ADX_BOVIN
ID ADX_BOVIN Reviewed; 186 AA.
AC P00257; A5D9I2; P08498; P12713; Q32KZ0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Adrenodoxin, mitochondrial;
DE AltName: Full=Adrenal ferredoxin;
DE AltName: Full=Ferredoxin-1;
DE AltName: Full=Hepato-ferredoxin;
DE Flags: Precursor;
GN Name=FDX1; Synonyms=ADX;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2994043; DOI=10.1073/pnas.82.17.5705;
RA Okamura T., John M.E., Zuber M.X., Simpson E.R., Waterman M.R.;
RT "Molecular cloning and amino acid sequence of the precursor form of bovine
RT adrenodoxin: evidence for a previously unidentified COOH-terminal
RT peptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:5705-5709(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=2440863; DOI=10.1016/s0021-9258(18)61117-2;
RA Okamura T., Kagimoto M., Simpson E.R., Waterman M.R.;
RT "Multiple species of bovine adrenodoxin mRNA. Occurrence of two different
RT mitochondrial precursor sequences associated with the same mature
RT sequence.";
RL J. Biol. Chem. 262:10335-10338(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=2332422; DOI=10.1093/oxfordjournals.jbchem.a123015;
RA Sagara Y., Sawae H., Kimura A., Sagara-Nakano Y., Morohashi K., Miyoshi K.,
RA Horiuchi T.;
RT "Structural organization of the bovine adrenodoxin gene.";
RL J. Biochem. 107:77-83(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=1733795; DOI=10.1016/0020-711x(92)90260-8;
RA Matsuo Y., Tomita S., Tsuneoka Y., Furukawa A., Ichikawa Y.;
RT "Molecular cloning and nucleotide sequences of bovine hepato-ferredoxin
RT cDNA; identical primary structures of hepato- and adreno-ferredoxins.";
RL Int. J. Biochem. 24:289-295(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-102.
RX PubMed=2454231; DOI=10.1016/s0021-9258(18)68396-6;
RA Kagimoto M., Kagimoto K., Simpson E.R., Waterman M.R.;
RT "Transcription of the bovine adrenodoxin gene produces two species of mRNA
RT of which only one is translated into adrenodoxin.";
RL J. Biol. Chem. 263:8925-8928(1988).
RN [8]
RP PROTEIN SEQUENCE OF 59-172 (ISOFORM 1).
RX PubMed=4686920; DOI=10.1016/s0021-9258(19)44275-0;
RA Tanaka M., Haniu M., Yasunobu K.T., Kimura T.;
RT "The amino acid sequence of bovine adrenodoxin.";
RL J. Biol. Chem. 248:1141-1157(1973).
RN [9]
RP PROTEIN SEQUENCE OF 171-185.
RX PubMed=3395121; DOI=10.1016/0003-9861(88)90565-6;
RA Sakihama N., Hiwatashi A., Miyatake A., Shin M., Ichikawa Y.;
RT "Isolation and purification of mature bovine adrenocortical ferredoxin with
RT an elongated carboxyl end.";
RL Arch. Biochem. Biophys. 264:23-29(1988).
RN [10]
RP FUNCTION.
RX PubMed=6766943; DOI=10.1016/s0021-9258(19)85851-9;
RA Hanukoglu I., Jefcoate C.R.;
RT "Mitochondrial cytochrome P-450scc. Mechanism of electron transport by
RT adrenodoxin.";
RL J. Biol. Chem. 255:3057-3061(1980).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=3011431; DOI=10.1111/j.1432-1033.1986.tb09633.x;
RA Hanukoglu I., Hanukoglu Z.;
RT "Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and
RT adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for
RT membrane organization and gene regulation.";
RL Eur. J. Biochem. 157:27-31(1986).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 59-186 IN COMPLEX WITH ADRENODOXIN
RP REDUCTASE.
