IAAA_ECOLI
ID IAAA_ECOLI Reviewed; 321 AA.
AC P37595; P75795;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Isoaspartyl peptidase;
DE EC=3.4.19.5;
DE AltName: Full=Beta-aspartyl-peptidase;
DE AltName: Full=EcAIII;
DE AltName: Full=Isoaspartyl dipeptidase;
DE Contains:
DE RecName: Full=Isoaspartyl peptidase subunit alpha;
DE Contains:
DE RecName: Full=Isoaspartyl peptidase subunit beta;
DE Flags: Precursor;
GN Name=iaaA; Synonyms=spt, ybiK; OrderedLocusNames=b0828, JW0812;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52.
RX PubMed=3045084; DOI=10.1128/jb.170.9.4097-4102.1988;
RA Nohno T., Kasai Y., Saito T.;
RT "Cloning and sequencing of the Escherichia coli chlEN operon involved in
RT molybdopterin biosynthesis.";
RL J. Bacteriol. 170:4097-4102(1988).
RN [5]
RP PROTEIN SEQUENCE OF 179-183, FUNCTION, SUBUNIT, AND AUTOCATALYTIC CLEAVAGE.
RX PubMed=11988085; DOI=10.1042/bj3640129;
RA Hejazi M., Piotukh K., Mattow J., Deutzmann R., Volkmer-Engert R.,
RA Lockau W.;
RT "Isoaspartyl dipeptidase activity of plant-type asparaginases.";
RL Biochem. J. 364:129-136(2002).
RN [6]
RP IDENTIFICATION.
RX PubMed=7984428; DOI=10.1093/nar/22.22.4756;
RA Borodovsky M., Rudd K.E., Koonin E.V.;
RT "Intrinsic and extrinsic approaches for detecting genes in a bacterial
RT genome.";
RL Nucleic Acids Res. 22:4756-4767(1994).
RN [7]
RP PROBABLE AUTOCATALYTIC CLEAVAGE, SUBUNIT, AND PRELIMINARY CRYSTALLIZATION.
RC STRAIN=K12 / JM108;
RX PubMed=11053866; DOI=10.1107/s0907444900010076;
RA Borek D., Jaskolski M.;
RT "Crystallization and preliminary crystallographic studies of a new L-
RT asparaginase encoded by the Escherichia coli genome.";
RL Acta Crystallogr. D 56:1505-1507(2000).
RN [8]
RP POSSIBLE FUNCTION IN GLUTATHIONE TRANSPORT, AND CONTROL OF EXPRESSION BY
RP CYSB.
RC STRAIN=K12;
RX PubMed=12007658; DOI=10.1111/j.1574-6968.2002.tb11113.x;
RA Parry J., Clark D.P.;
RT "Identification of a CysB-regulated gene involved in glutathione transport
RT in Escherichia coli.";
RL FEMS Microbiol. Lett. 209:81-85(2002).
RN [9]
RP MASS SPECTROMETRY, AND KINETIC PARAMETERS.
RC STRAIN=K12 / DH5-alpha;
RX PubMed=15265041; DOI=10.1111/j.1432-1033.2004.04254.x;
RA Borek D., Michalska K., Brzezinski K., Kisiel A., Podkowinski J.,
RA Bonthron D.T., Krowarsch D., Otlewski J., Jaskolski M.;
RT "Expression, purification and catalytic activity of Lupinus luteus
RT asparagine beta-amidohydrolase and its Escherichia coli homolog.";
RL Eur. J. Biochem. 271:3215-3226(2004).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-321.
RA Borek D.;
RT "Structural and biochemical studies of asparaginases.";
RL Thesis (2001), A. Mickiewicz University, Poland.
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 2-321, AND SUBUNIT.
RX PubMed=15159592; DOI=10.1107/s0907444904003403;
RA Prahl A., Pazgier M., Hejazi M., Lockau W., Lubkowski J.;
RT "Structure of the isoaspartyl peptidase with L-asparaginase activity from
RT Escherichia coli.";
RL Acta Crystallogr. D 60:1173-1176(2004).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-315 IN COMPLEX WITH L-ASPARTATE.
