GLPG_ECOLI
ID GLPG_ECOLI Reviewed; 276 AA.
AC P09391; P76691; Q2M788; Q6BF32;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 5.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Rhomboid protease GlpG;
DE EC=3.4.21.105;
DE AltName: Full=Intramembrane serine protease;
GN Name=glpG; OrderedLocusNames=b3424, JW5687;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=3045764; DOI=10.1093/nar/16.15.7732;
RA Choi Y.-L., Kawase S., Nishida T., Sakai H., Komano T., Kawamukai M.,
RA Utsumi R., Kohara Y., Akiyama K.;
RT "Nucleotide sequence of the glpR gene encoding the repressor for the
RT glycerol-3-phosphate regulon of Escherichia coli K12.";
RL Nucleic Acids Res. 16:7732-7732(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 1-8.
RC STRAIN=K12;
RX PubMed=8955387; DOI=10.1128/jb.178.24.7080-7089.1996;
RA Zeng G., Ye S., Larson T.J.;
RT "Repressor for the sn-glycerol 3-phosphate regulon of Escherichia coli K-
RT 12: primary structure and identification of the DNA-binding domain.";
RL J. Bacteriol. 178:7080-7089(1996).
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 51-52.
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 PARTIAL PROTEIN SEQUENCE, X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 87-272,
RP FUNCTION, TOPOLOGY, ACTIVE SITE, DOMAIN, AND MUTAGENESIS OF SER-201.
RX PubMed=17099694; DOI=10.1038/nsmb1179;
RA Wu Z., Yan N., Feng L., Oberstein A., Yan H., Baker R.P., Gu L.,
RA Jeffrey P.D., Urban S., Shi Y.;
RT "Structural analysis of a rhomboid family intramembrane protease reveals a
RT gating mechanism for substrate entry.";
RL Nat. Struct. Mol. Biol. 13:1084-1091(2006).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF ASN-154;
RP SER-201 AND HIS-254.
RX PubMed=16216077; DOI=10.1021/bi051363k;
RA Maegawa S., Ito K., Akiyama Y.;
RT "Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli
RT cytoplasmic membrane.";
RL Biochemistry 44:13543-13552(2005).
RN [8]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [9]
RP MUTAGENESIS OF ASN-154; SER-201 AND HIS-254.
RX PubMed=16621838; DOI=10.1128/jb.188.9.3415-3419.2006;
RA Clemmer K.M., Sturgill G.M., Veenstra A., Rather P.N.;
RT "Functional characterization of Escherichia coli GlpG and additional
RT rhomboid proteins using an aarA mutant of Providencia stuartii.";
RL J. Bacteriol. 188:3415-3419(2006).
RN [10]
RP TOPOLOGY, AND MUTAGENESIS OF GLY-199; SER-201 AND HIS-254.
RX PubMed=17493126; DOI=10.1111/j.1365-2958.2007.05679.x;
RA Maegawa S., Koide K., Ito K., Akiyama Y.;
RT "The intramembrane active site of GlpG, an E. coli rhomboid protease, is
RT accessible to water and hydrolyses an extramembrane peptide bond of
RT substrates.";
RL Mol. Microbiol. 64:435-447(2007).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 91-272, TOPOLOGY, AND ACTIVE SITE.
RX PubMed=17051161; DOI=10.1038/nature05255;
RA Wang Y., Zhang Y., Ha Y.;
RT "Crystal structure of a rhomboid family intramembrane protease.";
RL Nature 444:179-180(2006).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 92-273, TOPOLOGY, AND ACTIVE SITE.
RX PubMed=17190827; DOI=10.1073/pnas.0609773104;
RA Ben-Shem A., Fass D., Bibi E.;
RT "Structural basis for intramembrane proteolysis by rhomboid serine
RT proteases.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:462-466(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 93-272, AND ACTIVE SITE.
RX PubMed=17277078; DOI=10.1073/pnas.0611080104;
RA Wang Y., Ha Y.;
RT "Open-cap conformation of intramembrane protease GlpG.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2098-2102(2007).
CC -!- FUNCTION: Rhomboid-type serine protease that catalyzes intramembrane
CC proteolysis. {ECO:0000269|PubMed:16216077,
CC ECO:0000269|PubMed:17099694}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad
CC composed of serine and histidine that are contributed by different
CC transmembrane domains.; EC=3.4.21.105;
CC -!- INTERACTION:
CC P09391; P09391: glpG; NbExp=3; IntAct=EBI-9134140, EBI-9134140;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:16216077}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16216077}.
