PPCEL_HUMAN
ID PPCEL_HUMAN Reviewed; 727 AA.
AC Q4J6C6; A7E2X6; D6W5A3; O43163; Q4J6C3; Q4J6C4; Q4ZG39; Q6ZMW7; Q96DW7;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Prolyl endopeptidase-like;
DE EC=3.4.21.- {ECO:0000269|PubMed:16143824, ECO:0000269|PubMed:16385448, ECO:0000269|PubMed:28726805};
DE AltName: Full=Prolylendopeptidase-like;
GN Name=PREPL; Synonyms=KIAA0436;
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] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RX PubMed=15913950; DOI=10.1016/j.ygeno.2005.04.001;
RA Parvari R., Gonen Y., Alshafee I., Buriakovsky S., Regev K.,
RA Hershkovitz E.;
RT "The 2p21 deletion syndrome: characterization of the transcription
RT content.";
RL Genomics 86:195-211(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone;
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).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=16143824; DOI=10.1007/s00018-005-5262-5;
RA Szeltner Z., Alshafee I., Juhasz T., Parvari R., Polgar L.;
RT "The PREPL A protein, a new member of the prolyl oligopeptidase family,
RT lacking catalytic activity.";
RL Cell. Mol. Life Sci. 62:2376-2381(2005).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP TISSUE SPECIFICITY, INVOLVEMENT IN HCS, ACTIVE SITE, AND MUTAGENESIS OF
RP SER-559; ASP-645; HIS-690 AND HIS-696.
RX PubMed=16385448; DOI=10.1086/498852;
RA Jaeken J., Martens K., Francois I., Eyskens F., Lecointre C., Derua R.,
RA Meulemans S., Slootstra J.W., Waelkens E., de Zegher F., Creemers J.W.M.,
RA Matthijs G.;
RT "Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in
RT patients with hypotonia-cystinuria syndrome.";
RL Am. J. Hum. Genet. 78:38-51(2006).
RN [9]
RP INVOLVEMENT IN HCS.
RX PubMed=21686663; DOI=10.1136/bcr.08.2008.0719;
RA Chabrol B., Martens K., Meulemans S., Cano A., Jaeken J., Matthijs G.,
RA Creemers J.W.;
RT "Deletion of C2orf34, PREPL and SLC3A1 causes atypical hypotonia-cystinuria
RT syndrome.";
RL BMJ Case Rep. 2009:0-0(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 4), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP FUNCTION, SUBUNIT, AND INVOLVEMENT IN HCS.
RX PubMed=23321636; DOI=10.1242/jcs.116079;
RA Radhakrishnan K., Baltes J., Creemers J.W., Schu P.;
RT "Trans-Golgi network morphology and sorting is regulated by prolyl-
RT oligopeptidase-like protein PREPL and the AP-1 complex subunit mu1A.";
RL J. Cell Sci. 126:1155-1163(2013).
RN [12]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INVOLVEMENT IN HCS.
RX PubMed=23485813; DOI=10.1016/j.neuroscience.2013.02.038;
RA Morawski M., Nuytens K., Juhasz T., Zeitschel U., Seeger G., Waelkens E.,
RA Regal L., Schulz I., Arendt T., Szeltner Z., Creemers J., Rossner S.;
RT "Cellular and ultra structural evidence for cytoskeletal localization of
RT prolyl endopeptidase-like protein in neurons.";
RL Neuroscience 242:128-139(2013).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN CMS22.
RX PubMed=24610330; DOI=10.1212/wnl.0000000000000295;
RA Regal L., Shen X.M., Selcen D., Verhille C., Meulemans S., Creemers J.W.,
RA Engel A.G.;
RT "PREPL deficiency with or without cystinuria causes a novel myasthenic
RT syndrome.";
RL Neurology 82:1254-1260(2014).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INVOLVEMENT IN HCS.
RX PubMed=28726805; DOI=10.1038/gim.2017.74;
RA Regal L., Maartensson E., Maystadt I., Voermans N., Lederer D., Burlina A.,
RA Juan Fita M.J., Hoogeboom A.J.M., Olsson Engman M., Hollemans T.,
RA Schouten M., Meulemans S., Jonson T., Francois I., Gil Ortega D.,
RA Kamsteeg E.J., Creemers J.W.M.;
RT "PREPL deficiency: delineation of the phenotype and development of a
RT functional blood assay.";
RL Genet. Med. 20:109-118(2018).
RN [15]
RP INVOLVEMENT IN CMS22.