RC STRAIN=K12 / DH5-alpha;
RX PubMed=15946951; DOI=10.1074/jbc.m504501200;
RA Michalska K., Brzezinski K., Jaskolski M.;
RT "Crystal structure of isoaspartyl aminopeptidase in complex with L-
RT aspartate.";
RL J. Biol. Chem. 280:28484-28491(2005).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 2-321 OF MUTANT THR-179, AND
RP ACTIVE SITE.
RX PubMed=18323626; DOI=10.1107/s0907444907068072;
RA Michalska K., Borek D., Hernandez-Santoyo A., Jaskolski M.;
RT "Crystal packing of plant-type L-asparaginase from Escherichia coli.";
RL Acta Crystallogr. D 64:309-320(2008).
CC -!- FUNCTION: Degrades proteins damaged by L-isoaspartyl residue formation
CC (also known as beta-Asp residues). Degrades L-isoaspartyl-containing
CC di- and maybe also tripeptides. Also has L-asparaginase activity,
CC although this may not be its principal function.
CC {ECO:0000269|PubMed:11988085}.
CC -!- FUNCTION: May be involved in glutathione, and possibly other peptide,
CC transport, although these results could also be due to polar effects of
CC disruption. {ECO:0000269|PubMed:11988085}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of a beta-linked Asp residue from the N-terminus of a
CC polypeptide.; EC=3.4.19.5;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.138 mM for beta-L-Asp-L-Leu {ECO:0000269|PubMed:15265041};
CC KM=3.9 mM for L-Asn {ECO:0000269|PubMed:15265041};
CC Note=No activity for GlcNAc-Asn, Gly-L-Asn, L-Asp, L-Asn-alpha-amide,
CC L-Gln, aspartylglucosamides alpha- or gamma-aspartyl dipeptides.;
CC -!- SUBUNIT: Heterotetramer of two alpha and two beta chains arranged as a
CC dimer of alpha/beta heterodimers. {ECO:0000269|PubMed:11053866,
CC ECO:0000269|PubMed:11988085, ECO:0000269|PubMed:15159592,
CC ECO:0000269|PubMed:15946951}.
CC -!- INDUCTION: Repressed by cysteine, an effect that is attributed to CysB.
CC -!- PTM: Autocleaved. Generates the alpha and beta subunits. The N-terminal
CC residue of the beta subunit is thought to be responsible for the
CC nucleophile hydrolase activity.
CC -!- PTM: Both subunits undergo further processing at their C-termini. The
CC overexpressed alpha subunit seems to consist of residues 2-161, with an
CC oxidized Met residue and a tightly coordinated Na(+), whereas the
CC overexpressed beta subunit is processed to residue 315 and has 3
CC oxidized Met residues. Processing of the alpha subunit is inhibited by
CC Zn(2+).
CC -!- MASS SPECTROMETRY: [Isoaspartyl peptidase subunit alpha]: Mass=17091;
CC Method=Electrospray; Note=Subunit alpha.;
CC Evidence={ECO:0000269|PubMed:15265041};
CC -!- MASS SPECTROMETRY: [Isoaspartyl peptidase subunit beta]: Mass=13852;
CC Method=Electrospray; Note=Subunit beta.;
CC Evidence={ECO:0000269|PubMed:15265041};
CC -!- SIMILARITY: Belongs to the Ntn-hydrolase family. {ECO:0000305}.
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DR EMBL; U00096; AAC73915.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA35516.1; -; Genomic_DNA.
DR EMBL; M21151; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; D64820; D64820.
DR RefSeq; NP_415349.1; NC_000913.3.
DR RefSeq; WP_000513781.1; NZ_LN832404.1.
DR PDB; 1JN9; X-ray; 2.30 A; A/C=2-178, B/D=179-321.
DR PDB; 1K2X; X-ray; 1.65 A; A/C=2-178, B/D=179-321.
DR PDB; 1T3M; X-ray; 1.65 A; A/C=2-178, B/D=179-321.
DR PDB; 2ZAK; X-ray; 2.01 A; A/B=2-321.
DR PDB; 2ZAL; X-ray; 1.90 A; A/C=2-161, B/D=179-315.
DR PDB; 3C17; X-ray; 1.95 A; A/B=2-321.
