ID A0A351XP33_9GAMM Unreviewed; 462 AA. AC A0A351XP33; DT 07-NOV-2018, integrated into UniProtKB/TrEMBL. DT 07-NOV-2018, sequence version 1. DT 24-JUL-2024, entry version 23. DE RecName: Full=Siroheme synthase {ECO:0000256|HAMAP-Rule:MF_01646}; DE Includes: DE RecName: Full=Uroporphyrinogen-III C-methyltransferase {ECO:0000256|HAMAP-Rule:MF_01646}; DE Short=Urogen III methylase {ECO:0000256|HAMAP-Rule:MF_01646}; DE EC=2.1.1.107 {ECO:0000256|HAMAP-Rule:MF_01646}; DE AltName: Full=SUMT {ECO:0000256|HAMAP-Rule:MF_01646}; DE AltName: Full=Uroporphyrinogen III methylase {ECO:0000256|HAMAP-Rule:MF_01646}; DE Short=UROM {ECO:0000256|HAMAP-Rule:MF_01646}; DE Includes: DE RecName: Full=Precorrin-2 dehydrogenase {ECO:0000256|HAMAP-Rule:MF_01646}; DE EC=1.3.1.76 {ECO:0000256|HAMAP-Rule:MF_01646}; DE Includes: DE RecName: Full=Sirohydrochlorin ferrochelatase {ECO:0000256|HAMAP-Rule:MF_01646}; DE EC=4.99.1.4 {ECO:0000256|HAMAP-Rule:MF_01646}; GN Name=cobA {ECO:0000313|EMBL:HAO70285.1}; GN Synonyms=cysG {ECO:0000256|HAMAP-Rule:MF_01646}; GN ORFNames=DCG40_01275 {ECO:0000313|EMBL:HAD99074.1}, DCG46_00560 GN {ECO:0000313|EMBL:HAE70079.1}, DCL02_00290 GN {ECO:0000313|EMBL:HAG47336.1}, DCM52_05025 GN {ECO:0000313|EMBL:HAP92831.1}, DCQ55_01270 GN {ECO:0000313|EMBL:HAO44475.1}, DCQ62_05030 GN {ECO:0000313|EMBL:HAO53896.1}, DCQ65_01625 GN {ECO:0000313|EMBL:HAO70285.1}, DCQ66_00010 GN {ECO:0000313|EMBL:HAP44802.1}, DCQ71_02410 GN {ECO:0000313|EMBL:HAP05563.1}, DCQ74_02855 GN {ECO:0000313|EMBL:HAO97890.1}, DD382_04285 GN {ECO:0000313|EMBL:HBN58491.1}, DDW63_04190 GN {ECO:0000313|EMBL:HBG03696.1}, DEP15_05360 GN {ECO:0000313|EMBL:HCA68786.1}, DEU86_04000 GN {ECO:0000313|EMBL:HCH58704.1}, DGE70_04340 GN {ECO:0000313|EMBL:HCV74928.1}, DHI05_01315 GN {ECO:0000313|EMBL:HCW71725.1}; OS Gammaproteobacteria bacterium. OC Bacteria; Pseudomonadota; Gammaproteobacteria. OX NCBI_TaxID=1913989 {ECO:0000313|EMBL:HAO70285.1, ECO:0000313|Proteomes:UP000258990}; RN [1] {ECO:0000313|Proteomes:UP000257415, ECO:0000313|Proteomes:UP000257813} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=UBA10975 {ECO:0000313|EMBL:HBG03696.1}, UBA11104 RC {ECO:0000313|EMBL:HAP92831.1}, UBA11330 {ECO:0000313|EMBL:HAE70079.1}, RC UBA11335 {ECO:0000313|EMBL:HAD99074.1}, UBA8370 RC {ECO:0000313|EMBL:HAP44802.1}, UBA8371 {ECO:0000313|EMBL:HAO70285.1}, RC UBA8375 {ECO:0000313|EMBL:HAO53896.1}, UBA8376 RC {ECO:0000313|EMBL:HAO44475.1}, UBA8378 {ECO:0000313|EMBL:HAO97890.1}, RC UBA8379 {ECO:0000313|EMBL:HAP05563.1}, UBA8678 RC {ECO:0000313|EMBL:HCW71725.1}, UBA9056 {ECO:0000313|EMBL:HCH58704.1}, RC UBA9070 {ECO:0000313|EMBL:HCV74928.1}, UBA9316 RC {ECO:0000313|EMBL:HCA68786.1}, UBA9326 {ECO:0000313|EMBL:HBN58491.1}, RC and UBA9928 {ECO:0000313|EMBL:HAG47336.1}; RX PubMed=30148503; DOI=.1038/nbt.4229; RA Parks D.H., Chuvochina M., Waite D.W., Rinke C., Skarshewski A., RA Chaumeil P.A., Hugenholtz P.; RT "A standardized bacterial taxonomy based on genome phylogeny substantially RT revises the tree of life."; RL Nat. Biotechnol. 