ACCA3_MYCTU
ID ACCA3_MYCTU Reviewed; 600 AA.
AC P96890; F2GKV8; I6X6W5; Q7D5S3;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Biotin-dependent acyl-coenzyme A carboxylase alpha3 subunit {ECO:0000305};
DE Includes:
DE RecName: Full=Biotin carboxylase {ECO:0000303|PubMed:16354663};
DE Short=BC {ECO:0000303|PubMed:16354663};
DE EC=6.3.4.14 {ECO:0000269|PubMed:16354663};
DE Includes:
DE RecName: Full=Biotin carboxyl carrier protein {ECO:0000303|PubMed:16354663};
DE Short=BCCP {ECO:0000303|PubMed:16354663};
GN Name=accA3 {ECO:0000303|PubMed:16354663};
GN OrderedLocusNames=Rv3285 {ECO:0000312|EMBL:CCP46104.1};
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP PROTEIN SEQUENCE OF 2-14, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND SUBUNIT.
RX PubMed=16354663; DOI=10.1074/jbc.m511761200;
RA Oh T.J., Daniel J., Kim H.J., Sirakova T.D., Kolattukudy P.E.;
RT "Identification and characterization of Rv3281 as a novel subunit of a
RT biotin-dependent acyl-CoA carboxylase in Mycobacterium tuberculosis
RT H37Rv.";
RL J. Biol. Chem. 281:3899-3908(2006).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, AND SUBUNIT.
RX PubMed=16385038; DOI=10.1128/jb.188.2.477-486.2006;
RA Gago G., Kurth D., Diacovich L., Tsai S.C., Gramajo H.;
RT "Biochemical and structural characterization of an essential acyl coenzyme
RT A carboxylase from Mycobacterium tuberculosis.";
RL J. Bacteriol. 188:477-486(2006).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=17114269; DOI=10.1128/jb.01019-06;
RA Daniel J., Oh T.J., Lee C.M., Kolattukudy P.E.;
RT "AccD6, a member of the Fas II locus, is a functional carboxyltransferase
RT subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis.";
RL J. Bacteriol. 189:911-917(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP FUNCTION, AND SUBUNIT.
RX PubMed=28222482; DOI=10.1111/febs.14046;
RA Bazet Lyonnet B., Diacovich L., Gago G., Spina L., Bardou F., Lemassu A.,
RA Quemard A., Gramajo H.;
RT "Functional reconstitution of the Mycobacterium tuberculosis long-chain
RT acyl-CoA carboxylase from multiple acyl-CoA subunits.";
RL FEBS J. 284:1110-1125(2017).
RN [7] {ECO:0007744|PDB:5MLK}
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS), AND SUBUNIT.
RX PubMed=28469974; DOI=10.1002/2211-5463.12212;
RA Bennett M., Hogbom M.;
RT "Crystal structure of the essential biotin-dependent carboxylase AccA3 from
RT Mycobacterium tuberculosis.";
RL FEBS Open Bio 7:620-626(2017).
CC -!- FUNCTION: Component of a biotin-dependent acyl-CoA carboxylase complex.
