FXRD1_HUMAN
ID FXRD1_HUMAN Reviewed; 486 AA.
AC Q96CU9; B3KN84; B4DHU2; Q71MG0; Q9BU39; Q9UKY9;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=FAD-dependent oxidoreductase domain-containing protein 1 {ECO:0000312|HGNC:HGNC:26927};
DE EC=1.-.-.-;
GN Name=FOXRED1 {ECO:0000312|HGNC:HGNC:26927}; ORFNames=FP634;
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 [MRNA] (ISOFORM 1).
RX PubMed=10497265; DOI=10.1093/nar/27.20.4008;
RA Oh J.J., Grosshans D.R., Wong S.G., Slamon D.J.;
RT "Identification of differentially expressed genes associated with HER-2/neu
RT overexpression in human breast cancer cells.";
RL Nucleic Acids Res. 27:4008-4017(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Zhou X.M., Qin W.X., Wan D.F., Zhang P.P., Jiang H.Q., Huang Y., Zhao X.T.,
RA Gu J.R.;
RT "Novel human cDNA clones with function of affecting cancer cell growth.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Caudate nucleus;
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 [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-343.
RC TISSUE=Lung, and Placenta;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, CHARACTERIZATION OF VARIANTS
RP MC1DN19 TRP-352 AND SER-430, AND MUTAGENESIS OF TYR-327; TYR-349; TYR-359;
RP TYR-410 AND TYR-411.
RX PubMed=25678554; DOI=10.1093/hmg/ddv058;
RA Formosa L.E., Mimaki M., Frazier A.E., McKenzie M., Stait T.L.,
RA Thorburn D.R., Stroud D.A., Ryan M.T.;
RT "Characterization of mitochondrial FOXRED1 in the assembly of respiratory
RT chain complex I.";
RL Hum. Mol. Genet. 24:2952-2965(2015).
RN [10]
RP IDENTIFICATION.
RX PubMed=25681241; DOI=10.1016/j.bbabio.2015.01.014;
RA Lemire B.D.;
RT "Evolution of FOXRED1, an FAD-dependent oxidoreductase necessary for
RT NADH:ubiquinone oxidoreductase (Complex I) assembly.";
RL Biochim. Biophys. Acta 1847:451-457(2015).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [12]
RP VARIANT MC1DN19 TRP-352, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20858599; DOI=10.1093/hmg/ddq414;
RA Fassone E., Duncan A.J., Taanman J.W., Pagnamenta A.T., Sadowski M.I.,
RA Holand T., Qasim W., Rutland P., Calvo S.E., Mootha V.K.,
RA Bitner-Glindzicz M., Rahman S.;
RT "FOXRED1, encoding an FAD-dependent oxidoreductase complex-I-specific
RT molecular chaperone, is mutated in infantile-onset mitochondrial
RT encephalopathy.";
RL Hum. Mol. Genet. 19:4837-4847(2010).
RN [13]
RP VARIANTS MC1DN19 232-GLN--ILE-486 DEL AND SER-430.
RX PubMed=20818383; DOI=10.1038/ng.659;
RA Calvo S.E., Tucker E.J., Compton A.G., Kirby D.M., Crawford G., Burtt N.P.,
RA Rivas M., Guiducci C., Bruno D.L., Goldberger O.A., Redman M.C.,
RA Wiltshire E., Wilson C.J., Altshuler D., Gabriel S.B., Daly M.J.,
RA Thorburn D.R., Mootha V.K.;
RT "High-throughput, pooled sequencing identifies mutations in NUBPL and
RT FOXRED1 in human complex I deficiency.";
RL Nat. Genet. 42:851-858(2010).
CC -!- FUNCTION: Required for the assembly of the mitochondrial membrane
CC respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599,
CC PubMed:25678554). Involved in mid-late stages of complex I assembly
CC (PubMed:25678554). {ECO:0000269|PubMed:20858599,
CC ECO:0000269|PubMed:25678554}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- SUBUNIT: Associates with components of the mitochondrial respiratory
CC chain complex I. {ECO:0000269|PubMed:25678554}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20858599, ECO:0000305|PubMed:25678554}; Single-pass
CC membrane protein {ECO:0000255}. Note=According to a report, it is
CC associated with the matrix face of the mitochondrial inner membrane and
CC does not contain any transmembrane region. However, one transmembrane
CC domain is clearly predicted by different methods (Probable).
