ID   ACY1_MOUSE              Reviewed;         408 AA.
AC   Q99JW2; Q9CR15;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   08-NOV-2023, entry version 142.
DE   RecName: Full=Aminoacylase-1;
DE            Short=ACY-1;
DE            EC=3.5.1.14 {ECO:0000269|PubMed:31587987};
DE   AltName: Full=N-acyl-L-amino-acid amidohydrolase;
GN   Name=Acy1;
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 [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryo, and Kidney;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   [3]
RP   INTERACTION WITH SPHK1.
RX   PubMed=15196915; DOI=10.1016/j.febslet.2004.04.093;
RA   Maceyka M., Nava V.E., Milstien S., Spiegel S.;
RT   "Aminoacylase 1 is a sphingosine kinase 1-interacting protein.";
RL   FEBS Lett. 568:30-34(2004).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, 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   [5]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=31587987; DOI=10.1016/j.chembiol.2019.09.009;
RA   Kim J.T., Li V.L., Terrell S.M., Fischer C.R., Long J.Z.;
RT   "Family-wide Annotation of Enzymatic Pathways by Parallel In Vivo
RT   Metabolomics.";
RL   Cell Chem. Biol. 26:1623-1629(2019).
CC   -!- FUNCTION: Catalyzes the hydrolysis of N-acetylated amino acids to
CC       acetate and free amino acids. {ECO:0000269|PubMed:31587987}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an N-acyl-L-amino acid + H2O = a carboxylate + an L-alpha-
CC         amino acid; Xref=Rhea:RHEA:15565, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:29067, ChEBI:CHEBI:59869, ChEBI:CHEBI:59874; EC=3.5.1.14;
CC         Evidence={ECO:0000269|PubMed:31587987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15566;
CC         Evidence={ECO:0000269|PubMed:31587987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N(alpha)-acetyl-L-methionine = acetate + L-methionine;
CC         Xref=Rhea:RHEA:67440, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC         ChEBI:CHEBI:57844, ChEBI:CHEBI:71670;
CC         Evidence={ECO:0000250|UniProtKB:Q03154};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67441;
CC         Evidence={ECO:0000250|UniProtKB:Q03154};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + N-acetyl-L-glutamine = acetate + L-glutamine;
CC         Xref=Rhea:RHEA:67368, ChEBI:CHEBI:15377, ChEBI:CHEBI:30089,
CC         ChEBI:CHEBI:58359, ChEBI:CHEBI:143879;
CC         Evidence={ECO:0000269|PubMed:31587987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67369;
CC         Evidence={ECO:0000269|PubMed:31587987};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q03154};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q03154};
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with SPHK1. {ECO:0000250,
CC       ECO:0000269|PubMed:15196915}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
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DR   EMBL; AK003703; BAB22948.1; -; mRNA.
DR   EMBL; AK002423; BAB22090.1; -; mRNA.
DR   EMBL; BC005631; AAH05631.1; -; mRNA.
DR   CCDS; CCDS23477.1; -.
DR   RefSeq; NP_001263371.1; NM_001276442.1.
DR   RefSeq; NP_079647.1; NM_025371.3.
DR   AlphaFoldDB; Q99JW2; -.
DR   SMR; Q99JW2; -.
DR   BioGRID; 224933; 2.
DR   IntAct; Q99JW2; 1.
DR   STRING; 10090.ENSMUSP00000024031; -.
DR   MEROPS; M20.973; -.
DR   iPTMnet; Q99JW2; -.
DR   MetOSite; Q99JW2; -.
DR   PhosphoSitePlus; Q99JW2; -.
DR   REPRODUCTION-2DPAGE; Q99JW2; -.
DR   EPD; Q99JW2; -.
DR   jPOST; Q99JW2; -.
DR   MaxQB; Q99JW2; -.
DR   PaxDb; 10090-ENSMUSP00000024031; -.
DR   PeptideAtlas; Q99JW2; -.
DR   ProteomicsDB; 281934; -.
DR   Pumba; Q99JW2; -.
DR   DNASU; 109652; -.
DR   GeneID; 109652; -.
