 1 89 doi 10 1038 msb4100134 PMC 1847948 PMID 17353931 S2CID 670227 Vogel RO van den Brand MA Rodenburg RJ van den Heuvel LP Tsuneoka M Smeitink JA Nijtmans LG June 2007 Investigation of the complex I assembly chaperones B17 2L and NDUFAF1 in a cohort of CI deficient patients Molecular Genetics and Metabolism 91 2 176 82 doi 10 1016 j ymgme 2007 02 007 PMID 17383918 Dunning CJ McKenzie M Sugiana C Lazarou M Silke J Connelly A Fletcher JM Kirby DM Thorburn DR Ryan MT July 2007 Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease The EMBO Journal 26 13 3227 37 doi 10 1038 sj emboj 7601748 PMC 1914096 PMID 17557076 This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title NDUFAF1 amp oldid 1212955362, wikipedia, wiki, book, books, library,
