Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Carboxypeptidase E

Gene

Cpe

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.

Catalytic activityi

Release of C-terminal arginine or lysine residues from polypeptides.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi114 – 1141ZincBy similarity
Metal bindingi117 – 1171ZincBy similarity
Metal bindingi248 – 2481ZincBy similarity
Active sitei342 – 3421NucleophileBy similarity

GO - Molecular functioni

  1. carboxypeptidase activity Source: MGI
  2. cell adhesion molecule binding Source: MGI
  3. metallocarboxypeptidase activity Source: InterPro
  4. neurexin family protein binding Source: MGI
  5. zinc ion binding Source: InterPro

GO - Biological processi

  1. cardiac left ventricle morphogenesis Source: MGI
  2. insulin processing Source: MGI
  3. protein localization to membrane Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.17.10. 3474.
ReactomeiREACT_298481. Insulin processing.

Protein family/group databases

MEROPSiM14.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Carboxypeptidase E (EC:3.4.17.10)
Short name:
CPE
Alternative name(s):
Carboxypeptidase H
Short name:
CPH
Enkephalin convertase
Prohormone-processing carboxypeptidase
Gene namesi
Name:Cpe
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:101932. Cpe.

Subcellular locationi

  1. Cytoplasmic vesiclesecretory vesicle membrane By similarity; Peripheral membrane protein By similarity
  2. Secreted By similarity

  3. Note: Associated with the secretory granule membrane through direct binding to lipid rafts in intragranular conditions. This binding is Ca2+-dependent (By similarity).By similarity

GO - Cellular componenti

  1. extracellular vesicular exosome Source: MGI
  2. Golgi apparatus Source: MGI
  3. transport vesicle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Defects in Cpe are the cause of the fat phenotype. Mice homozygous for the fat mutation develop obesity and hyperglycemia that can be suppressed by treatment with exogenous insulin.

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727By similarityAdd
BLAST
Propeptidei28 – 4215Activation peptideBy similarityPRO_0000004386Add
BLAST
Chaini43 – 476434Carboxypeptidase EPRO_0000004387Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi139 – 1391N-linked (GlcNAc...)Sequence Analysis
Glycosylationi390 – 3901N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ00493.
PaxDbiQ00493.
PRIDEiQ00493.

PTM databases

PhosphoSiteiQ00493.

Expressioni

Gene expression databases

BgeeiQ00493.
CleanExiMM_CPE.
ExpressionAtlasiQ00493. baseline and differential.
GenevestigatoriQ00493.

Interactioni

Protein-protein interaction databases

BioGridi198855. 1 interaction.
IntActiQ00493. 3 interactions.
MINTiMINT-4090042.

Structurei

3D structure databases

ProteinModelPortaliQ00493.
SMRiQ00493. Positions 49-450.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M14 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG322453.
HOGENOMiHOG000232185.
HOVERGENiHBG003410.
InParanoidiQ00493.
KOiK01294.
OMAiTLKTYWE.
OrthoDBiEOG7B8S32.
PhylomeDBiQ00493.
TreeFamiTF315592.

