Full text data of APEH
APEH
(D3F15S2, D3S48E, DNF15S2)
[Confidence: high (present in two of the MS resources)]
Acylamino-acid-releasing enzyme; AARE; 3.4.19.1 (Acyl-peptide hydrolase; APH; Acylaminoacyl-peptidase; Oxidized protein hydrolase; OPH)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Acylamino-acid-releasing enzyme; AARE; 3.4.19.1 (Acyl-peptide hydrolase; APH; Acylaminoacyl-peptidase; Oxidized protein hydrolase; OPH)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00337741
IPI00337741 Acylamino-acid-releasing enzyme Acyl-peptide hydrolase, oxidized hydrolase, acyl aminoacyl peptidase, It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00337741 Acylamino-acid-releasing enzyme Acyl-peptide hydrolase, oxidized hydrolase, acyl aminoacyl peptidase, It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P13798
ID ACPH_HUMAN Reviewed; 732 AA.
AC P13798; Q9BQ33; Q9P0Y2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-NOV-2003, sequence version 4.
DT 22-JAN-2014, entry version 135.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT project: 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
RT cell 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.,
RA Manning J.M.;
RT "Structural investigations on human erythrocyte acylpeptide hydrolase
RT by 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;
RA Scaloni A., Jones W.M., Barra D., Pospischil M., Sassa S.,
RA Popowicz A., Manning L.R., Schneewind O., Manning J.M.;
RT "Acylpeptide hydrolase: inhibitors and some active site residues of
RT the human enzyme.";
RL J. Biol. Chem. 267:3811-3818(1992).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187, AND MASS
RP SPECTROMETRY.
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 MASS SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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 MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
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-
CC acetylated amino acid and a peptide with a free N-terminus. It
CC preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser.
CC -!- CATALYTIC ACTIVITY: Cleavage of an N-acetyl or N-formyl amino acid
CC from the N-terminus of a polypeptide.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- MASS SPECTROMETRY: Mass=81269.9; Mass_error=8.7;
CC Method=Electrospray; Range=1-732; Source=PubMed:10395453;
CC -!- SIMILARITY: Belongs to the peptidase S9C family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35769.1; Type=Frameshift; Positions=Several;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; JC4655; JC4655.
DR RefSeq; NP_001631.3; NM_001640.3.
DR UniGene; Hs.517969; -.
DR ProteinModelPortal; P13798; -.
DR SMR; P13798; 375-729.
DR IntAct; P13798; 3.
DR MINT; MINT-5004051; -.
DR STRING; 9606.ENSP00000296456; -.
DR ChEMBL; CHEMBL1741174; -.
DR MEROPS; S09.004; -.
DR PhosphoSite; P13798; -.
DR DMDM; 38258902; -.
DR PaxDb; P13798; -.
DR PeptideAtlas; P13798; -.
DR PRIDE; P13798; -.
DR DNASU; 327; -.
DR Ensembl; ENST00000296456; ENSP00000296456; ENSG00000164062.
DR GeneID; 327; -.
DR KEGG; hsa:327; -.
DR UCSC; uc003cxf.3; human.
DR CTD; 327; -.
DR GeneCards; GC03P049711; -.
DR HGNC; HGNC:586; APEH.
DR HPA; HPA029700; -.
DR HPA; HPA029701; -.
DR HPA; HPA029702; -.
DR HPA; HPA029703; -.
DR MIM; 102645; gene.
DR neXtProt; NX_P13798; -.
DR PharmGKB; PA24878; -.
DR eggNOG; COG1506; -.
DR HOGENOM; HOG000007443; -.
DR HOVERGEN; HBG000869; -.
DR InParanoid; P13798; -.
DR KO; K01303; -.
DR OrthoDB; EOG776SPB; -.
DR PhylomeDB; P13798; -.
DR ChiTaRS; APEH; human.
DR GeneWiki; APEH_(gene); -.
DR GenomeRNAi; 327; -.
DR NextBio; 1343; -.
DR PRO; PR:P13798; -.
DR ArrayExpress; P13798; -.
DR Bgee; P13798; -.
