NDUF5_HUMAN
ID NDUF5_HUMAN Reviewed; 345 AA.
AC Q5TEU4; A8K166; Q6GPH3; Q9H6F4;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Arginine-hydroxylase NDUFAF5, mitochondrial {ECO:0000305};
DE EC=1.-.-.- {ECO:0000305|PubMed:27226634};
DE AltName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 5 {ECO:0000312|HGNC:HGNC:15899};
DE AltName: Full=Putative methyltransferase NDUFAF5;
DE EC=2.1.1.- {ECO:0000305};
DE Flags: Precursor;
GN Name=NDUFAF5 {ECO:0000312|HGNC:HGNC:15899};
GN Synonyms=C20orf7 {ECO:0000312|HGNC:HGNC:15899};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 50-345 (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MC1DN16, AND VARIANT MC1DN16
RP PRO-229.
RX PubMed=18940309; DOI=10.1016/j.ajhg.2008.09.009;
RA Sugiana C., Pagliarini D.J., McKenzie M., Kirby D.M., Salemi R.,
RA Abu-Amero K.K., Dahl H.-H.M., Hutchison W.M., Vascotto K.A., Smith S.M.,
RA Newbold R.F., Christodoulou J., Calvo S., Mootha V.K., Ryan M.T.,
RA Thorburn D.R.;
RT "Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal
RT mitochondrial disease.";
RL Am. J. Hum. Genet. 83:468-478(2008).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NDUFS7.
RX PubMed=27226634; DOI=10.1074/jbc.m116.734970;
RA Rhein V.F., Carroll J., Ding S., Fearnley I.M., Walker J.E.;
RT "NDUFAF5 hydroxylates NDUFS7 at an early stage in the assembly of human
RT complex I.";
RL J. Biol. Chem. 291:14851-14860(2016).
RN [7]
RP INTERACTION WITH NDUFAF8.
RX PubMed=27499296; DOI=10.1016/j.molcel.2016.06.033;
RA Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T.,
RA Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K.,
RA Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A.,
RA Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.J.,
RA Coon J.J., Pagliarini D.J.;
RT "Mitochondrial protein interaction mapping identifies regulators of
RT respiratory chain function.";
RL Mol. Cell 63:621-632(2016).
RN [8]
RP INVOLVEMENT IN MC1DN16, AND VARIANT MC1DN16 PHE-159.
RX PubMed=19542079; DOI=10.1136/jmg.2009.067553;
RA Gerards M., Sluiter W., van den Bosch B.J., de Wit L.E., Calis C.M.,
RA Frentzen M., Akbari H., Schoonderwoerd K., Scholte H.R., Jongbloed R.J.,
RA Hendrickx A.T., de Coo I.F., Smeets H.J.;
RT "Defective complex I assembly due to C20orf7 mutations as a new cause of
RT Leigh syndrome.";
RL J. Med. Genet. 47:507-512(2010).
RN [9]
RP INVOLVEMENT IN MC1DN16, AND VARIANT MC1DN16 VAL-250.
RX PubMed=21607760; DOI=10.1007/s10545-011-9348-y;
RA Saada A., Edvardson S., Shaag A., Chung W.K., Segel R., Miller C.,
RA Jalas C., Elpeleg O.;
RT "Combined OXPHOS complex I and IV defect, due to mutated complex I assembly
RT factor C20ORF7.";
RL J. Inherit. Metab. Dis. 35:125-131(2012).
CC -!- FUNCTION: Arginine hydroxylase involved in the assembly of
CC mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-
CC ND1) at early stages (PubMed:18940309, PubMed:27226634). Acts by
CC mediating hydroxylation of 'Arg-111' of NDUFS7 (PubMed:27226634). May
CC also have methyltransferase activity (Probable).
CC {ECO:0000269|PubMed:18940309, ECO:0000269|PubMed:27226634,
CC ECO:0000305}.
CC -!- SUBUNIT: Interacts with NDUFAF8, leading to stabilize NDUFAF5
CC (PubMed:27499296). Interacts with NDUFS7 (PubMed:27226634).
CC {ECO:0000269|PubMed:27226634, ECO:0000269|PubMed:27499296}.
CC -!- INTERACTION:
CC Q5TEU4; A1L188: NDUFAF8; NbExp=9; IntAct=EBI-10762958, EBI-20593474;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:18940309, ECO:0000269|PubMed:27226634}.
CC Note=Peripherally localized on the matrix face of the mitochondrial
CC inner membrane. {ECO:0000269|PubMed:18940309}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5TEU4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5TEU4-2; Sequence=VSP_028637;
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 16 (MC1DN16)
CC [MIM:618238]: A form of mitochondrial complex I deficiency, the most
CC common biochemical signature of mitochondrial disorders, a group of
CC highly heterogeneous conditions characterized by defective oxidative
CC phosphorylation, which collectively affects 1 in 5-10000 live births.
CC Clinical disorders have variable severity, ranging from lethal neonatal
CC disease to adult-onset neurodegenerative disorders. Phenotypes include
CC macrocephaly with progressive leukodystrophy, non-specific
CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh
CC syndrome, Leber hereditary optic neuropathy, and some forms of
CC Parkinson disease. MC1DN16 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:18940309,
CC ECO:0000269|PubMed:19542079, ECO:0000269|PubMed:21607760}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK025977; BAB15305.1; -; mRNA.
DR EMBL; AK289781; BAF82470.1; -; mRNA.
DR EMBL; AL161659; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL109657; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10311.1; -; Genomic_DNA.
DR EMBL; BC005984; AAH05984.1; -; mRNA.
DR EMBL; BC073158; AAH73158.1; -; mRNA.
