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 27-MAR-2024, entry version 195. 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; 9913-ENSBTAP00000015660; -. DR Ensembl; ENSBTAT00000015660.6; ENSBTAP00000015660.5; ENSBTAG00000011793.6. [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; TPMEEDM; -. DR OrthoDB; 36668at2759; -. DR TreeFam; TF319845; -. DR Reactome; R-BTA-1362409; Mitochondrial iron-sulfur cluster biogenesis. DR Reactome; R-BTA-196108; Pregnenolone biosynthesis. DR Reactome; R-BTA-211976; Endogenous sterols. DR Reactome; R-BTA-2395516; Electron transport from NADPH to Ferredoxin. DR EvolutionaryTrace; P00257; -. DR Proteomes; UP000009136; Chromosome 15. DR Bgee; ENSBTAG00000011793; Expressed in diaphragm and 104 other cell types or 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: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: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:SF26; ADRENODOXIN, MITOCHONDRIAL; 1. DR PANTHER; PTHR23426; FERREDOXIN/ADRENODOXIN; 1. DR Pfam; PF00111; Fer2; 1. DR PRINTS; PR00355; ADRENODOXIN. DR SUPFAM; SSF54292; 2Fe-2S ferredoxin-like; 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 //