PPCEL_MOUSE
ID PPCEL_MOUSE Reviewed; 725 AA.
AC Q8C167; Q3TR35; Q6ZQB4; Q8BUP5; Q99KJ9;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Prolyl endopeptidase-like;
DE EC=3.4.21.- {ECO:0000269|PubMed:21692504};
DE AltName: Full=Prolylendopeptidase-like;
GN Name=Prepl; Synonyms=Kiaa0436;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Aorta, Skin, Spinal cord, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP SER-557.
RX PubMed=21692504; DOI=10.1021/ja2036095;
RA Lone A.M., Bachovchin D.A., Westwood D.B., Speers A.E., Spicer T.P.,
RA Fernandez-Vega V., Chase P., Hodder P.S., Rosen H., Cravatt B.F.,
RA Saghatelian A.;
RT "A substrate-free activity-based protein profiling screen for the discovery
RT of selective PREPL inhibitors.";
RL J. Am. Chem. Soc. 133:11665-11674(2011).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP SER-557.
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 [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=24586561; DOI=10.1371/journal.pone.0089160;
RA Lone A.M., Leidl M., McFedries A.K., Horner J.W., Creemers J.,
RA Saghatelian A.;
RT "Deletion of PREPl causes growth impairment and hypotonia in mice.";
RL PLoS ONE 9:E89160-E89160(2014).
CC -!- FUNCTION: Serine peptidase whose precise substrate specificity remains
CC unclear (PubMed:21692504). Does not cleave peptides after a arginine or
CC lysine residue (By similarity). Regulates trans-Golgi network
CC morphology and sorting by regulating the membrane binding of the AP-1
CC complex (PubMed:23321636). May play a role in the regulation of
CC synaptic vesicle exocytosis (By similarity).
CC {ECO:0000250|UniProtKB:Q4J6C6, ECO:0000269|PubMed:21692504,
CC ECO:0000269|PubMed:23321636}.
CC -!- ACTIVITY REGULATION: Inhibited by 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-
CC 2H-cyclopenta[c]pyridine-4-carbonitrile. {ECO:0000269|PubMed:21692504}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with the AP-1 complex (By
CC similarity). {ECO:0000250|UniProtKB:Q4J6C6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23321636,
CC ECO:0000269|PubMed:23485813}. Golgi apparatus, trans-Golgi network
CC {ECO:0000269|PubMed:23321636}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:23485813}. Golgi apparatus
CC {ECO:0000269|PubMed:23485813}. Nucleus {ECO:0000250|UniProtKB:Q4J6C6}.
CC Note=Co-localizes with AP-1 in the trans-Golgi network
CC (PubMed:23321636). Co-localizes with MAP2 and ACTB on the cytoskeleton
CC (PubMed:23485813). Co-localizes with STX6 and GOSR2 at the Golgi
CC apparatus (PubMed:23485813). {ECO:0000269|PubMed:23321636,
CC ECO:0000269|PubMed:23485813}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8C167-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C167-2; Sequence=VSP_030405;
CC Name=3;
CC IsoId=Q8C167-3; Sequence=VSP_030404;
CC Name=4;
CC IsoId=Q8C167-4; Sequence=VSP_030406, VSP_030407;
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, specifically in
CC neurons of the neocortex, substantia nigra, locus coeruleus, and
CC cerebellum, and a slightly lesser extent in neurons in the hypothalamus
CC and hippocampus (at protein level) (PubMed:23321636, PubMed:23485813).
CC Also expressed in interneurons in the stratum lacunosum moleculare and
CC stratum radiatum (PubMed:23485813). {ECO:0000269|PubMed:23321636,
CC ECO:0000269|PubMed:23485813}.
CC -!- DISRUPTION PHENOTYPE: PREPL-null mice are significantly shorter and
CC lighter than their wild-type littermates and suffer from neonatal
CC hypotonia. {ECO:0000269|PubMed:24586561}.
CC -!- SIMILARITY: Belongs to the peptidase S9A family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC97952.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK129142; BAC97952.1; ALT_INIT; mRNA.
DR EMBL; AK028877; BAC26168.1; -; mRNA.
DR EMBL; AK083070; BAC38751.1; -; mRNA.
DR EMBL; AK163108; BAE37195.1; -; mRNA.
DR EMBL; BC004612; AAH04612.1; -; mRNA.
DR CCDS; CCDS29005.1; -. [Q8C167-2]
DR CCDS; CCDS50202.1; -. [Q8C167-1]
DR RefSeq; NP_001157094.1; NM_001163622.1. [Q8C167-1]
DR RefSeq; NP_001157095.1; NM_001163623.1. [Q8C167-2]
DR RefSeq; NP_001157096.1; NM_001163624.1. [Q8C167-2]
DR RefSeq; NP_666096.3; NM_145984.3. [Q8C167-2]
DR RefSeq; XP_006524064.1; XM_006524001.3. [Q8C167-2]
DR AlphaFoldDB; Q8C167; -.
DR SMR; Q8C167; -.
DR BioGRID; 229467; 1.
DR IntAct; Q8C167; 1.
DR STRING; 10090.ENSMUSP00000130967; -.
