CPE Gene

Name	carboxypeptidase E
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Carboxypeptidase E (CPE) is a multifunctional protein that not only acts as an exopeptidase in the final processing of neuropeptides and prohormones but also serves as a sorting receptor in the regulated secretory pathway. Structural and biochemical studies have shown that CPE directly interacts with specific sorting motifs on substrates such as pro–brain‐derived neurotrophic factor and pro–peptide precursors, thereby targeting them into secretory vesicles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the central nervous system, CPE is crucial for the proper processing of prohormones in hypothalamic neurons. For example, in pro‐opiomelanocortin (POMC) neurons, CPE‐mediated cleavage is essential for the generation of bioactive products, such as α-melanocyte–stimulating hormone and cleaved β-endorphin, which in turn modulate food intake and energy expenditure. Notably, enhanced CPE expression in these neurons is associated with improved neuropeptide processing, while its downregulation relates to diet-induced obesity and leptin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pancreatic β cells, CPE’s enzymatic activity is vital for efficient proinsulin conversion to insulin. Disruptions in CPE function, whether through proteolytic degradation induced by lipotoxic agents like palmitate or through genetic deletion, lead to increased proinsulin accumulation, endoplasmic reticulum stress, and β-cell apoptosis. Consistent with these findings, CPE knockout models display hyperproinsulinemia, defective glucose clearance, and obesity, while rare missense mutations in CPE are linked to early-onset type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in peptide processing, CPE is involved in secretory granule biogenesis in neuroendocrine tissues. It cooperates with partners such as secretogranin III by anchoring to cholesterol-rich granule membranes, thus facilitating the sorting of cargo like chromogranin A and POMC-derived intermediates."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n Moreover, interactions between CPE and neuronal adaptor proteins such as NOS1AP-L have been implicated in the regulation of dendritic outgrowth and branching, suggesting a broader role in neuronal development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic association studies further support the involvement of CPE in metabolic and neuropsychiatric conditions. Variants in the CPE gene have been associated with body mass index and obesity phenotypes, as well as with alcohol dependence. In addition, differential expression analyses reveal that CPE levels are higher in visceral compared with subcutaneous adipose tissue, implicating its role in depot-specific metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hong Lou, Soo-Kyung Kim, Eugene Zaitsev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase e."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2004.12.037"}], "href": "https://doi.org/10.1016/j.neuron.2004.12.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15664176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15664176"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Masahiro Hosaka, Tsuyoshi Watanabe, Yuko Sakai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction between secretogranin III and carboxypeptidase E facilitates prohormone sorting within secretory granules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02608"}], "href": "https://doi.org/10.1242/jcs.02608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16219686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16219686"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Leona Plum, Hua V Lin, Roxanne Dutia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2026"}], "href": "https://doi.org/10.1038/nm.2026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19767734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19767734"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kristin D Jeffrey, Emilyn U Alejandro, Dan S Luciani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxypeptidase E mediates palmitate-induced beta-cell ER stress and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0711232105"}], "href": "https://doi.org/10.1073/pnas.0711232105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18550819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18550819"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Niamh X Cawley, Jiechun Zhou, Joanna M Hill, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2004-0847"}], "href": "https://doi.org/10.1210/en.2004-0847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15358678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15358678"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "H Chen, S Jawahar, Y Qian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.1161"}], "href": "https://doi.org/10.1002/humu.1161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11462236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11462236"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Masahiro Hosaka, Masayuki Suda, Yuko Sakai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Secretogranin III binds to cholesterol in the secretory granule membrane as an adapter for chromogranin A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M310104200"}], "href": "https://doi.org/10.1074/jbc.M310104200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14597614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14597614"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Damien Carrel, Yangzhou Du, Daniel Komlos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NOS1AP regulates dendrite patterning of hippocampal neurons through a carboxypeptidase E-mediated pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5287-08.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.5287-08.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19553464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19553464"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "P