P06983 (HEM3_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Porphobilinogen deaminase
Short name=PBG
EC=2.5.1.61

Alternative name(s):
Hydroxymethylbilane synthase
Short name=HMBS
Pre-uroporphyrinogen synthase

Gene names

Name:	hemC
Synonyms:	popE
Ordered Locus Names:	b3805, JW5932

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

General annotation (Comments)

Function	Tetrapolymerization of the monopyrrole PBG into the hydroxymethylbilane pre-uroporphyrinogen in several discrete steps. HAMAP-Rule MF_00260
Catalytic activity	4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3. HAMAP-Rule MF_00260
Cofactor	Binds 1 dipyrromethane group covalently.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4. HAMAP-Rule MF_00260
Subunit structure	Monomer.
Miscellaneous	Arginine residues that are closely associated with one another might be involved in substrate binding. HAMAP-Rule MF_00260 The porphobilinogen subunits are added to the dipyrromethane group. HAMAP-Rule MF_00260
Sequence similarities	Belongs to the HMBS family.
Sequence caution	The sequence AAA67601.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Porphyrin biosynthesis
Molecular function	Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	chlorophyll biosynthetic process Inferred from electronic annotation. Source: HAMAP heme biosynthetic process Inferred from mutant phenotype PubMed 379277. Source: EcoliWiki peptidyl-pyrromethane cofactor linkage Inferred from direct assay PubMed 8727319. Source: EcoliWiki protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytoplasm Inferred from direct assay Ref.8. Source: EcoliWiki
Molecular_function	hydroxymethylbilane synthase activity Inferred from mutant phenotype PubMed 379277. Source: EcoliWiki
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 313

