ID   BGA2_ECOLI              Reviewed;        1030 AA.
AC   P06864; P76660; Q2M9D0; Q6BF50;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2004, sequence version 4.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Evolved beta-galactosidase subunit alpha;
DE            Short=Beta-gal;
DE            EC=3.2.1.23;
DE   AltName: Full=Lactase;
GN   Name=ebgA; OrderedLocusNames=b3076, JW5511;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2515108; DOI=10.1093/genetics/123.4.635;
RA   Hall B.G., Betts P.W., Wootton J.C.;
RT   "DNA sequence analysis of artificially evolved ebg enzyme and ebg repressor
RT   genes.";
RL   Genetics 123:635-648(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3939707; DOI=10.1093/oxfordjournals.molbev.a040372;
RA   Stokes H.W., Betts P.W., Hall B.G.;
RT   "Sequence of the ebgA gene of Escherichia coli: comparison with the lacZ
RT   gene.";
RL   Mol. Biol. Evol. 2:469-477(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [4]
RP   SEQUENCE REVISION TO 275 AND 891-892.
RX   PubMed=16397293; DOI=10.1093/nar/gkj405;
RA   Riley M., Abe T., Arnaud M.B., Berlyn M.K.B., Blattner F.R.,
RA   Chaudhuri R.R., Glasner J.D., Horiuchi T., Keseler I.M., Kosuge T.,
RA   Mori H., Perna N.T., Plunkett G. III, Rudd K.E., Serres M.H., Thomas G.H.,
RA   Thomson N.R., Wishart D., Wanner B.L.;
RT   "Escherichia coli K-12: a cooperatively developed annotation snapshot
RT   -- 2005.";
RL   Nucleic Acids Res. 34:1-9(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [6]
RP   ACTIVE SITE REGIONS.
RX   PubMed=6411710; DOI=10.1016/s0021-9258(17)44440-1;
RA   Fowler A.V., Smith P.J.;
RT   "The active site regions of lacZ and ebg beta-galactosidases are
RT   homologous.";
RL   J. Biol. Chem. 258:10204-10207(1983).
RN   [7]
RP   SUBUNIT.
RX   PubMed=1540130; DOI=10.1042/bj2820155;
RA   Elliott A.C., Sinnott M.L., Smith P.J., Bommuswamy J., Guo Z., Hall B.G.,
RA   Zhang Y.;
RT   "The catalytic consequences of experimental evolution. Studies on the
RT   subunit structure of the second (ebg) beta-galactosidase of Escherichia
RT   coli, and on catalysis by ebgab, an experimental evolvant containing two
RT   amino acid substitutions.";
RL   Biochem. J. 282:155-164(1992).
CC   -!- FUNCTION: The wild-type enzyme is an ineffective lactase. Two classes
CC       of point mutations dramatically improve activity of the enzyme.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of terminal non-reducing beta-D-galactose residues
CC         in beta-D-galactosides.; EC=3.2.1.23;
CC   -!- SUBUNIT: Heterooctamer of 4 alpha and 4 beta subunits.
CC       {ECO:0000269|PubMed:1540130}.
CC   -!- INTERACTION:
CC       P06864; P32053: intA; NbExp=3; IntAct=EBI-558098, EBI-552967;
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA57877.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; M64441; AAA61971.1; -; Genomic_DNA.
DR   EMBL; X52031; CAA36274.1; -; Genomic_DNA.
DR   EMBL; X03228; CAA26977.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; U18997; AAA57877.1; ALT_INIT; Genomic_DNA.
DR   EMBL; U00096; AAT48164.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAE77126.1; -; Genomic_DNA.
DR   PIR; A65096; GBECE.
DR   RefSeq; WP_001082856.1; NZ_LN832404.1.
DR   RefSeq; YP_026199.1; NC_000913.3.
DR   AlphaFoldDB; P06864; -.
DR   SMR; P06864; -.
DR   BioGRID; 4263419; 6.
DR   BioGRID; 851899; 6.
DR   DIP; DIP-2893N; -.
DR   IntAct; P06864; 7.
DR   STRING; 511145.b3076; -.
DR   DrugBank; DB00581; Lactulose.
DR   CAZy; GH2; Glycoside Hydrolase Family 2.
DR   PaxDb; 511145-b3076; -.
DR   EnsemblBacteria; AAT48164; AAT48164; b3076.
DR   GeneID; 947583; -.
DR   KEGG; ecj:JW5511; -.
DR   KEGG; eco:b3076; -.
DR   PATRIC; fig|511145.12.peg.3170; -.
DR   EchoBASE; EB0248; -.
DR   eggNOG; COG3250; Bacteria.
DR   HOGENOM; CLU_002346_0_2_6; -.
DR   InParanoid; P06864; -.
DR   OMA; WCDHGIL; -.
DR   OrthoDB; 9758603at2; -.
DR   PhylomeDB; P06864; -.
DR   BioCyc; EcoCyc:EG10252-MONOMER; -.
DR   SABIO-RK; P06864; -.
DR   PRO; PR:P06864; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0009341; C:beta-galactosidase complex; IBA:GO_Central.
DR   GO; GO:0004565; F:beta-galactosidase activity; IBA:GO_Central.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
DR   GO; GO:0005990; P:lactose catabolic process; IBA:GO_Central.
DR   Gene3D; 2.70.98.10; -; 1.
DR   Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR004199; B-gal_small/dom_5.
