P0A7E9 (PYRH_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Uridylate kinase
Short name=UK
EC=2.7.4.22

Alternative name(s):
Uridine monophosphate kinase
Short name=UMP kinase
Short name=UMPK

Gene names

Name:	pyrH
Synonyms:	smbA
Ordered Locus Names:	b0171, JW0166

Organism

Escherichia coli (strain K12)

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	241 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the reversible phosphorylation of UMP to UDP, with ATP as the most efficient phosphate donor. Ref.3
Catalytic activity	ATP + UMP = ADP + UDP. HAMAP MF_01220_B
Enzyme regulation	Allosterically activated by GTP. Competitively inhibited by magnesium-free UTP. Magnesium-bound UTP is unable to inhibit enzyme activity. Ref.12 Ref.13
Pathway	Pyrimidine metabolism; CTP biosynthesis via de novo pathway; UDP from UMP (UMPK route): step 1/1. HAMAP MF_01220_B
Subunit structure	Homohexamer. Ref.3
Subcellular location	Cytoplasm. Note: Is predominantly localized near the bacterial membranes. Ref.10
Miscellaneous	The peripheral distribution of pyrH is related most probably to its role in the synthesis of membrane sugar components. HAMAP MF_01220_B
Sequence similarities	Belongs to the UMP kinase family.
Biophysicochemical properties	Kinetic parameters: KM=120 µM for ATP Ref.3 KM=50 µM for UMP Vmax=96 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cellular amino acid biosynthetic process Inferred from electronic annotation. Source: InterPro pyrimidine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW UMP kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
deoD	P0ABP8	1	EBI-370182,EBI-907568

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 241

240

Uridylate kinase HAMAP MF_01220_B

PRO_0000143842

Regions

Nucleotide binding

15 – 18

4

ATP By similarity

Nucleotide binding

138 – 145

8

UMP HAMAP MF_01220_B

Region

23 – 28

6

Involved in allosteric activation by GTP Potential

Sites

Binding site

57

1

UMP; via amide nitrogen

Binding site

58

1

ATP; via amide nitrogen By similarity

Binding site

62

1

ATP By similarity

Binding site

77

1

UMP

Binding site

165

1

ATP By similarity

Binding site

171

1

ATP; via amide nitrogen and carbonyl oxygen By similarity

Binding site

174

1

ATP By similarity

Natural variations

Natural variant

62

1

R → H in Smba9.

Natural variant

201

1

D → N in Smba2.

Experimental info

Mutagenesis

62

1

R → H: Loss of activation by GTP and decreased affinity for UTP. Ref.11

Mutagenesis

77

1

D → N: Loss of activation by GTP and decreased affinity for UTP. Ref.11

Mutagenesis

138

1

T → A: Loss of activation by GTP. Moderate loss of sensitivity to UTP inhibition. 4-fold and 2-fold decrease in affinity for UMP and ATP, respectively. Ref.13

Mutagenesis

140

1

N → A: Loss of activation by GTP. Moderate loss of sensitivity to UTP inhibition. Ref.13

Mutagenesis

146

1

D → N: Drastically reduced activity. Ref.11

Mutagenesis

159

1

D → N: Increased solubility at neutral pH. Nearly no change in kinetic properties and stability. Ref.11

Mutagenesis

174

1

D → N: Reduced UMP-binding affinity. Ref.11

Mutagenesis

201

1

D → N: Loss of activation by GTP. Ref.3 Ref.11

Sequence conflict

64 – 69

6

AGLAKA → RWSGET in CAA55388. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

241

Helix Strand Turn

Details...