DR CleanEx; HS_APEH; -.
DR Genevestigator; P13798; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR Gene3D; 2.120.10.30; -; 2.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR001375; Peptidase_S9.
DR Pfam; PF00326; Peptidase_S9; 1.
DR PROSITE; PS00708; PRO_ENDOPEP_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 732 Acylamino-acid-releasing enzyme.
FT /FTId=PRO_0000122430.
FT ACT_SITE 587 587 Charge relay system.
FT ACT_SITE 675 675 Charge relay system (By similarity).
FT ACT_SITE 707 707 Charge relay system.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 185 185 Phosphoserine.
FT MOD_RES 187 187 Phosphoserine.
FT VARIANT 541 541 T -> M (in dbSNP:rs3816877).
FT /FTId=VAR_051580.
FT CONFLICT 101 101 T -> S (in Ref. 1; BAA07476).
FT CONFLICT 137 137 A -> V (in Ref. 1; BAA07476).
FT CONFLICT 168 168 K -> R (in Ref. 1; BAA07476).
FT CONFLICT 200 200 A -> P (in Ref. 1; BAA07476).
FT CONFLICT 403 403 A -> V (in Ref. 2; AAF37321).
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
//
ID ACPH_HUMAN Reviewed; 732 AA.
AC P13798; Q9BQ33; Q9P0Y2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-NOV-2003, sequence version 4.
DT 22-JAN-2014, entry version 135.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT project: 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
RT cell 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.,
RA Manning J.M.;
RT "Structural investigations on human erythrocyte acylpeptide hydrolase
RT by 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;
RA Scaloni A., Jones W.M., Barra D., Pospischil M., Sassa S.,
RA Popowicz A., Manning L.R., Schneewind O., Manning J.M.;
RT "Acylpeptide hydrolase: inhibitors and some active site residues of
RT the human enzyme.";
RL J. Biol. Chem. 267:3811-3818(1992).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187, AND MASS
RP SPECTROMETRY.
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 MASS SPECTROMETRY.
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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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 MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
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-
CC acetylated amino acid and a peptide with a free N-terminus. It
CC preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser.
CC -!- CATALYTIC ACTIVITY: Cleavage of an N-acetyl or N-formyl amino acid
CC from the N-terminus of a polypeptide.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- MASS SPECTROMETRY: Mass=81269.9; Mass_error=8.7;
CC Method=Electrospray; Range=1-732; Source=PubMed:10395453;
CC -!- SIMILARITY: Belongs to the peptidase S9C family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35769.1; Type=Frameshift; Positions=Several;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; JC4655; JC4655.
DR RefSeq; NP_001631.3; NM_001640.3.
DR UniGene; Hs.517969; -.
DR ProteinModelPortal; P13798; -.
DR SMR; P13798; 375-729.
DR IntAct; P13798; 3.
DR MINT; MINT-5004051; -.
DR STRING; 9606.ENSP00000296456; -.
DR ChEMBL; CHEMBL1741174; -.
DR MEROPS; S09.004; -.
DR PhosphoSite; P13798; -.
DR DMDM; 38258902; -.
DR PaxDb; P13798; -.
DR PeptideAtlas; P13798; -.
DR PRIDE; P13798; -.
DR DNASU; 327; -.
DR Ensembl; ENST00000296456; ENSP00000296456; ENSG00000164062.
DR GeneID; 327; -.
DR KEGG; hsa:327; -.
DR UCSC; uc003cxf.3; human.
DR CTD; 327; -.
DR GeneCards; GC03P049711; -.
DR HGNC; HGNC:586; APEH.
DR HPA; HPA029700; -.
DR HPA; HPA029701; -.
DR HPA; HPA029702; -.
DR HPA; HPA029703; -.
DR MIM; 102645; gene.
DR neXtProt; NX_P13798; -.
DR PharmGKB; PA24878; -.
DR eggNOG; COG1506; -.
DR HOGENOM; HOG000007443; -.
DR HOVERGEN; HBG000869; -.
DR InParanoid; P13798; -.
DR KO; K01303; -.
DR OrthoDB; EOG776SPB; -.
