ACPH_HUMAN
ID ACPH_HUMAN Reviewed; 732 AA.
AC P13798; Q9BQ33; Q9P0Y2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2003, sequence version 4.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Acylamino-acid-releasing enzyme;
DE Short=AARE;
DE EC=3.4.19.1;
DE AltName: Full=Acyl-peptide hydrolase;
DE Short=APH;
DE AltName: Full=Acylaminoacyl-peptidase;
DE AltName: Full=Oxidized protein hydrolase;
DE Short=OPH;
GN Name=APEH; Synonyms=D3F15S2, D3S48E, DNF15S2;
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].
RC TISSUE=Liver;
RX PubMed=8724851; DOI=10.1093/dnares/3.1.31;
RA Mitta M., Ohnogi H., Mizutani S., Sakiyama F., Kato I., Tsunasawa S.;
RT "The nucleotide sequence of human acylamino acid-releasing enzyme.";
RL DNA Res. 3:31-35(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=10719179; DOI=10.1016/s0167-4838(00)00004-2;
RA Fujino T., Watanabe K., Beppu M., Kikugawa K., Yasuda H.;
RT "Identification of oxidized protein hydrolase of human erythrocytes as
RT acylpeptide hydrolase.";
RL Biochim. Biophys. Acta 1478:102-112(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 PRELIMINARY NUCLEOTIDE SEQUENCE OF 102-732.
RX PubMed=2565880; DOI=10.1016/0888-7543(89)90342-x;
RA Naylor S.L., Marshall A., Hensel C., Martinez P.F., Holley B.,
RA Sakaguchi A.Y.;
RT "The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell
RT lung cancer.";
RL Genomics 4:355-361(1989).
RN [5]
RP PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, AND ACETYLATION AT MET-1.
RX PubMed=10395453; DOI=10.1023/a:1021047730831;
RA Scaloni A., Ingallinella P., Andolfo A., Jones W., Marino G., Manning J.M.;
RT "Structural investigations on human erythrocyte acylpeptide hydrolase by
RT mass spectrometric procedures.";
RL J. Protein Chem. 18:349-360(1999).
RN [6]
RP FUNCTION.
RX PubMed=1861871;
RA Erlandsson R., Boldog F., Persson B., Zabarovsky E.R., Allikmets R.L.,
RA Sumegi J., Klein G., Joernvall H.;
RT "The gene from the short arm of chromosome 3, at D3F15S2, frequently
RT deleted in renal cell carcinoma, encodes acylpeptide hydrolase.";
RL Oncogene 6:1293-1295(1991).
RN [7]
RP FUNCTION.
RX PubMed=2006156; DOI=10.1073/pnas.88.6.2194;
RA Jones W.M., Scaloni A., Bossa F., Popowicz A.M., Schneewind O.,
RA Manning J.M.;
RT "Genetic relationship between acylpeptide hydrolase and acylase, two
RT hydrolytic enzymes with similar binding but different catalytic
RT specificities.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:2194-2198(1991).
RN [8]
RP ACTIVE SITES SER-587 AND HIS-707.
RX PubMed=1740429; DOI=10.1016/s0021-9258(19)50598-1;
RA Scaloni A., Jones W.M., Barra D., Pospischil M., Sassa S., Popowicz A.,
RA Manning L.R., Schneewind O., Manning J.M.;
RT "Acylpeptide hydrolase: inhibitors and some active site residues of the
RT human enzyme.";
RL J. Biol. Chem. 267:3811-3818(1992).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185 AND SER-187, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185 AND SER-187, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187, AND IDENTIFICATION BY
RP 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).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=8411161; DOI=10.1006/jmbi.1993.1531;
RA Feese M., Scaloni A., Jones W.M., Mannig J.M., Remington S.J.;
RT "Crystallization and preliminary X-ray studies of human erythrocyte
RT acylpeptide hydrolase.";
RL J. Mol. Biol. 233:546-549(1993).
