PGPI_HUMAN
ID PGPI_HUMAN Reviewed; 209 AA.
AC Q9NXJ5; A8K1Q3; Q8IVT1;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Pyroglutamyl-peptidase 1;
DE EC=3.4.19.3;
DE AltName: Full=5-oxoprolyl-peptidase;
DE AltName: Full=Pyroglutamyl aminopeptidase I;
DE Short=PAP-I;
DE AltName: Full=Pyroglutamyl-peptidase I;
DE Short=PGP-I;
DE AltName: Full=Pyrrolidone-carboxylate peptidase;
GN Name=PGPEP1; Synonyms=PGPI;
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=12651114; DOI=10.1016/s1046-5928(02)00632-0;
RA Dando P.M., Fortunato M., Strand G.B., Smith T.S., Barrett A.J.;
RT "Pyroglutamyl-peptidase I: cloning, sequencing, and characterisation of the
RT recombinant human enzyme.";
RL Protein Expr. Purif. 28:111-119(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Amygdala, Colon mucosa, and Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Blood;
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).
CC -!- FUNCTION: Removes 5-oxoproline from various penultimate amino acid
CC residues except L-proline. {ECO:0000269|PubMed:12651114}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal pyroglutamyl group from a
CC polypeptide, the second amino acid generally not being Pro.;
CC EC=3.4.19.3; Evidence={ECO:0000255|PROSITE-ProRule:PRU10076,
CC ECO:0000255|PROSITE-ProRule:PRU10077, ECO:0000269|PubMed:12651114};
CC -!- ACTIVITY REGULATION: Inhibited by transition metal ions including
CC Ni(2+), Zn(2+), and Cu(2+) and by sulfhydryl-blocking agents.
CC {ECO:0000269|PubMed:12651114}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:12651114}.
CC -!- INTERACTION:
CC Q9NXJ5-2; P29972: AQP1; NbExp=3; IntAct=EBI-12813581, EBI-745213;
CC Q9NXJ5-2; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-12813581, EBI-741158;
CC Q9NXJ5-2; Q96LR5: UBE2E2; NbExp=6; IntAct=EBI-12813581, EBI-2129763;
CC Q9NXJ5-2; Q969T4: UBE2E3; NbExp=5; IntAct=EBI-12813581, EBI-348496;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NXJ5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXJ5-2; Sequence=VSP_056472;
CC -!- SIMILARITY: Belongs to the peptidase C15 family. {ECO:0000305}.
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DR EMBL; AJ278828; CAC03610.1; -; mRNA.
DR EMBL; AK000215; BAA91015.1; -; mRNA.
DR EMBL; AK289968; BAF82657.1; -; mRNA.
DR EMBL; AK294497; BAG57716.1; -; mRNA.
DR EMBL; AC008397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84691.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84692.1; -; Genomic_DNA.
DR EMBL; BC042138; AAH42138.1; -; mRNA.
DR CCDS; CCDS12375.1; -. [Q9NXJ5-1]
DR CCDS; CCDS82319.1; -. [Q9NXJ5-2]
DR RefSeq; NP_001287856.1; NM_001300927.1.
DR RefSeq; NP_001295295.1; NM_001308366.1.
DR RefSeq; NP_001316400.1; NM_001329471.1.
DR RefSeq; NP_001316405.1; NM_001329476.1.
DR RefSeq; NP_001316406.1; NM_001329477.1. [Q9NXJ5-2]
DR RefSeq; NP_001316407.1; NM_001329478.1. [Q9NXJ5-2]
DR RefSeq; NP_060182.1; NM_017712.3. [Q9NXJ5-1]
DR AlphaFoldDB; Q9NXJ5; -.
DR SMR; Q9NXJ5; -.
DR BioGRID; 120208; 20.
DR IntAct; Q9NXJ5; 11.
DR STRING; 9606.ENSP00000269919; -.
DR MEROPS; C15.010; -.
DR iPTMnet; Q9NXJ5; -.
DR PhosphoSitePlus; Q9NXJ5; -.
DR BioMuta; PGPEP1; -.
DR DMDM; 14548183; -.
DR EPD; Q9NXJ5; -.
DR jPOST; Q9NXJ5; -.
DR MassIVE; Q9NXJ5; -.
DR MaxQB; Q9NXJ5; -.
DR PaxDb; Q9NXJ5; -.
DR PeptideAtlas; Q9NXJ5; -.
DR PRIDE; Q9NXJ5; -.