DR CCDS; CCDS13118.1; -. [Q5TEU4-1]
DR CCDS; CCDS33441.1; -. [Q5TEU4-2]
DR RefSeq; NP_001034464.1; NM_001039375.2. [Q5TEU4-2]
DR RefSeq; NP_077025.2; NM_024120.4. [Q5TEU4-1]
DR AlphaFoldDB; Q5TEU4; -.
DR SMR; Q5TEU4; -.
DR BioGRID; 122554; 106.
DR IntAct; Q5TEU4; 45.
DR MINT; Q5TEU4; -.
DR STRING; 9606.ENSP00000367346; -.
DR iPTMnet; Q5TEU4; -.
DR PhosphoSitePlus; Q5TEU4; -.
DR BioMuta; NDUFAF5; -.
DR DMDM; 74762247; -.
DR EPD; Q5TEU4; -.
DR jPOST; Q5TEU4; -.
DR MassIVE; Q5TEU4; -.
DR MaxQB; Q5TEU4; -.
DR PaxDb; Q5TEU4; -.
DR PeptideAtlas; Q5TEU4; -.
DR PRIDE; Q5TEU4; -.
DR ProteomicsDB; 65062; -. [Q5TEU4-1]
DR ProteomicsDB; 65063; -. [Q5TEU4-2]
DR Antibodypedia; 24277; 127 antibodies from 21 providers.
DR DNASU; 79133; -.
DR Ensembl; ENST00000378106.10; ENSP00000367346.5; ENSG00000101247.18. [Q5TEU4-1]
DR Ensembl; ENST00000463598.1; ENSP00000420497.1; ENSG00000101247.18. [Q5TEU4-2]
DR GeneID; 79133; -.
DR KEGG; hsa:79133; -.
DR MANE-Select; ENST00000378106.10; ENSP00000367346.5; NM_024120.5; NP_077025.2.
DR UCSC; uc002wom.4; human. [Q5TEU4-1]
DR CTD; 79133; -.
DR DisGeNET; 79133; -.
DR GeneCards; NDUFAF5; -.
DR HGNC; HGNC:15899; NDUFAF5.
DR HPA; ENSG00000101247; Tissue enhanced (skeletal).
DR MalaCards; NDUFAF5; -.
DR MIM; 612360; gene.
DR MIM; 618238; phenotype.
DR neXtProt; NX_Q5TEU4; -.
DR OpenTargets; ENSG00000101247; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA25780; -.
DR VEuPathDB; HostDB:ENSG00000101247; -.
DR eggNOG; KOG2940; Eukaryota.
DR GeneTree; ENSGT00390000014687; -.
DR HOGENOM; CLU_046586_0_2_1; -.
DR InParanoid; Q5TEU4; -.
DR OMA; PSMWELM; -.
DR OrthoDB; 691814at2759; -.
DR PhylomeDB; Q5TEU4; -.
DR TreeFam; TF315222; -.
DR PathwayCommons; Q5TEU4; -.
DR Reactome; R-HSA-6799198; Complex I biogenesis.
DR SignaLink; Q5TEU4; -.
DR BioGRID-ORCS; 79133; 126 hits in 1090 CRISPR screens.
DR ChiTaRS; NDUFAF5; human.
DR GenomeRNAi; 79133; -.
DR Pharos; Q5TEU4; Tbio.
DR PRO; PR:Q5TEU4; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q5TEU4; protein.
DR Bgee; ENSG00000101247; Expressed in apex of heart and 178 other tissues.
DR ExpressionAtlas; Q5TEU4; baseline and differential.
DR Genevisible; Q5TEU4; HS.
DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR GO; GO:0030961; P:peptidyl-arginine hydroxylation; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08241; Methyltransf_11; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Leigh syndrome; Membrane;
KW Methyltransferase; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Primary mitochondrial disease; Reference proteome;
KW Transferase; Transit peptide.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 37..345
FT /note="Arginine-hydroxylase NDUFAF5, mitochondrial"
FT /id="PRO_0000307213"
FT VAR_SEQ 110..160
FT /note="ETIGKFFQADIAENALKNSSETEIPTVSVLADEEFLPFKENTFDLVVSSLS
FT -> LQLFHCRKLLESFSKLTLQKMLC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_028637"
FT VARIANT 159
FT /note="L -> F (in MC1DN16; dbSNP:rs267606689)"
FT /evidence="ECO:0000269|PubMed:19542079"
FT /id="VAR_067956"
FT VARIANT 229
FT /note="L -> P (in MC1DN16; dbSNP:rs118203929)"
FT /evidence="ECO:0000269|PubMed:18940309"
FT /id="VAR_054119"
FT VARIANT 250
FT /note="G -> V (in MC1DN16; dbSNP:rs757043077)"
FT /evidence="ECO:0000269|PubMed:21607760"
FT /id="VAR_076864"
FT VARIANT 337
FT /note="L -> F (in dbSNP:rs6042368)"
FT /id="VAR_035376"
SQ SEQUENCE 345 AA; 38918 MW; 96E1D29B91980026 CRC64;
MLRPAGLWRL CRRPWAARVP AENLGRREVT SGVSPRGSTS PRTLNIFDRD LKRKQKNWAA
RQPEPTKFDY LKEEVGSRIA DRVYDIPRNF PLALDLGCGR GYIAQYLNKE TIGKFFQADI
AENALKNSSE TEIPTVSVLA DEEFLPFKEN TFDLVVSSLS LHWVNDLPRA LEQIHYILKP
DGVFIGAMFG GDTLYELRCS LQLAETEREG GFSPHISPFT AVNDLGHLLG RAGFNTLTVD
TDEIQVNYPG MFELMEDLQG MGESNCAWNR KALLHRDTML AAAAVYREMY RNEDGSVPAT
YQIYYMIGWK YHESQARPAE RGSATVSFGE LGKINNLMPP GKKSQ