CC -!- DOMAIN: The loop between transmembrane domains 5 and 6 is flexible and
CC may readily open to the extracellular side to allow water entry into
CC the active site cavity. {ECO:0000269|PubMed:17099694}.
CC -!- SIMILARITY: Belongs to the peptidase S54 family. {ECO:0000305}.
CC -!- CAUTION: Was originally identified as a repressor of the glycerol-3-
CC phosphate regulon. {ECO:0000305|PubMed:8955387}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA58222.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M54940; AAA23890.1; -; Genomic_DNA.
DR EMBL; X07520; CAA30398.1; -; Genomic_DNA.
DR EMBL; M96795; AAC28166.1; -; Genomic_DNA.
DR EMBL; U18997; AAA58222.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAT48182.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77868.1; -; Genomic_DNA.
DR PIR; C65138; BVECGG.
DR RefSeq; WP_000928723.1; NZ_LN832404.1.
DR RefSeq; YP_026220.1; NC_000913.3.
DR PDB; 2IC8; X-ray; 2.10 A; A=91-272.
DR PDB; 2IRV; X-ray; 2.30 A; A/B=92-273.
DR PDB; 2LEP; NMR; -; A=1-61.
DR PDB; 2NRF; X-ray; 2.60 A; A/B=91-272.
DR PDB; 2O7L; X-ray; 2.50 A; A=93-272.
DR PDB; 2XOV; X-ray; 1.65 A; A=91-271.
DR PDB; 2XOW; X-ray; 2.09 A; A=92-270.
DR PDB; 2XTU; X-ray; 1.85 A; A=91-271.
DR PDB; 2XTV; X-ray; 1.70 A; A=93-272.
DR PDB; 3B44; X-ray; 1.70 A; A=91-270.
DR PDB; 3B45; X-ray; 1.90 A; A=91-270.
DR PDB; 3TXT; X-ray; 2.30 A; A=92-270.
DR PDB; 3UBB; X-ray; 2.60 A; A=91-272.
DR PDB; 3ZEB; X-ray; 2.20 A; A=92-270.
DR PDB; 3ZMH; X-ray; 2.30 A; A=91-270.
DR PDB; 3ZMI; X-ray; 2.20 A; A=92-270.
DR PDB; 3ZMJ; X-ray; 2.30 A; A=92-270.
DR PDB; 3ZOT; X-ray; 2.40 A; A=92-271.
DR PDB; 4H1D; X-ray; 2.90 A; A=92-270.
DR PDB; 4HDD; X-ray; 1.35 A; A=2-74.
DR PDB; 4NJN; X-ray; 2.40 A; A=87-276.
DR PDB; 4NJP; X-ray; 2.40 A; A=87-276.
DR PDB; 5F5B; X-ray; 2.30 A; A=87-276.
DR PDB; 5F5D; X-ray; 2.50 A; A=87-276.
DR PDB; 5F5G; X-ray; 2.30 A; A=87-276.
DR PDB; 5F5J; X-ray; 2.40 A; A=87-276.
DR PDB; 5F5K; X-ray; 2.40 A; A=87-276.
DR PDB; 5MT6; X-ray; 2.16 A; A=91-270.
DR PDB; 5MT7; X-ray; 2.05 A; A=91-271.
DR PDB; 5MT8; X-ray; 1.95 A; A=92-270.
DR PDB; 6PJ4; X-ray; 2.30 A; A=87-276.
DR PDB; 6PJ5; X-ray; 2.40 A; A=87-276.
DR PDB; 6PJ7; X-ray; 2.30 A; A=87-276.
DR PDB; 6PJ8; X-ray; 2.40 A; A=87-276.
DR PDB; 6PJ9; X-ray; 2.50 A; A=87-276.
DR PDB; 6PJA; X-ray; 2.60 A; A=87-276.
DR PDB; 6PJP; X-ray; 2.45 A; A=87-276.
DR PDB; 6PJQ; X-ray; 2.50 A; A=87-276.
DR PDB; 6PJR; X-ray; 2.40 A; A=87-276.
DR PDB; 6PJU; X-ray; 2.50 A; A=87-276.
DR PDB; 6VJ8; X-ray; 2.30 A; A=87-276.
DR PDB; 6VJ9; X-ray; 2.30 A; A=87-276.