RX PubMed=11053423; DOI=10.1074/jbc.m008501200;
RA Mueller J.J., Lapko A., Bourenkov G., Ruckpaul K., Heinemann U.;
RT "Adrenodoxin reductase-adrenodoxin complex structure suggests electron
RT transfer path in steroid biosynthesis.";
RL J. Biol. Chem. 276:2786-2789(2001).
RN [13]
RP STRUCTURE BY NMR OF 59-186.
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 [14]
RP STRUCTURE BY NMR OF 59-186.
RX PubMed=12069587; DOI=10.1021/bi0160361;
RA Beilke D., Weiss R., Loehr F., Pristovsek P., Hannemann F., Bernhardt R.,
RA Rueterjans H.;
RT "A new electron transport mechanism in mitochondrial steroid hydroxylase
RT systems based on structural changes upon the reduction of adrenodoxin.";
RL Biochemistry 41:7969-7978(2002).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 63-166.
RX PubMed=9551550; DOI=10.1016/s0969-2126(98)00031-8;
RA Mueller A., Mueller J.J., Muller Y.A., Uhlmann H., Bernhardt R.,
RA Heinemann U.;
RT "New aspects of electron transfer revealed by the crystal structure of a
RT truncated bovine adrenodoxin, Adx(4-108).";
RL Structure 6:269-280(1998).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=10620322; DOI=10.1006/abbi.1999.1536;
RA Pikuleva I.A., Tesh K., Waterman M.R., Kim Y.;
RT "The tertiary structure of full-length bovine adrenodoxin suggests
RT functional dimers.";
RL Arch. Biochem. Biophys. 373:44-55(2000).
CC -!- FUNCTION: Essential for the synthesis of various steroid hormones.
CC Participates in the reduction of mitochondrial cytochrome P450 for
CC steroidogenesis. Transfers electrons from adrenodoxin reductase to
CC CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain
CC cleavage to produce pregnenolone, the precursor of most steroid
CC hormones. Does not form a ternary complex with adrenodoxin reductase
CC and CYP11A1 but shuttles between the two enzymes to transfer electrons.
CC {ECO:0000269|PubMed:6766943}.
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Note=Binds 1 [2Fe-2S] cluster.;
CC -!- SUBUNIT: Interacts with CYP11A1. {ECO:0000250|UniProtKB:P10109}.
CC -!- INTERACTION:
CC P00257; P08165: FDXR; NbExp=2; IntAct=EBI-593992, EBI-593948;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P00257-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00257-2; Sequence=VSP_016558;
CC -!- TISSUE SPECIFICITY: Detected in adrenal cortex and corpus luteum (at
CC protein level). {ECO:0000269|PubMed:3011431}.
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; M11746; AAA30357.1; -; mRNA.
DR EMBL; M16934; AAA30358.1; -; mRNA.
DR EMBL; D00467; BAA00362.1; -; mRNA.
DR EMBL; D00471; BAA00363.1; -; Genomic_DNA.
DR EMBL; M19656; AAA78950.1; -; Genomic_DNA.
DR EMBL; M19474; AAA78950.1; JOINED; Genomic_DNA.
DR EMBL; BT030601; ABQ13041.1; -; mRNA.
DR EMBL; BC109849; AAI09850.1; -; mRNA.
DR EMBL; S78831; AAB21264.1; -; mRNA.
DR PIR; JX0094; AXBO.
DR RefSeq; NP_851354.1; NM_181011.2. [P00257-2]
DR PDB; 1AYF; X-ray; 1.85 A; A/B=62-166.
DR PDB; 1CJE; X-ray; 2.50 A; A/B/C/D=60-186.
DR PDB; 1E6E; X-ray; 2.30 A; B/D=59-186.
DR PDB; 1L6U; NMR; -; A=59-186.
DR PDB; 1L6V; NMR; -; A=59-186.
DR PDB; 2BT6; X-ray; 1.50 A; A/B=63-166.
DR PDB; 2JQR; NMR; -; B=62-166.
DR PDBsum; 1AYF; -.
DR PDBsum; 1CJE; -.
DR PDBsum; 1E6E; -.