DR PDBsum; 1JN9; -.
DR PDBsum; 1K2X; -.
DR PDBsum; 1T3M; -.
DR PDBsum; 2ZAK; -.
DR PDBsum; 2ZAL; -.
DR PDBsum; 3C17; -.
DR AlphaFoldDB; P37595; -.
DR SMR; P37595; -.
DR BioGRID; 4259980; 8.
DR IntAct; P37595; 9.
DR STRING; 511145.b0828; -.
DR MEROPS; T02.002; -.
DR jPOST; P37595; -.
DR PaxDb; P37595; -.
DR PRIDE; P37595; -.
DR EnsemblBacteria; AAC73915; AAC73915; b0828.
DR EnsemblBacteria; BAA35516; BAA35516; BAA35516.
DR GeneID; 945456; -.
DR KEGG; ecj:JW0812; -.
DR KEGG; eco:b0828; -.
DR PATRIC; fig|1411691.4.peg.1450; -.
DR EchoBASE; EB2307; -.
DR eggNOG; COG1446; Bacteria.
DR HOGENOM; CLU_021603_1_0_6; -.
DR InParanoid; P37595; -.
DR OMA; YSRMRWK; -.
DR PhylomeDB; P37595; -.
DR BioCyc; EcoCyc:EG12407-MON; -.
DR BioCyc; MetaCyc:EG12407-MON; -.
DR BRENDA; 3.4.19.5; 2026.
DR BRENDA; 3.5.1.1; 2026.
DR SABIO-RK; P37595; -.
DR EvolutionaryTrace; P37595; -.
DR PRO; PR:P37595; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004067; F:asparaginase activity; IDA:EcoCyc.
DR GO; GO:0008798; F:beta-aspartyl-peptidase activity; IDA:EcoCyc.
DR GO; GO:0016787; F:hydrolase activity; IDA:EcoliWiki.
DR GO; GO:0016540; P:protein autoprocessing; IMP:EcoCyc.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR000246; Peptidase_T2.
DR PANTHER; PTHR10188; PTHR10188; 1.
DR Pfam; PF01112; Asparaginase_2; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Direct protein sequencing; Hydrolase;
KW Protease; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..178
FT /note="Isoaspartyl peptidase subunit alpha"
FT /id="PRO_0000002349"
FT CHAIN 179..321
FT /note="Isoaspartyl peptidase subunit beta"
FT /id="PRO_0000329014"
FT ACT_SITE 179
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:18323626"
FT BINDING 207..210
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15946951,
FT ECO:0007744|PDB:2ZAL"
FT BINDING 230..233
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15946951,
FT ECO:0007744|PDB:2ZAL"
FT SITE 178..179
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:11988085"
FT MUTAGEN 179
FT /note="T->A: Catalytically inactive."
FT /evidence="ECO:0000305|PubMed:18323626"
FT STRAND 5..13
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 17..19
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 22..44
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 49..62
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:1K2X"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 94..102
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 106..116
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 124..132
FT /evidence="ECO:0007829|PDB:1K2X"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 147..156
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:3C17"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:3C17"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 191..197
FT /evidence="ECO:0007829|PDB:1K2X"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 233..238
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 241..250
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:1K2X"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 275..281
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 290..301
FT /evidence="ECO:0007829|PDB:1K2X"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:1K2X"
SQ SEQUENCE 321 AA; 33394 MW; 85C6D5377DA0B84D CRC64;
MGKAVIAIHG GAGAISRAQM SLQQELRYIE ALSAIVETGQ KMLEAGESAL DVVTEAVRLL
EECPLFNAGI GAVFTRDETH ELDACVMDGN TLKAGAVAGV SHLRNPVLAA RLVMEQSPHV
MMIGEGAENF AFARGMERVS PEIFSTSLRY EQLLAARKEG ATVLDHSGAP LDEKQKMGTV
GAVALDLDGN LAAATSTGGM TNKLPGRVGD SPLVGAGCYA NNASVAVSCT GTGEVFIRAL
AAYDIAALMD YGGLSLAEAC ERVVMEKLPA LGGSGGLIAI DHEGNVALPF NTEGMYRAWG
YAGDTPTTGI YREKGDTVAT Q
