FDX2_HUMAN
ID FDX2_HUMAN Reviewed; 186 AA.
AC Q6P4F2; B7Z6L7; Q8N8B8;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Ferredoxin-2, mitochondrial {ECO:0000303|PubMed:20547883};
DE AltName: Full=Adrenodoxin-like protein;
DE AltName: Full=Ferredoxin-1-like protein;
DE Flags: Precursor;
GN Name=FDX2 {ECO:0000312|HGNC:HGNC:30546}; Synonyms=FDX1L;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Small intestine;
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-186 (ISOFORM 1).
RC TISSUE=Brain;
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20547883; DOI=10.1073/pnas.1004250107;
RA Sheftel A.D., Stehling O., Pierik A.J., Elsasser H.P., Muhlenhoff U.,
RA Webert H., Hobler A., Hannemann F., Bernhardt R., Lill R.;
RT "Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct
RT roles in steroidogenesis, heme, and Fe/S cluster biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11775-11780(2010).
RN [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 69-174 IN COMPLEX WITH
RP IRON-SULFUR (2FE-2S), AND COFACTOR.
RA Webert H., Hobler A., Sheftel A.D., Molik S., Maestre-Reyna M.,
RA Essen L.-O., Vorniscescu D., Keusgen M., Hannemann F., Bernhardt R.,
RA Lill R.;
RT "Structure and functional studies on human mitochondrial ferredoxins.";
RL Submitted (JAN-2011) to the PDB data bank.
RN [7]
RP INVOLVEMENT IN MEOAL, VARIANT MEOAL LEU-4, CHARACTERIZATION OF VARIANT
RP MEOAL LEU-4, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24281368; DOI=10.1038/ejhg.2013.269;
RA Spiegel R., Saada A., Halvardson J., Soiferman D., Shaag A., Edvardson S.,
RA Horovitz Y., Khayat M., Shalev S.A., Feuk L., Elpeleg O.;
RT "Deleterious mutation in FDX1L gene is associated with a novel
RT mitochondrial muscle myopathy.";
RL Eur. J. Hum. Genet. 22:902-906(2014).
RN [8]
RP INVOLVEMENT IN MEOAL, VARIANT MEOAL LEU-144, CHARACTERIZATION OF VARIANT
RP MEOAL LEU-144, AND TISSUE SPECIFICITY.
RX PubMed=30010796; DOI=10.1093/brain/awy172;
RA Gurgel-Giannetti J., Lynch D.S., Paiva A.R.B., Lucato L.T., Yamamoto G.,
RA Thomsen C., Basu S., Freua F., Giannetti A.V., de Assis B.D.R.,
RA Ribeiro M.D.O., Barcelos I., Sayao Souza K., Monti F., Melo U.S.,
RA Amorim S., Silva L.G.L., Macedo-Souza L.I., Vianna-Morgante A.M.,
RA Hirano M., Van der Knaap M.S., Lill R., Vainzof M., Oldfors A., Houlden H.,
RA Kok F.;
RT "A novel complex neurological phenotype due to a homozygous mutation in
RT FDX2.";
RL Brain 141:2289-2298(2018).
CC -!- FUNCTION: Essential for heme A and Fe/S protein biosynthesis.
CC {ECO:0000269|PubMed:20547883}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0007744|PDB:2Y5C};
CC Note=Binds 1 [2Fe-2S] cluster. {ECO:0007744|PDB:2Y5C};
CC -!- INTERACTION:
CC Q6P4F2; Q969G2: LHX4; NbExp=3; IntAct=EBI-10252800, EBI-2865388;
CC Q6P4F2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-10252800, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:20547883,
CC ECO:0000269|PubMed:24281368}. Mitochondrion matrix {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P4F2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P4F2-2; Sequence=VSP_056826;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in testis,
CC kidney and brain (at protein level) (PubMed:20547883). Expressed in
CC muscle (at protein level) (PubMed:24281368, PubMed:30010796). Expressed
CC in fibroblasts (at protein level) (PubMed:24281368).
