ACY3_HUMAN
ID ACY3_HUMAN Reviewed; 319 AA.
AC Q96HD9;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
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-3;
DE Short=ACY-3;
DE AltName: Full=Aspartoacylase-2;
DE AltName: Full=Hepatitis C virus core-binding protein 1;
DE Short=HCBP1;
DE Short=HCV core-binding protein 1;
GN Name=ACY3; Synonyms=ASPA2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Pushkin A., Carpenito G., Abuladze N., Newman D., Kurtz I.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 [4]
RP INTERACTION WITH HCV CORE PROTEIN (MICROBIAL INFECTION), AND SUBCELLULAR
RP LOCATION.
RX PubMed=19486448; DOI=10.1111/j.1440-1746.2009.05846.x;
RA Chen Y.R., Chen T.Y., Zhang S.L., Lin S.M., Zhao Y.R., Ye F., Zhang X.,
RA Shi L., Dang S.S., Liu M.;
RT "Identification of a novel protein binding to hepatitis C virus core
RT protein.";
RL J. Gastroenterol. Hepatol. 24:1300-1304(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Plays an important role in deacetylating mercapturic acids in
CC kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids (By
CC similarity). {ECO:0000250}.
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; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Exists as a mixture of homodimers and homotetramer, both
CC catalytically active. {ECO:0000250|UniProtKB:Q91XE4}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus/HCV
CC core protein. {ECO:0000269|PubMed:19486448}.
CC -!- INTERACTION:
CC Q96HD9; Q9H7C9: AAMDC; NbExp=3; IntAct=EBI-3916242, EBI-10308705;
CC Q96HD9; P84085: ARF5; NbExp=3; IntAct=EBI-3916242, EBI-4289908;
CC Q96HD9; P45381: ASPA; NbExp=15; IntAct=EBI-3916242, EBI-750475;
CC Q96HD9; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-3916242, EBI-3867333;
CC Q96HD9; Q96D03: DDIT4L; NbExp=5; IntAct=EBI-3916242, EBI-742054;
CC Q96HD9; Q9H8Y8: GORASP2; NbExp=15; IntAct=EBI-3916242, EBI-739467;
CC Q96HD9; Q0VD86: INCA1; NbExp=5; IntAct=EBI-3916242, EBI-6509505;
CC Q96HD9; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-3916242, EBI-10171774;
CC Q96HD9; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-3916242, EBI-11992140;
CC Q96HD9; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-3916242, EBI-3957672;
CC Q96HD9; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-3916242, EBI-739832;
CC Q96HD9; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-3916242, EBI-945833;
CC Q96HD9; O75928: PIAS2; NbExp=3; IntAct=EBI-3916242, EBI-348555;
CC Q96HD9; Q9H8W4: PLEKHF2; NbExp=4; IntAct=EBI-3916242, EBI-742388;
CC Q96HD9; O15305: PMM2; NbExp=9; IntAct=EBI-3916242, EBI-10182608;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:19486448}; Peripheral membrane protein
CC {ECO:0000269|PubMed:19486448}. Cytoplasm {ECO:0000269|PubMed:19486448}.
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 -!- SIMILARITY: Belongs to the AspA/AstE family. Aspartoacylase subfamily.
CC {ECO:0000305}.
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DR EMBL; AY040761; AAK94770.1; -; mRNA.
DR EMBL; AY169233; AAN87896.1; -; mRNA.
DR EMBL; BC008689; AAH08689.1; -; mRNA.
DR CCDS; CCDS8175.1; -.
DR RefSeq; NP_542389.1; NM_080658.1.
DR AlphaFoldDB; Q96HD9; -.
DR SMR; Q96HD9; -.
DR BioGRID; 124869; 28.
DR IntAct; Q96HD9; 20.
DR MINT; Q96HD9; -.
DR STRING; 9606.ENSP00000255082; -.
DR iPTMnet; Q96HD9; -.
DR PhosphoSitePlus; Q96HD9; -.
DR BioMuta; ACY3; -.
DR DMDM; 34395507; -.
DR jPOST; Q96HD9; -.
