ID   CBPE_MOUSE              Reviewed;         476 AA.
AC   Q00493; Q64439;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 2.
DT   27-MAR-2024, entry version 199.
DE   RecName: Full=Carboxypeptidase E;
DE            Short=CPE;
DE            EC=3.4.17.10;
DE   AltName: Full=Carboxypeptidase H;
DE            Short=CPH;
DE   AltName: Full=Enkephalin convertase;
DE   AltName: Full=Prohormone-processing carboxypeptidase;
DE   Flags: Precursor;
GN   Name=Cpe;
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 [MRNA].
RA   Parkinson D.;
RL   Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-244, AND DISEASE.
RC   STRAIN=HRS/J;
RX   PubMed=7663508; DOI=10.1038/ng0695-135;
RA   Naggert J.K., Fricker L.D., Varlamov O., Nishina P.M., Rouille Y.,
RA   Steiner D.F., Carroll R.J., Paigen B.J., Leiter E.H.;
RT   "Hyperproinsulinaemia in obese fat/fat mice associated with a
RT   carboxypeptidase E mutation which reduces enzyme activity.";
RL   Nat. Genet. 10:135-142(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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   PROTEIN SEQUENCE OF 43-55; 87-108; 363-374 AND 413-420, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY.
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (APR-2007) to UniProtKB.
RN   [5]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=10896946; DOI=10.1074/jbc.m005364200;
RA   Dhanvantari S., Loh Y.P.;
RT   "Lipid raft association of carboxypeptidase E is necessary for its function
RT   as a regulated secretory pathway sorting receptor.";
RL   J. Biol. Chem. 275:29887-29893(2000).
RN   [6]
RP   FUNCTION, INTERACTION WITH SCG3, AND SUBCELLULAR LOCATION.
RX   PubMed=16219686; DOI=10.1242/jcs.02608;
RA   Hosaka M., Watanabe T., Sakai Y., Kato T., Takeuchi T.;
RT   "Interaction between secretogranin III and carboxypeptidase E facilitates
RT   prohormone sorting within secretory granules.";
RL   J. Cell Sci. 118:4785-4795(2005).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Heart;
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).
CC   -!- FUNCTION: Sorting receptor that directs prohormones to the regulated
CC       secretory pathway. Acts also as a prohormone processing enzyme in
CC       neuro/endocrine cells, removing dibasic residues from the C-terminal
CC       end of peptide hormone precursors after initial endoprotease cleavage.
CC       {ECO:0000269|PubMed:10896946, ECO:0000269|PubMed:16219686}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of C-terminal arginine or lysine residues from
CC         polypeptides.; EC=3.4.17.10;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P00730};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P00730};
CC   -!- SUBUNIT: Interacts with secretogranin III/SCG3.
CC       {ECO:0000269|PubMed:16219686}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC       {ECO:0000269|PubMed:16219686}. Cytoplasmic vesicle, secretory vesicle
CC       membrane {ECO:0000250|UniProtKB:P15087}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P15087}. Secreted
CC       {ECO:0000250|UniProtKB:P15087}. Note=Associated with the secretory
CC       granule membrane through direct binding to lipid rafts in intragranular
CC       conditions. {ECO:0000269|PubMed:10896946}.
CC   -!- DISEASE: Note=Defects in Cpe are the cause of the fat phenotype. Mice
CC       homozygous for the fat mutation develop obesity and hyperglycemia that
CC       can be suppressed by treatment with exogenous insulin.
CC       {ECO:0000269|PubMed:7663508}.
CC   -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR   EMBL; X61232; CAA43550.1; -; mRNA.
DR   EMBL; U23184; AAB60488.1; -; mRNA.
DR   EMBL; BC010197; AAH10197.1; -; mRNA.
DR   CCDS; CCDS22327.1; -.
DR   PIR; S16383; S16383.
DR   RefSeq; NP_038522.2; NM_013494.4.
DR   AlphaFoldDB; Q00493; -.
DR   SMR; Q00493; -.
DR   BioGRID; 198855; 6.
DR   IntAct; Q00493; 2.
DR   STRING; 10090.ENSMUSP00000048555; -.
DR   MEROPS; M14.005; -.
DR   GlyConnect; 2185; 12 N-Linked glycans (2 sites).
DR   GlyCosmos; Q00493; 2 sites, 11 glycans.
DR   GlyGen; Q00493; 2 sites, 16 N-linked glycans (2 sites).
DR   iPTMnet; Q00493; -.
DR   PhosphoSitePlus; Q00493; -.
DR   SwissPalm; Q00493; -.
DR   PaxDb; 10090-ENSMUSP00000048555; -.
DR   PeptideAtlas; Q00493; -.
DR   ProteomicsDB; 283706; -.
DR   Pumba; Q00493; -.
DR   Antibodypedia; 16998; 388 antibodies from 36 providers.
DR   CPTC; Q00493; 3 antibodies.
DR   DNASU; 12876; -.
DR   Ensembl; ENSMUST00000048967.9; ENSMUSP00000048555.8; ENSMUSG00000037852.9.
DR   GeneID; 12876; -.
DR   KEGG; mmu:12876; -.
DR   UCSC; uc009luw.2; mouse.
DR   AGR; MGI:101932; -.
DR   MGI; MGI:101932; Cpe.
DR   VEuPathDB; HostDB:ENSMUSG00000037852; -.
DR   eggNOG; KOG2649; Eukaryota.
DR   GeneTree; ENSGT00940000157158; -.
DR   HOGENOM; CLU_006722_1_3_1; -.
DR   InParanoid; Q00493; -.
DR   OMA; WEQNRDS; -.