CC {ECO:0000269|PubMed:20547883, ECO:0000269|PubMed:24281368,
CC ECO:0000269|PubMed:30010796}.
CC -!- DISEASE: Mitochondrial myopathy, episodic, with optic atrophy and
CC reversible leukoencephalopathy (MEOAL) [MIM:251900]: An autosomal
CC recessive neuromuscular disorder characterized by childhood onset of
CC recurrent episodes of proximal weakness and myalgia often precipitated
CC by exercise, infections or low temperature. Additional features are
CC optic atrophy, axonal polyneuropathy, and reversible or partially
CC reversible leukoencephalopathy. {ECO:0000269|PubMed:24281368,
CC ECO:0000269|PubMed:30010796}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adrenodoxin/putidaredoxin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH63460.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK097022; BAC04929.1; -; mRNA.
DR EMBL; AC011511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK300568; BAH13303.1; -; mRNA.
DR EMBL; BC063460; AAH63460.1; ALT_INIT; mRNA.
DR RefSeq; NP_001026904.2; NM_001031734.3. [Q6P4F2-1]
DR PDB; 2Y5C; X-ray; 1.70 A; A/B=69-174.
DR PDBsum; 2Y5C; -.
DR AlphaFoldDB; Q6P4F2; -.
DR SMR; Q6P4F2; -.
DR ComplexPortal; CPX-5641; Mitochondrial NIAUFX iron-sulfur cluster assembly complex.
DR IntAct; Q6P4F2; 3.
DR STRING; 9606.ENSP00000377311; -.
DR iPTMnet; Q6P4F2; -.
DR PhosphoSitePlus; Q6P4F2; -.
DR BioMuta; FDX2; -.
DR DMDM; 74749111; -.
DR EPD; Q6P4F2; -.
DR jPOST; Q6P4F2; -.
DR MassIVE; Q6P4F2; -.
DR MaxQB; Q6P4F2; -.
DR PaxDb; Q6P4F2; -.
DR PeptideAtlas; Q6P4F2; -.
DR PRIDE; Q6P4F2; -.
DR ProteomicsDB; 66974; -. [Q6P4F2-1]
DR ProteomicsDB; 72397; -.
DR Antibodypedia; 76687; 7 antibodies from 6 providers.
DR DNASU; 112812; -.
DR Ensembl; ENST00000393708.3; ENSP00000377311.4; ENSG00000267673.6. [Q6P4F2-1]
DR GeneID; 112812; -.
DR MANE-Select; ENST00000393708.3; ENSP00000377311.5; NM_001397406.1; NP_001384335.1.
DR UCSC; uc002mny.2; human. [Q6P4F2-1]
DR CTD; 112812; -.
DR DisGeNET; 112812; -.
DR GeneCards; FDX2; -.
DR HGNC; HGNC:30546; FDX2.
DR HPA; ENSG00000267673; Low tissue specificity.
DR MalaCards; FDX2; -.
DR MIM; 251900; phenotype.
DR MIM; 614585; gene.
DR neXtProt; NX_Q6P4F2; -.
DR OpenTargets; ENSG00000267673; -.
DR PharmGKB; PA162388212; -.
DR VEuPathDB; HostDB:ENSG00000267673; -.
DR eggNOG; KOG3309; Eukaryota.
DR GeneTree; ENSGT00940000161143; -.
DR HOGENOM; CLU_082632_0_2_1; -.
DR InParanoid; Q6P4F2; -.
DR OMA; ERRTHGW; -.
DR OrthoDB; 1380051at2759; -.
DR PhylomeDB; Q6P4F2; -.
DR TreeFam; TF354319; -.
DR PathwayCommons; Q6P4F2; -.
DR Reactome; R-HSA-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR Reactome; R-HSA-196108; Pregnenolone biosynthesis.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-2395516; Electron transport from NADPH to Ferredoxin.
DR Reactome; R-HSA-5579026; Defective CYP11A1 causes AICSR.
