ID ACPH_BOVIN Reviewed; 730 AA. AC P80227; A4FUX4; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 2. DT 02-SEP-2026, entry version 142. DE RecName: Full=Acylamino-acid-releasing enzyme; DE Short=AARE; DE EC=3.4.19.1 {ECO:0000269|PubMed:8375399}; DE AltName: Full=Acyl-peptide hydrolase; DE Short=APH; DE AltName: Full=Acylaminoacyl-peptidase; GN Name=APEH; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Thalamus; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP PROTEIN SEQUENCE OF 194-213, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND RP TISSUE SPECIFICITY. RC TISSUE=Lens; RX PubMed=8375399; DOI=10.1111/j.1432-1033.1993.tb18183.x; RA Sharma K.K., Ortwerth B.J.; RT "Bovine lens acylpeptide hydrolase. Purification and characterization of a RT tetrameric enzyme resistant to urea denaturation and proteolytic RT inactivation."; RL Eur. J. Biochem. 216:631-637(1993). CC -!- FUNCTION: Aminopeptidase involved in the degradation of N(alpha)- CC acylated peptides. Displays exopeptidase activity toward N-formyl and CC N-acetyl peptides with a preference for dipeptide substrates (By CC similarity). Catalyzes the hydrolysis of the N-terminal peptide bond of CC an N-acetylated peptide to generate an N-acetylated amino acid and a CC peptide with a free N-terminus (PubMed:8375399). It preferentially CC cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Hydrolyzes N- CC formylated peptides likely arising from N-terminal proteolytic cleavage CC of bacterial and mitochondrial proteins. May act sequentially with ACY1 CC in the degradation of N-acylated peptides: APEH first cleaves N- CC acylaminoacids from N-acylated peptides, then ACY1 further hydrolyzes CC the N-acylaminoacid into free aminoacid and a carboxylate (By CC similarity). Displays endopeptidase activity involved in the CC degradation of oxidized and glycated proteins (By similarity). CC {ECO:0000250|UniProtKB:P13676, ECO:0000250|UniProtKB:P13798, CC ECO:0000269|PubMed:8375399}. 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 Evidence={ECO:0000269|PubMed:8375399}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-formyl-L-methionyl-L-leucyl-L-phenylalanine + H2O = CC L-leucyl-L-phenylalanine + N(alpha)-formyl-L-methionine; CC Xref=Rhea:RHEA:83443, ChEBI:CHEBI:15377, ChEBI:CHEBI:57809, CC ChEBI:CHEBI:194314, ChEBI:CHEBI:233080; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83444; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-formyl-L-methionyl-L-alanyl-L-serine + H2O = L- CC alanyl-L-serine + N(alpha)-formyl-L-methionine; Xref=Rhea:RHEA:83495, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57809, ChEBI:CHEBI:233101, CC ChEBI:CHEBI:233102; Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83496; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-formyl-L-methionyl-L-phenylalanine + H2O = N(alpha)- CC formyl-L-methionine + L-phenylalanine; Xref=Rhea:RHEA:83487, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57809, ChEBI:CHEBI:58095, CC ChEBI:CHEBI:233099; Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83488; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-formyl-L-methionyl-L-alanine + H2O = N(alpha)-formyl- CC L-methionine + L-alanine; Xref=Rhea:RHEA:83491, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57809, ChEBI:CHEBI:57972, ChEBI:CHEBI:233100; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83492; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-formyl-L-methionyl-L-serine + H2O = N(alpha)-formyl- CC L-methionine + L-serine; Xref=Rhea:RHEA:83499, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57809, ChEBI:CHEBI:233103; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83500; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-acetyl-L-methionyl-L-alanyl-L-serine + H2O = L- CC alanyl-L-serine + N-acetyl-L-methionine; Xref=Rhea:RHEA:83503, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:71670, ChEBI:CHEBI:233101, CC ChEBI:CHEBI:233104; Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83504; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-acetyl-L-alanyl-L-alanyl-L-alanine + H2O = N(alpha)- CC acetyl-L-alanine + L-alanyl-L-alanine; Xref=Rhea:RHEA:83511, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:133520, ChEBI:CHEBI:195181, CC ChEBI:CHEBI:233106; Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83512; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(alpha)-acetyl-L-alanyl-L-alanine + H2O = N(alpha)-acetyl-L- CC alanine + L-alanine; Xref=Rhea:RHEA:83507, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57972, ChEBI:CHEBI:133520, ChEBI:CHEBI:233105; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83508; CC Evidence={ECO:0000250|UniProtKB:P13676}; CC -!