DR PDB; 6XRO; X-ray; 2.30 A; A=87-276.
DR PDB; 6XRP; X-ray; 2.40 A; A=87-276.
DR PDBsum; 2IC8; -.
DR PDBsum; 2IRV; -.
DR PDBsum; 2LEP; -.
DR PDBsum; 2NRF; -.
DR PDBsum; 2O7L; -.
DR PDBsum; 2XOV; -.
DR PDBsum; 2XOW; -.
DR PDBsum; 2XTU; -.
DR PDBsum; 2XTV; -.
DR PDBsum; 3B44; -.
DR PDBsum; 3B45; -.
DR PDBsum; 3TXT; -.
DR PDBsum; 3UBB; -.
DR PDBsum; 3ZEB; -.
DR PDBsum; 3ZMH; -.
DR PDBsum; 3ZMI; -.
DR PDBsum; 3ZMJ; -.
DR PDBsum; 3ZOT; -.
DR PDBsum; 4H1D; -.
DR PDBsum; 4HDD; -.
DR PDBsum; 4NJN; -.
DR PDBsum; 4NJP; -.
DR PDBsum; 5F5B; -.
DR PDBsum; 5F5D; -.
DR PDBsum; 5F5G; -.
DR PDBsum; 5F5J; -.
DR PDBsum; 5F5K; -.
DR PDBsum; 5MT6; -.
DR PDBsum; 5MT7; -.
DR PDBsum; 5MT8; -.
DR PDBsum; 6PJ4; -.
DR PDBsum; 6PJ5; -.
DR PDBsum; 6PJ7; -.
DR PDBsum; 6PJ8; -.
DR PDBsum; 6PJ9; -.
DR PDBsum; 6PJA; -.
DR PDBsum; 6PJP; -.
DR PDBsum; 6PJQ; -.
DR PDBsum; 6PJR; -.
DR PDBsum; 6PJU; -.
DR PDBsum; 6VJ8; -.
DR PDBsum; 6VJ9; -.
DR PDBsum; 6XRO; -.
DR PDBsum; 6XRP; -.
DR AlphaFoldDB; P09391; -.
DR SMR; P09391; -.
DR BioGRID; 4262105; 40.
DR BioGRID; 852245; 1.
DR DIP; DIP-9796N; -.
DR IntAct; P09391; 3.
DR MINT; P09391; -.
DR STRING; 511145.b3424; -.
DR BindingDB; P09391; -.
DR ChEMBL; CHEMBL4296282; -.
DR DrugBank; DB02451; B-nonylglucoside.
DR DrugBank; DB04147; Dodecyldimethylamine N-oxide.
DR MEROPS; S54.016; -.
DR TCDB; 9.B.104.1.1; the rhomboid protease (rhomboid) family.
DR PaxDb; P09391; -.
DR PRIDE; P09391; -.
DR EnsemblBacteria; AAT48182; AAT48182; b3424.
DR EnsemblBacteria; BAE77868; BAE77868; BAE77868.
DR GeneID; 58460244; -.
DR GeneID; 947936; -.
DR KEGG; ecj:JW5687; -.
DR KEGG; eco:b3424; -.
DR PATRIC; fig|1411691.4.peg.3305; -.
DR EchoBASE; EB0392; -.
DR eggNOG; COG0705; Bacteria.
DR HOGENOM; CLU_058989_0_0_6; -.
DR InParanoid; P09391; -.
DR OMA; LLGHCWI; -.
DR PhylomeDB; P09391; -.
DR BioCyc; EcoCyc:EG10397-MON; -.
DR BioCyc; MetaCyc:EG10397-MON; -.
DR BRENDA; 3.4.21.105; 2026.
DR EvolutionaryTrace; P09391; -.
DR PRO; PR:P09391; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:EcoCyc.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0004175; F:endopeptidase activity; IMP:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:EcoCyc.
DR GO; GO:0006508; P:proteolysis; IDA:EcoCyc.
DR Gene3D; 1.20.1540.10; -; 1.
DR Gene3D; 3.30.70.2350; -; 1.
DR HAMAP; MF_01594; Rhomboid_GlpG; 1.
DR InterPro; IPR038236; GlpG_N_sf.
DR InterPro; IPR022732; Peptidase_S54_GlpG_N.
DR InterPro; IPR022764; Peptidase_S54_rhomboid_dom.
DR InterPro; IPR035952; Rhomboid-like_sf.
DR InterPro; IPR023662; Rhomboid_protease_GlpG.