DR PhylomeDB; P13798; -.
DR ChiTaRS; APEH; human.
DR GeneWiki; APEH_(gene); -.
DR GenomeRNAi; 327; -.
DR NextBio; 1343; -.
DR PRO; PR:P13798; -.
DR ArrayExpress; P13798; -.
DR Bgee; P13798; -.
DR CleanEx; HS_APEH; -.
DR Genevestigator; P13798; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR Gene3D; 2.120.10.30; -; 2.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR002471; Pept_S9_AS.
DR InterPro; IPR001375; Peptidase_S9.
DR Pfam; PF00326; Peptidase_S9; 1.
DR PROSITE; PS00708; PRO_ENDOPEP_SER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 732 Acylamino-acid-releasing enzyme.
FT /FTId=PRO_0000122430.
FT ACT_SITE 587 587 Charge relay system.
FT ACT_SITE 675 675 Charge relay system (By similarity).
FT ACT_SITE 707 707 Charge relay system.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 185 185 Phosphoserine.
FT MOD_RES 187 187 Phosphoserine.
FT VARIANT 541 541 T -> M (in dbSNP:rs3816877).
FT /FTId=VAR_051580.
FT CONFLICT 101 101 T -> S (in Ref. 1; BAA07476).
FT CONFLICT 137 137 A -> V (in Ref. 1; BAA07476).
FT CONFLICT 168 168 K -> R (in Ref. 1; BAA07476).
FT CONFLICT 200 200 A -> P (in Ref. 1; BAA07476).
FT CONFLICT 403 403 A -> V (in Ref. 2; AAF37321).
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
//
MIM
102645
*RECORD*
*FIELD* NO
102645
*FIELD* TI
*102645 ACYLPEPTIDE HYDROLASE; APH
;;N-ACYLAMINOACYLPEPTIDE HYDROLASE; APEH
*FIELD* TX
read more
CLONING
Naylor et al. (1989) showed that the DNF15S2 locus is transcribed in
normal lung and in small cell lung cancer. They presented the sequence
of the gene. They pointed out that the activity of aminoacylase-1, which
is encoded by the ACY1 gene located at 3p21 (104620), was lacking in the
same small cell lung cancer cell line that lacked DNF15S1.
Jones et al. (1991) pointed out an 87% identity between the cDNA
sequence that encodes acylpeptide hydrolase from porcine liver (Mitta et
al., 1989) and the cDNA transcribed from DNF15S2 (Naylor et al., 1989).
GENE FUNCTION
Acylpeptide hydrolase (EC 3.4.19.1) catalyzes the hydrolysis of the
terminal acetylated amino acid preferentially from small acetylated
peptides. The acetylamino acid formed by acylpeptide hydrolase is
further processed to acetate and a free amino acid by an aminoacylase.
The substrates for the acylpeptide hydrolase and the acylase behave in a
reciprocal manner since acylpeptide hydrolase binds but does not process
acetylamino acids and the acylase binds acetylpeptides but does not
hydrolyze them; however, the 2 enzymes share the same specificity for
the acyl group. All of these findings indicate common functional
features in the protein structures of the 2 enzymes, which are encoded
by the same region of human chromosome 3, namely, 3p21. Jones et al.
(1991) suggested that there may be a relationship between the expression
of these 2 enzymes and acetylated peptide growth factors in some
carcinomas.
A polymorphic locus, D3S94, previously localized to 3pter-p14.2 (Kiousis
et al., 1989), contains 2 CpG islands and sequences conserved in the
hamster and mouse. Ginzinger et al. (1992) isolated cDNAs homologous to
the conserved fragments and found 96% sequence similarity to a cDNA
derived from the DNF15S2 locus. Furthermore, the sequence of cDNAs
derived from both the rat and pig acylpeptide hydrolase showed a high
degree of sequence similarity to cDNAs derived from D3S94 and DNF15S2,
suggesting that they are all the same locus.
