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Protein

Isoaspartyl peptidase

Gene

iaaA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Degrades proteins damaged by L-isoaspartyl residue formation (also known as beta-Asp residues). Degrades L-isoaspartyl-containing di- and maybe also tripeptides. Also has L-asparaginase activity, although this may not be its principal function.1 Publication
May be involved in glutathione, and possibly other peptide, transport, although these results could also be due to polar effects of disruption.1 Publication

Catalytic activityi

Cleavage of a beta-linked Asp residue from the N-terminus of a polypeptide.

Kineticsi

No activity for GlcNAc-Asn, Gly-L-Asn, L-Asp, L-Asn-alpha-amide, L-Gln, aspartylglucosamides alpha- or gamma-aspartyl dipeptides.

  1. KM=0.138 mM for beta-L-Asp-L-Leu1 Publication
  2. KM=3.9 mM for L-Asn1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei179 – 1791Nucleophile1 Publication

    GO - Molecular functioni

    • asparaginase activity Source: EcoCyc
    • beta-aspartyl-peptidase activity Source: EcoCyc
    • hydrolase activity Source: EcoliWiki

    GO - Biological processi

    • protein autoprocessing Source: EcoCyc
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease

    Enzyme and pathway databases

    BioCyciEcoCyc:EG12407-MONOMER.
    ECOL316407:JW0812-MONOMER.
    MetaCyc:EG12407-MONOMER.
    BRENDAi3.4.19.5. 2026.
    3.5.1.1. 2026.
    SABIO-RKP37595.

    Protein family/group databases

    MEROPSiT02.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Isoaspartyl peptidase (EC:3.4.19.5)
    Alternative name(s):
    Beta-aspartyl-peptidase
    EcAIII
    Isoaspartyl dipeptidase
    Cleaved into the following 2 chains:
    Gene namesi
    Name:iaaA
    Synonyms:spt, ybiK
    Ordered Locus Names:b0828, JW0812
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG12407. iaaA.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi179 – 1791T → A: Catalytically inactive. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methionineiRemoved
    Chaini2 – 178177Isoaspartyl peptidase subunit alphaPRO_0000002349Add
    BLAST
    Chaini179 – 321143Isoaspartyl peptidase subunit betaPRO_0000329014Add
    BLAST

    Post-translational modificationi

    Autocleaved. Generates the alpha and beta subunits. The N-terminal residue of the beta subunit is thought to be responsible for the nucleophile hydrolase activity.
    Both subunits undergo further processing at their C-termini. The overexpressed alpha subunit seems to consist of residues 2-161, with an oxidized Met residue and a tightly coordinated Na+, whereas the overexpressed beta subunit is processed to residue 315 and has 3 oxidized Met residues. Processing of the alpha subunit is inhibited by Zn2+.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei178 – 1792Cleavage; by autolysis1 Publication

    Keywords - PTMi

    Autocatalytic cleavage

    Proteomic databases

    PaxDbiP37595.

    Expressioni

    Inductioni

    Repressed by cysteine, an effect that is attributed to CysB.

    Interactioni

    Subunit structurei

    Heterotetramer of two alpha and two beta chains arranged as a dimer of alpha/beta heterodimers.4 Publications

    Protein-protein interaction databases

    BioGridi4259980. 8 interactions.
    IntActiP37595. 9 interactions.
    STRINGi511145.b0828.

    Structurei

    Secondary structure

    1
    321
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 139Combined sources
    Helixi17 – 193Combined sources
    Helixi22 – 4423Combined sources
    Helixi49 – 6214Combined sources
    Beta strandi66 – 694Combined sources
    Beta strandi82 – 887Combined sources
    Turni89 – 913Combined sources
    Beta strandi94 – 1029Combined sources
    Helixi106 – 11611Combined sources
    Beta strandi120 – 1234Combined sources
    Helixi124 – 1329Combined sources
    Turni133 – 1353Combined sources
    Helixi141 – 1444Combined sources
    Helixi147 – 15610Combined sources
    Beta strandi170 – 1723Combined sources
    Turni174 – 1763Combined sources
    Beta strandi180 – 1856Combined sources
    Beta strandi191 – 1977Combined sources
    Turni214 – 2163Combined sources
    Beta strandi217 – 2204Combined sources
    Beta strandi224 – 2318Combined sources
    Helixi233 – 2386Combined sources
    Helixi241 – 25010Combined sources
    Helixi256 – 26510Combined sources
    Helixi267 – 2704Combined sources
    Beta strandi275 – 2817Combined sources
    Beta strandi290 – 30112Combined sources
    Beta strandi307 – 3115Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1JN9X-ray2.30A/C2-178[»]
    B/D179-321[»]
    1K2XX-ray1.65A/C2-178[»]
    B/D179-321[»]
    1T3MX-ray1.65A/C2-178[»]
    B/D179-321[»]
    2ZAKX-ray2.01A/B2-321[»]
    2ZALX-ray1.90A/C2-161[»]
    B/D179-315[»]
    3C17X-ray1.95A/B2-321[»]
    ProteinModelPortaliP37595.
    SMRiP37595. Positions 2-313.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP37595.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni207 – 2104Substrate bindingCombined sources1 Publication
    Regioni230 – 2334Substrate bindingCombined sources1 Publication