DR SignaLink; Q6P4F2; -.
DR BioGRID-ORCS; 112812; 456 hits in 1086 CRISPR screens.
DR ChiTaRS; FDX1L; human.
DR GenomeRNAi; 112812; -.
DR Pharos; Q6P4F2; Tdark.
DR PRO; PR:Q6P4F2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6P4F2; protein.
DR Bgee; ENSG00000267673; Expressed in prefrontal cortex and 100 other tissues.
DR ExpressionAtlas; Q6P4F2; baseline and differential.
DR Genevisible; Q6P4F2; HS.
DR GO; GO:1990229; C:iron-sulfur cluster assembly complex; IC:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0009055; F:electron transfer activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0022900; P:electron transport chain; IBA:GO_Central.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IC:ComplexPortal.
DR GO; GO:0140647; P:P450-containing electron transport chain; IEA:InterPro.
DR GO; GO:0051353; P:positive regulation of oxidoreductase activity; IBA:GO_Central.
DR CDD; cd00207; fer2; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR001055; Adrenodoxin.
DR InterPro; IPR018298; Adrenodoxin_Fe-S_BS.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR PANTHER; PTHR23426; PTHR23426; 1.
DR Pfam; PF00111; Fer2; 1.
DR PRINTS; PR00355; ADRENODOXIN.
DR SUPFAM; SSF54292; SSF54292; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS00814; ADX; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 3D-structure; Alternative splicing; Disease variant;
KW Electron transport; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW Primary mitochondrial disease; Reference proteome; Transit peptide;
KW Transport.
FT TRANSIT 1..55
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 56..186
FT /note="Ferredoxin-2, mitochondrial"
FT /id="PRO_0000325952"
FT DOMAIN 71..173
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT REGION 48..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 108
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465,
FT ECO:0007744|PDB:2Y5C"
FT BINDING 114
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465,
FT ECO:0007744|PDB:2Y5C"
FT BINDING 117
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465,
FT ECO:0007744|PDB:2Y5C"
FT BINDING 154
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465,
FT ECO:0007744|PDB:2Y5C"
FT VAR_SEQ 136..186
FT /note="EDDMLDMAPLLQENSRLGCQIVLTPELEGAEFTLPKITRNFYVDGHVPKPH
FT -> RTRGWAARLC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056826"
FT VARIANT 4
FT /note="M -> L (in MEOAL; unknown pathological significance;
FT expressed at low levels in fibroblasts and muscles from a
FT homozygous patient; dbSNP:rs587777600)"
FT /evidence="ECO:0000269|PubMed:24281368"
FT /id="VAR_082099"
FT VARIANT 144
FT /note="P -> L (in MEOAL; strongly reduced protein
FT expression in muscle in affected homozygous patients
FT compared to control individuals; dbSNP:rs888630930)"
FT /evidence="ECO:0000269|PubMed:30010796"
FT /id="VAR_082100"
FT CONFLICT 7
FT /note="S -> T (in Ref. 1; BAH13303)"
FT /evidence="ECO:0000305"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:2Y5C"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:2Y5C"
FT HELIX 93..99
FT /evidence="ECO:0007829|PDB:2Y5C"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:2Y5C"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:2Y5C"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:2Y5C"
FT HELIX 134..141
FT /evidence="ECO:0007829|PDB:2Y5C"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:2Y5C"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:2Y5C"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:2Y5C"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:2Y5C"
SQ SEQUENCE 186 AA; 19888 MW; 0268718ECF0F8E98 CRC64;
MHVMAASMAR GGVSARVLLQ AARGTWWNRP GGTSGSGEGV ALGTTRKFQA TGSRPAGEED
AGGPERPGDV VNVVFVDRSG QRIPVSGRVG DNVLHLAQRH GVDLEGACEA SLACSTCHVY
VSEDHLDLLP PPEEREDDML DMAPLLQENS RLGCQIVLTP ELEGAEFTLP KITRNFYVDG
HVPKPH
