LIAS_RAT
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 03-AUG-2022, entry version 116.
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 = (R)-
CC N(6)-dihydrolipoyl-L-lysyl-[protein] + 2 5'-deoxyadenosine + [[Fe-S]
CC cluster scaffold protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 L-
CC 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}.
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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 PaxDb; Q5XIH4; -.
DR PRIDE; Q5XIH4; -.
DR Ensembl; ENSRNOT00000003779; ENSRNOP00000003779; ENSRNOG00000002759.
DR GeneID; 305348; -.
DR KEGG; rno:305348; -.
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; 610833at2759; -.
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 tissues.
DR Genevisible; Q5XIH4; RN.
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:0102552; F:lipoyl synthase activity (acting on glycine-cleavage complex H protein; IEA:UniProtKB-EC.
DR GO; GO:0102553; F:lipoyl synthase activity (acting on pyruvate dehydrogenase E2 protein); IEA:UniProtKB-EC.
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:0009249; P:protein lipoylation; IEA:UniProtKB-UniRule.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00206; Lipoyl_synth; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR031691; LIAS_N.
DR InterPro; IPR003698; Lipoyl_synth.
DR InterPro; IPR007197; rSAM.
DR PANTHER; PTHR10949; PTHR10949; 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 SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR00510; lipA; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
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