CC This subunit catalyzes the ATP-dependent carboxylation of the biotin
CC carried by the biotin carboxyl carrier (BCC) domain, resulting in the
CC formation of carboxyl biotin (PubMed:16354663, PubMed:16385038,
CC PubMed:17114269). When associated with the beta5 subunit AccD5, is
CC involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a
CC preference for propionyl-CoA (PubMed:16354663, PubMed:16385038). When
CC associated with the beta6 subunit AccD6, is involved in the
CC carboxylation of acetyl-CoA and propionyl-CoA, with a preference for
CC acetyl-CoA (PubMed:17114269). When associated with the beta4 subunit
CC AccD4, the beta5 subunit AccD5 and the epsilon subunit AccE5, forms the
CC LCC complex, which is involved in the carboxylation of long chain acyl-
CC CoA (PubMed:16354663, PubMed:28222482). The LCC complex can use C16-C24
CC substrates, the highest specific activity is obtained with carboxy-C20-
CC CoA (PubMed:28222482). {ECO:0000269|PubMed:16354663,
CC ECO:0000269|PubMed:16385038, ECO:0000269|PubMed:17114269,
CC ECO:0000269|PubMed:28222482}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + hydrogencarbonate + N(6)-biotinyl-L-lysyl-[protein] =
CC ADP + H(+) + N(6)-carboxybiotinyl-L-lysyl-[protein] + phosphate;
CC Xref=Rhea:RHEA:13501, Rhea:RHEA-COMP:10505, Rhea:RHEA-COMP:10506,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:83144, ChEBI:CHEBI:83145,
CC ChEBI:CHEBI:456216; EC=6.3.4.14;
CC Evidence={ECO:0000269|PubMed:16354663, ECO:0000269|PubMed:16385038,
CC ECO:0000269|PubMed:17114269};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13502;
CC Evidence={ECO:0000269|PubMed:16354663, ECO:0000269|PubMed:16385038,
CC ECO:0000269|PubMed:17114269};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409, ECO:0000255|PROSITE-
CC ProRule:PRU00969};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01066};
CC -!- ACTIVITY REGULATION: Carboxylase activity of the AccA3/AccD5 complex is
CC stimulated by interaction with the epsilon subunit AccE5
CC (PubMed:16354663, PubMed:16385038). Activity of the AccA3/AccD6 complex
CC is inhibited by interaction with AccE5 and by dimethyl itaconate, C75,
CC haloxyfop, cerulenin, and 1,2-cyclohexanedione (PubMed:17114269).
CC {ECO:0000269|PubMed:16354663, ECO:0000269|PubMed:16385038,
CC ECO:0000269|PubMed:17114269}.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000305|PubMed:17114269}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000305|PubMed:16385038, ECO:0000305|PubMed:17114269}.
CC -!- SUBUNIT: Homodimer (PubMed:28469974). The biotin-dependent acyl-CoA
CC carboxylase complex is composed of AccA3, which contains the biotin
CC carboxylase (BC) and biotin carboxyl carrier protein (BCCP) domains,
CC and an AccD protein, which contains the carboxyl transferase (CT)
CC domain (PubMed:16354663, PubMed:16385038, PubMed:17114269,
CC PubMed:28222482). Can interact with AccD4, AccD5 and AccD6
CC (PubMed:16354663, PubMed:16385038, PubMed:17114269, PubMed:28222482).
CC The AccA3/AccD5 complex forms a dodecamer, and can associate with the
CC epsilon subunit AccE5 (Rv3280), which stimulates carboxylation by the
CC complex (PubMed:16354663, PubMed:16385038). The AccA3/AccD6 complex
CC forms a dodecamer. Interaction of AccA3/AccD6 with the epsilon subunit
CC AccE5 (Rv3280) decreases carboxylation by the complex
CC (PubMed:17114269). The long-chain acyl-CoA carboxylase (LCC) complex is
CC composed of AccA3, AccD4, AccD5 and AccE5. The four subunits are
CC essential for activity, but AccD5, together with AccE5, probably plays
CC a structural role rather than a catalytic one (PubMed:28222482).
CC {ECO:0000269|PubMed:16354663, ECO:0000269|PubMed:16385038,
CC ECO:0000269|PubMed:17114269, ECO:0000269|PubMed:28222482,
CC ECO:0000269|PubMed:28469974}.
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; AL123456; CCP46104.1; -; Genomic_DNA.
DR RefSeq; NP_217802.1; NC_000962.3.
DR RefSeq; WP_003417156.1; NZ_NVQJ01000003.1.
DR PDB; 5MLK; X-ray; 1.94 A; A/B=1-600.
DR PDBsum; 5MLK; -.
DR AlphaFoldDB; P96890; -.
DR SMR; P96890; -.
DR STRING; 83332.Rv3285; -.
DR PaxDb; P96890; -.
DR PRIDE; P96890; -.
DR DNASU; 887912; -.
DR GeneID; 887912; -.
DR KEGG; mtu:Rv3285; -.
DR PATRIC; fig|83332.111.peg.3667; -.