RX PubMed=29483676; DOI=10.1038/s10038-018-0426-y;
RA Silva S., Miyake N., Tapia C., Matsumoto N.;
RT "The second point mutation in PREPL: a case report and literature review.";
RL J. Hum. Genet. 63:677-681(2018).
RN [16]
RP VARIANT 483-GLY--PHE-727 DEL.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- FUNCTION: Serine peptidase whose precise substrate specificity remains
CC unclear (PubMed:16143824, PubMed:16385448, PubMed:28726805). Does not
CC cleave peptides after a arginine or lysine residue (PubMed:16143824).
CC Regulates trans-Golgi network morphology and sorting by regulating the
CC membrane binding of the AP-1 complex (PubMed:23321636). May play a role
CC in the regulation of synaptic vesicle exocytosis (PubMed:24610330).
CC {ECO:0000269|PubMed:16143824, ECO:0000269|PubMed:16385448,
CC ECO:0000269|PubMed:23321636, ECO:0000269|PubMed:24610330,
CC ECO:0000269|PubMed:28726805}.
CC -!- ACTIVITY REGULATION: Inhibited by PMSF and Prefabloc, as well as
CC leupeptin at high concentrations (PubMed:16385448). Partially inhibited
CC by TPCK, a chymotrypsin inhibitor and E64, a cysteine protease
CC inhibitor (PubMed:16385448). Not affected by 4-amidinophenyl-
CC methanesulfonyl fluoride (APMSF), pepstatin or EDTA (PubMed:16385448).
CC Inhibited by 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-
CC cyclopenta[c]pyridine-4-carbonitrile (PubMed:28726805).
CC {ECO:0000269|PubMed:16385448, ECO:0000269|PubMed:28726805}.
CC -!- SUBUNIT: Homodimer (PubMed:16143824). Interacts with the AP-1 complex
CC (PubMed:23321636). {ECO:0000269|PubMed:16143824,
CC ECO:0000269|PubMed:23321636}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16385448,
CC ECO:0000269|PubMed:23485813}. Golgi apparatus, trans-Golgi network
CC {ECO:0000250|UniProtKB:Q8C167}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q8C167}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q8C167}. Nucleus {ECO:0000269|PubMed:23485813}.
CC Note=Co-localizes with AP-1 in the trans-Golgi network (By similarity).
CC Co-localizes with MAP2 and ACTB on the cytoskeleton (By similarity).
CC Co-localizes with STX6 and GOSR2 at the Golgi apparatus (By
CC similarity). {ECO:0000250|UniProtKB:Q8C167}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q4J6C6-1; Sequence=Displayed;
CC Name=2; Synonyms=D;
CC IsoId=Q4J6C6-2; Sequence=VSP_030403;
CC Name=3; Synonyms=E;
CC IsoId=Q4J6C6-3; Sequence=VSP_030402;
CC Name=4;
CC IsoId=Q4J6C6-4; Sequence=VSP_030401;
CC -!- TISSUE SPECIFICITY: Expressed in pyramidal neurons of the temporal
CC cortex and neocortex (at protein level) (PubMed:23485813). Widely
CC expressed (PubMed:15913950, PubMed:16385448). Expressed at higher level
CC in brain, skeletal muscle, heart and kidney (PubMed:15913950,
CC PubMed:16385448). Expressed at the endplates in the neuromuscular
CC junction (PubMed:24610330). {ECO:0000269|PubMed:15913950,
CC ECO:0000269|PubMed:16385448, ECO:0000269|PubMed:23485813,
CC ECO:0000269|PubMed:24610330}.
CC -!- DISEASE: Hypotonia-cystinuria syndrome (HCS) [MIM:606407]:
CC Characterized generalized hypotonia at birth, nephrolithiasis, growth
CC hormone deficiency, minor facial dysmorphism, failure to thrive,
CC followed by hyperphagia and rapid weight gain in late childhood.
CC {ECO:0000269|PubMed:16385448, ECO:0000269|PubMed:21686663,
CC ECO:0000269|PubMed:23321636, ECO:0000269|PubMed:23485813,
CC ECO:0000269|PubMed:28726805}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. Hypotonia-cystinuria syndrome is a
CC contiguous gene syndrome caused by a homozygous deletion on chromosome
CC 2p21 that disrupts the gene represented in this entry and SLC3A1
CC (PubMed:16385448, PubMed:21686663). A homozygous 77.4-kb deletion that
CC disrupts the gene represented in this entry, SLC3A1 and CAMKMT, causes
CC atypical hypotonia-cystinuria syndrome, characterized by mild to
CC moderate intellectual disability and respiratory chain complex IV
CC deficiency (PubMed:21686663). Patient cells exhibit a larger trans-
CC Golgi network and a reduced redistribution of AP-1 complex, which
CC causes impairment in AP-1 mediated membrane-cytoplasm recycling and
CC secretion (PubMed:23321636). {ECO:0000269|PubMed:16385448,
CC ECO:0000269|PubMed:21686663, ECO:0000269|PubMed:23321636}.
