CBPE_RAT
ID CBPE_RAT Reviewed; 476 AA.
AC P15087;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 149.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=2784437; DOI=10.1016/s0021-9258(18)83647-x;
RA Rodriquez C., Brayton K.A., Brownstein M., Dixon J.E.;
RT "Rat preprocarboxypeptidase H. Cloning, characterization, and sequence of
RT the cDNA and regulation of the mRNA by corticotropin-releasing factor.";
RL J. Biol. Chem. 264:5988-5995(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2725530; DOI=10.1210/mend-3-4-666;
RA Fricker L.D., Adelman J.P., Douglass J., Thompsom R.C.,
RA von Strandmann R.P., Hutton J.;
RT "Isolation and sequence analysis of cDNA for rat carboxypeptidase E [EC
RT 3.4.17.10], a neuropeptide processing enzyme.";
RL Mol. Endocrinol. 3:666-673(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=2334405; DOI=10.1042/bj2670517;
RA Manser E., Fernandez D., Loo L., Goh P.Y., Monfries C., Hall C., Lim L.;
RT "Human carboxypeptidase E. Isolation and characterization of the cDNA,
RT sequence conservation, expression and processing in vitro.";
RL Biochem. J. 267:517-525(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1770952; DOI=10.1210/mend-5-9-1257;
RA Jung Y.K., Kunczt C.J., Pearson R.K., Dixon J.E., Fricker L.D.;
RT "Structural characterization of the rat carboxypeptidase-E gene.";
RL Mol. Endocrinol. 5:1257-1268(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 200-335.
RX PubMed=1955501; DOI=10.1210/jcem-73-6-1197;
RA Castano L., Russo E., Zhou L., Lipes M.A., Eisenbarth G.S.;
RT "Identification and cloning of a granule autoantigen (carboxypeptidase-H)
RT associated with type I diabetes.";
RL J. Clin. Endocrinol. Metab. 73:1197-1201(1991).
RN [6]
RP SUBCELLULAR LOCATION, AND LIPID RAFT-BINDING.
RX PubMed=14597614; DOI=10.1074/jbc.m310104200;
RA Hosaka M., Suda M., Sakai Y., Izumi T., Watanabe T., Takeuchi T.;
RT "Secretogranin III binds to cholesterol in the secretory granule membrane
RT as an adapter for chromogranin A.";
RL J. Biol. Chem. 279:3627-3634(2004).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-139 AND ASN-390, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
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:0000250|UniProtKB:Q00493}.
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:0000250|UniProtKB:Q00493}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:14597614}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000269|PubMed:14597614}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14597614}. Secreted {ECO:0000269|PubMed:14597614}.
CC Note=Associated with the secretory granule membrane through direct
CC binding to lipid rafts in intragranular conditions.
CC {ECO:0000269|PubMed:14597614}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart and anterior pituitary
CC gland. Also expressed in pancreatic islets and adrenal gland.
CC {ECO:0000269|PubMed:2784437}.
CC -!- MISCELLANEOUS: An autoantigen recognized by serum of pretype I
CC diabetes.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; J04625; AAA40875.1; -; mRNA.
DR EMBL; M31602; AAA40873.1; -; mRNA.
DR EMBL; X51406; CAA35768.1; -; mRNA.
DR EMBL; L07281; AAA40957.1; ALT_SEQ; Genomic_DNA.
DR EMBL; L07273; AAA40957.1; JOINED; Genomic_DNA.
DR EMBL; L07274; AAA40957.1; JOINED; Genomic_DNA.
DR EMBL; L07275; AAA40957.1; JOINED; Genomic_DNA.
DR EMBL; L07277; AAA40957.1; JOINED; Genomic_DNA.
DR EMBL; L07278; AAA40957.1; JOINED; Genomic_DNA.
DR EMBL; L07279; AAA40957.1; JOINED; Genomic_DNA.
DR EMBL; L07280; AAA40957.1; JOINED; Genomic_DNA.
DR PIR; A40469; A40469.
DR PIR; S12461; S12461.
DR RefSeq; NP_037260.1; NM_013128.1.
DR AlphaFoldDB; P15087; -.
DR SMR; P15087; -.
DR BioGRID; 247698; 3.
DR STRING; 10116.ENSRNOP00000061172; -.
DR MEROPS; M14.005; -.
DR GlyGen; P15087; 2 sites, 10 N-linked glycans (2 sites).
DR iPTMnet; P15087; -.
DR jPOST; P15087; -.
DR PRIDE; P15087; -.
DR GeneID; 25669; -.
DR KEGG; rno:25669; -.
DR CTD; 1363; -.
DR RGD; 2394; Cpe.
DR InParanoid; P15087; -.
DR OrthoDB; 101221at2759; -.
DR PhylomeDB; P15087; -.
DR PRO; PR:P15087; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030425; C:dendrite; IDA:BHF-UCL.
DR GO; GO:0031045; C:dense core granule; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:BHF-UCL.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0030667; C:secretory granule membrane; IDA:RGD.
DR GO; GO:0097060; C:synaptic membrane; IDA:RGD.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004180; F:carboxypeptidase activity; IDA:RGD.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:RGD.
DR GO; GO:0050897; F:cobalt ion binding; IMP:RGD.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0042043; F:neurexin family protein binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISO:RGD.
DR GO; GO:0034230; P:enkephalin processing; IDA:RGD.
DR GO; GO:0030070; P:insulin processing; IDA:RGD.
DR GO; GO:2000173; P:negative regulation of branching morphogenesis of a nerve; IMP:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IDA:RGD.
DR GO; GO:0016486; P:peptide hormone processing; TAS:RGD.
DR GO; GO:0030072; P:peptide hormone secretion; ISO:RGD.
DR GO; GO:0006518; P:peptide metabolic process; IDA:RGD.
DR GO; GO:0072657; P:protein localization to membrane; ISO:RGD.
DR GO; GO:0033366; P:protein localization to secretory granule; ISO:RGD.
DR GO; GO:0016485; P:protein processing; IDA:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
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 Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..27
FT /note="Or 34"
FT PROPEP 28..42
FT /note="Activation peptide"
FT /id="PRO_0000004388"
FT CHAIN 43..476
FT /note="Carboxypeptidase E"
FT /id="PRO_0000004389"
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:0007744|PubMed:24090084"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CONFLICT 82
FT /note="S -> T (in Ref. 2; AAA40873)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="V -> A (in Ref. 3; CAA35768)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="S -> Y (in Ref. 3; CAA35768)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 53309 MW; C2213D1FD6ECA120 CRC64;
MAGRGGRVLL ALCAALVAGG WLLAAEAQEP GAPAAGMRRR RRLQQEDGIS FEYHRYPELR
EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH EPGEPEFKYI GNMHGNEAVG
RELLIFLAQY LCNEYQRGNE TIVNLIHSTR IHIMPSLNPD GFEKAASQPG ELKDWFVGRS
NAQGIDLNRN FPDLDRIVYV NEKEGGPNNH LLKNLKKIVD QNSKLAPETK AVIHWIMDIP
FVLSANLHGG DLVANYPYDE TRSGTAHEYS SCPDDAIFQS LARAYSSFNP VMSDPNRPPC
RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP EETLKSYWED
NKNSLINYLE QIHRGVKGFV RDLQGNPIAN ATISVDGIDH DVTSAKDGDY WRLLVPGNYK
LTASAPGYLA ITKKVAVPFS PAVGVDFELE SFSERKEEEK EELMEWWKMM SETLNF