DR ProteomicsDB; 83105; -. [Q9NXJ5-1]
DR Antibodypedia; 28025; 108 antibodies from 22 providers.
DR DNASU; 54858; -.
DR Ensembl; ENST00000252813.5; ENSP00000252813.5; ENSG00000130517.14. [Q9NXJ5-2]
DR Ensembl; ENST00000269919.11; ENSP00000269919.3; ENSG00000130517.14. [Q9NXJ5-1]
DR GeneID; 54858; -.
DR KEGG; hsa:54858; -.
DR MANE-Select; ENST00000269919.11; ENSP00000269919.3; NM_017712.4; NP_060182.1.
DR UCSC; uc002nis.2; human. [Q9NXJ5-1]
DR CTD; 54858; -.
DR DisGeNET; 54858; -.
DR GeneCards; PGPEP1; -.
DR HGNC; HGNC:13568; PGPEP1.
DR HPA; ENSG00000130517; Low tissue specificity.
DR MIM; 610694; gene.
DR neXtProt; NX_Q9NXJ5; -.
DR OpenTargets; ENSG00000130517; -.
DR PharmGKB; PA33247; -.
DR VEuPathDB; HostDB:ENSG00000130517; -.
DR eggNOG; KOG4755; Eukaryota.
DR GeneTree; ENSGT00390000015368; -.
DR HOGENOM; CLU_043960_3_0_1; -.
DR InParanoid; Q9NXJ5; -.
DR OMA; KLAYNHK; -.
DR OrthoDB; 1248044at2759; -.
DR PhylomeDB; Q9NXJ5; -.
DR TreeFam; TF313278; -.
DR BioCyc; MetaCyc:HS05394-MON; -.
DR BRENDA; 3.4.19.3; 2681.
DR PathwayCommons; Q9NXJ5; -.
DR SignaLink; Q9NXJ5; -.
DR BioGRID-ORCS; 54858; 99 hits in 1079 CRISPR screens.
DR ChiTaRS; PGPEP1; human.
DR GeneWiki; PGPEP1; -.
DR GenomeRNAi; 54858; -.
DR Pharos; Q9NXJ5; Tbio.
DR PRO; PR:Q9NXJ5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NXJ5; protein.
DR Bgee; ENSG00000130517; Expressed in cardia of stomach and 181 other tissues.
DR ExpressionAtlas; Q9NXJ5; baseline and differential.
DR Genevisible; Q9NXJ5; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016920; F:pyroglutamyl-peptidase activity; IEA:InterPro.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00501; Peptidase_C15; 1.
DR Gene3D; 3.40.630.20; -; 1.
DR InterPro; IPR000816; Peptidase_C15.
DR InterPro; IPR016125; Peptidase_C15-like.
DR InterPro; IPR036440; Peptidase_C15-like_sf.
DR InterPro; IPR029761; PGP-I_metazoa.
DR InterPro; IPR033694; PGPEP1_Cys_AS.
DR InterPro; IPR033693; PGPEP1_Glu_AS.
DR PANTHER; PTHR23402; PTHR23402; 1.
DR PANTHER; PTHR23402:SF16; PTHR23402:SF16; 1.
DR Pfam; PF01470; Peptidase_C15; 1.
DR PIRSF; PIRSF015592; Prld-crbxl_pptds; 1.
DR PRINTS; PR00706; PYROGLUPTASE.
DR SUPFAM; SSF53182; SSF53182; 1.
DR PROSITE; PS01334; PYRASE_CYS; 1.
DR PROSITE; PS01333; PYRASE_GLU; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Protease; Reference proteome;
KW Thiol protease.
FT CHAIN 1..209
FT /note="Pyroglutamyl-peptidase 1"
FT /id="PRO_0000184761"
FT ACT_SITE 85
FT /evidence="ECO:0000250"
FT ACT_SITE 149
FT /evidence="ECO:0000250"
FT ACT_SITE 168
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..77
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_056472"
SQ SEQUENCE 209 AA; 23138 MW; 91456CB1D52B04AB CRC64;
MEQPRKAVVV TGFGPFGEHT VNASWIAVQE LEKLGLGDSV DLHVYEIPVE YQTVQRLIPA
LWEKHSPQLV VHVGVSGMAT TVTLEKCGHN KGYKGLDNCR FCPGSQCCVE DGPESIDSII
DMDAVCKRVT TLGLDVSVTI SQDAGRYLCD FTYYTSLYQS HGRSAFVHVP PLGKPYNADQ
LGRALRAIIE EMLDLLEQSE GKINYCHKH