- ACTIVITY REGULATION: Homotetramerization is required for activity. CC Tetramerization results in the formation of a gated channel which is CC involved in substrate selection and substrate access to the catalytic CC sites. {ECO:0000250|UniProtKB:P19205}. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:8375399}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P13798}. CC -!- TISSUE SPECIFICITY: Expressed in lens (at protein level). CC {ECO:0000269|PubMed:8375399}. CC -!- SIMILARITY: Belongs to the peptidase S9C family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC123400; AAI23401.1; -; mRNA. DR PIR; S36842; S36842. DR RefSeq; NP_001076900.1; NM_001083431.1. DR AlphaFoldDB; P80227; -. DR SMR; P80227; -. DR FunCoup; P80227; 2356. DR STRING; 9913.ENSBTAP00000015388; -. DR ESTHER; bovin-acph; ACPH_Peptidase_S9. DR MEROPS; S09.004; -. DR PaxDb; 9913-ENSBTAP00000015388; -. DR GeneID; 514666; -. DR KEGG; bta:514666; -. DR CTD; 327; -. DR VEuPathDB; HostDB:ENSBTAG00000011583; -. DR VGNC; VGNC:26010; APEH. DR eggNOG; KOG2100; Eukaryota. DR HOGENOM; CLU_014230_1_1_1; -. DR InParanoid; P80227; -. DR OMA; QEIATPF; -. DR OrthoDB; 416344at2759; -. DR Reactome; R-BTA-6798695; Neutrophil degranulation. DR Reactome; R-BTA-72764; Eukaryotic Translation Termination. DR Proteomes; UP000009136; Chromosome 22. DR Bgee; ENSBTAG00000011583; Expressed in digestive system secreted substance and 107 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0008242; F:omega peptidase activity; EXP:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro. DR GO; GO:0006508; P:proteolysis; IEA:InterPro. DR FunFam; 2.120.10.30:FF:000047; Acylamino-acid-releasing enzyme; 1. DR FunFam; 3.40.50.1820:FF:000043; acylamino-acid-releasing enzyme; 1. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR045550; AARE_N. DR InterPro; IPR029058; AB_hydrolase_fold. DR InterPro; IPR002471; Pept_S9_AS. DR InterPro; IPR001375; Peptidase_S9_cat. DR InterPro; IPR004106; Peptidase_S9_N_sf. DR PANTHER; PTHR42776:SF4; ACYLAMINO-ACID-RELEASING ENZYME; 1. DR PANTHER; PTHR42776; SERINE PEPTIDASE S9 FAMILY MEMBER; 1. DR Pfam; PF19283; APEH_N; 1. DR Pfam; PF00326; Peptidase_S9; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR SUPFAM; SSF50993; Peptidase/esterase 'gauge' domain; 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..730 FT /note="Acylamino-acid-releasing enzyme" FT /id="PRO_0000122429" FT ACT_SITE 585 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084" FT ACT_SITE 673 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084" FT ACT_SITE 705 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10084" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P13798" FT MOD_RES 183 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13798" FT MOD_RES 185 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P13798" SQ SEQUENCE 730 AA; 81093 MW; 838882B5B703DF15 CRC64; MERQVLLSEP EEAAALYRGL SRQPALSAAC LGPEVTTQYG GRYRTVHTEW TQRDLERMEN IRFCRQYLVF HDGDSVVFAG PAGNSVETRG ELLSRESPSG TMKAVLRKAG STGEEKQFLE VWEKNRKLKS FNLSALEKHG PVYEDDCFGC LSWSHSETHL LYVAEKKRPK AESFFQTKAL DISGSDDEMA RPKKPDQAIK GDQFLFYEDW GENMVSKGSP VLCVLDIESG NISVLEGVPE SVSPGQAFWA PGDTGVVFAG WWHEPFRLGI RFCTNRRSAL YYVDLTGGNC ELLSDDSLAV TSPRLSPDQC RIVYLQFPSL VPHQQCGQLC LYDWYTRVTV VVVDVVPRQL GENFSGIYCS LLPLGCWSAD SQRVVFDTAQ RSRQDLFAVD TQMGTVTPLT AGGSGGSWKL LTIDRDLMVA QFSTPNLPPC LKVGFLPPAG MEQEVVWVSL EEAEPIPDIS WSIRVLQPPP EQEHAQYVGL DFEAILIQPS NPPDKTQVPM VVMPHGGPHS SFVTSWMLLP AMLCKMGFAA LLVNYRGSTG FGQDSILSLP GNVGSQDVKD VQFAVEQVLQ EEHFDAGRVA LLGGSHGGFL SCHLIGQYPE TYGACVVRNP VINIASMMGS TDIPDWCVVE AGYLYSSDCL PDPNVWSEML NKSPIKYTPQ VKTPVLLMLG QEDRRVPFKQ GMEYYRALKA RNVPVRLLLY PKSTHSLSEV EVESDSFMNA VIWMCTHLGH //