Cpe carboxypeptidase E [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cpeprovided by MGI
Official Full Name: carboxypeptidase Eprovided by MGI
Primary source: MGI:MGI:101932
See related: Ensembl:ENSMUSG00000037852 AllianceGenome:MGI:101932
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: CPH; fat; Cph1; Cph-1; NF-alpha1
Summary: This gene encodes carboxypeptidase E, a prohormone-processing exopeptidase found in secretory granules of endocrine and neuroendocrine cells. The encoded preproprotein undergoes proteolytic processing to generate a mature, functional enzyme that cleaves the C-terminal basic residues of protein substrates. A missense mutation in this gene is responsible for the obesity phenotype in a mouse model known as the "fat mouse." Mice lacking the functional product of this gene exhibit impaired processing of multiple peptide hormones such as proinsulin, prodynorphin, proneurotensin, promelanin-concentrating hormone and pro-opiomelanocortin. [provided by RefSeq, Jan 2016]
Expression: Biased expression in frontal lobe adult (RPKM 416.8), cortex adult (RPKM 400.4) and 14 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 B3.1; 8 32.3 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (65045576..65146143, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (64592542..64693109, complement)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing.
Title: Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing.
Deletion of Carboxypeptidase E in beta-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice.
Title: Deletion of Carboxypeptidase E in β-Cells Disrupts Proinsulin Processing but Does Not Lead to Spontaneous Development of Diabetes in Mice.
Carboxypeptidase E Regulates Activity-Dependent TrkB Neuronal Surface Insertion and Hippocampal Memory.
Title: Carboxypeptidase E Regulates Activity-Dependent TrkB Neuronal Surface Insertion and Hippocampal Memory.
It shows that although carboxypeptidase E (CPE) is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in beta-cells, increases islet CPE levels, and fully reverses betaOGTKO islet-induced hyperproinsulinemia.
Title: eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
HT22 cells and embryonic cortical neurons overexpressing 40 kDa (CPE/NF-alpha1)-DeltaN exhibited enhanced proliferation, which was inhibited by IGFBP2 short interfering RNA treatment
Title: Cloning, gene regulation, and neuronal proliferation functions of novel N-terminal-truncated carboxypeptidase E/neurotrophic factor-αl variants in embryonic mouse brain.
Cpe knockout leads to dysfunction of BDNF-TRKB signaling in hippocampus and lack of long-term potentiation formation.
Title: Absence of Carboxypeptidase E/Neurotrophic Factor-Α1 in Knock-Out Mice Leads to Dysfunction of BDNF-TRKB Signaling in Hippocampus.
NF-alpha1 is critical for regulating antiproliferation and cell fate determination, through differentiating embryonic stem cells to GFAP-positive astrocytes for normal neurodevelopment.
Title: Neurotrophic Factor-α1: A Key Wnt-β-Catenin Dependent Anti-Proliferation Factor and ERK-Sox9 Activated Inducer of Embryonic Neural Stem Cell Differentiation to Astrocytes in Neurodevelopment.
we show by RNA silencing that CPE and SgIII play a synergistic role in the trafficking of POMC to granules of the regulated secretory pathway in AtT20 cells
Title: Carboxypeptidase E and Secretogranin III Coordinately Facilitate Efficient Sorting of Proopiomelanocortin to the Regulated Secretory Pathway in AtT20 Cells.
An anti-inflammatory role of CPE in the intestine by influencing local cytokine levels and thus regulating the migration of myeloid immune cells into the mucosa.
Title: Carboxypeptidase E modulates intestinal immune homeostasis and protects against experimental colitis in mice.
This study shown that NF-alpha1-mediated upregulation of hippocampal FGF2 and neurogenesis prevents an onset of chronic stress-induced depressive-like behavior
Title: Neurotrophic factor-α1 prevents stress-induced depression through enhancement of neurogenesis and is activated by rosiglitazone.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1)
Targeted (6) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Cpe (e-PCR), detects polymorphism
- UniSTS:532483

Cpe (e-PCR), detects polymorphism
- UniSTS:141389

Cpe (e-PCR), detects polymorphism
- UniSTS:141390

RH125093 (e-PCR)
- UniSTS:161915

D8Mit25 (e-PCR), detects polymorphism
- UniSTS:131459

Cpe (e-PCR), detects polymorphism
- UniSTS:506813

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables carboxypeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables carboxypeptidase activity	ISO Inferred from Sequence Orthology more info
enables cell adhesion molecule binding	ISO Inferred from Sequence Orthology more info
enables cobalt ion binding	ISO Inferred from Sequence Orthology more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metallocarboxypeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metallocarboxypeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metallopeptidase activity	IEA Inferred from Electronic Annotation more info
enables neurexin family protein binding	ISO Inferred from Sequence Orthology more info
enables peptidase activity	IEA Inferred from Electronic Annotation more info
enables peptidase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cardiac left ventricle morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in enkephalin processing	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within insulin processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin processing	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of branching morphogenesis of a nerve	ISO Inferred from Sequence Orthology more info
involved_in peptide catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within peptide hormone secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptide metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptide metabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein localization to membrane	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization to secretory granule	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein processing	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within proteolysis	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in dense core granule	ISO Inferred from Sequence Orthology more info
located_in extracellular region	ISO Inferred from Sequence Orthology more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in perikaryon	ISO Inferred from Sequence Orthology more info
is_active_in secretory granule	IDA Inferred from Direct Assay more info	PubMed
located_in secretory granule	ISO Inferred from Sequence Orthology more info
located_in secretory granule membrane	IDA Inferred from Direct Assay more info	PubMed
located_in secretory granule membrane	TAS Traceable Author Statement more info
located_in synaptic membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: carboxypeptidase E

Names: carboxypeptidase H; enkephalin convertase; prohormone-processing carboxypeptidase

NP_038522.2

EC 3.4.17.10

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_013494.4 → NP_038522.2 carboxypeptidase E preproprotein

See identical proteins and their annotated locations for NP_038522.2

Status: REVIEWED

Source sequence(s)

AK047891, BE849320, CX241703

Consensus CDS

CCDS22327.1

UniProtKB/Swiss-Prot

Q00493, Q64439

UniProtKB/TrEMBL

Q543R4

Related

ENSMUSP00000048555.8, ENSMUST00000048967.9

Conserved Domains (2) summary

cd11308
Location:375 → 449

Peptidase_M14NE-CP-C_like; Peptidase associated domain: C-terminal domain of M14 N/E carboxypeptidase; putative folding, regulation, or interaction domain

cl11393
Location:49 → 371

Peptidase_M14_like; M14 family of metallocarboxypeptidases and related proteins