    Sequence similaritiesi

    Belongs to the Ntn-hydrolase family.Curated

    Phylogenomic databases

    eggNOGiENOG4105D44. Bacteria.
    COG1446. LUCA.
    HOGENOMiHOG000174613.
    InParanoidiP37595.
    KOiK13051.
    OMAiEVFMRTV.
    OrthoDBiEOG676Z2J.
    PhylomeDBiP37595.

    Family and domain databases

    InterProiIPR029055. Ntn_hydrolases_N.
    IPR000246. Peptidase_T2.
    [Graphical view]
    PANTHERiPTHR10188. PTHR10188. 1 hit.
    PfamiPF01112. Asparaginase_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF56235. SSF56235. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P37595-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MGKAVIAIHG GAGAISRAQM SLQQELRYIE ALSAIVETGQ KMLEAGESAL
    60 70 80 90 100
    DVVTEAVRLL EECPLFNAGI GAVFTRDETH ELDACVMDGN TLKAGAVAGV
    110 120 130 140 150
    SHLRNPVLAA RLVMEQSPHV MMIGEGAENF AFARGMERVS PEIFSTSLRY
    160 170 180 190 200
    EQLLAARKEG ATVLDHSGAP LDEKQKMGTV GAVALDLDGN LAAATSTGGM
    210 220 230 240 250
    TNKLPGRVGD SPLVGAGCYA NNASVAVSCT GTGEVFIRAL AAYDIAALMD
    260 270 280 290 300
    YGGLSLAEAC ERVVMEKLPA LGGSGGLIAI DHEGNVALPF NTEGMYRAWG
    310 320
    YAGDTPTTGI YREKGDTVAT Q
    Length:321
    Mass (Da):33,394
    Last modified:November 1, 1997 - v2
    Checksum:i85C6D5377DA0B84D
    GO

    Mass spectrometryi

    Molecular mass is 17091 Da from positions 2 - 161. Determined by ESI. Subunit alpha.1 Publication
    Molecular mass is 13852 Da from positions 179 - 315. Determined by ESI. Subunit beta.1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U00096 Genomic DNA. Translation: AAC73915.1.
    AP009048 Genomic DNA. Translation: BAA35516.1.
    M21151 Genomic DNA. No translation available.
    PIRiD64820.
    RefSeqiNP_415349.1. NC_000913.3.
    WP_000513781.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC73915; AAC73915; b0828.
    BAA35516; BAA35516; BAA35516.
    GeneIDi945456.
    KEGGiecj:JW0812.
    eco:b0828.
    PATRICi32116859. VBIEscCol129921_0855.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U00096 Genomic DNA. Translation: AAC73915.1.
    AP009048 Genomic DNA. Translation: BAA35516.1.
    M21151 Genomic DNA. No translation available.
    PIRiD64820.
    RefSeqiNP_415349.1. NC_000913.3.
    WP_000513781.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1JN9X-ray2.30A/C2-178[»]
    B/D179-321[»]
    1K2XX-ray1.65A/C2-178[»]
    B/D179-321[»]
    1T3MX-ray1.65A/C2-178[»]
    B/D179-321[»]
    2ZAKX-ray2.01A/B2-321[»]
    2ZALX-ray1.90A/C2-161[»]
    B/D179-315[»]
    3C17X-ray1.95A/B2-321[»]
    ProteinModelPortaliP37595.
    SMRiP37595. Positions 2-313.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4259980. 8 interactions.
    IntActiP37595. 9 interactions.
    STRINGi511145.b0828.

    Protein family/group databases

    MEROPSiT02.002.

    Proteomic databases

    PaxDbiP37595.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC73915; AAC73915; b0828.
    BAA35516; BAA35516; BAA35516.
    GeneIDi945456.
    KEGGiecj:JW0812.
    eco:b0828.
    PATRICi32116859. VBIEscCol129921_0855.

