P09391 (GLPG_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rhomboid protease GlpG
EC=3.4.21.105

Alternative name(s):
Intramembrane serine protease

Gene names

Name:	glpG
Ordered Locus Names:	b3424, JW5687

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	276 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Rhomboid-type serine protease that catalyzes intramembrane proteolysis. Ref.6 Ref.7
Catalytic activity	Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains. HAMAP-Rule MF_01594
Subcellular location	Cell inner membrane; Multi-pass membrane protein Ref.7.
Domain	The loop between transmembrane domains 5 and 6 is flexible and may readily open to the extracellular side to allow water entry into the active site cavity. Ref.6
Sequence similarities	Belongs to the peptidase S54 family.
Caution	Was originally (Ref.2) identified as a repressor of the glycerol-3-phosphate regulon.
Sequence caution	The sequence AAA58222.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell inner membrane Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease Serine protease
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: HAMAP
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.7. Source: EcoCyc
Molecular_function	serine-type endopeptidase activity Inferred from electronic annotation. Source: HAMAP serine-type peptidase activity Inferred from direct assay Ref.7. Source: EcoCyc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 276

276

Rhomboid protease GlpG HAMAP-Rule MF_01594

PRO_0000087515

Regions

Topological domain

1 – 93

93

Cytoplasmic Probable

Transmembrane

94 – 114

21

Helical; Name=1; Probable

Topological domain

115 – 141

27

Periplasmic Probable

Transmembrane

142 – 162

21

Helical; Name=2; Probable

Topological domain

163 – 168

6

Cytoplasmic Probable

Transmembrane

169 – 189

21

Helical; Name=3; Probable

Topological domain

190 – 191

2

Periplasmic Probable

Transmembrane

192 – 212

21

Helical; Name=4; Probable

Topological domain

213 – 222

10

Cytoplasmic Probable

Transmembrane

223 – 245

23

Helical; Name=5; Probable

Topological domain

246 – 249

4

Periplasmic Probable

Transmembrane

250 – 272

23

Helical; Name=6; Probable

Topological domain

273 – 276

4

Cytoplasmic Probable

Sites

Active site

201

1

Nucleophile Ref.6 Ref.11 Ref.12 Ref.13

Active site

254

1

Ref.6 Ref.11 Ref.12 Ref.13

Experimental info

Mutagenesis

154

1

N → A: Reduced catalytic activity. Ref.7 Ref.9

Mutagenesis

199

1

G → C: Loss of catalytic activity. Ref.10

Mutagenesis

201

1

S → A or C: Loss of catalytic activity. Ref.6 Ref.7 Ref.9 Ref.10

Mutagenesis

254

1

H → A or C: Loss of catalytic activity. Ref.7 Ref.9 Ref.10

Sequence conflict

51 – 52

2

EL → DV in AAA23890. Ref.1

Sequence conflict

51 – 52

2

EL → DV in CAA30398. Ref.1

Sequence conflict

51 – 52

2

EL → DV in AAC28166. Ref.2

Sequence conflict

51 – 52

2

EL → DV in AAA58222. Ref.3

Sequence conflict

178 – 179

2

TL → RS in AAA23890. Ref.1

Sequence conflict

178 – 179

2

TL → RS in CAA30398. Ref.1

Sequence conflict

193

1

S → T in AAA23890. Ref.1

Sequence conflict

193

1

S → T in CAA30398. Ref.1

Secondary structure

1

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276

Helix Strand Turn

Details...