CC -!- FUNCTION: This enzyme catalyzes the hydrolysis of the N-terminal
CC peptide bond of an N-acetylated peptide to generate an N-acetylated
CC amino acid and a peptide with a free N-terminus. It preferentially
CC cleaves off Ac-Ala, Ac-Met and Ac-Ser. {ECO:0000269|PubMed:1861871,
CC ECO:0000269|PubMed:2006156}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of an N-acetyl or N-formyl amino acid from the N-
CC terminus of a polypeptide.; EC=3.4.19.1;
CC -!- SUBUNIT: Homotetramer.
CC -!- INTERACTION:
CC P13798; P13798: APEH; NbExp=6; IntAct=EBI-723792, EBI-723792;
CC P13798; P53990: IST1; NbExp=5; IntAct=EBI-723792, EBI-945994;
CC P13798; P53990-3: IST1; NbExp=3; IntAct=EBI-723792, EBI-12188567;
CC P13798; O00214: LGALS8; NbExp=4; IntAct=EBI-723792, EBI-740058;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- MASS SPECTROMETRY: Mass=81269.9; Mass_error=8.7; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10395453};
CC -!- SIMILARITY: Belongs to the peptidase S9C family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35769.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D38441; BAA07476.1; -; mRNA.
DR EMBL; AF141383; AAF37321.1; -; mRNA.
DR EMBL; BC000362; AAH00362.1; -; mRNA.
DR EMBL; BC001499; AAH01499.1; -; mRNA.
DR EMBL; BC001826; AAH01826.1; -; mRNA.
DR EMBL; J03068; AAA35769.1; ALT_FRAME; mRNA.
DR CCDS; CCDS2801.1; -.
DR PIR; JC4655; JC4655.
DR RefSeq; NP_001631.3; NM_001640.3.
DR RefSeq; XP_011531962.1; XM_011533660.2.
DR AlphaFoldDB; P13798; -.
DR SMR; P13798; -.
DR BioGRID; 106824; 55.
DR IntAct; P13798; 14.
DR STRING; 9606.ENSP00000296456; -.
DR ChEMBL; CHEMBL1741174; -.
DR GuidetoPHARMACOLOGY; 2328; -.
DR ESTHER; human-APEH; ACPH_Peptidase_S9.
DR MEROPS; S09.004; -.
DR GlyGen; P13798; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P13798; -.
DR MetOSite; P13798; -.
DR PhosphoSitePlus; P13798; -.
DR SwissPalm; P13798; -.
DR BioMuta; APEH; -.
DR DMDM; 38258902; -.
DR CPTAC; CPTAC-21; -.
DR CPTAC; CPTAC-22; -.
DR EPD; P13798; -.
DR jPOST; P13798; -.
DR MassIVE; P13798; -.
DR MaxQB; P13798; -.
DR PaxDb; P13798; -.
DR PeptideAtlas; P13798; -.
DR PRIDE; P13798; -.
DR ProteomicsDB; 52988; -.
DR Antibodypedia; 30567; 248 antibodies from 29 providers.
DR DNASU; 327; -.
DR Ensembl; ENST00000296456.10; ENSP00000296456.5; ENSG00000164062.13.
DR GeneID; 327; -.
DR KEGG; hsa:327; -.
DR MANE-Select; ENST00000296456.10; ENSP00000296456.5; NM_001640.4; NP_001631.3.
DR UCSC; uc003cxf.4; human.
DR CTD; 327; -.
DR DisGeNET; 327; -.
DR GeneCards; APEH; -.
DR HGNC; HGNC:586; APEH.
DR HPA; ENSG00000164062; Low tissue specificity.
DR MIM; 102645; gene.
DR neXtProt; NX_P13798; -.
DR OpenTargets; ENSG00000164062; -.
DR PharmGKB; PA24878; -.
DR VEuPathDB; HostDB:ENSG00000164062; -.
DR eggNOG; KOG2100; Eukaryota.
DR GeneTree; ENSGT00390000013172; -.
DR HOGENOM; CLU_014230_1_1_1; -.