DR   KEGG; mmu:109652; -.
DR   UCSC; uc009rjp.2; mouse.
DR   AGR; MGI:87913; -.
DR   CTD; 95; -.
DR   MGI; MGI:87913; Acy1.
DR   eggNOG; KOG2275; Eukaryota.
DR   InParanoid; Q99JW2; -.
DR   OrthoDB; 158507at2759; -.
DR   PhylomeDB; Q99JW2; -.
DR   TreeFam; TF313693; -.
DR   BRENDA; 3.5.1.14; 3474.
DR   Reactome; R-MMU-5423646; Aflatoxin activation and detoxification.
DR   Reactome; R-MMU-9753281; Paracetamol ADME.
DR   BioGRID-ORCS; 109652; 5 hits in 76 CRISPR screens.
DR   PRO; PR:Q99JW2; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q99JW2; Protein.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR   GO; GO:0004046; F:aminoacylase activity; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006520; P:amino acid metabolic process; IEA:InterPro.
DR   CDD; cd05646; M20_AcylaseI_like; 1.
DR   Gene3D; 1.10.150.900; -; 1.
DR   Gene3D; 3.30.70.360; -; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR001261; ArgE/DapE_CS.
DR   InterPro; IPR036264; Bact_exopeptidase_dim_dom.
DR   InterPro; IPR010159; N-acyl_aa_amidohydrolase.
DR   InterPro; IPR002933; Peptidase_M20.
DR   InterPro; IPR011650; Peptidase_M20_dimer.
DR   NCBIfam; TIGR01880; Ac-peptdase-euk; 1.
DR   PANTHER; PTHR45892; AMINOACYLASE-1; 1.
DR   PANTHER; PTHR45892:SF1; AMINOACYLASE-1; 1.
DR   Pfam; PF07687; M20_dimer; 1.
DR   Pfam; PF01546; Peptidase_M20; 1.
DR   PIRSF; PIRSF036696; ACY-1; 1.
DR   SUPFAM; SSF55031; Bacterial exopeptidase dimerisation domain; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PROSITE; PS00758; ARGE_DAPE_CPG2_1; 1.
DR   PROSITE; PS00759; ARGE_DAPE_CPG2_2; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT   CHAIN           1..408
FT                   /note="Aminoacylase-1"
FT                   /id="PRO_0000274007"
FT   ACT_SITE        82
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        147
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         80
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q03154"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q03154"
FT   BINDING         113
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q03154"
FT   BINDING         148
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q03154"
FT   BINDING         175
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:Q03154"
FT   BINDING         373
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q03154"
FT   CONFLICT        172
FT                   /note="A -> V (in Ref. 1; BAB22090/BAB22948)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        197
FT                   /note="R -> Q (in Ref. 1; BAB22090/BAB22948)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        351
FT                   /note="Y -> F (in Ref. 1; BAB22090/BAB22948)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        406
FT                   /note="G -> S (in Ref. 1; BAB22090/BAB22948)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   408 AA;  45781 MW;  384C70B9AB87CDC3 CRC64;
     MTTKDPESEH PSVTLFRQYL RICTVQPNPD YGGAITFLEE RARQLGLSCQ KIEVVPGFVI
     TVLTWPGTNP SLPSILLNSH TDVVPVFKEH WHHDPFEAFK DSEGYIYARG SQDMKSVSIQ
     YLEAVRRLKS EGHRFPRTIH MTFVPDEEVG GHKGMELFVK RPEFQALRAG FALDEGLANP
     TDAFTVFYSE RSPWWVRVTS TGKPGHASRF IEDTAAEKLH KVISSILAFR EKERQRLQAN
     PHLKEGAVTS VNLTKLEGGV AYNVVPATMS ASFDFRVAPD VDMKAFEKQL QRWCQEAGEG
     VTFEFAQKFT EPRMTPTDDS DPWWAAFSGA CKAMNLTLEP EIFPAATDSR YIRAVGIPAL
     GFSPMNRTPV LLHDHNERLH EDIFLRGVDI YTGLLSALAS VPTLPGES
//