Beta strand

10 – 16

7

Helix

18 – 21

4

Beta strand

26 – 28

3

Helix

31 – 46

16

Beta strand

50 – 55

6

Turn

58 – 60

3

Helix

63 – 68

6

Helix

73 – 97

25

Beta strand

102 – 108

7

Turn

111 – 113

3

Beta strand

114 – 116

3

Helix

119 – 127

9

Beta strand

131 – 136

6

Helix

145 – 155

11

Beta strand

159 – 169

11

Beta strand

171 – 173

3

Beta strand

185 – 188

4

Helix

189 – 194

6

Helix

202 – 210

9

Beta strand

215 – 219

5

Helix

225 – 230

6

Beta strand

236 – 240

5

Sequences

	Sequence		Length	Mass (Da)
	P0A7E9 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 82EFA75F7226E201	FASTA	241	25,970
	10 20 30 40 50 60 MATNAKPVYK RILLKLSGEA LQGTEGFGID ASILDRMAQE IKELVELGIQ VGVVIGGGNL 70 80 90 100 110 120 FRGAGLAKAG MNRVVGDHMG MLATVMNGLA MRDALHRAYV NARLMSAIPL NGVCDSYSWA 130 140 150 160 170 180 EAISLLRNNR VVILSAGTGN PFFTTDSAAC LRGIEIEADV VLKATKVDGV FTADPAKDPT 190 200 210 220 230 240 ATMYEQLTYS EVLEKELKVM DLAAFTLARD HKLPIRVFNM NKPGALRRVV MGEKEGTLIT E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, nucleotide sequence and expression of the Escherichia coli K-12 pyrH gene encoding UMP kinase." Smallshaw J.E., Kelln R.A. Life Sci. Adv. (Genet.) 11:59-65(1992) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION. Strain: K12.
[2]	"Identification and characterization of the smbA gene, a suppressor of the mukB null mutant of Escherichia coli." Yamanaka K., Ogura T., Niki H., Hiraga S. J. Bacteriol. 174:7517-7526(1992) [PubMed: 1447125] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Escherichia coli UMP-kinase, a member of the aspartokinase family, is a hexamer regulated by guanine nucleotides and UTP." Serina L., Blondin C., Krin E., Sismeiro O., Danchin A., Sakamoto H., Gilles A.-M., Barzu O. Biochemistry 34:5066-5074(1995) [PubMed: 7711027] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-8, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION, SUBUNIT, MUTAGENESIS OF ASP-201.
[4]	"Systematic sequencing of the Escherichia coli genome: analysis of the 2.4-4.1 min (110,917-193,643 bp) region." Fujita N., Mori H., Yura T., Ishihama A. Nucleic Acids Res. 22:1637-1639(1994) [PubMed: 8202364] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Systematic sequencing of the Escherichia coli genome: analysis of the 4.0 - 6.0 min (189,987 - 281,416bp) region." Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T., Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S., Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]	"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.
[7]	"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: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[8]	"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: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[9]	"Multicopy suppressors, mssA and mssB, of an smbA mutation of Escherichia coli." Yamanaka K., Ogura T., Koonin E.V., Niki H., Hiraga S. Mol. Gen. Genet. 243:9-16(1994) [PubMed: 8190075] [Abstract] Cited for: CHARACTERIZATION.
[10]	"Immunochemical analysis of UMP kinase from Escherichia coli." Landais S., Gounon P., Laurent-Winter C., Mazie J.-C., Danchin A., Barzu O., Sakamoto H. J. Bacteriol. 181:833-840(1999) [PubMed: 9922246] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"Mutational analysis of UMP kinase from Escherichia coli." Bucurenci N., Serina L., Zaharia C., Landais S., Danchin A., Barzu O. J. Bacteriol. 180:473-477(1998) [PubMed: 9457846] [Abstract] Cited for: MUTAGENESIS OF ARG-62; ASP-77; ASP-146; ASP-159; ASP-174 AND ASP-201.
[12]	"Regulatory mechanisms differ in UMP kinases from Gram-negative and Gram-positive bacteria." Evrin C., Straut M., Slavova-Azmanova N., Bucurenci N., Onu A., Assairi L., Ionescu M., Palibroda N., Barzu O., Gilles A.-M. J. Biol. Chem. 282:7242-7253(2007) [PubMed: 17210578] [Abstract] Cited for: ENZYME REGULATION.
[13]	"Structure of Escherichia coli UMP kinase differs from that of other nucleoside monophosphate kinases and sheds new light on enzyme regulation." Briozzo P., Evrin C., Meyer P., Assairi L., Joly N., Barzu O., Gilles A.-M. J. Biol. Chem. 280:25533-25540(2005) [PubMed: 15857829] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ASN-159 IN COMPLEX WITH UMP; UDP AND UTP, ENZYME REGULATION, MUTAGENESIS OF THR-138 AND ASN-140.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X78809 Genomic DNA. Translation: CAA55388.1.
D13334 Genomic DNA. Translation: BAA02598.1.
U70214 Genomic DNA. Translation: AAB08600.1.
U00096 Genomic DNA. Translation: AAC73282.1.
AP009048 Genomic DNA. Translation: BAB96747.1.

PIR

B45269.

RefSeq

NP_414713.1. NC_000913.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BND	X-ray	2.60	A/B	1-241	[»]
2BNE	X-ray	2.30	A/B	1-241	[»]
2BNF	X-ray	2.45	A/B	1-241	[»]
2V4Y	X-ray	2.80	A/B/C/D/E/F	1-241	[»]

ProteinModelPortal

P0A7E9.

SMR

P0A7E9. Positions 3-241.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31830N.

IntAct

P0A7E9. 53 interactions.

MINT

MINT-1222953.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBESCT00000004594; EBESCP00000004594; EBESCG00000003743.
EBESCT00000016112; EBESCP00000015403; EBESCG00000015172.

GeneID

944989.

GenomeReviews

Gene locus JW0166 in contig AP009048_GR.
Gene locus b0171 in contig U00096_GR.

KEGG

ecj:JW0166.
eco:b0171.

PATRIC

32115451. VBIEscCol129921_0177.

Organism-specific databases

EchoBASE

EB1501.

EcoGene

EG11539. pyrH.

Phylogenomic databases

eggNOG

COG0528.

GeneTree

EBGT00050000010956.

HOGENOM

HBG497552.

OMA

RHMEKGR.

PhylomeDB

P0A7E9.

ProtClustDB

PRK00358.

Enzyme and pathway databases

BioCyc

EcoCyc:UMPKI-MONOMER.
MetaCyc:UMPKI-MONOMER.

BRENDA

2.7.4.22. 2026.

Gene expression databases

Genevestigator

P0A7E9.

Family and domain databases

HAMAP

MF_01220_B. PyrH_B.
[Tree]

InterPro

IPR001048. Asp/Glu/Uridylate_kinase.
IPR011817. Uridylate_kinase.
IPR015963. Uridylate_kinase_bac.
[Graphical view]

Gene3D

G3DSA:3.40.1160.10. Aa_kinase. 1 hit.

KO

K09903.

PANTHER

PTHR26059. PTHR26059. 1 hit.

Pfam

PF00696. AA_kinase. 1 hit.
[Graphical view]

PIRSF

PIRSF005650. Uridylate_kin. 1 hit.

SUPFAM

SSF53633. Aa_kinase. 1 hit.

TIGRFAMs

TIGR02075. PyrH_bact. 1 hit.

ProtoNet

Search...

Entry information

Entry name

PYRH_ECOLI

Accession

Primary (citable) accession number: P0A7E9
Secondary accession number(s): P29464

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2005
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 67 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program