DR InParanoid; P13798; -.
DR OMA; FVVDTQM; -.
DR OrthoDB; 265965at2759; -.
DR PhylomeDB; P13798; -.
DR TreeFam; TF312937; -.
DR BioCyc; MetaCyc:HS08997-MON; -.
DR BRENDA; 3.4.19.1; 2681.
DR PathwayCommons; P13798; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-72764; Eukaryotic Translation Termination.
DR SignaLink; P13798; -.
DR BioGRID-ORCS; 327; 9 hits in 1079 CRISPR screens.
DR ChiTaRS; APEH; human.
DR GeneWiki; APEH_(gene); -.
DR GenomeRNAi; 327; -.
DR Pharos; P13798; Tchem.
DR PRO; PR:P13798; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P13798; protein.
DR Bgee; ENSG00000164062; Expressed in mucosa of transverse colon and 189 other tissues.
DR ExpressionAtlas; P13798; baseline and differential.
DR Genevisible; P13798; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008242; F:omega peptidase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0006415; P:translational termination; TAS:Reactome.
DR Gene3D; 2.120.10.30; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR045550; AARE_N.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR001375; Peptidase_S9.
DR Pfam; PF19283; APEH_N; 1.
DR Pfam; PF00326; Peptidase_S9; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00708; PRO_ENDOPEP_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..732
FT /note="Acylamino-acid-releasing enzyme"
FT /id="PRO_0000122430"
FT ACT_SITE 587
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084,
FT ECO:0000269|PubMed:1740429"
FT ACT_SITE 675
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084"
FT ACT_SITE 707
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084,
FT ECO:0000269|PubMed:1740429"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:10395453"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VARIANT 541
FT /note="T -> M (in dbSNP:rs3816877)"
FT /id="VAR_051580"
FT CONFLICT 101
FT /note="T -> S (in Ref. 1; BAA07476)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="A -> V (in Ref. 1; BAA07476)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="K -> R (in Ref. 1; BAA07476)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="A -> P (in Ref. 1; BAA07476)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="A -> V (in Ref. 2; AAF37321)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 732 AA; 81225 MW; A2C370516324D851 CRC64;
MERQVLLSEP EEAAALYRGL SRQPALSAAC LGPEVTTQYG GQYRTVHTEW TQRDLERMEN
IRFCRQYLVF HDGDSVVFAG PAGNSVETRG ELLSRESPSG TMKAVLRKAG GTGPGEEKQF
LEVWEKNRKL KSFNLSALEK HGPVYEDDCF GCLSWSHSET HLLYVAEKKR PKAESFFQTK
ALDVSASDDE IARLKKPDQA IKGDQFVFYE DWGENMVSKS IPVLCVLDVE SGNISVLEGV
PENVSPGQAF WAPGDAGVVF VGWWHEPFRL GIRFCTNRRS ALYYVDLIGG KCELLSDDSL
AVSSPRLSPD QCRIVYLQYP SLIPHHQCSQ LCLYDWYTKV TSVVVDVVPR QLGENFSGIY
CSLLPLGCWS ADSQRVVFDS AQRSRQDLFA VDTQVGTVTS LTAGGSGGSW KLLTIDQDLM
VAQFSTPSLP PTLKVGFLPS AGKEQSVLWV SLEEAEPIPD IHWGIRVLQP PPEQENVQYA
GLDFEAILLQ PGSPPDKTQV PMVVMPHGGP HSSFVTAWML FPAMLCKMGF AVLLVNYRGS
TGFGQDSILS LPGNVGHQDV KDVQFAVEQV LQEEHFDASH VALMGGSHGG FISCHLIGQY
PETYRACVAR NPVINIASML GSTDIPDWCV VEAGFPFSSD CLPDLSVWAE MLDKSPIRYI
PQVKTPLLLM LGQEDRRVPF KQGMEYYRAL KTRNVPVRLL LYPKSTHALS EVEVESDSFM
NAVLWLRTHL GS