CC {ECO:0000305|PubMed:25678554}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96CU9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96CU9-2; Sequence=VSP_022629;
CC Name=3;
CC IsoId=Q96CU9-3; Sequence=VSP_039003;
CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 19 (MC1DN19)
CC [MIM:618241]: 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. MC1DN19 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:20818383,
CC ECO:0000269|PubMed:20858599, ECO:0000269|PubMed:25678554}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; AF103801; AAF02421.1; -; mRNA.
DR EMBL; AL136923; CAB66857.1; -; mRNA.
DR EMBL; AF447877; AAQ04652.1; -; mRNA.
DR EMBL; AK023987; BAG51246.1; -; mRNA.
DR EMBL; AK295267; BAG58254.1; -; mRNA.
DR EMBL; CH471065; EAW67683.1; -; Genomic_DNA.
DR EMBL; BC002910; AAH02910.2; -; mRNA.
DR EMBL; BC013902; AAH13902.1; -; mRNA.
DR CCDS; CCDS8471.1; -. [Q96CU9-1]
DR RefSeq; NP_060017.1; NM_017547.3. [Q96CU9-1]
DR RefSeq; XP_006718944.1; XM_006718881.3. [Q96CU9-2]
DR RefSeq; XP_016873492.1; XM_017018003.1. [Q96CU9-2]
DR RefSeq; XP_016873493.1; XM_017018004.1. [Q96CU9-2]
DR RefSeq; XP_016873494.1; XM_017018005.1. [Q96CU9-2]
DR AlphaFoldDB; Q96CU9; -.
DR SMR; Q96CU9; -.
DR BioGRID; 120725; 69.
DR IntAct; Q96CU9; 27.
DR MINT; Q96CU9; -.
DR STRING; 9606.ENSP00000263578; -.
DR GlyGen; Q96CU9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96CU9; -.
DR PhosphoSitePlus; Q96CU9; -.
DR BioMuta; FOXRED1; -.
DR DMDM; 124007188; -.
DR EPD; Q96CU9; -.
DR jPOST; Q96CU9; -.
DR MassIVE; Q96CU9; -.
DR MaxQB; Q96CU9; -.
DR PaxDb; Q96CU9; -.
DR PeptideAtlas; Q96CU9; -.
DR PRIDE; Q96CU9; -.
DR ProteomicsDB; 76223; -. [Q96CU9-1]
DR ProteomicsDB; 76224; -. [Q96CU9-2]
DR ProteomicsDB; 76225; -. [Q96CU9-3]
DR Antibodypedia; 32986; 170 antibodies from 27 providers.
DR DNASU; 55572; -.
DR Ensembl; ENST00000263578.10; ENSP00000263578.5; ENSG00000110074.12. [Q96CU9-1]
DR GeneID; 55572; -.
DR KEGG; hsa:55572; -.
DR MANE-Select; ENST00000263578.10; ENSP00000263578.5; NM_017547.4; NP_060017.1.
DR UCSC; uc001qdi.4; human. [Q96CU9-1]
DR CTD; 55572; -.
DR DisGeNET; 55572; -.
DR GeneCards; FOXRED1; -.
DR HGNC; HGNC:26927; FOXRED1.
DR HPA; ENSG00000110074; Low tissue specificity.
DR MalaCards; FOXRED1; -.
DR MIM; 613622; gene.
DR MIM; 618241; phenotype.
DR neXtProt; NX_Q96CU9; -.
DR OpenTargets; ENSG00000110074; -.
DR Orphanet; 2609; Isolated complex I deficiency.
DR Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR PharmGKB; PA143485473; -.
DR VEuPathDB; HostDB:ENSG00000110074; -.
DR eggNOG; KOG2853; Eukaryota.
DR GeneTree; ENSGT00390000006114; -.
DR HOGENOM; CLU_007884_4_4_1; -.
DR InParanoid; Q96CU9; -.
DR OMA; PDHNALI; -.
DR OrthoDB; 752680at2759; -.
DR PhylomeDB; Q96CU9; -.
DR TreeFam; TF314003; -.
DR PathwayCommons; Q96CU9; -.
DR SignaLink; Q96CU9; -.
DR BioGRID-ORCS; 55572; 130 hits in 1082 CRISPR screens.
DR ChiTaRS; FOXRED1; human.
DR GeneWiki; FOXRED1; -.
DR GenomeRNAi; 55572; -.
DR Pharos; Q96CU9; Tbio.
DR PRO; PR:Q96CU9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96CU9; protein.
