ID LIAS_CAEEL Reviewed; 354 AA. AC Q21452; DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 149. DE RecName: Full=Lipoyl synthase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03123}; DE EC=2.8.1.8 {ECO:0000255|HAMAP-Rule:MF_03123}; DE AltName: Full=Lipoate synthase {ECO:0000255|HAMAP-Rule:MF_03123}; DE Short=LS {ECO:0000255|HAMAP-Rule:MF_03123}; DE Short=Lip-syn {ECO:0000255|HAMAP-Rule:MF_03123}; DE AltName: Full=Lipoic acid synthase {ECO:0000255|HAMAP-Rule:MF_03123}; GN ORFNames=M01F1.3; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for investigating RT biology."; RL Science 282:2012-2018(1998). CC -!- FUNCTION: Catalyzes the radical-mediated insertion of two sulfur atoms CC into the C-6 and C-8 positions of the octanoyl moiety bound to the CC lipoyl domains of lipoate-dependent enzymes, thereby converting the CC octanoylated domains into lipoylated derivatives. {ECO:0000255|HAMAP- CC Rule:MF_03123}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[[Fe-S] cluster scaffold protein carrying a second [4Fe- CC 4S](2+) cluster] + 4 H(+) + N(6)-octanoyl-L-lysyl-[protein] + 2 CC oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine = 2 5'- CC deoxyadenosine + [[Fe-S] cluster scaffold protein] + 4 Fe(3+) + 2 CC hydrogen sulfide + 2 L-methionine + N(6)-[(R)-dihydrolipoyl]-L-lysyl- CC [protein] + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:16585, CC Rhea:RHEA-COMP:9928, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, CC Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:14568, Rhea:RHEA-COMP:14569, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:29034, CC ChEBI:CHEBI:29919, ChEBI:CHEBI:33722, ChEBI:CHEBI:33737, CC ChEBI:CHEBI:33738, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:78809, ChEBI:CHEBI:83100; EC=2.8.1.8; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03123}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03123}; CC Note=Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine. CC {ECO:0000255|HAMAP-Rule:MF_03123}; CC -!- PATHWAY: Protein modification; protein lipoylation via endogenous CC pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier- CC protein]: step 2/2. {ECO:0000255|HAMAP-Rule:MF_03123}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03123}. CC -!- MISCELLANEOUS: This protein may be expected to contain an N-terminal CC transit peptide but none has been predicted. {ECO:0000255|HAMAP- CC Rule:MF_03123}. CC -!- SIMILARITY: Belongs to the radical SAM superfamily. Lipoyl synthase CC family. {ECO:0000255|HAMAP-Rule:MF_03123}. 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; Z46381; CAA86516.1; -; Genomic_DNA. DR PIR; T23655; T23655. DR RefSeq; NP_497722.3; NM_065321.6. DR AlphaFoldDB; Q21452; -. DR SMR; Q21452; -. DR BioGRID; 532131; 10. DR STRING; 6239.M01F1.3.3; -. DR EPD; Q21452; -. DR PaxDb; 6239-M01F1-3-1; -. DR PeptideAtlas; Q21452; -. DR EnsemblMetazoa; M01F1.3.1; M01F1.3.1; WBGene00010809. DR EnsemblMetazoa; M01F1.3.2; M01F1.3.2; WBGene00010809. DR GeneID; 3564813; -. DR KEGG; cel:CELE_M01F1.3; -. DR UCSC; M01F1.3.1; c. elegans. DR AGR; WB:WBGene00010809; -. DR WormBase; M01F1.3; CE01031; WBGene00010809; -. DR eggNOG; KOG2672; Eukaryota. DR GeneTree; ENSGT00390000006234; -. DR HOGENOM; CLU_033144_1_2_1; -. DR InParanoid; Q21452; -. DR OMA; PYCDIDF; -. DR OrthoDB; 575at2759; -. DR PhylomeDB; Q21452; -. DR Reactome; R-CEL-389661; Glyoxylate metabolism and glycine degradation. DR UniPathway; UPA00538; UER00593. DR PRO; PR:Q21452; -. DR Proteomes; UP000001940; Chromosome III. DR Bgee; WBGene00010809; Expressed in larva and 4 other cell types or tissues. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule. DR GO; GO:0016992; F:lipoate synthase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0009107; P:lipoate biosynthetic process; IBA:GO_Central. DR CDD; cd01335; Radical_SAM; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR HAMAP; MF_00206; Lipoyl_synth; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR006638; Elp3/MiaA/NifB-like_rSAM. DR InterPro; IPR031691; LIAS_N. DR InterPro; IPR003698; Lipoyl_synth. DR InterPro; IPR007197; rSAM. DR NCBIfam; TIGR00510; lipA; 1. DR PANTHER; PTHR10949; LIPOYL SYNTHASE; 1. DR PANTHER; PTHR10949:SF0; LIPOYL SYNTHASE, MITOCHONDRIAL; 1. DR Pfam; PF16881; LIAS_N; 1. DR Pfam; PF04055; Radical_SAM; 1. DR PIRSF; PIRSF005963; Lipoyl_synth; 1. DR SFLD; SFLDF00271; lipoyl_synthase; 1. DR SFLD; SFLDS00029; Radical_SAM; 1. DR SMART; SM00729; Elp3; 1. DR SUPFAM; SSF102114; Radical SAM enzymes; 1. DR PROSITE; PS51918; RADICAL_SAM; 1. PE 3: Inferred from homology; KW 4Fe-4S; Iron; Iron-sulfur; Metal-binding; Mitochondrion; KW Reference proteome; S-adenosyl-L-methionine; Transferase. FT CHAIN 1..354 FT /note="Lipoyl synthase, mitochondrial" FT /id="PRO_0000398228" FT DOMAIN 107..326 FT /note="Radical SAM core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266" FT BINDING 91 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT BINDING 96 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT BINDING 102 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT BINDING 122 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /ligand_note="4Fe-4S-S-AdoMet" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT BINDING 126 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /ligand_note="4Fe-4S-S-AdoMet" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT BINDING 129 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /ligand_note="4Fe-4S-S-AdoMet" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT BINDING 337 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" SQ SEQUENCE 354 AA; 39767 MW; 5428CFA42A7FCDEE CRC64; MLARVWVRGL AATKKKPQVL VKDGPSLQDF ISSASVAEAV EKYEGKLKLE KGDRRLRLPP WLKKEKILPS ENENVSRLKK QLKHLKLATV CQEARCPNLG ECWGGSDDSL ATATIMLMGD TCTRGCKFCS VKTARAPPPL DPMEPENTST AVASWGVEYI VLTSVDRDDL PDGGADHLRK TVQLMKLKKP ELLIECLLPD FAGDKISVEK MATSGLDVYA HNIETVERLT PWVRDPRAKY RQSLDALRYA KEVSPKLITK TSIMLGLGEA EDEIKQCLAD LRASNVDVVT FGQYMQPTKR HLLVKEWVTP EKFDQWAEYS KKLGFLYVAS GPLVRSSYKA GEFYLKNVLR NRQN //