DR   InterPro; IPR036156; Beta-gal/glucu_dom_sf.
DR   InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR   InterPro; IPR008979; Galactose-bd-like_sf.
DR   InterPro; IPR014718; GH-type_carb-bd.
DR   InterPro; IPR006101; Glyco_hydro_2.
DR   InterPro; IPR023232; Glyco_hydro_2_AS.
DR   InterPro; IPR006103; Glyco_hydro_2_cat.
DR   InterPro; IPR023230; Glyco_hydro_2_CS.
DR   InterPro; IPR006102; Glyco_hydro_2_Ig-like.
DR   InterPro; IPR006104; Glyco_hydro_2_N.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR032312; LacZ_4.
DR   PANTHER; PTHR46323; BETA-GALACTOSIDASE; 1.
DR   PANTHER; PTHR46323:SF2; BETA-GALACTOSIDASE; 1.
DR   Pfam; PF02929; Bgal_small_N; 1.
DR   Pfam; PF00703; Glyco_hydro_2; 1.
DR   Pfam; PF02836; Glyco_hydro_2_C; 1.
DR   Pfam; PF02837; Glyco_hydro_2_N; 1.
DR   Pfam; PF16353; LacZ_4; 1.
DR   PRINTS; PR00132; GLHYDRLASE2.
DR   SMART; SM01038; Bgal_small_N; 1.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   SUPFAM; SSF49303; beta-Galactosidase/glucuronidase domain; 2.
DR   SUPFAM; SSF74650; Galactose mutarotase-like; 1.
DR   SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR   PROSITE; PS00719; GLYCOSYL_HYDROL_F2_1; 1.
DR   PROSITE; PS00608; GLYCOSYL_HYDROL_F2_2; 1.
PE   1: Evidence at protein level;
KW   Glycosidase; Hydrolase; Reference proteome.
FT   CHAIN           1..1030
FT                   /note="Evolved beta-galactosidase subunit alpha"
FT                   /id="PRO_0000057651"
FT   ACT_SITE        449
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000269|PubMed:6411710"
FT   ACT_SITE        512
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   VARIANT         92
FT                   /note="D -> N (improve activity)"
FT   VARIANT         93
FT                   /note="E -> K (improve activity)"
FT   VARIANT         976
FT                   /note="W -> C (improve activity)"
FT   VARIANT         978
FT                   /note="S -> G (improve activity)"
FT   CONFLICT        275
FT                   /note="S -> T (in Ref. 1, 2 and 3; AAA57877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        465
FT                   /note="A -> R (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        640
FT                   /note="T -> S (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        649
FT                   /note="R -> P (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        767
FT                   /note="M -> MM (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        891..892
FT                   /note="ST -> QA (in Ref. 1, 2 and 3; AAA57877)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1026
FT                   /note="S -> T (in Ref. 1 and 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1030 AA;  117879 MW;  FEC4D7A558C6EE94 CRC64;
     MNRWENIQLT HENRLAPRAY FFSYDSVAQA RTFARETSSL FLPLSGQWNF HFFDHPLQVP
     EAFTSELMAD WGHITVPAMW QMEGHGKLQY TDEGFPFPID VPFVPSDNPT GAYQRIFTLS
     DGWQGKQTLI KFDGVETYFE VYVNGQYVGF SKGSRLTAEF DISAMVKTGD NLLCVRVMQW
     ADSTYVEDQD MWWSAGIFRD VYLVGKHLTH INDFTVRTDF DEAYCDATLS CEVVLENLAA
     SPVVTTLEYT LFDGERVVHS SAIDHLAIEK LTSASFAFTV EQPQQWSAES PYLYHLVMTL
     KDANGNVLEV VPQRVGFRDI KVRDGLFWIN NRYVMLHGVN RHDNDHRKGR AVGMDRVEKD
     LQLMKQHNIN SVRTAHYPND PRFYELCDIY GLFVMAETDV ESHGFANVGD ISRITDDPQW
     EKVYVERIVR HIHAQKNHPS IIIWSLGNES GYGCNIRAMY HAAKALDDTR LVHYEEDRDA
     EVVDIISTMY TRVPLMNEFG EYPHPKPRII CEYAHAMGNG PGGLTEYQNV FYKHDCIQGH
     YVWEWCDHGI QAQDDHGNVW YKFGGDYGDY PNNYNFCLDG LIYSDQTPGP GLKEYKQVIA
     PVKIHARDLT RGELKVENKL WFTTLDDYTL HAEVRAEGET LATQQIKLRD VAPNSEAPLQ
     ITLPQLDARE AFLNITVTKD SRTRYSEAGH PIATYQFPLK ENTAQPVPFA PNNARPLTLE
     DDRLSCTVRG YNFAITFSKM SGKPTSWQVN GESLLTREPK INFFKPMIDN HKQEYEGLWQ
     PNHLQIMQEH LRDFAVEQSD GEVLIISRTV IAPPVFDFGM RCTYIWRIAA DGQVNVALSG
     ERYGDYPHII PCIGFTMGIN GEYDQVAYYG RGPGENYADS QQANIIDIWR STVDAMFENY
     PFPQNNGNRQ HVRWTALTNR HGNGLLVVPQ RPINFSAWHY TQENIHAAQH CNELQRSDDI
     TLNLDHQLLG LGSNSWGSEV LDSWRVWFRD FSYGFTLLPV SGGEATAQSL ASYEFGAGFF
     STNLHSENKQ
//