P46891 (COF_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
HMP-PP phosphatase
EC=3.6.1.-

Gene names

Name:	cof
Ordered Locus Names:	b0446, JW0436

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	272 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the hydrolysis of 4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate (HMP-PP) to 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate (HMP-P). Can also hydrolyze other substrates such as MeO-HMP-PP and 4-amino-2-trifluoromethyl 5-hydroxymethylpyrimidine pyrophosphate (CF3-HMP-PP) to give MeO-HMP-P and 4-amino-2-trifluoromethyl-5-hydroxymethylpyrimidine phosphate. This hydrolysis generates resistance to the antibiotics (bacimethrin, CF3-HMP) by reducing the formation of their toxic forms, 2'-methoxythiamin pyrophosphate (MeO-TPP) and CF3-HMP-PP. Also hydrolyzes pyridoxal-phosphate (PLP) and flavin mononucleotide (FMN), and purines (GMP and IMP) as secondary substrates. Ref.6 Ref.7
Cofactor	Magnesium. Can also use other divalent metal cations as manganese, cobalt and zinc. Ref.7
Sequence similarities	Belongs to the HAD-like hydrolase superfamily. Cof family.
Biophysicochemical properties	Kinetic parameters: KM=0.68 mM for PLP (with magnesium ions as cofactor and at pH 9) Ref.7 KM=2.5 mM for 2-deoxyglucose-6-P (with magnesium ions as cofactor and at pH 9) pH dependence: Optimum pH is between 6 and 7.5.
Sequence caution	The sequence AAB40202.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAA91181.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	antibiotic catabolic process Inferred from direct assay Ref.6. Source: UniProtKB thiamine biosynthetic process Inferred from mutant phenotype Ref.6. Source: EcoliWiki
Molecular_function	magnesium ion binding Inferred from electronic annotation. Source: HAMAP nucleoside-diphosphatase activity Inferred from direct assay Ref.6. Source: EcoliWiki phosphatase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
groL	P0A6F5	1	EBI-1117256,EBI-543750

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 272	272	HMP-PP phosphatase HAMAP-Rule MF_01847		PRO_0000054418
Regions
	Region	8 – 10	3	Substrate By similarity
Sites
	Active site	8	1	Nucleophile By similarity
	Metal binding	8	1	Magnesium By similarity
	Metal binding	10	1	Magnesium By similarity
	Metal binding	212	1	Magnesium By similarity
Experimental info
	Sequence conflict	173	1	C → S in BAA11650. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P46891 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: D8FC034BF81E41AC	FASTA	272	30,371
	10 20 30 40 50 60 MARLAAFDMD GTLLMPDHHL GEKTLSTLAR LRERDITLTF ATGRHALEMQ HILGALSLDA 70 80 90 100 110 120 YLITGNGTRV HSLEGELLHR DDLPADVAEL VLYQQWDTRA SMHIFNDDGW FTGKEIPALL 130 140 150 160 170 180 QAFVYSGFRY QIIDVKKMPL GSVTKICFCG DHDDLTRLQI QLYEALGERA HLCFSATDCL 190 200 210 220 230 240 EVLPVGCNKG AALTVLTQHL GLSLRDCMAF GDAMNDREML VSVGSGFIMG NAMPQLRAEL 250 260 270 PHLPVIGHCR NQAVSHYLTH WLDYPHLPYS PE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Patzer S.I., Hantke K. Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
[2]	"Nucleotide sequence analysis of the E. coli chromosome around the 10.0 min region." Hatada E., Ohmori H., Qiao Y., Tsuji M., Fukuda R. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]	"Sequence of minutes 4-25 of Escherichia coli." Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"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.
[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]	"A genetic screen for the identification of thiamin metabolic genes." Lawhorn B.G., Gerdes S.Y., Begley T.P. J. Biol. Chem. 279:43555-43559(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A PYROPHOSPHATASE AND IN THE ANTIBIOTIC RESISTANCE. Strain: K12 / MG1655 / ATCC 47076.
[7]	"Genome-wide analysis of substrate specificities of the Escherichia coli haloacid dehalogenase-like phosphatase family." Kuznetsova E., Proudfoot M., Gonzalez C.F., Brown G., Omelchenko M.V., Borozan I., Carmel L., Wolf Y.I., Mori H., Savchenko A.V., Arrowsmith C.H., Koonin E.V., Edwards A.M., Yakunin A.F. J. Biol. Chem. 281:36149-36161(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A PHOSPHATASE, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, COFACTOR.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z54355 Genomic DNA. Translation: CAA91181.1. Different initiation. D82943 Genomic DNA. Translation: BAA11650.1. U82664 Genomic DNA. Translation: AAB40202.1. Different initiation. U00096 Genomic DNA. Translation: AAC73549.2. AP009048 Genomic DNA. Translation: BAE76226.1.
PIR	F64774.
RefSeq	NP_414980.2. NC_000913.2. YP_488738.1. NC_007779.1.
3D structure databases
ProteinModelPortal	P46891.
SMR	P46891. Positions 1-258.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46891. 1 interaction.
STRING	511145.b0446.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAC73549; AAC73549; b0446. BAE76226; BAE76226; BAE76226.
GeneID	12931657. 945089.
KEGG	ecj:Y75_p0434. eco:b0446.
PATRIC	32116045. VBIEscCol129921_0464.
Organism-specific databases
EchoBASE	EB3007.
EcoGene	EG13216. cof.
Phylogenomic databases
eggNOG	COG0561.
HOGENOM	HOG000184784.
KO	K11938.
OMA	LMPDHRL.
ProtClustDB	PRK15126.
Enzyme and pathway databases
BioCyc	EcoCyc:G6246-MONOMER. ECOL316407:JW0436-MONOMER. MetaCyc:G6246-MONOMER.
Gene expression databases
Genevestigator	P46891.
Family and domain databases
Gene3D	3.40.50.1000. 2 hits.
HAMAP	MF_01847. HMP-PP_phosphat.
InterPro	IPR023214. HAD-like_dom. IPR006379. HAD-SF_hydro_IIB. IPR023938. HMP-PP_phosphatase. IPR000150. Hypothet_cof. [Graphical view]
Pfam	PF08282. Hydrolase_3. 1 hit. [Graphical view]
SUPFAM	SSF56784. HAD-like_dom. 1 hit.
TIGRFAMs	TIGR00099. Cof-subfamily. 1 hit. TIGR01484. HAD-SF-IIB. 1 hit.
PROSITE	PS01228. COF_1. 1 hit. PS01229. COF_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

COF_ECOLI

Accession

Primary (citable) accession number: P46891
Secondary accession number(s): P71208, P77198, Q2MBY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program