DR GuidetoPHARMACOLOGY; 2870; -.
DR ESTHER; mouse-Q8C167; S9N_PREPL_Peptidase_S9.
DR MEROPS; S09.015; -.
DR iPTMnet; Q8C167; -.
DR PhosphoSitePlus; Q8C167; -.
DR EPD; Q8C167; -.
DR MaxQB; Q8C167; -.
DR PaxDb; Q8C167; -.
DR PeptideAtlas; Q8C167; -.
DR PRIDE; Q8C167; -.
DR ProteomicsDB; 289799; -. [Q8C167-1]
DR ProteomicsDB; 289800; -. [Q8C167-2]
DR ProteomicsDB; 289801; -. [Q8C167-3]
DR ProteomicsDB; 289802; -. [Q8C167-4]
DR Antibodypedia; 29901; 127 antibodies from 24 providers.
DR DNASU; 213760; -.
DR Ensembl; ENSMUST00000072406; ENSMUSP00000072239; ENSMUSG00000024127. [Q8C167-2]
DR Ensembl; ENSMUST00000171795; ENSMUSP00000130967; ENSMUSG00000024127. [Q8C167-1]
DR GeneID; 213760; -.
DR KEGG; mmu:213760; -.
DR UCSC; uc008dtm.2; mouse. [Q8C167-1]
DR UCSC; uc008dtr.2; mouse. [Q8C167-4]
DR CTD; 9581; -.
DR MGI; MGI:2441932; Prepl.
DR VEuPathDB; HostDB:ENSMUSG00000024127; -.
DR eggNOG; KOG2237; Eukaryota.
DR GeneTree; ENSGT00530000063426; -.
DR HOGENOM; CLU_011290_2_1_1; -.
DR InParanoid; Q8C167; -.
DR OrthoDB; 1124637at2759; -.
DR PhylomeDB; Q8C167; -.
DR TreeFam; TF333309; -.
DR BioGRID-ORCS; 213760; 8 hits in 73 CRISPR screens.
DR ChiTaRS; Prepl; mouse.
DR PRO; PR:Q8C167; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8C167; protein.
DR Bgee; ENSMUSG00000024127; Expressed in subparaventricular zone and 256 other tissues.
DR ExpressionAtlas; Q8C167; baseline and differential.
DR Genevisible; Q8C167; MM.
DR GO; GO:0005856; C:cytoskeleton; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP: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 Alternative splicing; Cytoplasm; Cytoskeleton; Golgi apparatus; Hydrolase;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Serine protease.
FT CHAIN 1..725
FT /note="Prolyl endopeptidase-like"
FT /id="PRO_0000314862"
FT ACT_SITE 557
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:21692504"
FT ACT_SITE 643
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q4J6C6"
FT ACT_SITE 688
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q4J6C6"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..267
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_030404"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_030405"
FT VAR_SEQ 249..261
FT /note="SYFVFLYLTKDSR -> RCQRAALTALQALTIQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030406"
FT VAR_SEQ 262..725
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030407"
FT MUTAGEN 557
FT /note="S->A: Loss of catalytic activity. No effect on the
FT redistribution of AP-1 from the membrane to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:21692504,
FT ECO:0000269|PubMed:23321636"
SQ SEQUENCE 725 AA; 83194 MW; 111579DFA45CE68B CRC64;
MLQTAKFSLR ALKHSIPHLG NCMQKQSYRN VAGPYYSRVR LKKYHLTKCL QNKPRIAGLA
RNIPSRSFSC KDLLPIKPES EKPISENMDA FEKVRTRLET QPQEEYEVVN AEIKHGGFVY
YQEGCCLVRS KDEEADSDNY EVLFNLEELK LDQPFIDCIR VAPDEKYVAA KIRTEDSETS
TLVVVKLSDQ PVMEASFPNV SSFEWVKDEE DEDVLFYTFQ RNLRCHDVYR ATFGDNKRNE
RFYTEKDPSY FVFLYLTKDS RFLTLNIMNK TTSEVWLIDG LSPWDPPVLI QKRIHGMLYY
VEHRDDELYI LTNVGEPTEF KLMRTAADAP AIMNWDLFFT MKRNTKVVDL DMFKDHCVLF
LKHSNLLYVN VIGLADDSVR SLKLPPWACG FIMDTNSDPK NCPFQLCSPI RPPKYYTYKF
AEGKLFEETG HEDPITKTSR VLRIEAKSKD GKLVPMTVFH KTDSEDLQRK PLLVHVYGAY
GMDLKMNFRP EKRVLVDDGW ILAYCHVRGG GELGLQWHAD GRLTKKLNGL ADLVACIKTL
HSQGFSQPSL TTLSAFSAGG VLVGALCNSK PELLRAVTLE APFLDVLNTM LDTTLPLTLE
ELEEWGNPSS DEKHKNYIKR YCPCQNIKPQ HYPSVHITAY ENDERVPLKG IVNYTEKLKE
AVAEHTKGAG EGYQPPNIIL DIQPGGNHVI EDSHKKITTQ MKFLYEELGL DSTDAFEALK
KYLKF