CC -!- DISEASE: Myasthenic syndrome, congenital, 22 (CMS22) [MIM:616224]: A
CC form of congenital myasthenic syndrome, a group of disorders
CC characterized by failure of neuromuscular transmission, including pre-
CC synaptic, synaptic, and post-synaptic disorders that are not of
CC autoimmune origin. Clinical features include easy fatigability and
CC muscle weakness. CMS22 is an autosomal recessive form characterized by
CC neonatal hypotonia. {ECO:0000269|PubMed:24610330,
CC ECO:0000269|PubMed:29483676}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S9A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX88956.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA23709.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ023503; AAY89634.1; -; mRNA.
DR EMBL; DQ023504; AAY89635.1; -; mRNA.
DR EMBL; DQ023505; AAY89636.1; -; mRNA.
DR EMBL; DQ023506; AAY89637.1; -; mRNA.
DR EMBL; DQ023507; AAY89638.1; -; mRNA.
DR EMBL; AB007896; BAA23709.1; ALT_INIT; mRNA.
DR EMBL; AK131463; BAD18608.1; -; mRNA.
DR EMBL; AC013717; AAX88956.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471053; EAX00275.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00276.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00277.1; -; Genomic_DNA.
DR EMBL; BC013193; AAH13193.1; -; mRNA.
DR EMBL; BC151236; AAI51237.1; -; mRNA.
DR CCDS; CCDS33190.1; -. [Q4J6C6-1]
DR CCDS; CCDS42675.1; -. [Q4J6C6-3]
DR CCDS; CCDS42676.1; -. [Q4J6C6-2]
DR CCDS; CCDS54353.1; -. [Q4J6C6-4]
DR RefSeq; NP_001035844.1; NM_001042385.2. [Q4J6C6-3]
DR RefSeq; NP_001035845.1; NM_001042386.2. [Q4J6C6-2]
DR RefSeq; NP_001165074.1; NM_001171603.1. [Q4J6C6-1]
DR RefSeq; NP_001165077.1; NM_001171606.1. [Q4J6C6-1]
DR RefSeq; NP_001165084.1; NM_001171613.1. [Q4J6C6-4]
DR RefSeq; NP_001165088.1; NM_001171617.1. [Q4J6C6-4]
DR RefSeq; NP_006027.2; NM_006036.4. [Q4J6C6-1]
DR RefSeq; XP_011531500.1; XM_011533198.1.
DR RefSeq; XP_011531502.1; XM_011533200.1.
DR RefSeq; XP_011531504.1; XM_011533202.1.
DR RefSeq; XP_016860873.1; XM_017005384.1. [Q4J6C6-1]
DR RefSeq; XP_016860874.1; XM_017005385.1. [Q4J6C6-1]
DR PDB; 7OBM; X-ray; 3.10 A; A=90-727.
DR PDBsum; 7OBM; -.
DR AlphaFoldDB; Q4J6C6; -.
DR SMR; Q4J6C6; -.
DR BioGRID; 114949; 108.
DR IntAct; Q4J6C6; 45.
DR MINT; Q4J6C6; -.
DR STRING; 9606.ENSP00000386543; -.
DR BindingDB; Q4J6C6; -.
DR ChEMBL; CHEMBL2189128; -.
DR ESTHER; human-PREPL; S9N_PREPL_Peptidase_S9.
DR MEROPS; S09.015; -.
DR GlyGen; Q4J6C6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q4J6C6; -.
DR PhosphoSitePlus; Q4J6C6; -.
DR BioMuta; PREPL; -.
DR DMDM; 121944206; -.
DR EPD; Q4J6C6; -.
DR jPOST; Q4J6C6; -.
DR MassIVE; Q4J6C6; -.
DR MaxQB; Q4J6C6; -.
DR PaxDb; Q4J6C6; -.
DR PeptideAtlas; Q4J6C6; -.
DR PRIDE; Q4J6C6; -.
DR ProteomicsDB; 62170; -. [Q4J6C6-1]
DR ProteomicsDB; 62171; -. [Q4J6C6-2]
DR ProteomicsDB; 62172; -. [Q4J6C6-3]
DR ProteomicsDB; 62173; -. [Q4J6C6-4]
DR Antibodypedia; 29901; 127 antibodies from 24 providers.