36:996-1004(2018). CC -!- FUNCTION: Multifunctional enzyme that catalyzes the SAM-dependent CC methylations of uroporphyrinogen III at position C-2 and C-7 to form CC precorrin-2 via precorrin-1. Then it catalyzes the NAD-dependent ring CC dehydrogenation of precorrin-2 to yield sirohydrochlorin. Finally, it CC catalyzes the ferrochelation of sirohydrochlorin to yield siroheme. CC {ECO:0000256|HAMAP-Rule:MF_01646}. 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:0000256|HAMAP-Rule:MF_01646}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 S-adenosyl-L-methionine + uroporphyrinogen III = H(+) + CC precorrin-2 + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:32459, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57308, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:58827, ChEBI:CHEBI:59789; EC=2.1.1.107; CC Evidence={ECO:0000256|HAMAP-Rule:MF_01646}; 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:0000256|ARBA:ARBA00001156, ECO:0000256|HAMAP- CC Rule:MF_01646}; CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis; CC precorrin-2 from uroporphyrinogen III: step 1/1. {ECO:0000256|HAMAP- CC Rule:MF_01646}. CC -!- PATHWAY: Cofactor biosynthesis; adenosylcobalamin biosynthesis; CC sirohydrochlorin from precorrin-2: step 1/1. {ECO:0000256|HAMAP- CC Rule:MF_01646}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; precorrin-2 from uroporphyrinogen III: step 1/1. CC {ECO:0000256|ARBA:ARBA00025705, ECO:0000256|HAMAP-Rule:MF_01646}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; siroheme from sirohydrochlorin: step 1/1. CC {ECO:0000256|HAMAP-Rule:MF_01646}. CC -!- PATHWAY: Porphyrin-containing compound metabolism; siroheme CC biosynthesis; sirohydrochlorin from precorrin-2: step 1/1. CC {ECO:0000256|ARBA:ARBA00005010, ECO:0000256|HAMAP-Rule:MF_01646}. CC -!- SIMILARITY: Belongs to the precorrin methyltransferase family. CC {ECO:0000256|ARBA:ARBA00005879, ECO:0000256|RuleBase:RU003960}. CC -!- SIMILARITY: In the C-terminal section; belongs to the precorrin CC methyltransferase family. {ECO:0000256|HAMAP-Rule:MF_01646}. CC -!- SIMILARITY: In the N-terminal section; belongs to the precorrin-2 CC dehydrogenase / sirohydrochlorin ferrochelatase family. CC {ECO:0000256|HAMAP-Rule:MF_01646}. CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:HAO70285.1}. 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; DMBH01000028; HAD99074.1; -; Genomic_DNA. DR EMBL; DMBK01000009; HAE70079.1; -; Genomic_DNA. DR EMBL; DMDS01000008; HAG47336.1; -; Genomic_DNA. DR EMBL; DMQZ01000024; HAO44475.1; -; Genomic_DNA. DR EMBL; DMRA01000124; HAO53896.1; -; Genomic_DNA. DR EMBL; DMRD01000050; HAO70285.1; -; Genomic_DNA. DR EMBL; DMRG01000076; HAO97890.1; -; Genomic_DNA. DR EMBL; DMRF01000064; HAP05563.1; -; Genomic_DNA. DR EMBL; DMRE01000001; HAP44802.1; -; Genomic_DNA. DR EMBL; DMJS01000116; HAP92831.1; -; Genomic_DNA. DR