ID MET8_YEAST Reviewed; 274 AA. AC P15807; D6VQK9; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 08-NOV-2023, entry version 190. DE RecName: Full=Siroheme biosynthesis protein MET8 {ECO:0000303|PubMed:10051442}; DE Includes: DE RecName: Full=Precorrin-2 dehydrogenase {ECO:0000303|PubMed:11980703}; DE EC=1.3.1.76 {ECO:0000269|PubMed:11980703}; DE Includes: DE RecName: Full=Sirohydrochlorin ferrochelatase {ECO:0000303|PubMed:11980703}; DE EC=4.99.1.4 {ECO:0000269|PubMed:11980703}; GN Name=MET8 {ECO:0000303|PubMed:2408020}; OrderedLocusNames=YBR213W; GN ORFNames=YBR1461; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 26786 / X2180-1A; RX PubMed=2408020; DOI=10.1093/nar/18.3.659; RA Cherest H., Thomas D., Surdin-Kerjan Y.; RT "Nucleotide sequence of the MET8 gene of Saccharomyces cerevisiae."; RL Nucleic Acids Res. 18:659-659(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x; RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H., RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., RA Mewes H.-W., Kleine K.; RT "Complete DNA sequence of yeast chromosome II."; RL EMBO J. 13:5795-5809(1994). RN [3] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP FUNCTION. RX PubMed=10051442; DOI=10.1042/bj3380701; RA Raux E., McVeigh T., Peters S.E., Leustek T., Warren M.J.; RT "The role of Saccharomyces cerevisiae Met1p and Met8p in sirohaem and RT cobalamin biosynthesis."; RL Biochem. J. 338:701-708(1999). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 11-274 IN COMPLEX WITH NAD, RP SUBUNIT, MUTAGENESIS OF GLY-22; ASP-141 AND HIS-237, AND CATALYTIC RP ACTIVITY. RX PubMed=11980703; DOI=10.1093/emboj/21.9.2068; RA Schubert H.L., Raux E., Brindley A.A., Leech H.K., Wilson K.S., Hill C.P., RA Warren M.J.; RT "The structure of Saccharomyces cerevisiae Met8p, a bifunctional RT dehydrogenase and ferrochelatase."; RL EMBO J. 21:2068-2075(2002). CC -!- FUNCTION: Catalyzes the conversion of precorrin-2 into siroheme. This CC reaction consist of the NAD-dependent oxidation of precorrin-2 into CC sirohydrochlorin and its subsequent ferrochelation into siroheme. CC {ECO:0000269|PubMed:10051442}. CC -!- CATALYTIC ACTIVITY: CC Reaction=NAD(+) + precorrin-2 = 2 H(+) + NADH + sirohydrochlorin; CC Xref=Rhea:RHEA:15613, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58351, ChEBI:CHEBI:58827; EC=1.3.1.76; CC Evidence={ECO:0000269|PubMed:11980703}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15614; CC Evidence={ECO:0000269|PubMed:11980703}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 H(+) + siroheme = Fe(2+) + sirohydrochlorin; CC Xref=Rhea:RHEA:24360, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, CC ChEBI:CHEBI:58351, ChEBI:CHEBI:60052; EC=4.99.1.4; CC Evidence={ECO:0000269|PubMed:11980703}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24361; CC Evidence={ECO:0000269|PubMed:11980703}; CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; siroheme from sirohydrochlorin: step 1/1. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11980703}. CC -!- SIMILARITY: Belongs to the precorrin-2 dehydrogenase / sirohydrochlorin CC ferrochelatase family. MET8 subfamily. {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; X17271; CAA35173.1; -; Genomic_DNA. DR EMBL; Z36082; CAA85177.1; -; Genomic_DNA. DR EMBL; BK006936; DAA07329.1; -; Genomic_DNA. DR PIR; S20155; S20155. DR RefSeq; NP_009772.1; NM_001178561.1. DR PDB; 1KYQ; X-ray; 2.20 A; A/B/C=1-274. DR PDBsum; 1KYQ; -. DR AlphaFoldDB; P15807; -. DR SMR; P15807; -. DR BioGRID; 32910; 113. DR DIP; DIP-4944N; -. DR IntAct; P15807; 2. DR MINT; P15807; -. DR STRING; 4932.YBR213W; -. DR iPTMnet; P15807; -. DR MaxQB; P15807; -. DR PaxDb; 4932-YBR213W; -. DR PeptideAtlas; P15807; -. DR EnsemblFungi; YBR213W_mRNA; YBR213W; YBR213W. DR GeneID; 852514; -. DR KEGG; sce:YBR213W; -. DR AGR; SGD:S000000417; -. DR SGD; S000000417; MET8. DR VEuPathDB; FungiDB:YBR213W; -. DR eggNOG; ENOG502RYIW; Eukaryota. DR HOGENOM; CLU_011276_8_5_1; -. DR InParanoid; P15807; -. DR OMA; PTGCKLT; -. DR OrthoDB; 296644at2759; -. DR BioCyc; MetaCyc:G3O-29150-MONOMER; -. DR BioCyc; YEAST:G3O-29150-MONOMER; -. DR BRENDA; 1.3.1.76; 984. DR BRENDA; 4.99.1.4; 984. DR UniPathway; UPA00262; UER00222. DR UniPathway; UPA00262; UER00376. DR BioGRID-ORCS; 852514; 1 hit in 10 CRISPR screens. DR EvolutionaryTrace; P15807; -. DR PRO; PR:P15807; -. DR Proteomes; UP000002311; Chromosome II. DR RNAct; P15807; Protein. DR GO; GO:0004325; F:ferrochelatase activity; IDA:SGD. DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IDA:SGD. DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC. DR GO; GO:0019354; P:siroheme biosynthetic process; IMP:SGD. DR GO; GO:0000103; P:sulfate assimilation; IMP:SGD. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR028161; Met8. DR InterPro; IPR028162; Met8_C. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR028281; Sirohaem_synthase_central. DR PANTHER; PTHR35330; SIROHEME BIOSYNTHESIS PROTEIN MET8; 1. DR PANTHER; PTHR35330:SF1; SIROHEME BIOSYNTHESIS PROTEIN MET8; 1. DR Pfam; PF13241; NAD_binding_7; 1. DR Pfam; PF14823; Sirohm_synth_C; 1. DR Pfam; PF14824; Sirohm_synth_M; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF75615; Siroheme synthase middle domains-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Lyase; Multifunctional enzyme; NAD; Oxidoreductase; KW Porphyrin biosynthesis; Reference proteome. FT CHAIN 1..274 FT /note="Siroheme biosynthesis protein MET8" FT /id="PRO_0000096446" FT ACT_SITE 141 FT /note="Proton acceptor" FT /evidence="ECO:0000255" FT BINDING 23..24 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:11980703" FT BINDING 43..45 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:11980703" FT BINDING 93 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:11980703" FT MUTAGEN 22 FT /note="G->D: Loss of dehydrogenase activity. No effect on FT chelatase activity." FT /evidence="ECO:0000269|PubMed:11980703" FT MUTAGEN 141 FT /note="D->A: Loss of chelatase and dehydrogenase activity." FT /evidence="ECO:0000269|PubMed:11980703" FT MUTAGEN 237 FT /note="H->A: No effect on dehydrogenase or chelatase FT activity." FT /evidence="ECO:0000269|PubMed:11980703" FT CONFLICT 15 FT /note="K -> R (in Ref. 5)" FT /evidence="ECO:0000305" FT CONFLICT 33 FT /note="I -> M (in Ref. 5)" FT /evidence="ECO:0000305" FT CONFLICT 61 FT /note="E -> K (in Ref. 5)" FT /evidence="ECO:0000305" FT CONFLICT 102 FT /note="D -> N (in Ref. 5)" FT /evidence="ECO:0000305" FT STRAND 5..9 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 15..22 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 23..32 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 33..35 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 38..46 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 50..54 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 56..58 FT /evidence="ECO:0007829|PDB:1KYQ" FT TURN 68..70 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 86..89 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 95..98 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 107..112 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 117..131 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 135..139 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 143..145 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 146..149 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:1KYQ" FT TURN 157..159 FT /evidence="ECO:0007829|PDB:1KYQ" FT STRAND 160..169 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 171..188 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 193..210 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 214..216 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 217..235 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 241..252 FT /evidence="ECO:0007829|PDB:1KYQ" FT TURN 253..256 FT /evidence="ECO:0007829|PDB:1KYQ" FT HELIX 264..270 FT /evidence="ECO:0007829|PDB:1KYQ" SQ SEQUENCE 274 AA; 31918 MW; 0EE9A6DE8A43673E CRC64; MVKSLQLAHQ LKDKKILLIG GGEVGLTRLY KLIPTGCKLT LVSPDLHKSI IPKFGKFIQN EDQPDYREDA KRFINPNWDP TKNEIYEYIR SDFKDEYLDL EDENDAWYII MTCIPDHPES ARIYHLCKER FGKQQLVNVA DKPDLCDFYF GANLEIGDRL QILISTNGLS PRFGALVRDE IRNLFTQMGD LALEDAVVKL GELRRGIRLL APDDKDVKYR MDWARRCTDL FGIQHCHNID VKRLLDLFKV MFQEQNCSLQ FPPRERLLSE YCSS //