DR DNASU; 9581; -.
DR Ensembl; ENST00000260648.10; ENSP00000260648.6; ENSG00000138078.16. [Q4J6C6-1]
DR Ensembl; ENST00000378511.7; ENSP00000367772.3; ENSG00000138078.16. [Q4J6C6-3]
DR Ensembl; ENST00000378520.7; ENSP00000367781.3; ENSG00000138078.16. [Q4J6C6-2]
DR Ensembl; ENST00000409272.5; ENSP00000386909.1; ENSG00000138078.16. [Q4J6C6-1]
DR Ensembl; ENST00000409411.6; ENSP00000387095.2; ENSG00000138078.16. [Q4J6C6-4]
DR Ensembl; ENST00000409936.5; ENSP00000386543.1; ENSG00000138078.16. [Q4J6C6-1]
DR Ensembl; ENST00000409957.5; ENSP00000387241.1; ENSG00000138078.16. [Q4J6C6-4]
DR Ensembl; ENST00000410081.5; ENSP00000386509.1; ENSG00000138078.16. [Q4J6C6-1]
DR Ensembl; ENST00000425263.5; ENSP00000391456.1; ENSG00000138078.16. [Q4J6C6-1]
DR Ensembl; ENST00000426481.5; ENSP00000409480.1; ENSG00000138078.16. [Q4J6C6-1]
DR Ensembl; ENST00000541738.5; ENSP00000439626.1; ENSG00000138078.16. [Q4J6C6-4]
DR GeneID; 9581; -.
DR KEGG; hsa:9581; -.
DR MANE-Select; ENST00000409411.6; ENSP00000387095.2; NM_001171613.2; NP_001165084.1. [Q4J6C6-4]
DR UCSC; uc002ruf.4; human. [Q4J6C6-1]
DR CTD; 9581; -.
DR DisGeNET; 9581; -.
DR GeneCards; PREPL; -.
DR GeneReviews; PREPL; -.
DR HGNC; HGNC:30228; PREPL.
DR HPA; ENSG00000138078; Low tissue specificity.
DR MalaCards; PREPL; -.
DR MIM; 606407; phenotype.
DR MIM; 609557; gene.
DR MIM; 616224; phenotype.
DR neXtProt; NX_Q4J6C6; -.
DR OpenTargets; ENSG00000138078; -.
DR Orphanet; 163693; 2p21 microdeletion syndrome.
DR Orphanet; 369881; 2p21 microdeletion syndrome without cystinuria.
DR Orphanet; 238523; Atypical hypotonia-cystinuria syndrome.
DR Orphanet; 163690; Hypotonia-cystinuria syndrome.
DR PharmGKB; PA142671134; -.
DR VEuPathDB; HostDB:ENSG00000138078; -.
DR eggNOG; KOG2237; Eukaryota.
DR GeneTree; ENSGT00530000063426; -.
DR HOGENOM; CLU_011290_2_1_1; -.
DR InParanoid; Q4J6C6; -.
DR OrthoDB; 1124637at2759; -.
DR PhylomeDB; Q4J6C6; -.
DR TreeFam; TF333309; -.
DR BRENDA; 3.4.21.26; 2681.
DR PathwayCommons; Q4J6C6; -.
DR SignaLink; Q4J6C6; -.
DR BioGRID-ORCS; 9581; 23 hits in 1082 CRISPR screens.
DR ChiTaRS; PREPL; human.
DR GeneWiki; PREPL; -.
DR GenomeRNAi; 9581; -.
DR Pharos; Q4J6C6; Tchem.
DR PRO; PR:Q4J6C6; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q4J6C6; protein.
DR Bgee; ENSG00000138078; Expressed in Brodmann (1909) area 23 and 209 other tissues.
DR ExpressionAtlas; Q4J6C6; baseline and differential.
DR Genevisible; Q4J6C6; HS.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR GO; GO:0008233; F:peptidase activity; IMP:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IMP:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR023302; Pept_S9A_N.
DR InterPro; IPR001375; Peptidase_S9.
DR InterPro; IPR002470; Peptidase_S9A.
DR Pfam; PF00326; Peptidase_S9; 1.
DR Pfam; PF02897; Peptidase_S9_N; 1.
DR PRINTS; PR00862; PROLIGOPTASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Congenital myasthenic syndrome; Cytoplasm; Cytoskeleton; Disease variant;
KW Golgi apparatus; Hydrolase; Nucleus; Protease; Reference proteome;
KW Serine protease.