EMBL; DNRK01000101; HBG03696.1; -; Genomic_DNA. DR EMBL; DOBR01000126; HBN58491.1; -; Genomic_DNA. DR EMBL; DOWW01000119; HCA68786.1; -; Genomic_DNA. DR EMBL; DPFW01000094; HCH58704.1; -; Genomic_DNA. DR EMBL; DPMG01000119; HCV74928.1; -; Genomic_DNA. DR EMBL; DPPC01000045; HCW71725.1; -; Genomic_DNA. DR AlphaFoldDB; A0A351XP33; -. DR UniPathway; UPA00148; UER00211. DR UniPathway; UPA00262; UER00211. DR Proteomes; UP000257415; Unassembled WGS sequence. DR Proteomes; UP000257813; Unassembled WGS sequence. DR Proteomes; UP000258425; Unassembled WGS sequence. DR Proteomes; UP000258887; Unassembled WGS sequence. DR Proteomes; UP000258990; Unassembled WGS sequence. DR Proteomes; UP000259895; Unassembled WGS sequence. DR Proteomes; UP000259995; Unassembled WGS sequence. DR Proteomes; UP000260054; Unassembled WGS sequence. DR Proteomes; UP000260090; Unassembled WGS sequence. DR Proteomes; UP000260443; Unassembled WGS sequence. DR Proteomes; UP000262282; Unassembled WGS sequence. DR Proteomes; UP000262502; Unassembled WGS sequence. DR Proteomes; UP000262822; Unassembled WGS sequence. DR Proteomes; UP000263410; Unassembled WGS sequence. DR Proteomes; UP000263978; Unassembled WGS sequence. DR Proteomes; UP000264040; Unassembled WGS sequence. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0043115; F:precorrin-2 dehydrogenase activity; IEA:UniProtKB-UniRule. DR GO; GO:0051266; F:sirohydrochlorin ferrochelatase activity; IEA:UniProtKB-EC. DR GO; GO:0004851; F:uroporphyrin-III C-methyltransferase activity; IEA:UniProtKB-UniRule. DR GO; GO:0009236; P:cobalamin biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0019354; P:siroheme biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd11642; SUMT; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 1.10.8.210; Sirohaem synthase, dimerisation domain; 1. DR HAMAP; MF_01646; Siroheme_synth; 1. DR InterPro; IPR000878; 4pyrrol_Mease. DR InterPro; IPR035996; 4pyrrol_Methylase_sf. DR InterPro; IPR014777; 4pyrrole_Mease_sub1. DR InterPro; IPR014776; 4pyrrole_Mease_sub2. DR InterPro; IPR006366; CobA/CysG_C. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR050161; Siro_Cobalamin_biosynth. DR InterPro; IPR037115; Sirohaem_synt_dimer_dom_sf. DR InterPro; IPR012409; Sirohaem_synth. DR InterPro; IPR028281; Sirohaem_synthase_central. DR InterPro; IPR019478; Sirohaem_synthase_dimer_dom. DR InterPro; IPR006367; Sirohaem_synthase_N. DR InterPro; IPR003043; Uropor_MeTrfase_CS. DR NCBIfam; TIGR01469; cobA_cysG_Cterm; 1. DR NCBIfam; TIGR01470; cysG_Nterm; 1. DR PANTHER; PTHR45790:SF1; SIROHEME SYNTHASE; 1. DR PANTHER; PTHR45790; SIROHEME SYNTHASE-RELATED; 1. DR Pfam; PF10414; CysG_dimeriser; 1. DR Pfam; PF13241; NAD_binding_7; 1. DR Pfam; PF14824; Sirohm_synth_M; 1. DR Pfam; PF00590; TP_methylase; 1. DR PIRSF; PIRSF036426; Sirohaem_synth; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF75615; Siroheme synthase middle domains-like; 1. DR