ID LIPA_TALSN Reviewed; 422 AA. AC B8MLU5; DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot. DT 03-MAR-2009, sequence version 1. DT 02-SEP-2026, entry version 79. 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}; DE Flags: Precursor; GN ORFNames=TSTA_101110; OS Talaromyces stipitatus (strain ATCC 10500 / CBS 375.48 / QM 6759 / NRRL OS 1006) (Penicillium stipitatum). OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes; OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces; OC Talaromyces sect. Talaromyces. OX NCBI_TaxID=441959; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 10500 / CBS 375.48 / QM 6759 / NRRL 1006; RX PubMed=25676766; DOI=10.1128/genomea.01559-14; RA Nierman W.C., Fedorova-Abrams N.D., Andrianopoulos A.; RT "Genome sequence of the AIDS-associated pathogen Penicillium marneffei RT (ATCC18224) and its near taxonomic relative Talaromyces stipitatus RT (ATCC10500)."; RL Genome Announc. 3:E0155914-E0155914(2015). 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] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe- CC 2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) = [[Fe-S] CC cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl- CC [protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 CC L-methionine + 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 -!- 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; EQ962658; EED13871.1; -; Genomic_DNA. DR RefSeq; XP_002486109.1; XM_002486064.1. DR AlphaFoldDB; B8MLU5; -. DR SMR; B8MLU5; -. DR FunCoup; B8MLU5; 577. DR STRING; 441959.B8MLU5; -. DR GeneID; 8101799; -. DR VEuPathDB; FungiDB:TSTA_101110; -. DR eggNOG; KOG2672; Eukaryota. DR HOGENOM; CLU_033144_0_1_1; -. DR InParanoid; B8MLU5; -. DR OMA; PYCDIDF; -. DR OrthoDB; 3231at2759; -. DR PhylomeDB; B8MLU5; -. DR UniPathway; UPA00538; UER00593. DR Proteomes; UP000001745; Unassembled WGS sequence. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule. DR GO; GO:0016992; F:lipoate synthase activity; IEA:UniProtKB-UniRule. DR GO; GO:0009249; P:protein lipoylation; IEA:UniProtKB-UniRule. 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 InterPro; IPR058240; rSAM_sf. DR NCBIfam; TIGR00510; lipA; 1. DR NCBIfam; NF004019; PRK05481.1; 1. DR NCBIfam; NF009544; PRK12928.1; 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 SFLD; SFLDF00271; lipoyl_synthase; 1. DR SFLD; SFLDG01058; lipoyl_synthase_like; 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; Transit peptide. FT TRANSIT 1..34 FT /note="Mitochondrion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT CHAIN 35..422 FT /note="Lipoyl synthase, mitochondrial" FT /id="PRO_0000398294" FT DOMAIN 160..372 FT /note="Radical SAM core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266" FT REGION 37..70 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 37..48 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 146 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 151 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 157 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 177 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 181 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 184 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 383 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 422 AA; 46127 MW; 9F9C7823717AFD54 CRC64; MAASSTRLRC LYASSAPAWK KSPSQSIISL SRHYATTSST TPSLNPDESS SSSSSTIPKR RKTTTFRDKL NAGPSFADFV TGGNGNNASL DPEEAYALEK VMIPGPAGRK KEHTRLPSWL KTPIPDSTNY KRIKKDLRGL DLHTVCEEAR CPNISDCWGG SDKSAATATI MLMGDTCTRG CRFCSVKTLR TPGPLDPHEP ENTAEALSRW GLGDDLPDGG AHHFAETVIK IKQKAPGILV ECLTGDFAGD LDMVSLVAKS GLDVYAHNVE TVEALTPHVR DRRATFKQSL RVLEAAKRAK PSLITKTSMM LGFGETEDQL WDALRQLRAS NVDVVTFGQY MRPTKRHMAV HEYVTPDKFE LWRQRALEMG FLYVASGPLV RSSYKAGEAF IENVLKKRRG VGNTPGAEVA SAKDVPVDVL GK //