ADX_HUMAN
ID ADX_HUMAN Reviewed; 184 AA.
AC P10109; B0YJ14; Q53YD6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Adrenodoxin, mitochondrial;
DE AltName: Full=Adrenal ferredoxin;
DE AltName: Full=Ferredoxin-1;
DE AltName: Full=Hepatoredoxin;
DE Flags: Precursor;
GN Name=FDX1; Synonyms=ADX;
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 [GENOMIC DNA].
RX PubMed=3229285; DOI=10.1089/dna.1988.7.609;
RA Chang C.-Y., Wu D.-A., Lai C.-C., Miller W.L., Chung B.-C.;
RT "Cloning and structure of the human adrenodoxin gene.";
RL DNA 7:609-615(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3343244; DOI=10.1016/s0021-9258(18)69061-1;
RA Picado-Leonard J., Voutilainen R., Kao L.-C., Chung B.-C.,
RA Strauss J.F. III, Miller W.L.;
RT "Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in
RT JEG-3 cells.";
RL J. Biol. Chem. 263:3240-3244(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=2969697; DOI=10.1016/0003-9861(88)90303-7;
RA Mittal S., Zhu Y.-Z., Vickery L.E.;
RT "Molecular cloning and sequence analysis of human placental ferredoxin.";
RL Arch. Biochem. Biophys. 264:383-391(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=2340092; DOI=10.1089/dna.1990.9.205;
RA Chang C.-Y., Wu D.-A., Mohandas T.K., Chung B.-C.;
RT "Structure, sequence, chromosomal location, and evolution of the human
RT ferredoxin gene family.";
RL DNA Cell Biol. 9:205-212(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
RP CYCLIC VOLTAMMETRY.
RX PubMed=12699818; DOI=10.1016/s1567-5394(02)00188-3;
RA Johnson D., Norman S., Tuckey R.C., Martin L.L.;
RT "Electrochemical behaviour of human adrenodoxin on a pyrolytic graphite
RT electrode.";
RL Bioelectrochemistry 59:41-47(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
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 [14]
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 [15]
RP STRUCTURE BY NMR.
RX PubMed=1909889; DOI=10.1021/bi00101a024;
RA Skjeldal L., Markley J.L., Coghlan V.M., Vickery L.E.;
RT "1H NMR spectra of vertebrate [2Fe-2S] ferredoxins. Hyperfine resonances
RT suggest different electron delocalization patterns from plant
RT ferredoxins.";
RL Biochemistry 30:9078-9083(1991).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 61-184 IN COMPLEX WITH
RP IRON-SULFUR CLUSTER, AND COFACTOR.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human ferredoxin-1 (FDX1) in complex with iron-sulfur
RT cluster.";
RL Submitted (NOV-2010) to the PDB data bank.
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 62-175 IN COMPLEX WITH IRON-SULFUR
RP CLUSTER AND CYP11A1, FUNCTION, COFACTOR, AND INTERACTION WITH CYP11A1.
RX PubMed=21636783; DOI=10.1073/pnas.1019441108;
RA Strushkevich N., MacKenzie F., Cherkesova T., Grabovec I., Usanov S.,
RA Park H.W.;
RT "Structural basis for pregnenolone biosynthesis by the mitochondrial
RT monooxygenase system.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10139-10143(2011).
CC -!- FUNCTION: Essential for the synthesis of various steroid hormones
CC (PubMed:20547883, PubMed:21636783). Participates in the reduction of
CC mitochondrial cytochrome P450 for steroidogenesis (PubMed:20547883,
CC PubMed:21636783). Transfers electrons from adrenodoxin reductase to
CC CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain
CC cleavage (PubMed:20547883, PubMed:21636783). Does not form a ternary
CC complex with adrenodoxin reductase and CYP11A1 but shuttles between the
CC two enzymes to transfer electrons (By similarity).
CC {ECO:0000250|UniProtKB:P00257, ECO:0000269|PubMed:20547883,
CC ECO:0000269|PubMed:21636783}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:21636783, ECO:0000269|Ref.16};
CC Note=Binds 1 [2Fe-2S] cluster. {ECO:0000269|PubMed:21636783,
CC ECO:0000269|Ref.16};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Redox potential:
CC E(0) is -448 mV.;
CC -!- SUBUNIT: Interacts with CYP11A1. {ECO:0000269|PubMed:21636783,
CC ECO:0000269|Ref.16}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:20547883}.
CC -!- TISSUE SPECIFICITY: Highest levels in the adrenal gland (at protein
CC level). Also detected in kidney and testis (at protein level).
CC {ECO:0000269|PubMed:20547883}.
CC -!- SIMILARITY: Belongs to the adrenodoxin/putidaredoxin family.
CC {ECO:0000305}.
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DR EMBL; M23668; AAA50462.1; -; Genomic_DNA.
DR EMBL; J03548; AAA96806.1; -; mRNA.
DR EMBL; M18003; AAA76853.1; -; mRNA.
DR EMBL; M34788; AAA35829.1; -; mRNA.
DR EMBL; M34786; AAA35856.1; -; Genomic_DNA.
DR EMBL; M34784; AAA35856.1; JOINED; Genomic_DNA.
DR EMBL; M34785; AAA35855.1; -; Genomic_DNA.
DR EMBL; M34783; AAA35855.1; JOINED; Genomic_DNA.
DR EMBL; BT006681; AAP35327.1; -; mRNA.
DR EMBL; EF444978; ACA05992.1; -; Genomic_DNA.
DR EMBL; BC010284; AAH10284.1; -; mRNA.
DR EMBL; BC017063; AAH17063.1; -; mRNA.
DR CCDS; CCDS8344.1; -.
