CBPE_MOUSE
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 03-AUG-2022, entry version 190.
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 GlyGen; Q00493; 2 sites, 11 N-linked glycans (2 sites).
DR PhosphoSitePlus; Q00493; -.
DR PaxDb; Q00493; -.
DR PeptideAtlas; Q00493; -.
DR PRIDE; Q00493; -.
DR ProteomicsDB; 283706; -.
DR Antibodypedia; 16998; 360 antibodies from 36 providers.
DR CPTC; Q00493; 3 antibodies.
DR DNASU; 12876; -.
DR Ensembl; ENSMUST00000048967; ENSMUSP00000048555; ENSMUSG00000037852.
DR GeneID; 12876; -.
DR KEGG; mmu:12876; -.
DR UCSC; uc009luw.2; mouse.
DR CTD; 1363; -.
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; 101221at2759; -.
DR PhylomeDB; Q00493; -.
DR TreeFam; TF315592; -.
DR BRENDA; 3.4.17.10; 3474.
DR BioGRID-ORCS; 12876; 2 hits in 74 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 271 other tissues.
DR ExpressionAtlas; Q00493; baseline and differential.
DR Genevisible; Q00493; MM.
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:0045121; C:membrane raft; 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; ISO: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; IBA:GO_Central.
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 InterPro; IPR008969; CarboxyPept-like_regulatory.
DR InterPro; IPR034232; M14_CPE_CPD.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF00246; Peptidase_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00631; Zn_pept; 1.
DR SUPFAM; SSF49464; SSF49464; 1.
DR PROSITE; PS00132; CARBOXYPEPT_ZN_1; 1.
DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1.
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 ACT_SITE 342
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P14384"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
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
