ACY3_MOUSE
ID ACY3_MOUSE Reviewed; 318 AA.
AC Q91XE4; Q3UP59; Q9DD17;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming);
DE EC=3.5.1.114;
DE AltName: Full=Acylase III;
DE AltName: Full=Aminoacylase III;
DE Short=AAIII;
DE AltName: Full=Aminoacylase-3;
DE Short=ACY-3;
DE AltName: Full=Aspartoacylase-2;
DE AltName: Full=Hepatitis C virus core-binding protein 1;
DE Short=HCBP1;
GN Name=Acy3; Synonyms=Aspa2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Kidney;
RA Chen H., Peng J., Huang C.-H.;
RT "The mouse aspartoacylase-3 gene (ACY-3) generates two mRNA isoforms by
RT alternative splicing of 5' untranslated region.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BALB/cJ;
RA Huang C.-H., Chen H., Peng J., Chen Y.;
RT "Identification of a novel aspartoacylase homolog (ACY-3) in human and
RT mouse kidneys.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=14656720; DOI=10.1152/ajpcell.00192.2003;
RA Pushkin A., Carpenito G., Abuladze N., Newman D., Tsuprun V.,
RA Ryazantsev S., Motemoturu S., Sassani P., Solovieva N., Dukkipati R.,
RA Kurtz I.;
RT "Structural characterization, tissue distribution, and functional
RT expression of murine aminoacylase III.";
RL Am. J. Physiol. 286:C848-C856(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Li K., Cheng J., Zhang L., Wang L., Lu Y., Wang G., Liu Y.;
RT "Cloning and sequence analysis of cDNA encoding hepatitis C virus core-
RT binding protein 1 (HCBP1) from mouse.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=17012540; DOI=10.1124/dmd.106.012062;
RA Newman D., Abuladze N., Scholz K., Dekant W., Tsuprun V., Ryazantsev S.,
RA Bondar G., Sassani P., Kurtz I., Pushkin A.;
RT "Specificity of aminoacylase III-mediated deacetylation of mercapturic
RT acids.";
RL Drug Metab. Dispos. 35:43-50(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP STRUCTURE BY ELECTRON MICROSCOPY (16 ANGSTROMS), AND SUBUNIT.
RX PubMed=17434493; DOI=10.1016/j.febslet.2007.03.088;
RA Ryazantsev S., Abuladze N., Newman D., Bondar G., Kurtz I., Pushkin A.;
RT "Structural characterization of dimeric murine aminoacylase III.";
RL FEBS Lett. 581:1898-1902(2007).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATES,
RP ZINC-BINDING SITES, SUBUNIT, COFACTOR, AND MUTAGENESIS OF ARG-63 AND
RP TYR-287.
RX PubMed=20921362; DOI=10.1073/pnas.1006687107;
RA Hsieh J.M., Tsirulnikov K., Sawaya M.R., Magilnick N., Abuladze N.,
RA Kurtz I., Abramson J., Pushkin A.;
RT "Structures of aminoacylase 3 in complex with acetylated substrates.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:17962-17967(2010).
CC -!- FUNCTION: Plays an important role in deacetylating mercapturic acids in
CC kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids.
CC {ECO:0000269|PubMed:14656720, ECO:0000269|PubMed:17012540}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acyl-aromatic L-alpha-amino acid + H2O = a carboxylate +
CC an aromatic L-alpha-amino acid; Xref=Rhea:RHEA:54184,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29067, ChEBI:CHEBI:84824,
CC ChEBI:CHEBI:138093; EC=3.5.1.114;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acetyl-L-cysteine-S-conjugate + H2O = acetate + an S-
CC substituted L-cysteine; Xref=Rhea:RHEA:36855, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:58717, ChEBI:CHEBI:58718;
CC EC=3.5.1.114;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:20921362};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:20921362};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 mM for S-benzyl-N-acetyl-L-cysteine
CC {ECO:0000269|PubMed:14656720};
CC KM=1.8 mM for N-acetyl-L-histidine {ECO:0000269|PubMed:14656720};
CC KM=1.4 mM for N-acetyl-L-tyrosine {ECO:0000269|PubMed:14656720};
CC KM=1.6 mM for N-acetyl-L-phenylalanine {ECO:0000269|PubMed:14656720};
CC Vmax=11.7 umol/min/mg enzyme with S-benzyl-N-acetyl-L-cysteine as
CC substrate {ECO:0000269|PubMed:14656720};
CC Vmax=5.9 umol/min/mg enzyme with N-acetyl-L-histidine as substrate
CC {ECO:0000269|PubMed:14656720};
CC Vmax=7.5 umol/min/mg enzyme with N-acetyl-L-tyrosine as substrate
CC {ECO:0000269|PubMed:14656720};
CC Vmax=7.9 umol/min/mg enzyme with N-acetyl-L-phenylalanine as
CC substrate {ECO:0000269|PubMed:14656720};
CC pH dependence:
CC Optimum pH is 7.5 with S-benzyl-N-acetyl-L-cysteine as substrate, 7.6
CC with N-acetyl-L-histidine as substrate, 7.6 with N-acetyl-L-tyrosine
CC as substrate, and 7.7 with N-acetyl-L-phenylalanine as substrate.