DR MassIVE; Q96HD9; -.
DR MaxQB; Q96HD9; -.
DR PaxDb; Q96HD9; -.
DR PeptideAtlas; Q96HD9; -.
DR PRIDE; Q96HD9; -.
DR ProteomicsDB; 76736; -.
DR Antibodypedia; 30490; 304 antibodies from 25 providers.
DR DNASU; 91703; -.
DR Ensembl; ENST00000255082.8; ENSP00000255082.3; ENSG00000132744.8.
DR GeneID; 91703; -.
DR KEGG; hsa:91703; -.
DR MANE-Select; ENST00000255082.8; ENSP00000255082.3; NM_080658.2; NP_542389.1.
DR UCSC; uc001omq.3; human.
DR CTD; 91703; -.
DR DisGeNET; 91703; -.
DR GeneCards; ACY3; -.
DR HGNC; HGNC:24104; ACY3.
DR HPA; ENSG00000132744; Tissue enhanced (intestine, kidney, liver).
DR MIM; 614413; gene.
DR neXtProt; NX_Q96HD9; -.
DR OpenTargets; ENSG00000132744; -.
DR PharmGKB; PA134936640; -.
DR VEuPathDB; HostDB:ENSG00000132744; -.
DR eggNOG; ENOG502QRAK; Eukaryota.
DR GeneTree; ENSGT00390000001189; -.
DR HOGENOM; CLU_083292_0_0_1; -.
DR InParanoid; Q96HD9; -.
DR OMA; AMHLCHH; -.
DR OrthoDB; 1074294at2759; -.
DR PhylomeDB; Q96HD9; -.
DR TreeFam; TF328708; -.
DR BioCyc; MetaCyc:HS13441-MON; -.
DR BRENDA; 3.5.1.114; 2681.
DR PathwayCommons; Q96HD9; -.
DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR SignaLink; Q96HD9; -.
DR BioGRID-ORCS; 91703; 20 hits in 1074 CRISPR screens.
DR GenomeRNAi; 91703; -.
DR Pharos; Q96HD9; Tbio.
DR PRO; PR:Q96HD9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96HD9; protein.
DR Bgee; ENSG00000132744; Expressed in ileal mucosa and 119 other tissues.
DR ExpressionAtlas; Q96HD9; baseline and differential.
DR Genevisible; Q96HD9; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004046; F:aminoacylase activity; ISS: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; IEA:Ensembl.
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 Cell membrane; Cytoplasm; Host-virus interaction; Hydrolase; Membrane;
KW Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..319
FT /note="N-acyl-aromatic-L-amino acid amidohydrolase
FT (carboxylate-forming)"
FT /id="PRO_0000216875"
FT REGION 1..210
FT /note="Hydrolytic domain"
FT /evidence="ECO:0000250"
FT REGION 211..318
FT /note="Shielding domain"
FT /evidence="ECO:0000250"
FT BINDING 21
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 70..71
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VARIANT 8
FT /note="R -> Q (in dbSNP:rs948445)"
FT /id="VAR_048341"
FT VARIANT 281
FT /note="V -> M (in dbSNP:rs2290959)"
FT /id="VAR_048342"
SQ SEQUENCE 319 AA; 35241 MW; 2595358AC8B5BEFB CRC64;
MCSLPVPREP LRRVAVTGGT HGNEMSGVYL ARHWLHAPAE LQRASFSAVP VLANPAATSG
CRRYVDHDLN RTFTSSFLNS RPTPDDPYEV TRARELNQLL GPKASGQAFD FVLDLHNTTA
NMGTCLIAKS SHEVFAMHLC RHLQLQYPEL SCQVFLYQRS GEESYNLDSV AKNGLGLELG
PQPQGVLRAD IFSRMRTLVA TVLDFIELFN QGTAFPAFEM EAYRPVGVVD FPRTEAGHLA
GTVHPQLQDR DFQPLQPGAP IFQMFSGEDL LYEGESTVYP VFINEAAYYE KGVAFVQTEK
FTFTVPAMPA LTPAPSPAS