NOMENCLATURE
The locus on 3p21 formerly called DNF15S2 and now symbolized APH is
known to have 2 polymorphic sites, both detectable with HindIII (Carritt
et al., 1986; Goode et al., 1986). (This locus was labeled DNF15S2 by
HGM9 in Paris in 1987, D3F15S2E by HGM10 in New Haven in 1989, and
D3F15S2 by HGM10.5 in Oxford in 1990.)
MAPPING
Harper and Saunders (1981) mapped a probe called lambda-H3 to chromosome
1 by in situ hybridization. This was subsequently called D1S1. Further
studies by Carritt et al. (1986) and Goode et al. (1986) indicated that
this single-copy sequence actually originated from chromosome 3 and that
several homologous sequences were located on chromosome 1. The locus on
chromosome 3 was designated DNF15S2 and the locus on chromosome 1 was
designated DNF15S1. The DNF15S2 locus was shown to have a high rate of
allele loss in both small cell lung cancer and renal cell carcinoma.
Naylor et al. (1989) showed that the DNF15S2 locus is located at 3p21.
Ginzinger et al. (1992) mapped the DNF15S2 locus to chromosome 3p21.3 by
fluorescence in situ hybridization (FISH). ACY1 and APH map to slightly
different regions of 3p, 3p21.1 and 3p21.3, respectively. Using pulsed
field gel electrophoresis, Boldog et al. (1989) showed that the DNF15S2
locus is not linked to D3S2; since D3S2 is within the same 2.5-Mb region
as ACY1, it is likely that ACY1 and APH are not closely linked
physically. The homologous gene is located on mouse chromosome 9 and rat
chromosome 8 in a region highly homologous to human chromosome 3
(Pausova et al., 1994).
*FIELD* RF
1. Boldog, F.; Erlandsson, R.; Klein, G.; Sumegi, J.: Long-range
restriction enzyme maps of DNF15S2, D3S2 and c-raf1 loci on the short
arm of human chromosome 3. Cancer Genet. Cytogenet. 42: 295-306,
1989.
2. Carritt, B.; Welch, H. M.; Parry-Jones, N. J.: Sequences homologous
to the human D1S1 locus present on human chromosome 3. Am. J. Hum.
Genet. 38: 428-436, 1986.
3. Ginzinger, D. G.; Shridhar, V.; Baldini, A.; Taggart, R. T.; Miller,
O. J.; Smith, D. I.: The human loci DNF15S2 and D3S94 have a high
degree of sequence similarity to acyl-peptide hydrolase and are located
at 3p21.3. Am. J. Hum. Genet. 50: 826-833, 1992.
4. Goode, M. E.; vanTuinen, P.; Ledbetter, D. H.; Daiger, S. P.:
The anonymous polymorphic DNA clone D1S1, previously mapped to human
chromosome 1p36 by in situ hybridization, is from chromosome 3 and
is duplicated on chromosome 1. Am. J. Hum. Genet. 38: 437-446, 1986.
5. Harper, M. E.; Saunders, G. E.: Localization of single copy DNA
sequences on G-banded human chromosomes by in situ hybridization. Chromosoma 83:
431-439, 1981.
6. Jones, W. M.; Scaloni, A.; Bossa, F.; Popowicz, A. M.; Schneewind,
O.; Manning, J. M.: Genetic relationship between acylpeptide hydrolase
and acylase, two hydrolytic enzymes with similar binding but different
catalytic specificities. Proc. Nat. Acad. Sci. 88: 2194-2198, 1991.
7. Kiousis, S.; Drabkin, H.; Smith, D. I.: Isolation and mapping
of a polymorphic DNA sequence (cA476) on chromosome 3 (D3S94). Nucleic
Acids Res. 17: 5876 only, 1989.
8. Mitta, M.; Asada, K.; Uchimura, Y.; Kimizuka, F.; Kato, I.; Sakiyama,
F.; Tsunasawa, S.: The primary structure of porcine liver acylamino
acid-releasing enzyme deduced from cDNA sequences. J. Biochem. 106:
548-551, 1989.
9. Naylor, S. L.; Marshall, A.; Hensel, C.; Martinez, P. F.; Holley,
B.; Sakaguchi, A. Y.: The DNF15S2 locus at 3p21 is transcribed in
normal lung and small cell lung cancer. Genomics 4: 355-361, 1989.
