XPP_CAEEL
ID XPP_CAEEL Reviewed; 616 AA.
AC O44750;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Xaa-Pro aminopeptidase app-1 {ECO:0000305|PubMed:11606206};
DE EC=3.4.11.9 {ECO:0000269|PubMed:11606206};
DE AltName: Full=Aminopeptidase P {ECO:0000303|PubMed:11606206};
GN Name=app-1 {ECO:0000303|PubMed:11606206};
GN ORFNames=W03G9.4 {ECO:0000312|WormBase:W03G9.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=11606206; DOI=10.1046/j.0014-2956.2001.02483.x;
RA Laurent V., Brooks D.R., Coates D., Isaac R.E.;
RT "Functional expression and characterization of the cytoplasmic
RT aminopeptidase P of Caenorhabditis elegans.";
RL Eur. J. Biochem. 268:5430-5438(2001).
RN [3]
RP INTERACTION WITH PID-2; PID-4 AND PID-5.
RX PubMed=33231880; DOI=10.15252/embj.2020105280;
RA Placentino M., de Jesus Domingues A.M., Schreier J., Dietz S., Hellmann S.,
RA de Albuquerque B.F., Butter F., Ketting R.F.;
RT "Intrinsically disordered protein PID-2 modulates Z granules and is
RT required for heritable piRNA-induced silencing in the Caenorhabditis
RT elegans embryo.";
RL EMBO J. 40:e105280-e105280(2021).
RN [4] {ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) ALONE AND IN COMPLEX WITH INHIBITOR
RP APSTATIN, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP SUBUNIT, AND ZINC-BINDING SITES.
RX PubMed=25905034; DOI=10.1016/j.fob.2015.03.013;
RA Iyer S., La-Borde P.J., Payne K.A., Parsons M.R., Turner A.J., Isaac R.E.,
RA Acharya K.R.;
RT "Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans:
RT A cytosolic enzyme with a di-nuclear active site.";
RL FEBS Open Bio 5:292-302(2015).
CC -!- FUNCTION: Catalyzes the removal of a penultimate prolyl residue from
CC the N-termini of peptides, such as Arg-Pro-Pro (PubMed:11606206,
CC PubMed:25905034). Has activity towards the flp-9 neuropeptide KPSFVRF-
CC amide (PubMed:11606206). {ECO:0000269|PubMed:11606206,
CC ECO:0000269|PubMed:25905034}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of any N-terminal amino acid, including proline, that
CC is linked to proline, even from a dipeptide or tripeptide.;
CC EC=3.4.11.9; Evidence={ECO:0000269|PubMed:11606206};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:25905034};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:25905034};
CC -!- ACTIVITY REGULATION: Strongly inhibited by the metal ion chelators EDTA
CC and 1,10-phenanthroline (PubMed:11606206). Also inhibited by apstatin
CC (PubMed:11606206, PubMed:25905034). Activity towards bradykinin is
CC inhibited by Mn(2+) and Zn(2+) at all concentrations tested, whereas
CC Co(2+) is inhibitory at concentrations above 100 uM and activatory at
CC 10 uM (PubMed:11606206). {ECO:0000269|PubMed:11606206,
CC ECO:0000269|PubMed:25905034}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=45 uM for bradykinin {ECO:0000269|PubMed:11606206};
CC pH dependence:
CC Optimum pH is 7-8. {ECO:0000269|PubMed:11606206};
CC -!- SUBUNIT: Homodimer (PubMed:25905034). May interact with pid-2, pid-4
CC and pid-5 (PubMed:33231880). {ECO:0000269|PubMed:25905034,
CC ECO:0000269|PubMed:33231880}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11606206}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in the intestine.
CC {ECO:0000269|PubMed:11606206}.
CC -!- DEVELOPMENTAL STAGE: Expressed in intestine from larval stage L2
CC onwards. Not detected in embryos. {ECO:0000269|PubMed:11606206}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000305}.
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DR EMBL; BX284601; CCD70128.1; -; Genomic_DNA.
DR PIR; T32753; T32753.
DR RefSeq; NP_491489.1; NM_059088.4.
DR PDB; 4S2R; X-ray; 1.95 A; P/Q=1-616.
DR PDB; 4S2T; X-ray; 2.15 A; P/Q=1-616.
DR PDBsum; 4S2R; -.
DR PDBsum; 4S2T; -.
DR AlphaFoldDB; O44750; -.
DR SMR; O44750; -.
DR DIP; DIP-26588N; -.
DR STRING; 6239.W03G9.4.1; -.
DR MEROPS; M24.032; -.
DR EPD; O44750; -.
DR PaxDb; O44750; -.
DR PeptideAtlas; O44750; -.
DR EnsemblMetazoa; W03G9.4.1; W03G9.4.1; WBGene00000155.
