GenomeNet

Database: UniProt
Entry: P10109
LinkDB: P10109
Original site: P10109 
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   29-SEP-2021, entry version 201.
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;
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:49601;
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}.
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; 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   BMRB; P10109; -.
DR   SMR; P10109; -.
DR   BioGRID; 108521; 38.
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; 116 antibodies.
DR   DNASU; 2230; -.
DR   Ensembl; ENST00000260270; ENSP00000260270; ENSG00000137714.
DR   GeneID; 2230; -.
DR   KEGG; hsa:2230; -.
DR   UCSC; uc001pkx.4; human.
DR   CTD; 2230; -.
DR   DisGeNET; 2230; -.
DR   GeneCards; FDX1; -.
DR   HGNC; HGNC:3638; FDX1.
DR   HPA; ENSG00000137714; Tissue enhanced (adrenal gland, seminal vesicle).
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; VMENAIR; -.
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   BioGRID-ORCS; 2230; 162 hits in 1005 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 metanephros and 223 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:0042446; P:hormone biosynthetic process; IDA:UniProtKB.
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   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   METAL           106
FT                   /note="Iron-sulfur (2Fe-2S)"
FT   METAL           112
FT                   /note="Iron-sulfur (2Fe-2S)"
FT   METAL           115
FT                   /note="Iron-sulfur (2Fe-2S)"
FT   METAL           152
FT                   /note="Iron-sulfur (2Fe-2S)"
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
//
DBGET integrated database retrieval system