CTAA_BACSU
ID CTAA_BACSU Reviewed; 306 AA.
AC P12946;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Heme A synthase {ECO:0000255|HAMAP-Rule:MF_01664, ECO:0000303|PubMed:12206660};
DE Short=HAS {ECO:0000255|HAMAP-Rule:MF_01664, ECO:0000303|PubMed:12206660};
DE EC=1.17.99.9 {ECO:0000255|HAMAP-Rule:MF_01664, ECO:0000269|PubMed:15236569, ECO:0000269|PubMed:16321940};
DE AltName: Full=Cytochrome aa3-controlling protein {ECO:0000255|HAMAP-Rule:MF_01664};
GN Name=ctaA {ECO:0000255|HAMAP-Rule:MF_01664, ECO:0000303|PubMed:2549006};
GN OrderedLocusNames=BSU14870;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RX PubMed=2549006; DOI=10.1128/jb.171.9.4967-4978.1989;
RA Mueller J.P., Taber H.W.;
RT "Isolation and sequence of ctaA, a gene required for cytochrome aa3
RT biosynthesis and sporulation in Bacillus subtilis.";
RL J. Bacteriol. 171:4967-4978(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RA Bertero M., Presecan E., Glaser P., Richou A., Danchin A.;
RT "Bacillus subtilis chromosomal region downstream nprE.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [4]
RP PROTEIN SEQUENCE OF 46-53, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=7961419; DOI=10.1128/jb.176.21.6663-6671.1994;
RA Svensson B., Hederstedt L.;
RT "Bacillus subtilis ctaA is a heme-containing membrane protein involved in
RT heme A biosynthesis.";
RL J. Bacteriol. 176:6663-6671(1994).
RN [5]
RP FUNCTION, IDENTIFICATION OF HEME INTERMEDIATES, PATHWAY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12206660; DOI=10.1021/bi0203536;
RA Brown K.R., Allan B.M., Do P., Hegg E.L.;
RT "Identification of novel hemes generated by heme A synthase: evidence for
RT two successive monooxygenase reactions.";
RL Biochemistry 41:10906-10913(2002).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15236569; DOI=10.1021/bi049056m;
RA Brown K.R., Brown B.M., Hoagland E., Mayne C.L., Hegg E.L.;
RT "Heme A synthase does not incorporate molecular oxygen into the formyl
RT group of heme A.";
RL Biochemistry 43:8616-8624(2004).
RN [7]
RP INTERACTION WITH CTAB.
RX PubMed=15491161; DOI=10.1021/bi048469k;
RA Brown B.M., Wang Z., Brown K.R., Cricco J.A., Hegg E.L.;
RT "Heme O synthase and heme A synthase from Bacillus subtilis and Rhodobacter
RT sphaeroides interact in Escherichia coli.";
RL Biochemistry 43:13541-13548(2004).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF HIS-60; HIS-123; HIS-216 AND HIS-278.
RX PubMed=16321940; DOI=10.1128/jb.187.24.8361-8369.2005;
RA Hederstedt L., Lewin A., Throne-Holst M.;
RT "Heme A synthase enzyme functions dissected by mutagenesis of Bacillus
RT subtilis ctaA.";
RL J. Bacteriol. 187:8361-8369(2005).
RN [9] {ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-303 IN COMPLEX WITH HEME B,
RP COFACTOR, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, AND PROBABLE ACTIVE SITE.
RX PubMed=30397130; DOI=10.1073/pnas.1813346115;
RA Niwa S., Takeda K., Kosugi M., Tsutsumi E., Mogi T., Miki K.;
RT "Crystal structure of heme A synthase from Bacillus subtilis.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:11953-11957(2018).
CC -!- FUNCTION: Catalyzes the conversion of heme O to heme A by two
CC successive hydroxylations of the methyl group at C8. The first
CC hydroxylation forms heme I, the second hydroxylation results in an
CC unstable dihydroxymethyl group, which spontaneously dehydrates,
CC resulting in the formyl group of heme A. {ECO:0000255|HAMAP-
CC Rule:MF_01664, ECO:0000269|PubMed:12206660,
CC ECO:0000269|PubMed:15236569, ECO:0000269|PubMed:16321940}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 A + Fe(II)-heme o + H2O = 2 AH2 + Fe(II)-heme a;
CC Xref=Rhea:RHEA:63388, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:60530, ChEBI:CHEBI:61715;
CC EC=1.17.99.9; Evidence={ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:15236569, ECO:0000269|PubMed:16321940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63389;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:15236569, ECO:0000269|PubMed:16321940};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:30397130, ECO:0000269|PubMed:7961419};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; heme A biosynthesis;
CC heme A from heme O: step 1/1. {ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:12206660, ECO:0000305|PubMed:7961419}.
CC -!- SUBUNIT: Interacts with CtaB. {ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:15491161}.
CC -!- INTERACTION:
CC P12946; O31652: ctaB1; NbExp=3; IntAct=EBI-2122325, EBI-2122343;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:12206660, ECO:0000269|PubMed:16321940,
CC ECO:0000269|PubMed:30397130, ECO:0000269|PubMed:7961419}; Multi-pass
CC membrane protein {ECO:0000255|HAMAP-Rule:MF_01664,
CC ECO:0000269|PubMed:30397130}.
CC -!- DOMAIN: The N-half (TM1-TM4) and C-half (TM5-TM8) domains are connected
CC by an intracellular loop. Each domain is formed from four-helix bundles
CC and they align in a pseudo twofold symmetry manner. The N-half domain
CC is the substrate-heme binding domain and the C-half domain is the
CC cofactor heme binding domain. {ECO:0000269|PubMed:30397130}.