DR Pfam; PF01694; Rhomboid; 1.
DR Pfam; PF12122; Rhomboid_N; 1.
DR SUPFAM; SSF144091; SSF144091; 1.
DR TIGRFAMs; TIGR04239; rhombo_GlpG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane;
KW Direct protein sequencing; Hydrolase; Membrane; Protease;
KW Reference proteome; Serine protease; Transmembrane; Transmembrane helix.
FT CHAIN 1..276
FT /note="Rhomboid protease GlpG"
FT /id="PRO_0000087515"
FT TOPO_DOM 1..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 94..114
FT /note="Helical; Name=1"
FT /evidence="ECO:0000305"
FT TOPO_DOM 115..141
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 142..162
FT /note="Helical; Name=2"
FT /evidence="ECO:0000305"
FT TOPO_DOM 163..168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 169..189
FT /note="Helical; Name=3"
FT /evidence="ECO:0000305"
FT TOPO_DOM 190..191
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 192..212
FT /note="Helical; Name=4"
FT /evidence="ECO:0000305"
FT TOPO_DOM 213..222
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 223..245
FT /note="Helical; Name=5"
FT /evidence="ECO:0000305"
FT TOPO_DOM 246..249
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 250..272
FT /note="Helical; Name=6"
FT /evidence="ECO:0000305"
FT TOPO_DOM 273..276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 201
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:17051161,
FT ECO:0000305|PubMed:17099694, ECO:0000305|PubMed:17190827,
FT ECO:0000305|PubMed:17277078"
FT ACT_SITE 254
FT /evidence="ECO:0000305|PubMed:17051161,
FT ECO:0000305|PubMed:17099694, ECO:0000305|PubMed:17190827,
FT ECO:0000305|PubMed:17277078"
FT MUTAGEN 154
FT /note="N->A: Reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:16216077,
FT ECO:0000269|PubMed:16621838"
FT MUTAGEN 199
FT /note="G->C: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:17493126"
FT MUTAGEN 201
FT /note="S->A,C: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16216077,
FT ECO:0000269|PubMed:16621838, ECO:0000269|PubMed:17099694,
FT ECO:0000269|PubMed:17493126"
FT MUTAGEN 254
FT /note="H->A,C: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16216077,
FT ECO:0000269|PubMed:16621838, ECO:0000269|PubMed:17493126"
FT CONFLICT 51..52
FT /note="EL -> DV (in Ref. 1; AAA23890/CAA30398, 2; AAC28166
FT and 3; AAA58222)"
FT /evidence="ECO:0000305"
FT CONFLICT 178..179
FT /note="TL -> RS (in Ref. 1; AAA23890/CAA30398)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="S -> T (in Ref. 1; AAA23890/CAA30398)"
FT /evidence="ECO:0000305"
FT STRAND 2..9
FT /evidence="ECO:0007829|PDB:2LEP"
FT HELIX 10..22
FT /evidence="ECO:0007829|PDB:4HDD"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:2LEP"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:2LEP"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:4HDD"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:4HDD"
FT HELIX 62..65
FT /evidence="ECO:0007829|PDB:4HDD"
FT HELIX 95..114
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 116..123
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 137..140
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 148..169
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 171..193
FT /evidence="ECO:0007829|PDB:2XOV"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:6PJU"
FT HELIX 201..217
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:2XOV"
FT HELIX 227..241
FT /evidence="ECO:0007829|PDB:2XOV"
FT TURN 242..245
FT /evidence="ECO:0007829|PDB:2XTU"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:2IRV"
FT HELIX 251..270
FT /evidence="ECO:0007829|PDB:2XOV"
SQ SEQUENCE 276 AA; 31307 MW; 6F67374E609968FC CRC64;
MLMITSFANP RVAQAFVDYM ATQGVILTIQ QHNQSDVWLA DESQAERVRA ELARFLENPA
DPRYLAASWQ AGHTGSGLHY RRYPFFAALR ERAGPVTWVM MIACVVVFIA MQILGDQEVM
LWLAWPFDPT LKFEFWRYFT HALMHFSLMH ILFNLLWWWY LGGAVEKRLG SGKLIVITLI
SALLSGYVQQ KFSGPWFGGL SGVVYALMGY VWLRGERDPQ SGIYLQRGLI IFALIWIVAG
WFDLFGMSMA NGAHIAGLAV GLAMAFVDSL NARKRK