    Organism-specific databases

    EchoBASEiEB2307.
    EcoGeneiEG12407. iaaA.

    Phylogenomic databases

    eggNOGiENOG4105D44. Bacteria.
    COG1446. LUCA.
    HOGENOMiHOG000174613.
    InParanoidiP37595.
    KOiK13051.
    OMAiEVFMRTV.
    OrthoDBiEOG676Z2J.
    PhylomeDBiP37595.

    Enzyme and pathway databases

    BioCyciEcoCyc:EG12407-MONOMER.
    ECOL316407:JW0812-MONOMER.
    MetaCyc:EG12407-MONOMER.
    BRENDAi3.4.19.5. 2026.
    3.5.1.1. 2026.
    SABIO-RKP37595.

    Miscellaneous databases

    EvolutionaryTraceiP37595.
    PROiP37595.

    Family and domain databases

    InterProiIPR029055. Ntn_hydrolases_N.
    IPR000246. Peptidase_T2.
    [Graphical view]
    PANTHERiPTHR10188. PTHR10188. 1 hit.
    PfamiPF01112. Asparaginase_2. 1 hit.
    [Graphical view]
    SUPFAMiSSF56235. SSF56235. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    3. "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.
    4. "Cloning and sequencing of the Escherichia coli chlEN operon involved in molybdopterin biosynthesis."
      Nohno T., Kasai Y., Saito T.
      J. Bacteriol. 170:4097-4102(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52.
    5. "Isoaspartyl dipeptidase activity of plant-type asparaginases."
      Hejazi M., Piotukh K., Mattow J., Deutzmann R., Volkmer-Engert R., Lockau W.
      Biochem. J. 364:129-136(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 179-183, FUNCTION, SUBUNIT, AUTOCATALYTIC CLEAVAGE.
    6. "Intrinsic and extrinsic approaches for detecting genes in a bacterial genome."
      Borodovsky M., Rudd K.E., Koonin E.V.
      Nucleic Acids Res. 22:4756-4767(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION.
    7. "Crystallization and preliminary crystallographic studies of a new L-asparaginase encoded by the Escherichia coli genome."
      Borek D., Jaskolski M.
      Acta Crystallogr. D 56:1505-1507(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROBABLE AUTOCATALYTIC CLEAVAGE, SUBUNIT, PRELIMINARY CRYSTALLIZATION.
      Strain: K12 / JM108.
    8. "Identification of a CysB-regulated gene involved in glutathione transport in Escherichia coli."
      Parry J., Clark D.P.
      FEMS Microbiol. Lett. 209:81-85(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: POSSIBLE FUNCTION IN GLUTATHIONE TRANSPORT, CONTROL OF EXPRESSION BY CYSB.
      Strain: K12.
    9. "Expression, purification and catalytic activity of Lupinus luteus asparagine beta-amidohydrolase and its Escherichia coli homolog."
      Borek D., Michalska K., Brzezinski K., Kisiel A., Podkowinski J., Bonthron D.T., Krowarsch D., Otlewski J., Jaskolski M.
      Eur. J. Biochem. 271:3215-3226(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: MASS SPECTROMETRY, KINETIC PARAMETERS.
      Strain: K12 / DH5-alpha.
    10. "Structural and biochemical studies of asparaginases."
      Borek D.
      Thesis (2001), A. Mickiewicz University, Poland
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-321.
    11. "Structure of the isoaspartyl peptidase with L-asparaginase activity from Escherichia coli."
      Prahl A., Pazgier M., Hejazi M., Lockau W., Lubkowski J.
      Acta Crystallogr. D 60:1173-1176(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 2-321, SUBUNIT.
    12. "Crystal structure of isoaspartyl aminopeptidase in complex with L-aspartate."
      Michalska K., Brzezinski K., Jaskolski M.
      J. Biol. Chem. 280:28484-28491(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-315 IN COMPLEX WITH L-ASPARTATE.
      Strain: K12 / DH5-alpha.
    13. "Crystal packing of plant-type L-asparaginase from Escherichia coli."
      Michalska K., Borek D., Hernandez-Santoyo A., Jaskolski M.
      Acta Crystallogr. D 64:309-320(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 2-321 OF MUTANT THR-179, ACTIVE SITE.

    Entry informationi

    Entry nameiIAAA_ECOLI
    AccessioniPrimary (citable) accession number: P37595
    Secondary accession number(s): P75795
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: November 1, 1997
    Last modified: January 20, 2016
    This is version 127 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.