CC {ECO:0000269|PubMed:14656720};
CC -!- SUBUNIT: Exists as a mixture of homodimers and homotetramer, both
CC catalytically active. {ECO:0000269|PubMed:14656720,
CC ECO:0000269|PubMed:17434493, ECO:0000269|PubMed:20921362}.
CC -!- INTERACTION:
CC Q91XE4; Q91XE4: Acy3; NbExp=4; IntAct=EBI-7378963, EBI-7378963;
CC Q91XE4; P26664; Xeno; NbExp=6; IntAct=EBI-7378963, EBI-6941357;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:14656720}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14656720}. Cytoplasm {ECO:0000269|PubMed:14656720}.
CC Note=Predominantly localized in the apical membrane of cells in the S1
CC segment. In the proximal straight tubules (S2 and S3 segments) is
CC expressed diffusely throughout the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in kidney and to a lesser
CC extent in liver. Weakly expressed in heart, small intestine, brain,
CC lung, testis, and stomach. {ECO:0000269|PubMed:14656720}.
CC -!- SIMILARITY: Belongs to the AspA/AstE family. Aspartoacylase subfamily.
CC {ECO:0000305}.
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DR EMBL; AF356878; AAM00224.1; -; mRNA.
DR EMBL; AF356879; AAM00225.1; -; mRNA.
DR EMBL; AY040762; AAK94771.1; -; Genomic_DNA.
DR EMBL; AY169234; AAN87897.1; -; mRNA.
DR EMBL; AF375479; AAM46090.1; -; mRNA.
DR EMBL; AK002247; BAB21963.1; -; mRNA.
DR EMBL; AK143782; BAE25538.1; -; mRNA.
DR EMBL; BC010795; AAH10795.1; -; mRNA.
DR CCDS; CCDS29406.1; -.
DR RefSeq; NP_001289408.1; NM_001302479.1.
DR RefSeq; NP_001289409.1; NM_001302480.1.
DR RefSeq; NP_001289410.1; NM_001302481.1.
DR RefSeq; NP_001289411.1; NM_001302482.1.
DR PDB; 3NFZ; X-ray; 2.15 A; A=1-318.
DR PDB; 3NH4; X-ray; 2.00 A; A=1-318.
DR PDB; 3NH5; X-ray; 2.09 A; A=1-318.
DR PDB; 3NH8; X-ray; 2.80 A; A=1-318.
DR PDBsum; 3NFZ; -.
DR PDBsum; 3NH4; -.
DR PDBsum; 3NH5; -.
DR PDBsum; 3NH8; -.
DR AlphaFoldDB; Q91XE4; -.
DR SMR; Q91XE4; -.
DR BioGRID; 214844; 3.
DR DIP; DIP-44060N; -.
DR IntAct; Q91XE4; 2.
DR MINT; Q91XE4; -.
DR STRING; 10090.ENSMUSP00000050056; -.
DR iPTMnet; Q91XE4; -.
DR PhosphoSitePlus; Q91XE4; -.
DR jPOST; Q91XE4; -.
DR MaxQB; Q91XE4; -.
DR PaxDb; Q91XE4; -.
DR PeptideAtlas; Q91XE4; -.
DR PRIDE; Q91XE4; -.
DR ProteomicsDB; 285600; -.
DR Antibodypedia; 30490; 304 antibodies from 25 providers.
DR DNASU; 71670; -.
DR Ensembl; ENSMUST00000054030; ENSMUSP00000050056; ENSMUSG00000024866.
DR Ensembl; ENSMUST00000235612; ENSMUSP00000158093; ENSMUSG00000024866.
