AACA_ENTFA
ID AACA_ENTFA Reviewed; 479 AA.
AC P0A0C2; P14507;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Bifunctional AAC/APH;
DE Includes:
DE RecName: Full=6'-aminoglycoside N-acetyltransferase;
DE EC=2.3.1.-;
DE AltName: Full=AAC(6');
DE Includes:
DE RecName: Full=Aminoglycoside 2''-phosphotransferase {ECO:0000305};
DE EC=2.7.1.190 {ECO:0000269|PubMed:23115238};
DE AltName: Full=2''-aminoglycoside phosphotransferase;
DE AltName: Full=APH(2'');
GN Name=aacA-aphD; OrderedLocusNames=EF_A0061;
OS Enterococcus faecalis (strain ATCC 700802 / V583).
OG Plasmid pIP800, and Plasmid pTEF1.
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=226185;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC PLASMID=pIP800;
RX PubMed=3015884; DOI=10.1128/jb.167.2.631-638.1986;
RA Ferretti J.J., Gilmore K.S., Courvalin P.;
RT "Nucleotide sequence analysis of the gene specifying the bifunctional 6'-
RT aminoglycoside acetyltransferase 2'-aminoglycoside phosphotransferase
RT enzyme in Streptococcus faecalis and identification and cloning of gene
RT regions specifying the two activities.";
RL J. Bacteriol. 167:631-638(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700802 / V583; PLASMID=pTEF1;
RX PubMed=12663927; DOI=10.1126/science.1080613;
RA Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R.,
RA Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,
RA Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C.,
RA DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C.,
RA Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M.,
RA Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.;
RT "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus
RT faecalis.";
RL Science 299:2071-2074(2003).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23115238; DOI=10.1074/jbc.m112.416453;
RA Frase H., Toth M., Vakulenko S.B.;
RT "Revisiting the nucleotide and aminoglycoside substrate specificity of the
RT bifunctional aminoglycoside acetyltransferase(6')-Ie/aminoglycoside
RT phosphotransferase(2'')-Ia enzyme.";
RL J. Biol. Chem. 287:43262-43269(2012).
CC -!- FUNCTION: Involved in resistance to gentamicin, tobramycin, and
CC kanamycin. Tobramycin and kanamycin resistance is due to the ACC
CC activity, specified by N-terminal region. The C-terminal region is a
CC kinase that phosphorylates several 4,6-disubstituted aminoglycosides.
CC {ECO:0000269|PubMed:23115238}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a gentamycin + GTP = a gentamycin 2''-phosphate + GDP + H(+);
CC Xref=Rhea:RHEA:48872, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:58189, ChEBI:CHEBI:90218, ChEBI:CHEBI:90219;
CC EC=2.7.1.190; Evidence={ECO:0000269|PubMed:23115238};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3 uM for GTP {ECO:0000269|PubMed:23115238};
CC KM=0.3 uM for dibekacin {ECO:0000269|PubMed:23115238};
CC KM=0.8 uM for arbekacin {ECO:0000269|PubMed:23115238};
CC KM=33 uM for amikacin {ECO:0000269|PubMed:23115238};
CC KM=0.6 uM for gentamicin C {ECO:0000269|PubMed:23115238};
CC KM=0.8 uM for sisomicin {ECO:0000269|PubMed:23115238};
CC KM=0.41 uM for netilmicin {ECO:0000269|PubMed:23115238};
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: In the C-terminal section; belongs to the aminoglycoside
CC phosphotransferase family. {ECO:0000305}.
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DR EMBL; M13771; AAA26865.1; -; Genomic_DNA.
DR EMBL; AE016833; AAO83055.1; -; Genomic_DNA.
DR PIR; A26048; A26048.
DR RefSeq; NP_816984.1; NC_004669.1.
DR RefSeq; WP_001028144.1; NZ_KE136530.1.
DR AlphaFoldDB; P0A0C2; -.
DR SMR; P0A0C2; -.
DR EnsemblBacteria; AAO83055; AAO83055; EF_A0061.
DR GeneID; 58049990; -.
DR GeneID; 61913521; -.
DR GeneID; 66882989; -.
DR KEGG; ag:AAA26865; -.
DR KEGG; efa:EFA0061; -.
DR PATRIC; fig|226185.45.peg.2781; -.
DR HOGENOM; CLU_632450_0_0_9; -.
DR OMA; IYKRTYR; -.
DR BioCyc; MetaCyc:MON-19347; -.
DR BRENDA; 2.3.1.82; 2095.
DR BRENDA; 2.7.1.190; 2095.
DR SABIO-RK; P0A0C2; -.
DR PRO; PR:P0A0C2; -.
DR Proteomes; UP000001415; Plasmid pTEF1.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0034071; F:aminoglycoside phosphotransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008080; F:N-acetyltransferase activity; IEA:InterPro.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR002575; Aminoglycoside_PTrfase.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR Pfam; PF01636; APH; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Antibiotic resistance; ATP-binding; Cytoplasm; Kinase;
KW Multifunctional enzyme; Nucleotide-binding; Plasmid; Reference proteome;
KW Transferase; Transposable element.
FT CHAIN 1..479
FT /note="Bifunctional AAC/APH"
FT /id="PRO_0000204796"
FT DOMAIN 8..180
FT /note="N-acetyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532"
FT REGION 110..153
FT /note="Acetyl-CoA binding site"
FT /evidence="ECO:0000250"
FT ACT_SITE 374
FT /note="Proton acceptor; for phosphotransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="a gentamycin"
FT /ligand_id="ChEBI:CHEBI:90218"
FT /evidence="ECO:0000250"
SQ SEQUENCE 479 AA; 56855 MW; 744D93D76299CFCE CRC64;
MNIVENEICI RTLIDDDFPL MLKWLTDERV LEFYGGRDKK YTLESLKKHY TEPWEDEVFR
VIIEYNNVPI GYGQIYKMYD ELYTDYHYPK TDEIVYGMDQ FIGEPNYWSK GIGTRYIKLI
FEFLKKERNA NAVILDPHKN NPRAIRAYQK SGFRIIEDLP EHELHEGKKE DCYLMEYRYD
DNATNVKAMK YLIEHYFDNF KVDSIEIIGS GYDSVAYLVN NEYIFKTKFS TNKKKGYAKE
KAIYNFLNTN LETNVKIPNI EYSYISDELS ILGYKEIKGT FLTPEIYSTM SEEEQNLLKR
DIASFLRQMH GLDYTDISEC TIDNKQNVLE EYILLRETIY NDLTDIEKDY IESFMERLNA
TTVFEGKKCL CHNDFSCNHL LLDGNNRLTG IIDFGDSGII DEYCDFIYLL EDSEEEIGTN
FGEDILRMYG NIDIEKAKEY QDIVEEYYPI ETIVYGIKNI KQEFIENGRK EIYKRTYKD