DR Bgee; ENSG00000110074; Expressed in right hemisphere of cerebellum and 159 other tissues.
DR ExpressionAtlas; Q96CU9; baseline and differential.
DR Genevisible; Q96CU9; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005747; C:mitochondrial respiratory chain complex I; IMP:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01266; DAO; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Electron transport; FAD;
KW Flavoprotein; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Oxidoreductase; Primary mitochondrial disease; Reference proteome;
KW Respiratory chain; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..486
FT /note="FAD-dependent oxidoreductase domain-containing
FT protein 1"
FT /id="PRO_0000274142"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..211
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_022629"
FT VAR_SEQ 1..28
FT /note="MIRRVLPHGMGRGLLTRRPGTRRGGFSL -> MAHTGRTVGRLGEG (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039003"
FT VARIANT 145
FT /note="V -> I (in dbSNP:rs34542988)"
FT /id="VAR_033856"
FT VARIANT 232..486
FT /note="Missing (in MC1DN19)"
FT /evidence="ECO:0000269|PubMed:20818383"
FT /id="VAR_081414"
FT VARIANT 343
FT /note="A -> P (in dbSNP:rs17855445)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030192"
FT VARIANT 352
FT /note="R -> W (in MC1DN19; hypomorphic variant in vitro;
FT dbSNP:rs387907087)"
FT /evidence="ECO:0000269|PubMed:20858599,
FT ECO:0000269|PubMed:25678554"
FT /id="VAR_073273"
FT VARIANT 380
FT /note="H -> R (in dbSNP:rs7116126)"
FT /id="VAR_051003"
FT VARIANT 430
FT /note="N -> S (in MC1DN19; hypomorphic variant in vitro;
FT dbSNP:rs267606830)"
FT /evidence="ECO:0000269|PubMed:20818383,
FT ECO:0000269|PubMed:25678554"
FT /id="VAR_064571"
FT MUTAGEN 327
FT /note="Y->A,F: No effect. Able to restore complex I
FT assembly when expressed in cells lacking FOXRED1."
FT /evidence="ECO:0000269|PubMed:25678554"
FT MUTAGEN 349
FT /note="Y->A,F: No effect. Able to restore complex I
FT assembly when expressed in cells lacking FOXRED1."
FT /evidence="ECO:0000269|PubMed:25678554"
FT MUTAGEN 359
FT /note="Y->A: Not able to restore complex I assembly when
FT expressed in cells lacking FOXRED1."
FT /evidence="ECO:0000269|PubMed:25678554"
FT MUTAGEN 359
FT /note="Y->F: No effect. Able to restore complex I assembly
FT when expressed in cells lacking FOXRED1."
FT /evidence="ECO:0000269|PubMed:25678554"
FT MUTAGEN 410
FT /note="Y->A,F: No effect. Able to restore complex I
FT assembly when expressed in cells lacking FOXRED1."
FT /evidence="ECO:0000269|PubMed:25678554"
FT MUTAGEN 411
FT /note="Y->A,F: No effect. Able to restore complex I
FT assembly when expressed in cells lacking FOXRED1."
FT /evidence="ECO:0000269|PubMed:25678554"
FT CONFLICT 425
FT /note="H -> HF (in Ref. 3; AAQ04652)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 486 AA; 53812 MW; 34A18ABED84BE676 CRC64;
MIRRVLPHGM GRGLLTRRPG TRRGGFSLDW DGKVSEIKKK IKSILPGRSC DLLQDTSHLP
PEHSDVVIVG GGVLGLSVAY WLKKLESRRG AIRVLVVERD HTYSQASTGL SVGGICQQFS
LPENIQLSLF SASFLRNINE YLAVVDAPPL DLRFNPSGYL LLASEKDAAA MESNVKVQRQ
EGAKVSLMSP DQLRNKFPWI NTEGVALASY GMEDEGWFDP WCLLQGLRRK VQSLGVLFCQ
GEVTRFVSSS QRMLTTDDKA VVLKRIHEVH VKMDRSLEYQ PVECAIVINA AGAWSAQIAA
LAGVGEGPPG TLQGTKLPVE PRKRYVYVWH CPQGPGLETP LVADTSGAYF RREGLGSNYL
GGRSPTEQEE PDPANLEVDH DFFQDKVWPH LALRVPAFET LKVQSAWAGY YDYNTFDQNG
VVGPHPLVVN MYFATGFSGH GLQQAPGIGR AVAEMVLKGR FQTIDLSPFL FTRFYLGEKI
QENNII