313

Porphobilinogen deaminase HAMAP-Rule MF_00260

PRO_0000142934

Amino acid modifications

Modified residue

242

1

S-(dipyrrolylmethanemethyl)cysteine HAMAP-Rule MF_00260

Experimental info

Mutagenesis

7

1

R → L: No loss of activity. Ref.12 Ref.13

Mutagenesis

11

1

R → L: Loss of activity. Ref.12 Ref.13

Mutagenesis

55

1

K → Q: No loss of activity. Ref.11 Ref.12 Ref.13

Mutagenesis

59

1

K → Q: 25-fold decrease in activity. Ref.11 Ref.12 Ref.13

Mutagenesis

101

1

R → L: No loss of activity. Ref.12 Ref.13

Mutagenesis

131

1

R → L: Complete loss of activity. Ref.12 Ref.13

Mutagenesis

132

1

R → L: Complete loss of activity. Ref.12 Ref.13

Mutagenesis

155

1

R → L: Loss of activity. Ref.12 Ref.13

Mutagenesis

176

1

R → L: Loss of activity. Ref.12 Ref.13

Sequence conflict

137

1

A → G in AAA67601. Ref.3

Sequence conflict

186

1

A → G in AAA67601. Ref.3

Sequence conflict

241

1

G → A in CAA27813. Ref.1

Sequence conflict

261

1

A → G in CAA27813. Ref.1

Sequence conflict

265

1

A → R in AAA67601. Ref.3

Secondary structure

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313

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Helix

14 – 30

17

Beta strand

35 – 40

6

Helix

44 – 47

4

Helix

63 – 71

9

Beta strand

76 – 81

6

Helix

82 – 84

3

Beta strand

93 – 98

6

Beta strand

106 – 109

4

Helix

116 – 118

3

Beta strand

124 – 126

3

Helix

130 – 139

10

Beta strand

143 – 146

4

Helix

152 – 160

9

Beta strand

165 – 170

6

Helix

171 – 176

6

Helix

180 – 182

3

Beta strand

184 – 186

3

Turn

189 – 191

3

Turn

196 – 199

4

Beta strand

201 – 206

6

Helix

210 – 216

7

Helix

217 – 219

3

Helix

222 – 238

17

Beta strand

242 – 244

3

Beta strand

246 – 253

8

Beta strand

256 – 264

9

Beta strand

271 – 278

8

Helix

280 – 282

3

Helix

283 – 296

14

Helix

299 – 304

6

Turn

305 – 308

4

Sequences

	Sequence		Length	Mass (Da)
	P06983 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 7276981B52C7D1E3	FASTA	313	33,852
	10 20 30 40 50 60 MLDNVLRIAT RQSPLALWQA HYVKDKLMAS HPGLVVELVP MVTRGDVILD TPLAKVGGKG 70 80 90 100 110 120 LFVKELEVAL LENRADIAVH SMKDVPVEFP QGLGLVTICE REDPRDAFVS NNYDSLDALP 130 140 150 160 170 180 AGSIVGTSSL RRQCQLAERR PDLIIRSLRG NVGTRLSKLD NGEYDAIILA VAGLKRLGLE 190 200 210 220 230 240 SRIRAALPPE ISLPAVGQGA VGIECRLDDS RTRELLAALN HHETALRVTA ERAMNTRLEG 250 260 270 280 290 300 GCQVPIGSYA ELIDGEIWLR ALVGAPDGSQ IIRGERRGAP QDAEQMGISL AEELLNNGAR 310 EILAEVYNGD APA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the hemC locus encoding porphobilinogen deaminase of Escherichia coli K12." Thomas S.D., Jordan P.M. Nucleic Acids Res. 14:6215-6226(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[2]	"The sequence of hemC, hemD and two additional E. coli genes." Alefounder P.R., Abell C., Battersby A.R. Nucleic Acids Res. 16:9871-9871(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / CS520.
[3]	"Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes." Daniels D.L., Plunkett G. III, Burland V.D., Blattner F.R. Science 257:771-778(1992) [PubMed] [Europe PMC] [Abstract] 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], SEQUENCE REVISION TO 137. Strain: K12 / MG1655 / ATCC 47076.
[5]	"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 186 AND 265.
[6]	"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.
[7]	"Comparative analysis of the cya locus in enterobacteria and related Gram-negative facultative anaerobes." Trotot P., Sismeiro O., Vivares C., Glaser P., Bresson-Roy A., Danchin A. Biochimie 78:277-287(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89. Strain: K12.
[8]	"Purification, crystallization and properties of porphobilinogen deaminase from a recombinant strain of Escherichia coli K12." Jordan P.M., Thomas S.D., Warren M.J. Biochem. J. 254:427-435(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-10.
[9]	"Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound to the protein through the sulphur atom of cysteine-242." Miller A.D., Hart G.J., Packman L.C., Battersby A.R. Biochem. J. 254:915-918(1988) [PubMed] [Europe PMC] [Abstract] Cited for: S-(DIPYRROLYLMETHANEMETHYL)CYSTEINE AT CYS-242.
[10]	"Evidence that pyridoxal phosphate modification of lysine residues (Lys-55 and Lys-59) causes inactivation of hydroxymethylbilane synthase (porphobilinogen deaminase)." Miller A.D., Packman L.C., Hart G.J., Alefounder P.R., Abell C., Battersby A.R. Biochem. J. 262:119-124(1989) [PubMed] [Europe PMC] [Abstract] Cited for: INACTIVATION BY PYRIDOXAL 5'-PHOSPHATE.
[11]	"Investigation of putative active-site lysine residues in hydroxymethylbilane synthase. Preparation and characterization of mutants in which (a) Lys-55, (b) Lys-59 and (c) both Lys-55 and Lys-59 have been replaced by glutamine." Hadener A., Alefounder P.R., Hart G.J., Abell C., Battersby A.R. Biochem. J. 271:487-491(1990) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-55 AND LYS-59.
[12]	"Studies on the mechanism of hydroxymethylbilane synthase concerning the role of arginine residues in substrate binding." Lander M., Pitt A.R., Alefounder P.R., Bardy D., Abell C., Battersby A.R. Biochem. J. 275:447-452(1991) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARGININE RESIDUES.
[13]	"Mutagenesis of arginine residues in the catalytic cleft of Escherichia coli porphobilinogen deaminase that affects dipyrromethane cofactor assembly and tetrapyrrole chain initiation and elongation." Jordan P.M., Woodcock S.C. Biochem. J. 280:445-449(1991) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARGININE RESIDUES.
[14]	"Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site." Louie G.V., Brownlie P.D., Labert R., Cooper J.B., Blundell T.L., Wood S.P., Warren M.J., Woodcock S.C., Jordan P.M. Nature 359:33-39(1992) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), S-(DIPYRROLYLMETHANEMETHYL)CYSTEINE AT CYS-242.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X04242 Genomic DNA. Translation: CAA27813.1.
X12614 Genomic DNA. Translation: CAA31132.1.
M87049 Genomic DNA. Translation: AAA67601.1. Different initiation.
U00096 Genomic DNA. Translation: AAT48218.1.
AP009048 Genomic DNA. Translation: BAE77496.1.
X66782 Genomic DNA. Translation: CAA47279.1.