Beta strand

2 – 9

8

Helix

10 – 22

13

Beta strand

27 – 30

4

Beta strand

32 – 40

9

Helix

42 – 44

3

Helix

45 – 57

13

Helix

62 – 65

4

Helix

95 – 114

20

Helix

116 – 123

8

Helix

129 – 131

3

Helix

137 – 140

4

Helix

141 – 143

3

Helix

148 – 169

22

Helix

171 – 193

23

Helix

201 – 217

17

Helix

219 – 221

3

Helix

227 – 241

15

Turn

242 – 245

4

Helix

251 – 270

20

Sequences

	Sequence		Length	Mass (Da)
	P09391 [UniParc]. Last modified October 11, 2004. Version 5. Checksum: 6F67374E609968FC	FASTA	276	31,307
	10 20 30 40 50 60 MLMITSFANP RVAQAFVDYM ATQGVILTIQ QHNQSDVWLA DESQAERVRA ELARFLENPA 70 80 90 100 110 120 DPRYLAASWQ AGHTGSGLHY RRYPFFAALR ERAGPVTWVM MIACVVVFIA MQILGDQEVM 130 140 150 160 170 180 LWLAWPFDPT LKFEFWRYFT HALMHFSLMH ILFNLLWWWY LGGAVEKRLG SGKLIVITLI 190 200 210 220 230 240 SALLSGYVQQ KFSGPWFGGL SGVVYALMGY VWLRGERDPQ SGIYLQRGLI IFALIWIVAG 250 260 270 WFDLFGMSMA NGAHIAGLAV GLAMAFVDSL NARKRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the glpR gene encoding the repressor for the glycerol-3-phosphate regulon of Escherichia coli K12." Choi Y.-L., Kawase S., Nishida T., Sakai H., Komano T., Kawamukai M., Utsumi R., Kohara Y., Akiyama K. Nucleic Acids Res. 16:7732-7732(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[2]	"Repressor for the sn-glycerol 3-phosphate regulon of Escherichia coli K-12: primary structure and identification of the DNA-binding domain." Zeng G., Ye S., Larson T.J. J. Bacteriol. 178:7080-7089(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-8. Strain: K12.
[3]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"Escherichia coli K-12: a cooperatively developed annotation snapshot -- 2005." Riley M., Abe T., Arnaud M.B., Berlyn M.K.B., Blattner F.R., Chaudhuri R.R., Glasner J.D., Horiuchi T., Keseler I.M., Kosuge T., Mori H., Perna N.T., Plunkett G. III, Rudd K.E., Serres M.H., Thomas G.H., Thomson N.R., Wishart D., Wanner B.L. Nucleic Acids Res. 34:1-9(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 51-52.
[5]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]	"Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry." Wu Z., Yan N., Feng L., Oberstein A., Yan H., Baker R.P., Gu L., Jeffrey P.D., Urban S., Shi Y. Nat. Struct. Mol. Biol. 13:1084-1091(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 87-272, FUNCTION, TOPOLOGY, ACTIVE SITE, DOMAIN, MUTAGENESIS OF SER-201.
[7]	"Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli cytoplasmic membrane." Maegawa S., Ito K., Akiyama Y. Biochemistry 44:13543-13552(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF ASN-154; SER-201 AND HIS-254.
[8]	"Global topology analysis of the Escherichia coli inner membrane proteome." Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G. Science 308:1321-1323(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY [LARGE SCALE ANALYSIS]. Strain: K12 / MG1655 / ATCC 47076.
[9]	"Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii." Clemmer K.M., Sturgill G.M., Veenstra A., Rather P.N. J. Bacteriol. 188:3415-3419(2006) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-154; SER-201 AND HIS-254.
[10]	"The intramembrane active site of GlpG, an E. coli rhomboid protease, is accessible to water and hydrolyses an extramembrane peptide bond of substrates." Maegawa S., Koide K., Ito K., Akiyama Y. Mol. Microbiol. 64:435-447(2007) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY, MUTAGENESIS OF GLY-199; SER-201 AND HIS-254.
[11]	"Crystal structure of a rhomboid family intramembrane protease." Wang Y., Zhang Y., Ha Y. Nature 444:179-180(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 91-272, TOPOLOGY, ACTIVE SITE.
[12]	"Structural basis for intramembrane proteolysis by rhomboid serine proteases." Ben-Shem A., Fass D., Bibi E. Proc. Natl. Acad. Sci. U.S.A. 104:462-466(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 92-273, TOPOLOGY, ACTIVE SITE.
[13]	"Open-cap conformation of intramembrane protease GlpG." Wang Y., Ha Y. Proc. Natl. Acad. Sci. U.S.A. 104:2098-2102(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 93-272, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M54940 Genomic DNA. Translation: AAA23890.1.
X07520 Genomic DNA. Translation: CAA30398.1.
M96795 Genomic DNA. Translation: AAC28166.1.
U18997 Genomic DNA. Translation: AAA58222.1. Different initiation.
U00096 Genomic DNA. Translation: AAT48182.1.
AP009048 Genomic DNA. Translation: BAE77868.1.

PIR

BVECGG. C65138.

RefSeq

YP_026220.1. NC_000913.2.
YP_492009.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IC8	X-ray	2.10	A	91-272	[»]
2IRV	X-ray	2.30	A/B	92-273	[»]
2LEP	NMR	-	A	1-61	[»]
2NRF	X-ray	2.60	A/B	91-272	[»]
2O7L	X-ray	2.50	A	93-272	[»]
2XOV	X-ray	1.65	A	91-271	[»]
2XOW	X-ray	2.09	A	92-270	[»]
2XTU	X-ray	1.85	A	91-271	[»]
2XTV	X-ray	1.70	A	93-272	[»]
3B44	X-ray	1.70	A	91-270	[»]
3B45	X-ray	1.90	A	91-270	[»]
3TXT	X-ray	2.30	A	92-270	[»]
3UBB	X-ray	2.60	A	91-272	[»]
3ZEB	X-ray	2.20	A	92-270	[»]
4HDD	X-ray	1.35	A	2-74	[»]

ProteinModelPortal

P09391.

SMR

P09391. Positions 1-61, 91-271.

ModBase

Search...

Protein-protein interaction databases

STRING

511145.b3424.

Protein family/group databases

MEROPS

S54.016.

Proteomic databases

PRIDE

P09391.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAT48182; AAT48182; b3424.
BAE77868; BAE77868; BAE77868.

GeneID

12933111.
947936.

KEGG

ecj:Y75_p3753.
eco:b3424.

PATRIC

32122284. VBIEscCol129921_3519.

Organism-specific databases

EchoBASE

EB0392.

EcoGene

EG10397. glpG.

Phylogenomic databases

eggNOG

COG0705.

HOGENOM

HOG000269640.

KO

K02441.

OMA

WYLGGKI.

ProtClustDB

PRK10907.

Enzyme and pathway databases

BioCyc

EcoCyc:EG10397-MONOMER.
ECOL316407:JW5687-MONOMER.
MetaCyc:EG10397-MONOMER.

BRENDA

3.4.21.105. 2026.

Gene expression databases

Genevestigator

P09391.

Family and domain databases

HAMAP

MF_01594. Rhomboid_GlpG.

InterPro

IPR022732. Peptidase_S54_GlpG_N.
IPR002610. Peptidase_S54_rhomboid.
IPR022764. Peptidase_S54_rhomboid_dom.
IPR023662. Rhomboid_protease_GlpG.
[Graphical view]

PANTHER

PTHR22936. PTHR22936. 1 hit.

Pfam

PF12122. DUF3582. 1 hit.
PF01694. Rhomboid. 1 hit.
[Graphical view]

TIGRFAMs

TIGR04239. rhombo_GlpG. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P09391.

Entry information

Entry name

GLPG_ECOLI

Accession

Primary (citable) accession number: P09391
Secondary accession number(s): P76691, Q2M788, Q6BF32

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 113 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program