DR PDBsum; 1L6U; -.
DR PDBsum; 1L6V; -.
DR PDBsum; 2BT6; -.
DR PDBsum; 2JQR; -.
DR AlphaFoldDB; P00257; -.
DR BMRB; P00257; -.
DR SMR; P00257; -.
DR IntAct; P00257; 2.
DR STRING; 9913.ENSBTAP00000015660; -.
DR iPTMnet; P00257; -.
DR PaxDb; P00257; -.
DR PRIDE; P00257; -.
DR Ensembl; ENSBTAT00000015660; ENSBTAP00000015660; ENSBTAG00000011793. [P00257-1]
DR GeneID; 281157; -.
DR KEGG; bta:281157; -.
DR CTD; 2230; -.
DR VEuPathDB; HostDB:ENSBTAG00000011793; -.
DR eggNOG; KOG3309; Eukaryota.
DR GeneTree; ENSGT00940000156916; -.
DR HOGENOM; CLU_082632_2_1_1; -.
DR InParanoid; P00257; -.
DR OMA; VFEDHIF; -.
DR OrthoDB; 1380051at2759; -.
DR TreeFam; TF319845; -.
DR Reactome; R-BTA-1362409; Mitochondrial iron-sulfur cluster biogenesis.
DR EvolutionaryTrace; P00257; -.
DR Proteomes; UP000009136; Chromosome 15.
DR Bgee; ENSBTAG00000011793; Expressed in diaphragm and 104 other tissues.
DR ExpressionAtlas; P00257; baseline and differential.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0009055; F:electron transfer activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; TAS:AgBase.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:AgBase.
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; ISS:UniProtKB.
DR GO; GO:0022900; P:electron transport chain; IDA:UniProtKB.
DR GO; GO:0042446; P:hormone biosynthetic process; ISS: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:0022904; P:respiratory electron transport chain; IDA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; TAS:UniProtKB.
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; Alternative splicing;
KW Cholesterol metabolism; Direct protein sequencing; Electron transport;
KW Iron; Iron-sulfur; Lipid metabolism; Metal-binding; Mitochondrion;
KW Phosphoprotein; Reference proteome; Steroid metabolism; Steroidogenesis;
KW Sterol metabolism; Transit peptide; Transport.
FT TRANSIT 1..58
FT /note="Mitochondrion"
FT CHAIN 59..186
FT /note="Adrenodoxin, mitochondrial"
FT /id="PRO_0000000986"
FT DOMAIN 65..169
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 104
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 110
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 113
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT BINDING 150
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 64
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 64
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 156
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P46656"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10109"
FT VAR_SEQ 24..60
FT /note="ARPRAGAGGLRGSRGPGLGGGAVATRTLSVSGRAQSS -> LKSSQFIKVSC
FT SGSWISAAQRAFICYSKSGNITCFLR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2440863"
FT /id="VSP_016558"
FT CONFLICT 6
FT /note="L -> M (in Ref. 6; AAI09850)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="A -> V (in Ref. 1; AAA30357)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="E -> Q (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="D -> N (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="D -> N (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:2BT6"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1L6V"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:2BT6"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:2BT6"
FT TURN 99..104
FT /evidence="ECO:0007829|PDB:2BT6"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:2BT6"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:2BT6"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:2BT6"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:2BT6"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:1L6V"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:2BT6"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:2BT6"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:2BT6"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:2BT6"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:1E6E"
SQ SEQUENCE 186 AA; 19756 MW; F0F2EE027BFAC371 CRC64;
MAARLLRVAS AALGDTAGRW RLLARPRAGA GGLRGSRGPG LGGGAVATRT LSVSGRAQSS
SEDKITVHFI NRDGETLTTK GKIGDSLLDV VVQNNLDIDG FGACEGTLAC STCHLIFEQH
IFEKLEAITD EENDMLDLAY GLTDRSRLGC QICLTKAMDN MTVRVPDAVS DARESIDMGM
NSSKIE