DR TubercuList; Rv3285; -.
DR eggNOG; COG4770; Bacteria.
DR OMA; ITHFHTP; -.
DR PhylomeDB; P96890; -.
DR BioCyc; MetaCyc:G185E-7559-MON; -.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00915; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009317; C:acetyl-CoA carboxylase complex; IDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003989; F:acetyl-CoA carboxylase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004075; F:biotin carboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004658; F:propionyl-CoA carboxylase activity; IDA:MTBBASE.
DR GO; GO:0015977; P:carbon fixation; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.1490.20; -; 1.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
DR InterPro; IPR005481; BC-like_N.
DR InterPro; IPR001882; Biotin_BS.
DR InterPro; IPR011764; Biotin_carboxylation_dom.
DR InterPro; IPR005482; Biotin_COase_C.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR InterPro; IPR011054; Rudment_hybrid_motif.
DR InterPro; IPR011053; Single_hybrid_motif.
DR Pfam; PF02785; Biotin_carb_C; 1.
DR Pfam; PF00289; Biotin_carb_N; 1.
DR Pfam; PF00364; Biotin_lipoyl; 1.
DR Pfam; PF02786; CPSase_L_D2; 1.
DR SMART; SM00878; Biotin_carb_C; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS50979; BC; 1.
DR PROSITE; PS00188; BIOTIN; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS00867; CPSASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Biotin; Direct protein sequencing;
KW Fatty acid biosynthesis; Fatty acid metabolism; Ligase; Lipid biosynthesis;
KW Lipid metabolism; Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:16354663"
FT CHAIN 2..600
FT /note="Biotin-dependent acyl-coenzyme A carboxylase alpha3
FT subunit"
FT /id="PRO_0000452367"
FT DOMAIN 11..455
FT /note="Biotin carboxylation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 130..327
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 524..600
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT BINDING 158..219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 285
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 285
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 298
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 298
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 298
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 298
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 300
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT MOD_RES 566
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 21..33
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:5MLK"
FT TURN 66..71
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 73..83
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:5MLK"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 99..107
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 117..124
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 126..135
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 187..202
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 217..225
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 231..243
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 246..253
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 259..275
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 294..300
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 307..314
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 318..326
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 341..351
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 375..380
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 393..404
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 405..418
FT /evidence="ECO:0007829|PDB:5MLK"
FT STRAND 420..424
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 428..434
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 438..441
FT /evidence="ECO:0007829|PDB:5MLK"
FT HELIX 453..456
FT /evidence="ECO:0007829|PDB:5MLK"
SQ SEQUENCE 600 AA; 63783 MW; 1B7507AB78E217F0 CRC64;
MASHAGSRIA RISKVLVANR GEIAVRVIRA ARDAGLPSVA VYAEPDAESP HVRLADEAFA
LGGQTSAESY LDFAKILDAA AKSGANAIHP GYGFLAENAD FAQAVIDAGL IWIGPSPQSI
RDLGDKVTAR HIAARAQAPL VPGTPDPVKG ADEVVAFAEE YGLPIAIKAA HGGGGKGMKV
ARTIDEIPEL YESAVREATA AFGRGECYVE RYLDKPRHVE AQVIADQHGN VVVAGTRDCS
LQRRYQKLVE EAPAPFLTDF QRKEIHDSAK RICKEAHYHG AGTVEYLVGQ DGLISFLEVN
TRLQVEHPVT EETAGIDLVL QQFRIANGEK LDITEDPTPR GHAIEFRING EDAGRNFLPA
PGPVTKFHPP SGPGVRVDSG VETGSVIGGQ FDSMLAKLIV HGADRAEALA RARRALNEFG
VEGLATVIPF HRAVVSDPAF IGDANGFSVH TRWIETEWNN TIEPFTDGEP LDEDARPRQK
VVVEIDGRRV EVSLPADLAL SNGGGCDPVG VIRRKPKPRK RGAHTGAAAS GDAVTAPMQG
TVVKFAVEEG QEVVAGDLVV VLEAMKMENP VTAHKDGTIT GLAVEAGAAI TQGTVLAEIK