PIR

IBEC. F65184.

RefSeq

YP_026260.1. NC_000913.2.
YP_491637.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AH5	X-ray	2.40	A	1-313	[»]
1GTK	X-ray	1.66	A	1-313	[»]
1PDA	X-ray	1.76	A	1-313	[»]
1YPN	X-ray	2.30	A	1-313	[»]
2YPN	X-ray	2.30	A	1-313	[»]

ProteinModelPortal

P06983.

SMR

P06983. Positions 3-307.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-9879N.

IntAct

P06983. 1 interaction.

MINT

MINT-1302039.

STRING

511145.b3805.

Proteomic databases

PaxDb

P06983.

PRIDE

P06983.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAT48218; AAT48218; b3805.
BAE77496; BAE77496; BAE77496.

GeneID

12930663.
947759.

KEGG

ecj:Y75_p3373.
eco:b3805.

PATRIC

32123109. VBIEscCol129921_3920.

Organism-specific databases

EchoBASE

EB0424.

EcoGene

EG10429. hemC.

Phylogenomic databases

eggNOG

COG0181.

HOGENOM

HOG000228588.

KO

K01749.

OMA

CLAERAF.

ProtClustDB

PRK00072.

Enzyme and pathway databases

BioCyc

EcoCyc:OHMETHYLBILANESYN-MONOMER.
ECOL316407:JW5932-MONOMER.
MetaCyc:OHMETHYLBILANESYN-MONOMER.

UniPathway

UPA00251; UER00319.

Gene expression databases

Genevestigator

P06983.

Family and domain databases

Gene3D

3.30.160.40. 1 hit.

HAMAP

MF_00260. Porphobil_deam.

InterPro

IPR000860. 4pyrrol_synth_OHMeBilane_synth.
IPR022419. Porphobilin_deaminase_cofac_BS.
IPR022417. Porphobilin_deaminase_N.
IPR022418. Porphobilinogen_deaminase_C.
[Graphical view]

PANTHER

PTHR11557. PTHR11557. 1 hit.

Pfam

PF01379. Porphobil_deam. 1 hit.
PF03900. Porphobil_deamC. 1 hit.
[Graphical view]

PIRSF

PIRSF001438. 4pyrrol_synth_OHMeBilane_synth. 1 hit.

PRINTS

PR00151. PORPHBDMNASE.

SUPFAM

SSF54782. Porphobil_deam. 1 hit.

TIGRFAMs

TIGR00212. hemC. 1 hit.

PROSITE

PS00533. PORPHOBILINOGEN_DEAM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P06983.

Entry information

Entry name

HEM3_ECOLI

Accession

Primary (citable) accession number: P06983
Secondary accession number(s): P78125, Q2M8B0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 145 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program