DR GeneID; 172118; -.
DR KEGG; cel:CELE_W03G9.4; -.
DR UCSC; W03G9.4.1; c. elegans.
DR CTD; 172118; -.
DR WormBase; W03G9.4; CE14560; WBGene00000155; app-1.
DR eggNOG; KOG2413; Eukaryota.
DR GeneTree; ENSGT00970000196568; -.
DR HOGENOM; CLU_011781_2_1_1; -.
DR InParanoid; O44750; -.
DR OMA; YRPGKWG; -.
DR OrthoDB; 417805at2759; -.
DR PhylomeDB; O44750; -.
DR BRENDA; 3.4.11.9; 1045.
DR PRO; PR:O44750; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000155; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:WormBase.
DR CDD; cd01085; APP; 1.
DR Gene3D; 3.40.350.10; -; 2.
DR Gene3D; 3.90.230.10; -; 1.
DR InterPro; IPR029149; Creatin/AminoP/Spt16_NTD.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000587; Creatinase_N.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR033740; Pept_M24B.
DR InterPro; IPR032416; Peptidase_M24_C.
DR Pfam; PF01321; Creatinase_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR Pfam; PF16188; Peptidase_M24_C; 1.
DR SUPFAM; SSF53092; SSF53092; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding;
KW Protease; Reference proteome; Zinc.
FT CHAIN 1..616
FT /note="Xaa-Pro aminopeptidase app-1"
FT /id="PRO_0000438731"
FT BINDING 78
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:25905034,
FT ECO:0007744|PDB:4S2T"
FT BINDING 392
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:25905034,
FT ECO:0007744|PDB:4S2T"
FT BINDING 413
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT BINDING 424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT BINDING 424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT BINDING 487
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:25905034,
FT ECO:0007744|PDB:4S2T"
FT BINDING 487
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT BINDING 496
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:25905034,
FT ECO:0007744|PDB:4S2T"
FT BINDING 522
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:25905034,
FT ECO:0007744|PDB:4S2T"
FT BINDING 522
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT BINDING 536
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT BINDING 536
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:25905034,
FT ECO:0007744|PDB:4S2R, ECO:0007744|PDB:4S2T"
FT HELIX 3..12
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 17..22
FT /evidence="ECO:0007829|PDB:4S2R"
FT TURN 23..25
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 50..55
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 80..86
FT /evidence="ECO:0007829|PDB:4S2R"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:4S2R"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 129..140
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 180..193
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 204..211
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 246..254
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 265..278
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 293..299
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 310..316
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 320..349
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 356..368
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 373..378
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 381..384
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 385..389
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 410..414
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 425..429
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 436..453
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 463..470
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 472..475
FT /evidence="ECO:0007829|PDB:4S2R"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 485..488
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 491..493
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 501..503
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 524..527
FT /evidence="ECO:0007829|PDB:4S2R"
FT TURN 528..530
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 531..534
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 536..543
FT /evidence="ECO:0007829|PDB:4S2R"
FT STRAND 553..559
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 571..573
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 576..599
FT /evidence="ECO:0007829|PDB:4S2R"
FT HELIX 603..612
FT /evidence="ECO:0007829|PDB:4S2R"
SQ SEQUENCE 616 AA; 69340 MW; 48EFBCA03B85DEC5 CRC64;
MTALEKLAKL RSLFHSERVL ALTSSKPMVA YLLPSTDAHH SEYLADYDFR VKFLSGFSGS
NAYVVVTDRE ALLWTDGRYF TQAGNQLDSN SWKLMKQGQP DSITVVDWLV RELERGSVIG
FDPTLSTFDA GSKTFKRLKA AGLQPVSIPG NLVDEFWTDR PRLAGEPVVV LDVEDTGLTT
SKKVENLREK LKQKKCDAAV FTLLDDVMWL LNIRGSDIPY NPLAYSYLFV AMREIHVFID
NEKLDEKSRA HFHKSNVSIH PYGEVYSWIS NWLKAKEASK EPHMVYLTPE TNYAIGSIIG
EENSMVDTSL VQTAKATKND HEMQGMRNSH LRDSAALVEF LCWLEKELLS GKRYTEIELA
DKIDHLRSLQ DKYVTLSFDT ISAVGDHAAL PHYKPLGESG NRKAAANQVF LLDSGAHYGD
GTTDVTRTVW YTNPPKEFIL HNTLVLKGHI NLARAKFPDG IYGSRLDTLT RDALWKLGLD
FEHGTGHGVG HYLNVHEGPI GIGHRSVPTG GELHASQVLT IEPGFYAKEK YGIRIENCYE
TVEAVVMSKA QNFLTFKSLT LVPIQTSIVD KSLLIEEEIN WLNQYHARVL KEVGEHLQKR
GKTDELKWLA EACKPI