10. Pausova, Z.; Bourdon, J.; Clayton, D.; Mattei, M.-G.; Seldin,
M. F.; Janicic, N.; Riviere, M.; Szpirer, J.; Levan, G.; Szpirer,
C.; Goltzman, D.; Hendy, G. N.: Cloning of a parathyroid hormone/parathyroid
hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma
(UMR 106) cell line: chromosomal assignment of the gene in the human,
mouse, and rat genomes. Genomics 20: 20-26, 1994.
*FIELD* CD
Victor A. McKusick: 3/25/1991
*FIELD* ED
alopez: 10/18/2010
dkim: 12/15/1998
carol: 4/5/1994
carol: 4/6/1993
carol: 10/13/1992
supermim: 7/28/1992
*RECORD*
*FIELD* NO
102645
*FIELD* TI
*102645 ACYLPEPTIDE HYDROLASE; APH
;;N-ACYLAMINOACYLPEPTIDE HYDROLASE; APEH
*FIELD* TX
read more
CLONING
Naylor et al. (1989) showed that the DNF15S2 locus is transcribed in
normal lung and in small cell lung cancer. They presented the sequence
of the gene. They pointed out that the activity of aminoacylase-1, which
is encoded by the ACY1 gene located at 3p21 (104620), was lacking in the
same small cell lung cancer cell line that lacked DNF15S1.
Jones et al. (1991) pointed out an 87% identity between the cDNA
sequence that encodes acylpeptide hydrolase from porcine liver (Mitta et
al., 1989) and the cDNA transcribed from DNF15S2 (Naylor et al., 1989).
GENE FUNCTION
Acylpeptide hydrolase (EC 3.4.19.1) catalyzes the hydrolysis of the
terminal acetylated amino acid preferentially from small acetylated
peptides. The acetylamino acid formed by acylpeptide hydrolase is
further processed to acetate and a free amino acid by an aminoacylase.
The substrates for the acylpeptide hydrolase and the acylase behave in a
reciprocal manner since acylpeptide hydrolase binds but does not process
acetylamino acids and the acylase binds acetylpeptides but does not
hydrolyze them; however, the 2 enzymes share the same specificity for
the acyl group. All of these findings indicate common functional
features in the protein structures of the 2 enzymes, which are encoded
by the same region of human chromosome 3, namely, 3p21. Jones et al.
(1991) suggested that there may be a relationship between the expression
of these 2 enzymes and acetylated peptide growth factors in some
carcinomas.
A polymorphic locus, D3S94, previously localized to 3pter-p14.2 (Kiousis
et al., 1989), contains 2 CpG islands and sequences conserved in the
hamster and mouse. Ginzinger et al. (1992) isolated cDNAs homologous to
the conserved fragments and found 96% sequence similarity to a cDNA
derived from the DNF15S2 locus. Furthermore, the sequence of cDNAs
derived from both the rat and pig acylpeptide hydrolase showed a high
degree of sequence similarity to cDNAs derived from D3S94 and DNF15S2,
suggesting that they are all the same locus.
NOMENCLATURE
The locus on 3p21 formerly called DNF15S2 and now symbolized APH is
known to have 2 polymorphic sites, both detectable with HindIII (Carritt
et al., 1986; Goode et al., 1986). (This locus was labeled DNF15S2 by
HGM9 in Paris in 1987, D3F15S2E by HGM10 in New Haven in 1989, and
D3F15S2 by HGM10.5 in Oxford in 1990.)
MAPPING
Harper and Saunders (1981) mapped a probe called lambda-H3 to chromosome
1 by in situ hybridization. This was subsequently called D1S1. Further
studies by Carritt et al. (1986) and Goode et al. (1986) indicated that
this single-copy sequence actually originated from chromosome 3 and that
several homologous sequences were located on chromosome 1. The locus on
chromosome 3 was designated DNF15S2 and the locus on chromosome 1 was
designated DNF15S1. The DNF15S2 locus was shown to have a high rate of
allele loss in both small cell lung cancer and renal cell carcinoma.