DR PIR; A31853; AXHU.
DR RefSeq; NP_004100.1; NM_004109.4.
DR PDB; 3N9Y; X-ray; 2.10 A; C/D=62-175.
DR PDB; 3N9Z; X-ray; 2.17 A; C/D=62-184.
DR PDB; 3NA0; X-ray; 2.50 A; C/D=88-155.
DR PDB; 3NA1; X-ray; 2.25 A; C/D=62-184.
DR PDB; 3P1M; X-ray; 2.54 A; A/B/C/D/E/F/G/H=61-184.
DR PDB; 7M8I; X-ray; 2.94 A; A/B/C=61-184.
DR PDBsum; 3N9Y; -.
DR PDBsum; 3N9Z; -.
DR PDBsum; 3NA0; -.
DR PDBsum; 3NA1; -.
DR PDBsum; 3P1M; -.
DR PDBsum; 7M8I; -.
DR AlphaFoldDB; P10109; -.
DR BMRB; P10109; -.
DR SMR; P10109; -.
DR BioGRID; 108521; 41.
DR IntAct; P10109; 12.
DR STRING; 9606.ENSP00000260270; -.
DR DrugBank; DB00648; Mitotane.
DR DrugCentral; P10109; -.
DR iPTMnet; P10109; -.
DR PhosphoSitePlus; P10109; -.
DR BioMuta; FDX1; -.
DR DMDM; 113471; -.
DR EPD; P10109; -.
DR jPOST; P10109; -.
DR MassIVE; P10109; -.
DR MaxQB; P10109; -.
DR PaxDb; P10109; -.
DR PeptideAtlas; P10109; -.
DR PRIDE; P10109; -.
DR ProteomicsDB; 52566; -.
DR TopDownProteomics; P10109; -.
DR Antibodypedia; 32013; 117 antibodies from 23 providers.
DR DNASU; 2230; -.
DR Ensembl; ENST00000260270.3; ENSP00000260270.2; ENSG00000137714.3.
DR GeneID; 2230; -.
DR KEGG; hsa:2230; -.
DR MANE-Select; ENST00000260270.3; ENSP00000260270.2; NM_004109.5; NP_004100.1.
DR UCSC; uc001pkx.4; human.
DR CTD; 2230; -.
DR DisGeNET; 2230; -.
DR GeneCards; FDX1; -.
DR HGNC; HGNC:3638; FDX1.
DR HPA; ENSG00000137714; Tissue enriched (adrenal).
DR MIM; 103260; gene.
DR neXtProt; NX_P10109; -.
DR OpenTargets; ENSG00000137714; -.
DR PharmGKB; PA28082; -.
DR VEuPathDB; HostDB:ENSG00000137714; -.
DR eggNOG; KOG3309; Eukaryota.
DR GeneTree; ENSGT00940000156916; -.
DR HOGENOM; CLU_082632_2_1_1; -.
DR InParanoid; P10109; -.
DR OMA; VFEDHIF; -.
DR OrthoDB; 1380051at2759; -.
DR PhylomeDB; P10109; -.
DR TreeFam; TF319845; -.
DR PathwayCommons; P10109; -.
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; P10109; -.
DR BioGRID-ORCS; 2230; 167 hits in 1069 CRISPR screens.
DR ChiTaRS; FDX1; human.
DR EvolutionaryTrace; P10109; -.
DR GeneWiki; Adrenal_ferredoxin; -.
DR GenomeRNAi; 2230; -.
DR Pharos; P10109; Tbio.
DR PRO; PR:P10109; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P10109; protein.
DR Bgee; ENSG00000137714; Expressed in adrenal tissue and 204 other tissues.
DR Genevisible; P10109; HS.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0009055; F:electron transfer activity; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; TAS:ProtInc.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:1904322; P:cellular response to forskolin; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR GO; GO:0022900; P:electron transport chain; IBA:GO_Central.
DR GO; GO:0042446; P:hormone biosynthetic process; IDA:UniProtKB.
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 GO; GO:0006694; P:steroid biosynthetic process; IEA:UniProtKB-KW.
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; Acetylation; Cholesterol metabolism;
KW Electron transport; Iron; Iron-sulfur; Lipid metabolism; Metal-binding;
KW Mitochondrion; Phosphoprotein; Reference proteome; Steroid metabolism;
KW Steroidogenesis; Sterol metabolism; Transit peptide; Transport.
FT TRANSIT 1..60
FT /note="Mitochondrion"
FT CHAIN 61..184
FT /note="Adrenodoxin, mitochondrial"
FT /id="PRO_0000000988"
FT DOMAIN 67..171
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT REGION 35..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 106
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 112
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 115
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 152
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 66
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 66
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 158
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:3P1M"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:3P1M"
FT HELIX 89..96
FT /evidence="ECO:0007829|PDB:3N9Y"
FT TURN 101..106
FT /evidence="ECO:0007829|PDB:3N9Y"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:3N9Y"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3N9Y"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:3N9Y"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:3N9Y"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:3N9Y"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:3N9Y"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:3N9Y"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:3P1M"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:3P1M"
FT HELIX 171..174
FT /evidence="ECO:0007829|PDB:3P1M"
SQ SEQUENCE 184 AA; 19393 MW; A234EC601136C85F CRC64;
MAAAGGARLL RAASAVLGGP AGRWLHHAGS RAGSSGLLRN RGPGGSAEAS RSLSVSARAR
SSSEDKITVH FINRDGETLT TKGKVGDSLL DVVVENNLDI DGFGACEGTL ACSTCHLIFE
DHIYEKLDAI TDEENDMLDL AYGLTDRSRL GCQICLTKSM DNMTVRVPET VADARQSIDV
GKTS