CC -!- DISRUPTION PHENOTYPE: Mutations alter both cytochrome aa3 formation and
CC sporulation. {ECO:0000269|PubMed:2549006}.
CC -!- SIMILARITY: Belongs to the COX15/CtaA family. Type 1 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01664, ECO:0000305}.
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DR EMBL; M23915; AAA50254.1; -; Genomic_DNA.
DR EMBL; Z98682; CAB11340.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB13360.1; -; Genomic_DNA.
DR PIR; A33960; A33960.
DR RefSeq; NP_389370.1; NC_000964.3.
DR RefSeq; WP_003245869.1; NZ_JNCM01000035.1.
DR PDB; 6A2J; X-ray; 2.20 A; A=1-303.
DR PDB; 6IED; X-ray; 3.00 A; A=1-303.
DR PDBsum; 6A2J; -.
DR PDBsum; 6IED; -.
DR AlphaFoldDB; P12946; -.
DR SMR; P12946; -.
DR IntAct; P12946; 1.
DR STRING; 224308.BSU14870; -.
DR TCDB; 3.D.4.4.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR PaxDb; P12946; -.
DR DNASU; 937030; -.
DR EnsemblBacteria; CAB13360; CAB13360; BSU_14870.
DR GeneID; 937030; -.
DR KEGG; bsu:BSU14870; -.
DR PATRIC; fig|224308.179.peg.1621; -.
DR eggNOG; COG1612; Bacteria.
DR InParanoid; P12946; -.
DR OMA; YTGAYVR; -.
DR PhylomeDB; P12946; -.
DR BioCyc; BSUB:BSU14870-MON; -.
DR BioCyc; MetaCyc:BSU14870-MON; -.
DR BRENDA; 1.17.99.9; 658.
DR UniPathway; UPA00269; UER00713.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016653; F:oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor; IEA:InterPro.
DR GO; GO:0006784; P:heme A biosynthetic process; IEA:UniProtKB-UniRule.
DR HAMAP; MF_01664; HemeA_synth_type1; 1.
DR InterPro; IPR003780; COX15/CtaA_fam.
DR InterPro; IPR023755; HemeA_Synthase_type1.
DR Pfam; PF02628; COX15-CtaA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Heme biosynthesis;
KW Iron; Membrane; Metal-binding; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..306
FT /note="Heme A synthase"
FT /id="PRO_0000079487"
FT TOPO_DOM 1..2
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 3..25
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 26..51
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 52..78
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 79..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 89..113
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 114..115
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 116..139
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 140..159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 160..185
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 186..210
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 211..236
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 237..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 243..268
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 269..271
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30397130"
FT TRANSMEM 272..294
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30397130,
FT ECO:0007744|PDB:6A2J, ECO:0007744|PDB:6IED"
FT TOPO_DOM 295..306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30397130"
FT ACT_SITE 57
FT /evidence="ECO:0000305|PubMed:30397130"
FT BINDING 216
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01664,
FT ECO:0000269|PubMed:30397130"
FT BINDING 278
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01664,
FT ECO:0000269|PubMed:30397130"
FT MUTAGEN 60
FT /note="H->L: Inactive. Contains heme B and heme O, with
FT mainly heme O bound to CtaA."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 60
FT /note="H->M: Contains heme B and heme A at levels
FT comparable to that of wild-type CtaA."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 123
FT /note="H->L: Inactive. Contains heme B and heme O."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 123
FT /note="H->M: Inactive. Contains heme B and heme O."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 216
FT /note="H->L: Could not be detected."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 216
FT /note="H->M: Decrease in heme A synthase activity and 5-
FT fold reduction in cytochrome c oxidase activity. Contains
FT heme B, heme O, and heme I, as well as trace amounts of
FT heme A."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 278
FT /note="H->L: Contains small amounts of heme B and heme A."
FT /evidence="ECO:0000269|PubMed:16321940"
FT MUTAGEN 278
FT /note="H->M: Contains small amounts of heme B and heme A."
FT /evidence="ECO:0000269|PubMed:16321940"
FT HELIX 2..21
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:6A2J"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:6A2J"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 52..82
FT /evidence="ECO:0007829|PDB:6A2J"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 89..113
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 123..144
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 159..184
FT /evidence="ECO:0007829|PDB:6A2J"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 208..237
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 242..267
FT /evidence="ECO:0007829|PDB:6A2J"
FT HELIX 272..302
FT /evidence="ECO:0007829|PDB:6A2J"
SQ SEQUENCE 306 AA; 34085 MW; D47FE9041851CDCD CRC64;
MNKALKALGV LTTFVMLIVL IGGALVTKTG SGQGCGRQWP LCHGRFFPEL NPASIIEWSH
RFASGISIIL VLSLAFWSWR KITPIFRETT FLAIMSIIFL FLQALLGALA VVFGSNALIM
ALHFGISLIS FASVLILTLL IFEADKSVRT LVKPLQIGKK MQFHMIGILI YSYIVVYTGA
YVRHTESSLA CPNVPLCSPL NNGLPTQFHE WVQMGHRAAA LLLFVWIIVA AVHAITSYKD
QKQIFWGWIS CLIFITLQAL SGIMIVYSEL ALGFALAHSF FIACLFGVLC YFLLLIARFR
YESRQS