Naylor et al. (1989) showed that the DNF15S2 locus is located at 3p21.
Ginzinger et al. (1992) mapped the DNF15S2 locus to chromosome 3p21.3 by
fluorescence in situ hybridization (FISH). ACY1 and APH map to slightly
different regions of 3p, 3p21.1 and 3p21.3, respectively. Using pulsed
field gel electrophoresis, Boldog et al. (1989) showed that the DNF15S2
locus is not linked to D3S2; since D3S2 is within the same 2.5-Mb region
as ACY1, it is likely that ACY1 and APH are not closely linked
physically. The homologous gene is located on mouse chromosome 9 and rat
chromosome 8 in a region highly homologous to human chromosome 3
(Pausova et al., 1994).
*FIELD* RF
1. Boldog, F.; Erlandsson, R.; Klein, G.; Sumegi, J.: Long-range
restriction enzyme maps of DNF15S2, D3S2 and c-raf1 loci on the short
arm of human chromosome 3. Cancer Genet. Cytogenet. 42: 295-306,
1989.
2. Carritt, B.; Welch, H. M.; Parry-Jones, N. J.: Sequences homologous
to the human D1S1 locus present on human chromosome 3. Am. J. Hum.
Genet. 38: 428-436, 1986.
3. Ginzinger, D. G.; Shridhar, V.; Baldini, A.; Taggart, R. T.; Miller,
O. J.; Smith, D. I.: The human loci DNF15S2 and D3S94 have a high
degree of sequence similarity to acyl-peptide hydrolase and are located
at 3p21.3. Am. J. Hum. Genet. 50: 826-833, 1992.
4. Goode, M. E.; vanTuinen, P.; Ledbetter, D. H.; Daiger, S. P.:
The anonymous polymorphic DNA clone D1S1, previously mapped to human
chromosome 1p36 by in situ hybridization, is from chromosome 3 and
is duplicated on chromosome 1. Am. J. Hum. Genet. 38: 437-446, 1986.
5. Harper, M. E.; Saunders, G. E.: Localization of single copy DNA
sequences on G-banded human chromosomes by in situ hybridization. Chromosoma 83:
431-439, 1981.
6. Jones, W. M.; Scaloni, A.; Bossa, F.; Popowicz, A. M.; Schneewind,
O.; Manning, J. M.: Genetic relationship between acylpeptide hydrolase
and acylase, two hydrolytic enzymes with similar binding but different
catalytic specificities. Proc. Nat. Acad. Sci. 88: 2194-2198, 1991.
7. Kiousis, S.; Drabkin, H.; Smith, D. I.: Isolation and mapping
of a polymorphic DNA sequence (cA476) on chromosome 3 (D3S94). Nucleic
Acids Res. 17: 5876 only, 1989.
8. Mitta, M.; Asada, K.; Uchimura, Y.; Kimizuka, F.; Kato, I.; Sakiyama,
F.; Tsunasawa, S.: The primary structure of porcine liver acylamino
acid-releasing enzyme deduced from cDNA sequences. J. Biochem. 106:
548-551, 1989.
9. Naylor, S. L.; Marshall, A.; Hensel, C.; Martinez, P. F.; Holley,
B.; Sakaguchi, A. Y.: The DNF15S2 locus at 3p21 is transcribed in
normal lung and small cell lung cancer. Genomics 4: 355-361, 1989.
10. Pausova, Z.; Bourdon, J.; Clayton, D.; Mattei, M.-G.; Seldin,
M. F.; Janicic, N.; Riviere, M.; Szpirer, J.; Levan, G.; Szpirer,
C.; Goltzman, D.; Hendy, G. N.: Cloning of a parathyroid hormone/parathyroid
hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma
(UMR 106) cell line: chromosomal assignment of the gene in the human,
mouse, and rat genomes. Genomics 20: 20-26, 1994.
*FIELD* CD
Victor A. McKusick: 3/25/1991
*FIELD* ED
alopez: 10/18/2010
dkim: 12/15/1998
carol: 4/5/1994
carol: 4/6/1993
carol: 10/13/1992
supermim: 7/28/1992