P39377 (IADA_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isoaspartyl dipeptidase
EC=3.4.19.-

Gene names

Name:	iadA
Synonyms:	yjiF
Ordered Locus Names:	b4328, JW4291

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

General annotation (Comments)

Function	Catalyzes the hydrolytic cleavage of a subset of L-isoaspartyl (L-beta-aspartyl) dipeptides. Used to degrade proteins damaged by L-isoaspartyl residues formation. The best substrate for the enzyme reported thus far is iso-Asp-Leu. Ref.5 Ref.6
Cofactor	Binds 2 zinc ions per subunit. Has highest activity with zinc ions, but is also active with cobalt ions. Ref.5 Ref.6
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase M38 family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	Cobalt Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	beta-aspartyl-peptidase activity Inferred from direct assay Ref.1. Source: EcoCyc hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds Inferred from electronic annotation. Source: InterPro metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from direct assay Ref.5. Source: EcoCyc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 390

390

Isoaspartyl dipeptidase

PRO_0000079178

Regions

Region

75 – 77

3

Substrate binding

Sites

Metal binding

68

1

Zinc 1

Metal binding

70

1

Zinc 1

Metal binding

162

1

Zinc 1

Metal binding

162

1

Zinc 2

Metal binding

201

1

Zinc 2

Metal binding

230

1

Zinc 2

Metal binding

285

1

Zinc 1

Binding site

106

1

Substrate

Binding site

137

1

Substrate

Binding site

169

1

Substrate

Binding site

233

1

Substrate

Binding site

289

1

Substrate; via amide nitrogen and carbonyl oxygen

Amino acid modifications

Modified residue

162

1

N6-carboxylysine

Experimental info

Mutagenesis

77

1

E → D or Q: Reduces activity 100000-fold. Ref.6 Ref.7

Mutagenesis

137

1

Y → A or F: Reduces activity 1000-fold. Ref.6 Ref.7

Mutagenesis

169

1

R → K: Reduces activity 1000-fold. Ref.6

Mutagenesis

169

1

R → M: Loss of activity. Ref.6

Mutagenesis

233

1

R → K: Reduces activity 1000-fold. Ref.6

Mutagenesis

233

1

R → M: Loss of activity. Ref.6

Mutagenesis

285

1

D → A: Reduces activity 100000-fold. Ref.6

Secondary structure

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390

Helix Strand Turn

Details...

