XPP_DROME
ID XPP_DROME Reviewed; 613 AA.
AC Q9VJG0;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Xaa-Pro aminopeptidase ApepP {ECO:0000305};
DE EC=3.4.11.9 {ECO:0000269|PubMed:11872174};
DE AltName: Full=Aminopeptidase P {ECO:0000303|PubMed:11872174};
DE Short=AP-P {ECO:0000303|PubMed:11872174};
GN Name=ApepP {ECO:0000312|FlyBase:FBgn0026150};
GN ORFNames=CG6291 {ECO:0000312|FlyBase:FBgn0026150};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|EMBL:AAL99293.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11872174; DOI=10.1093/oxfordjournals.jbchem.a003120;
RA Kulkarni G.V., Deobagkar D.D.;
RT "A cytosolic form of aminopeptidase P from Drosophila melanogaster:
RT molecular cloning and characterization.";
RL J. Biochem. 131:445-452(2002).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000312|EMBL:AAL28845.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL28845.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL28845.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
CC -!- FUNCTION: Catalyzes the removal of a penultimate prolyl residue from
CC the N-termini of peptides, such as Arg-Pro-Pro.
CC {ECO:0000269|PubMed:11872174}.
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:11872174};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000305|PubMed:11872174};
CC -!- ACTIVITY REGULATION: Inhibited by the chelating agent EDTA. Divalent
CC metal ions have substrate- and concentration-dependent effects on
CC activity. Activity towards bradykinin is inhibited with increasing
CC Mn(2+) concentration. Activity towards substance P is stimulated by low
CC Mn(2+) concentrations (in the range 10 uM-1 mM) but inhibited by Mn(2+)
CC concentrations in excess of 1 mM. Ca(2+), Mg(2+) and Co(2+) stimulate
CC activity towards substance P at concentrations of 10-100 uM but are
CC inhibitory at concentrations of 1 mM. Zn(2+), Ni(2+) and Cu(2+)
CC strongly inhibit activity towards substance P at concentrations of 1
CC mM. {ECO:0000269|PubMed:11872174}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.6. {ECO:0000269|PubMed:11872174};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11872174}.
CC -!- TISSUE SPECIFICITY: Detected in gut, brain, testes and ovary.
CC {ECO:0000269|PubMed:11872174}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos from 9-22 hours, but not
CC detected in first and second instar larvae. Expressed in 3rd instar
CC larvae and at high levels in pupae. {ECO:0000269|PubMed:11872174}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000305}.
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DR EMBL; AY082012; AAL99293.1; -; Genomic_DNA.
DR EMBL; AE014134; AAF53589.1; -; Genomic_DNA.
DR EMBL; AE014134; AFH03727.1; -; Genomic_DNA.
DR EMBL; AY061297; AAL28845.1; -; mRNA.
DR PIR; JC7827; JC7827.
DR RefSeq; NP_001246053.1; NM_001259124.2.
DR RefSeq; NP_477409.1; NM_058061.5.
DR AlphaFoldDB; Q9VJG0; -.
DR SMR; Q9VJG0; -.
DR DIP; DIP-21902N; -.
DR STRING; 7227.FBpp0080509; -.
DR MEROPS; M24.009; -.
DR PaxDb; Q9VJG0; -.
DR PRIDE; Q9VJG0; -.
DR DNASU; 35029; -.
DR EnsemblMetazoa; FBtr0080956; FBpp0080509; FBgn0026150.
DR EnsemblMetazoa; FBtr0304931; FBpp0293470; FBgn0026150.
DR GeneID; 35029; -.
DR KEGG; dme:Dmel_CG6291; -.
DR UCSC; CG6291-RA; d. melanogaster.
DR CTD; 35029; -.
DR FlyBase; FBgn0026150; ApepP.
DR VEuPathDB; VectorBase:FBgn0026150; -.
DR eggNOG; KOG2413; Eukaryota.
DR GeneTree; ENSGT00940000157716; -.
DR HOGENOM; CLU_011781_2_2_1; -.
DR InParanoid; Q9VJG0; -.
DR OMA; YRPGKWG; -.
DR OrthoDB; 417805at2759; -.
DR PhylomeDB; Q9VJG0; -.
DR BioGRID-ORCS; 35029; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 35029; -.
DR PRO; PR:Q9VJG0; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0026150; Expressed in embryonic/larval hemocyte (Drosophila) and 39 other tissues.
DR ExpressionAtlas; Q9VJG0; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
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 Aminopeptidase; Cytoplasm; Hydrolase; Manganese; Metal-binding; Protease;
KW Reference proteome.
FT CHAIN 1..613
FT /note="Xaa-Pro aminopeptidase ApepP"
FT /id="PRO_0000438801"
FT BINDING 77
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 388
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 408
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
FT BINDING 419
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
FT BINDING 419
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
FT BINDING 482
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
FT BINDING 482
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 491
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 517
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
FT BINDING 517
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 531
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
FT BINDING 531
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9NQW7"
SQ SEQUENCE 613 AA; 68506 MW; CF55A1FBB527EFD7 CRC64;
MKRSTTQILT RLRELMLRAQ VGDSCGISAY IVPSDDAHQS EYQCQHDERR SFVSGFDGSA
GTAVITTETA LLWTDGRYYQ QAEKQLDSNW VLMRDGLSAT PSIGAWLAKN LPKGSFVGVD
PRLLSFRVWK PIETELSSAE CQLVPIEGNL IDEVWGEDQP PQTSNKIITL KLEHSGVTIA
KKWDVVRQQL KEKNADALVV SALDEIAWFL NLRGSDIDFN PVFFSYLIVT NDELLLFVDS
GKLPTDFVQH QKENNVQISV LPYASIGIEI SKIVSTRESK IWIAPTSSYY LTALIPKSRR
IQEVTPICVL KAIKNDVEIA GFINSHIRDG VALCQYFAWL EDQVNKGAEV DEMSGADKLE
SFRSTKDKYM GLSFTTISAS GPNGSVIHYH PKKETNRKIN DKEIYLCDSG AQYLDGTTDV
TRTLHFGEPT EFQKEAYTRV LKGQLSFGST VFPAKVKGQV LDTLARKALW DVGLDYGHGT
GHGVGHFLNV HEGPMGVGIR LMPDDPGLQA NMFISNEPGF YQDGEFGIRV EDIVQIVPGQ
VAHNFSNRGA LTFKTITMCP KQTKMIKKEL LSDAEVKLLN SYHQQVWDTL SPILSREGDE
FTLSWLKKEV QPI