FT CHAIN 1..727
FT /note="Prolyl endopeptidase-like"
FT /id="PRO_0000314860"
FT ACT_SITE 559
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:16385448"
FT ACT_SITE 645
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:16385448"
FT ACT_SITE 690
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:16385448"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9455477"
FT /id="VSP_030401"
FT VAR_SEQ 323..384
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15913950"
FT /id="VSP_030402"
FT VAR_SEQ 385..450
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15913950"
FT /id="VSP_030403"
FT VARIANT 483..727
FT /note="Missing (found in a patient with intellectual
FT disability, short stature, chronic lung disease and failure
FT to thrive; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:30237576"
FT /id="VAR_082151"
FT MUTAGEN 559
FT /note="S->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16385448"
FT MUTAGEN 645
FT /note="D->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16385448"
FT MUTAGEN 690
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:16385448"
FT MUTAGEN 696
FT /note="H->A: No effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:16385448"
FT CONFLICT 9
FT /note="L -> P (in Ref. 3; BAD18608)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="M -> T (in Ref. 3; BAD18608)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="V -> I (in Ref. 3; BAD18608)"
FT /evidence="ECO:0000305"
FT CONFLICT 408
FT /note="L -> P (in Ref. 6; AAI51237)"
FT /evidence="ECO:0000305"
FT CONFLICT 511
FT /note="G -> Y (in Ref. 6; AAH13193)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="D -> G (in Ref. 6; AAI51237)"
FT /evidence="ECO:0000305"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 120..135
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 148..151
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 154..163
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 167..178
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 194..200
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 202..208
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 216..223
FT /evidence="ECO:0007829|PDB:7OBM"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 262..270
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 275..281
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 301..314
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 321..330
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 334..336
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 338..345
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 348..354
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 356..365
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 368..378
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 403..409
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 411..413
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 416..421
FT /evidence="ECO:0007829|PDB:7OBM"
FT TURN 422..425
FT /evidence="ECO:0007829|PDB:7OBM"
FT TURN 436..440
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 444..449
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 455..462
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 474..478
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 492..499
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 503..507
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 517..521
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 525..528
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 529..544
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 550..552
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 553..558
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 559..561
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 562..571
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 573..575
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 577..583
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 589..592
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 603..606
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 610..612
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 615..618
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 620..623
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 625..627
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 636..639
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 650..671
FT /evidence="ECO:0007829|PDB:7OBM"
FT STRAND 680..682
FT /evidence="ECO:0007829|PDB:7OBM"
FT HELIX 692..710
FT /evidence="ECO:0007829|PDB:7OBM"
FT MOD_RES Q4J6C6-4:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 727 AA; 83927 MW; D15B4F3642FC5BBF CRC64;
MQQKTKLFLQ ALKYSIPHLG KCMQKQHLNH YNFADHCYNR IKLKKYHLTK CLQNKPKISE
LARNIPSRSF SCKDLQPVKQ ENEKPLPENM DAFEKVRTKL ETQPQEEYEI INVEVKHGGF
VYYQEGCCLV RSKDEEADND NYEVLFNLEE LKLDQPFIDC IRVAPDEKYV AAKIRTEDSE
ASTCVIIKLS DQPVMEASFP NVSSFEWVKD EEDEDVLFYT FQRNLRCHDV YRATFGDNKR
NERFYTEKDP SYFVFLYLTK DSRFLTINIM NKTTSEVWLI DGLSPWDPPV LIQKRIHGVL
YYVEHRDDEL YILTNVGEPT EFKLMRTAAD TPAIMNWDLF FTMKRNTKVI DLDMFKDHCV
LFLKHSNLLY VNVIGLADDS VRSLKLPPWA CGFIMDTNSD PKNCPFQLCS PIRPPKYYTY
KFAEGKLFEE TGHEDPITKT SRVLRLEAKS KDGKLVPMTV FHKTDSEDLQ KKPLLVHVYG
AYGMDLKMNF RPERRVLVDD GWILAYCHVR GGGELGLQWH ADGRLTKKLN GLADLEACIK
TLHGQGFSQP SLTTLTAFSA GGVLAGALCN SNPELVRAVT LEAPFLDVLN TMMDTTLPLT
LEELEEWGNP SSDEKHKNYI KRYCPYQNIK PQHYPSIHIT AYENDERVPL KGIVSYTEKL
KEAIAEHAKD TGEGYQTPNI ILDIQPGGNH VIEDSHKKIT AQIKFLYEEL GLDSTSVFED
LKKYLKF