Family and domain databases

Gene3Di2.60.40.1120. 1 hit.
InterProiIPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR000834. Peptidase_M14.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF49464. SSF49464. 1 hit.
PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q00493-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGRGGRVLL ALCAALVAGG WLLTAEAQEP GAPAAGMRRR RRLQQEDGIS
60 70 80 90 100
FEYHRYPELR EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH
110 120 130 140 150
EPGEPEFKYI GNMHGNEAVG RELLIFLAQY LCNEYQKGNE TIVNLIHSTR
160 170 180 190 200
IHIMPSLNPD GFEKAASQPG ELKDWFVGRS NAQGIDLNRN FPDLDRIVYV
210 220 230 240 250
NEKEGGPNNH LLKNLKKIVD QNSKLAPETK AVIHWIMDIP FVLSANLHGG
260 270 280 290 300
DLVANYPYDE TRSGTAHEYS SCPDDAIFQS LARAYSSFNP VMSDPNRPPC
310 320 330 340 350
RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP
360 370 380 390 400
EETLKSYWED NKNSLISYLE QIHRGVKGFV RDLQGNPIAN ATISVDGIDH
410 420 430 440 450
DVTSAKDGDY WRLLAPGNYK LTASAPGYLA ITKKVAVPFS PAVGVDFELE
460 470
SFSERKEEEK EELMEWWKMM SETLNF
Length:476
Mass (Da):53,256
Last modified:July 15, 1998 - v2
Checksum:i82C5318A12A17567
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251A → R in CAA43550 (Ref. 1) Curated
Sequence conflicti81 – 811R → A in CAA43550 (Ref. 1) Curated
Sequence conflicti167 – 1671S → W in CAA43550 (Ref. 1) Curated
Sequence conflicti171 – 1711E → Q in CAA43550 (Ref. 1) Curated
Sequence conflicti301 – 3011R → C in CAA43550 (Ref. 1) Curated
Sequence conflicti310 – 3101V → D in CAA43550 (Ref. 1) Curated
Sequence conflicti334 – 3341S → SS in CAA43550 (Ref. 1) Curated
Sequence conflicti344 – 3441S → T in CAA43550 (Ref. 1) Curated
Sequence conflicti367 – 3671S → N in CAA43550 (Ref. 1) Curated
Sequence conflicti388 – 3881I → N in CAA43550 (Ref. 1) Curated
Sequence conflicti425 – 4251A → D in CAA43550 (Ref. 1) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti244 – 2441S → P in hyperproinsulinemia obese fat/fat mice; reduced activity. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61232 mRNA. Translation: CAA43550.1.
U23184 mRNA. Translation: AAB60488.1.
BC010197 mRNA. Translation: AAH10197.1.
CCDSiCCDS22327.1.
PIRiS16383.
RefSeqiNP_038522.2. NM_013494.3.
UniGeneiMm.31395.
Mm.470333.

Genome annotation databases

EnsembliENSMUST00000048967; ENSMUSP00000048555; ENSMUSG00000037852.
GeneIDi12876.
KEGGimmu:12876.
UCSCiuc009luw.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61232 mRNA. Translation: CAA43550.1.
U23184 mRNA. Translation: AAB60488.1.
BC010197 mRNA. Translation: AAH10197.1.
CCDSiCCDS22327.1.
PIRiS16383.
RefSeqiNP_038522.2. NM_013494.3.
UniGeneiMm.31395.
Mm.470333.

3D structure databases

ProteinModelPortaliQ00493.
SMRiQ00493. Positions 49-450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198855. 1 interaction.
IntActiQ00493. 3 interactions.
MINTiMINT-4090042.

Protein family/group databases

MEROPSiM14.005.

PTM databases

PhosphoSiteiQ00493.

Proteomic databases

MaxQBiQ00493.
PaxDbiQ00493.
PRIDEiQ00493.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000048967; ENSMUSP00000048555; ENSMUSG00000037852.
GeneIDi12876.
KEGGimmu:12876.
UCSCiuc009luw.2. mouse.

Organism-specific databases

CTDi1363.
MGIiMGI:101932. Cpe.

Phylogenomic databases

eggNOGiNOG322453.
HOGENOMiHOG000232185.
HOVERGENiHBG003410.
InParanoidiQ00493.
KOiK01294.
OMAiTLKTYWE.
OrthoDBiEOG7B8S32.
PhylomeDBiQ00493.
TreeFamiTF315592.

Enzyme and pathway databases

BRENDAi3.4.17.10. 3474.
ReactomeiREACT_298481. Insulin processing.

Miscellaneous databases

ChiTaRSiCpe. mouse.
NextBioi282472.
PROiQ00493.
SOURCEiSearch...

Gene expression databases

BgeeiQ00493.
CleanExiMM_CPE.
ExpressionAtlasiQ00493. baseline and differential.
GenevestigatoriQ00493.

Family and domain databases

Gene3Di2.60.40.1120. 1 hit.
InterProiIPR008969. CarboxyPept-like_regulatory.
IPR014766. CarboxyPept_regulatory_dom.
IPR000834. Peptidase_M14.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF49464. SSF49464. 1 hit.
PROSITEiPS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Parkinson D.
    Submitted (AUG-1991) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity."
    Naggert J.K., Fricker L.D., Varlamov O., Nishina P.M., Rouille Y., Steiner D.F., Carroll R.J., Paigen B.J., Leiter E.H.
    Nat. Genet. 10:135-142(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-244.
    Strain: HRS/J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  4. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 43-55; 87-108; 363-374 AND 413-420, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Brain.

Entry informationi

Entry nameiCBPE_MOUSE
AccessioniPrimary (citable) accession number: Q00493
Secondary accession number(s): Q64439
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: July 15, 1998
Last modified: April 1, 2015
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.