CPE

Protein identityUniProt · HPA

UniProt accession

P16870

Gene

CPE

Ensembl

ENSG00000109472

Chromosome

4

Canonical length

476 aa

Protein class

Disease related genes, Enzymes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Centrosome

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a member of the M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature peptidase. This peripheral membrane protein cleaves C-terminal amino acid residues and is involved in the biosynthesis of peptide hormones and neurotransmitters, including insulin. This protein may also function independently of its peptidase activity, as a neurotrophic factor that promotes neuronal survival, and as a sorting receptor that binds to regulated secretory pathway proteins, including prohormones. Mutations in this gene are implicated in type 2 diabetes. [provided by RefSeq, Nov 2015]

Canonical amino-acid sequenceUniProt

476 residues, UniProt reviewed canonical sequence.

>P16870|CPE
     1  MAGRGGSALL ALCGALAACG WLLGAEAQEP GAPAAGMRRR RRLQQEDGIS FEYHRYPELR
    61  EALVSVWLQC TAISRIYTVG RSFEGRELLV IELSDNPGVH EPGEPEFKYI GNMHGNEAVG
   121  RELLIFLAQY LCNEYQKGNE TIVNLIHSTR IHIMPSLNPD GFEKAASQPG ELKDWFVGRS
   181  NAQGIDLNRN FPDLDRIVYV NEKEGGPNNH LLKNMKKIVD QNTKLAPETK AVIHWIMDIP
   241  FVLSANLHGG DLVANYPYDE TRSGSAHEYS SSPDDAIFQS LARAYSSFNP AMSDPNRPPC
   301  RKNDDDSSFV DGTTNGGAWY SVPGGMQDFN YLSSNCFEIT VELSCEKFPP EETLKTYWED
   361  NKNSLISYLE QIHRGVKGFV RDLQGNPIAN ATISVEGIDH DVTSAKDGDY WRLLIPGNYK
   421  LTASAPGYLA ITKKVAVPYS PAAGVDFELE SFSERKEEEK EELMEWWKMM SETLNF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CPE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

1,047 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CPE.

Disease | AllUniProt

Conditions CPE is implicated in, by any mechanism.

• BDV syndrome (BDVS) MIM:619326

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 163 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• BDV syndrome
• Blakemore-Durmaz-Vasileiou (BDV) syndrome
• Inborn genetic diseases
• Early onset severe obesity

Disease | ImmuneIEDB

Conditions an epitope on CPE was assayed in.

• type 1 diabetes mellitus T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against CPE are reported. Each links to that disease's full target list.

• Diabetes Mellitus, Type 1 4

ReferencesPubMed · IEDB

Publications for CPE from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.27

gnomAD pLI

0.99

gnomAD missense Z

1.82

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cardiac left ventricle morphogenesis
• insulin processing
• neuropeptide signaling pathway
• peptide hormone secretion
• peptide metabolic process
• protein localization to membrane
• protein localization to secretory granule
• protein modification process
• protein processing
• Wnt signaling pathway

Molecular functions

• carboxypeptidase activity
• cell adhesion molecule binding
• metallocarboxypeptidase activity
• neurexin family protein binding
• zinc ion binding

Cellular components

• extracellular exosome
• extracellular space
• Golgi apparatus
• plasma membrane
• secretory granule membrane
• transport vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase M14, carboxypeptidase A
• Carboxypeptidase-like, regulatory domain superfamily
• Peptidase M14 domain-containing protein
• Zinc carboxypeptidases, zinc-binding region 1
• Zinc carboxypeptidases, zinc-binding region 2
• Zinc carboxypeptidase
• Carboxypeptidase regulatory-like domain
• Carboxypeptidase E, carboxypeptidase domain

KeywordsUniProt

• Carboxypeptidase
• Cleavage on pair of basic residues
• Cytoplasmic vesicle
• Glycoprotein
• Hydrolase
• Hypogonadotropic hypogonadism
• Intellectual disability
• Membrane
• Metal-binding
• Metalloprotease
• Obesity
• Protease
• Secreted
• Signal
• Zinc
• Zymogen