ID LIAS_RAT Reviewed; 373 AA. AC Q5XIH4; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 1. DT 24-JAN-2024, entry version 123. 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 Name=Lias; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; 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). 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 -!- 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; BC083708; AAH83708.1; -; mRNA. DR RefSeq; NP_001012037.1; NM_001012037.1. DR AlphaFoldDB; Q5XIH4; -. DR SMR; Q5XIH4; -. DR STRING; 10116.ENSRNOP00000003779; -. DR iPTMnet; Q5XIH4; -. DR PhosphoSitePlus; Q5XIH4; -. DR SwissPalm; Q5XIH4; -. DR PaxDb; 10116-ENSRNOP00000003779; -. DR Ensembl; ENSRNOT00000003779.5; ENSRNOP00000003779.3; ENSRNOG00000002759.5. DR Ensembl; ENSRNOT00055030457; ENSRNOP00055024511; ENSRNOG00055017981. DR Ensembl; ENSRNOT00060027312; ENSRNOP00060021910; ENSRNOG00060015945. DR Ensembl; ENSRNOT00065022100; ENSRNOP00065017132; ENSRNOG00065013434. DR GeneID; 305348; -. DR KEGG; rno:305348; -. DR AGR; RGD:1307270; -. DR CTD; 11019; -. DR RGD; 1307270; Lias. DR eggNOG; KOG2672; Eukaryota. DR GeneTree; ENSGT00390000006234; -. DR HOGENOM; CLU_033144_2_0_1; -. DR InParanoid; Q5XIH4; -. DR OMA; PYCDIDF; -. DR OrthoDB; 575at2759; -. DR PhylomeDB; Q5XIH4; -. DR TreeFam; TF300817; -. DR Reactome; R-RNO-389661; Glyoxylate metabolism and glycine degradation. DR UniPathway; UPA00538; UER00593. DR PRO; PR:Q5XIH4; -. DR Proteomes; UP000002494; Chromosome 14. DR Bgee; ENSRNOG00000002759; Expressed in heart and 20 other cell types or tissues. DR GO; GO:0005739; C:mitochondrion; ISO:RGD. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule. DR GO; GO:0016992; F:lipoate synthase activity; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006954; P:inflammatory response; ISO:RGD. DR GO; GO:0009107; P:lipoate biosynthetic process; ISO:RGD. DR GO; GO:0001843; P:neural tube closure; ISO:RGD. DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD. DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD. 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; SFLDG01058; lipoyl_synthase_like; 1. DR SMART; SM00729; Elp3; 1. DR SUPFAM; SSF102114; Radical SAM enzymes; 1. DR PROSITE; PS51918; RADICAL_SAM; 1. DR Genevisible; Q5XIH4; RN. PE 2: Evidence at transcript level; KW 4Fe-4S; Iron; Iron-sulfur; Metal-binding; Mitochondrion; KW Reference proteome; S-adenosyl-L-methionine; Transferase; Transit peptide. FT TRANSIT 1..26 FT /note="Mitochondrion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03123" FT CHAIN 27..373 FT /note="Lipoyl synthase, mitochondrial" FT /id="PRO_0000332311" FT DOMAIN 121..340 FT /note="Radical SAM core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266" FT BINDING 105 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 110 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 116 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 136 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 140 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 143 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 351 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 373 AA; 41874 MW; F2108A035F9C7B14 CRC64; MALRCWDAAR SLGSRIFGRY ACSVRALSSL PDEKKKFLHN GPDLQDFVSG DLADKSTWDD YKGNLKRQKG ERLRLPPWLK TKIPMGKNYN KLKNTLRNLN LHTVCEEARC PNIGECWGGG EYATATATIM LMGDTCTRGC RFCSVKTARN PPPLDPSEPD NTARAIAEWG LDYVVLTSVD RDDVVDGGAE HIAKTVSCLK ERNPKILVEC LTPDFRGDLR AVEKVALSGL DVYAHNVETV PELQRKVRDP RANFDQSLRV LKHAKEVQPD VVSKTSIMLG LGETDEQVYA TMKALRAADV DCLTLGQYMQ PTKRHLKVEE YVTPEKFKYW EEVGNELGFH YTASGPLVRS SYKAGEFFLK NLVAKRKTKV SKV //