DR Ensembl; ENSMUST00000236510; ENSMUSP00000158512; ENSMUSG00000024866.
DR GeneID; 71670; -.
DR KEGG; mmu:71670; -.
DR UCSC; uc008fxx.2; mouse.
DR CTD; 91703; -.
DR MGI; MGI:1918920; Acy3.
DR VEuPathDB; HostDB:ENSMUSG00000024866; -.
DR eggNOG; ENOG502QRAK; Eukaryota.
DR GeneTree; ENSGT00390000001189; -.
DR HOGENOM; CLU_083292_0_0_1; -.
DR InParanoid; Q91XE4; -.
DR OMA; AMHLCHH; -.
DR OrthoDB; 1074294at2759; -.
DR PhylomeDB; Q91XE4; -.
DR TreeFam; TF328708; -.
DR BRENDA; 3.5.1.114; 3474.
DR Reactome; R-MMU-5423646; Aflatoxin activation and detoxification.
DR BioGRID-ORCS; 71670; 3 hits in 72 CRISPR screens.
DR EvolutionaryTrace; Q91XE4; -.
DR PRO; PR:Q91XE4; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q91XE4; protein.
DR Bgee; ENSMUSG00000024866; Expressed in right kidney and 111 other tissues.
DR ExpressionAtlas; Q91XE4; baseline and differential.
DR Genevisible; Q91XE4; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0004046; F:aminoacylase activity; IDA:UniProtKB.
DR GO; GO:0016811; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides; IBA:GO_Central.
DR GO; GO:0016788; F:hydrolase activity, acting on ester bonds; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR HAMAP; MF_00704; Aspartoacylase; 1.
DR InterPro; IPR016708; Aspartoacylase.
DR InterPro; IPR007036; Aste_AspA.
DR Pfam; PF04952; AstE_AspA; 1.
DR PIRSF; PIRSF018001; Aspartoacylase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Hydrolase; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..318
FT /note="N-acyl-aromatic-L-amino acid amidohydrolase
FT (carboxylate-forming)"
FT /id="PRO_0000216876"
FT REGION 1..210
FT /note="Hydrolytic domain"
FT REGION 211..318
FT /note="Shielding domain"
FT BINDING 21
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 63
FT /ligand="substrate"
FT BINDING 70..71
FT /ligand="substrate"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 177
FT /ligand="substrate"
FT BINDING 287
FT /ligand="substrate"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5M876"
FT MUTAGEN 63
FT /note="R->A: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:20921362"
FT MUTAGEN 287
FT /note="Y->A: Drastically reduced activity."
FT /evidence="ECO:0000269|PubMed:20921362"
FT CONFLICT 66
FT /note="D -> G (in Ref. 3; AAN87897, 4; AAM46090 and 5;
FT BAB21963)"
FT /evidence="ECO:0000305"
FT STRAND 13..18
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 38..41
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:3NH5"
FT HELIX 88..100
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 110..117
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:3NH5"
FT STRAND 123..130
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 133..145
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:3NH5"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 170..179
FT /evidence="ECO:0007829|PDB:3NH4"
FT HELIX 188..209
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 217..228
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 238..242
FT /evidence="ECO:0007829|PDB:3NH4"
FT TURN 244..248
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:3NH8"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:3NH5"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:3NH4"
FT TURN 288..291
FT /evidence="ECO:0007829|PDB:3NH4"
FT STRAND 293..304
FT /evidence="ECO:0007829|PDB:3NH4"
SQ SEQUENCE 318 AA; 35286 MW; 8332731E7E9B30D2 CRC64;
MSSLPGSREP LLRVAVTGGT HGNEMCGVYL ARYWLQNPGE LQRPSFSAMP VLANPAATAA
CCRYLDRDLN RSCTLTFLGS TATPDDPYEV KRARELNQLL GPKGTGQAFD FTLDLHNTTA
NTGVCLISES NISFNLHLCH YLQRQNPGMP CRLFLYEPAG TETFSVESIS KNGICLEMGP
QPQGVLRADL FSRMRALVAS ILDFIELFNQ GMDLPAFEMD IYRNLGSVDF PRTADGDLAG
TVHPQLQDHD FEPLRPGEPI FKLFSGEDVL YEGDSIVYPV FINEAAYYEK HVAFLKSEKI
RVTVPALLRL TPRSTQTP