Helix

5 – 7

3

Beta strand

10 – 14

5

Beta strand

16 – 25

10

Beta strand

27 – 31

5

Beta strand

34 – 39

6

Beta strand

46 – 49

4

Beta strand

51 – 54

4

Beta strand

59 – 62

4

Beta strand

64 – 69

6

Helix

80 – 82

3

Helix

89 – 94

6

Beta strand

97 – 102

6

Helix

113 – 126

14

Beta strand

128 – 135

8

Beta strand

137 – 140

4

Beta strand

144 – 146

3

Helix

148 – 154

7

Beta strand

158 – 167

10

Helix

175 – 192

18

Beta strand

197 – 202

6

Turn

206 – 209

4

Helix

210 – 217

8

Helix

223 – 225

3

Beta strand

226 – 229

4

Helix

231 – 233

3

Helix

235 – 246

12

Beta strand

251 – 254

4

Beta strand

259 – 261

3

Helix

263 – 272

10

Helix

277 – 279

3

Beta strand

280 – 283

4

Beta strand

289 – 293

5

Beta strand

295 – 297

3

Beta strand

299 – 302

4

Helix

309 – 321

13

Helix

325 – 329

5

Helix

330 – 332

3

Helix

334 – 339

6

Beta strand

356 – 359

4

Beta strand

365 – 370

6

Beta strand

373 – 377

5

Beta strand

380 – 383

4

Sequences

	Sequence		Length	Mass (Da)
	P39377 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 9CEEC838381545B5	FASTA	390	41,084
	10 20 30 40 50 60 MIDYTAAGFT LLQGAHLYAP EDRGICDVLV ANGKIIAVAS NIPSDIVPNC TVVDLSGQIL 70 80 90 100 110 120 CPGFIDQHVH LIGGGGEAGP TTRTPEVALS RLTEAGVTSV VGLLGTDSIS RHPESLLAKT 130 140 150 160 170 180 RALNEEGISA WMLTGAYHVP SRTITGSVEK DVAIIDRVIG VKCAISDHRS AAPDVYHLAN 190 200 210 220 230 240 MAAESRVGGL LGGKPGVTVF HMGDSKKALQ PIYDLLENCD VPISKLLPTH VNRNVPLFEQ 250 260 270 280 290 300 ALEFARKGGT IDITSSIDEP VAPAEGIARA VQAGIPLARV TLSSDGNGSQ PFFDDEGNLT 310 320 330 340 350 360 HIGVAGFETL LETVQVLVKD YDFSISDALR PLTSSVAGFL NLTGKGEILP GNDADLLVMT 370 380 390 PELRIEQVYA RGKLMVKDGK ACVKGTFETA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification and characterization of an isoaspartyl dipeptidase from Escherichia coli." Gary J.D., Clarke S. J. Biol. Chem. 270:4076-4087(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[2]	"Analysis of the Escherichia coli genome VI: DNA sequence of the region from 92.8 through 100 minutes." Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R. Nucleic Acids Res. 23:2105-2119(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[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]	"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.
[5]	"High-resolution X-ray structure of isoaspartyl dipeptidase from Escherichia coli." Thoden J.B., Marti-Arbona R., Raushel F.M., Holden H.M. Biochemistry 42:4874-4882(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 13-389 IN COMPLEX WITH ASPARTATE AND ZINC IONS, FUNCTION, COFACTOR, CARBAMOYLATION AT LYS-162.
[6]	"Mechanism of the reaction catalyzed by isoaspartyl dipeptidase from Escherichia coli." Marti-Arbona R., Fresquet V., Thoden J.B., Davis M.L., Holden H.M., Raushel F.M. Biochemistry 44:7115-7124(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, CARBAMOYLATION AT LYS-162, MUTAGENESIS OF GLU-77; TYR-137; ARG-169; ARG-233 AND ASP-285.
[7]	"Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase." Marti-Arbona R., Thoden J.B., Holden H.M., Raushel F.M. Bioorg. Chem. 33:448-458(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS), MUTAGENESIS OF GLU-77 AND TYR-137.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U15029 Genomic DNA. Translation: AAC43299.1.
U14003 Genomic DNA. Translation: AAA97224.1.
U00096 Genomic DNA. Translation: AAC77284.1.
AP009048 Genomic DNA. Translation: BAE78321.1.

PIR

B55889.

RefSeq

NP_418748.1. NC_000913.2.
YP_492462.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ONW	X-ray	1.65	A/B	1-390	[»]
1ONX	X-ray	2.10	A/B	1-390	[»]
1PO9	X-ray	2.00	A/B	1-390	[»]
1POJ	X-ray	3.30	A/B	1-390	[»]
1POK	X-ray	2.70	A/B	1-390	[»]
1YBQ	X-ray	2.00	A/B	1-390	[»]
2AQO	X-ray	1.95	A/B	1-390	[»]
2AQV	X-ray	1.95	A/B	1-390	[»]

ProteinModelPortal

P39377.

SMR

P39377. Positions 1-389.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-10001N.

IntAct

P39377. 4 interactions.

STRING

511145.b4328.

Protein family/group databases

MEROPS

M38.001.

Proteomic databases

PaxDb

P39377.

PRIDE

P39377.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC77284; AAC77284; b4328.
BAE78321; BAE78321; BAE78321.

GeneID

12932011.
948853.

KEGG

ecj:Y75_p4214.
eco:b4328.

PATRIC

32124258. VBIEscCol129921_4472.

Organism-specific databases

EchoBASE

EB2455.

EcoGene

EG12567. iadA.

Phylogenomic databases

eggNOG

NOG04347.

HOGENOM

HOG000275891.

KO

K01305.

OMA

HRSSQPT.

ProtClustDB

PRK10657.

Enzyme and pathway databases

BioCyc

EcoCyc:G7925-MONOMER.
ECOL316407:JW4291-MONOMER.
MetaCyc:G7925-MONOMER.

Gene expression databases

Genevestigator

P39377.

Family and domain databases

InterPro

IPR011059. Metal-dep_hydrolase_composite.
IPR010229. Pept_M38_dipep.
[Graphical view]

PIRSF

PIRSF001238. IadA. 1 hit.

SUPFAM

SSF51338. Metalo_hydrolase. 1 hit.

TIGRFAMs

TIGR01975. isoAsp_dipep. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P39377.

Entry information

Entry name

IADA_ECOLI

Accession

Primary (citable) accession number: P39377
Secondary accession number(s): Q2M5Y5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program