DR   OrthoDB; 5490979at2759; -.
DR   PhylomeDB; Q00493; -.
DR   TreeFam; TF315592; -.
DR   BRENDA; 3.4.17.10; 3474.
DR   BioGRID-ORCS; 12876; 2 hits in 79 CRISPR screens.
DR   ChiTaRS; Cpe; mouse.
DR   PRO; PR:Q00493; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q00493; Protein.
DR   Bgee; ENSMUSG00000037852; Expressed in anterior amygdaloid area and 274 other cell types or tissues.
DR   ExpressionAtlas; Q00493; baseline and differential.
DR   GO; GO:0030425; C:dendrite; ISO:MGI.
DR   GO; GO:0031045; C:dense core granule; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0043204; C:perikaryon; ISO:MGI.
DR   GO; GO:0030141; C:secretory granule; IDA:MGI.
DR   GO; GO:0030667; C:secretory granule membrane; IDA:MGI.
DR   GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR   GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004180; F:carboxypeptidase activity; IMP:MGI.
DR   GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI.
DR   GO; GO:0050897; F:cobalt ion binding; ISO:MGI.
DR   GO; GO:0004181; F:metallocarboxypeptidase activity; IMP:MGI.
DR   GO; GO:0042043; F:neurexin family protein binding; ISO:MGI.
DR   GO; GO:0008233; F:peptidase activity; TAS:Reactome.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISO:MGI.
DR   GO; GO:0034230; P:enkephalin processing; ISO:MGI.
DR   GO; GO:0030070; P:insulin processing; IMP:MGI.
DR   GO; GO:2000173; P:negative regulation of branching morphogenesis of a nerve; ISO:MGI.
DR   GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR   GO; GO:0030072; P:peptide hormone secretion; IMP:MGI.
DR   GO; GO:0006518; P:peptide metabolic process; ISO:MGI.
DR   GO; GO:0072657; P:protein localization to membrane; ISO:MGI.
DR   GO; GO:0033366; P:protein localization to secretory granule; IMP:MGI.
DR   GO; GO:0016485; P:protein processing; ISO:MGI.
DR   GO; GO:0016055; P:Wnt signaling pathway; ISO:MGI.
DR   CDD; cd03865; M14_CPE; 1.
DR   CDD; cd11308; Peptidase_M14NE-CP-C_like; 1.
DR   Gene3D; 2.60.40.1120; Carboxypeptidase-like, regulatory domain; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR008969; CarboxyPept-like_regulatory.
DR   InterPro; IPR034232; M14_CPE_CPD.
DR   InterPro; IPR000834; Peptidase_M14.
DR   PANTHER; PTHR11532:SF92; CARBOXYPEPTIDASE E; 1.
DR   PANTHER; PTHR11532; PROTEASE M14 CARBOXYPEPTIDASE; 1.
DR   Pfam; PF13620; CarboxypepD_reg; 1.
DR   Pfam; PF00246; Peptidase_M14; 1.
DR   PRINTS; PR00765; CRBOXYPTASEA.
DR   SMART; SM00631; Zn_pept; 1.
DR   SUPFAM; SSF49464; Carboxypeptidase regulatory domain-like; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PROSITE; PS00132; CARBOXYPEPT_ZN_1; 1.
DR   PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1.
DR   PROSITE; PS52035; PEPTIDASE_M14; 1.
DR   Genevisible; Q00493; MM.
PE   1: Evidence at protein level;
KW   Carboxypeptidase; Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW   Direct protein sequencing; Disease variant; Glycoprotein; Hydrolase;
KW   Membrane; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW   Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000250"
FT   PROPEP          28..42
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000004386"
FT   CHAIN           43..476
FT                   /note="Carboxypeptidase E"
FT                   /id="PRO_0000004387"
FT   DOMAIN          52..372
FT                   /note="Peptidase M14"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   ACT_SITE        342
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         114
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         117
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   BINDING         248
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01379"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         244
FT                   /note="S -> P (in hyperproinsulinemia obese fat/fat mice;
FT                   reduced activity)"
FT                   /evidence="ECO:0000269|PubMed:7663508"
FT   CONFLICT        25
FT                   /note="A -> R (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        81
FT                   /note="R -> A (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        167
FT                   /note="S -> W (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        171
FT                   /note="E -> Q (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        301
FT                   /note="R -> C (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        310
FT                   /note="V -> D (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        334
FT                   /note="S -> SS (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        344
FT                   /note="S -> T (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        367
FT                   /note="S -> N (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        388
FT                   /note="I -> N (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        425
FT                   /note="A -> D (in Ref. 1; CAA43550)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   476 AA;  53256 MW;  82C5318A12A17567 CRC64;
     MAGRGGRVLL ALCAALVAGG WLLTAEAQEP GAPAAGMRRR RRLQQEDGIS FEYHRYPELR
     EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH EPGEPEFKYI GNMHGNEAVG
     RELLIFLAQY LCNEYQKGNE TIVNLIHSTR IHIMPSLNPD GFEKAASQPG ELKDWFVGRS
     NAQGIDLNRN FPDLDRIVYV NEKEGGPNNH LLKNLKKIVD QNSKLAPETK AVIHWIMDIP
     FVLSANLHGG DLVANYPYDE TRSGTAHEYS SCPDDAIFQS LARAYSSFNP VMSDPNRPPC
     RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP EETLKSYWED
     NKNSLISYLE QIHRGVKGFV RDLQGNPIAN ATISVDGIDH DVTSAKDGDY WRLLAPGNYK
     LTASAPGYLA ITKKVAVPFS PAVGVDFELE SFSERKEEEK EELMEWWKMM SETLNF
//