SUPFAM; SSF53790; Tetrapyrrole methylase; 1. DR PROSITE; PS00840; SUMT_2; 1. PE 3: Inferred from homology; KW Cobalamin biosynthesis {ECO:0000256|ARBA:ARBA00022573, ECO:0000256|HAMAP- KW Rule:MF_01646}; KW Lyase {ECO:0000256|ARBA:ARBA00023239, ECO:0000256|HAMAP-Rule:MF_01646}; KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603, ECO:0000256|HAMAP- KW Rule:MF_01646}; KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268, ECO:0000256|HAMAP- KW Rule:MF_01646}; KW NAD {ECO:0000256|ARBA:ARBA00023027, ECO:0000256|HAMAP-Rule:MF_01646}; KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002, ECO:0000256|HAMAP- KW Rule:MF_01646}; Phosphoprotein {ECO:0000256|HAMAP-Rule:MF_01646}; KW Porphyrin biosynthesis {ECO:0000256|ARBA:ARBA00023244, ECO:0000256|HAMAP- KW Rule:MF_01646}; KW S-adenosyl-L-methionine {ECO:0000256|ARBA:ARBA00022691, ECO:0000256|HAMAP- KW Rule:MF_01646}; KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|HAMAP- KW Rule:MF_01646}. FT DOMAIN 124..145 FT /note="Siroheme synthase central" FT /evidence="ECO:0000259|Pfam:PF14824" FT DOMAIN 150..207 FT /note="Sirohaem synthase dimerisation" FT /evidence="ECO:0000259|Pfam:PF10414" FT DOMAIN 218..427 FT /note="Tetrapyrrole methylase" FT /evidence="ECO:0000259|Pfam:PF00590" FT REGION 1..203 FT /note="Precorrin-2 dehydrogenase / sirohydrochlorin FT ferrochelatase" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT REGION 216..462 FT /note="Uroporphyrinogen-III C-methyltransferase" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT ACT_SITE 248 FT /note="Proton acceptor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646, FT ECO:0000256|PIRSR:PIRSR036426-1" FT ACT_SITE 270 FT /note="Proton donor" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646, FT ECO:0000256|PIRSR:PIRSR036426-1" FT BINDING 22..23 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 43..44 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 225 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 301..303 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 306 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 331..332 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 383 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT BINDING 412 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" FT MOD_RES 128 FT /note="Phosphoserine" FT /evidence="ECO:0000256|HAMAP-Rule:MF_01646" SQ SEQUENCE 462 AA; 50397 MW; 82D08BA0DC3DB415 CRC64; MNYLPIFIDI TQQPCLVVGG GDIALRKINL LLKANAAVTC VSKECCNGIE KLVKDNKIIR IEKAFEATDI NAQVLIVSAT DDSDLNAQVS ALAKTANIPV NVVDSPDLCS FVMPSIVDRS PIVIAISSAG KAPVLARLIR AKLESTIPHA YGKLAELAGN FRDQVKAKFN NIEDRRYFWE KTFSGIVAEK VFSGKVDEAK ADLQAQLDGS TDSGIGEVYL VGGGPGDPDL LTFKALRLMQ QADVILYDRL VSDGVMELVR RDAELIYVGK ERDNHAVPQG DINQLLVDLA KQGRRVCRLK GGDPFIFGRG GEEIETLAEN NIPFQVVPGI TAASGCSAYS GIPLTHRDYS QSCRFVTGHL KDGSMNLPWD ELAVEQQTIV FYMALVGARH LSEQLISHGM RGDMPVALVE KGTTPDHQVY VTTLAELPNL VENTTIHAPT LIIIGEVVKL REKLNWFDAD ND //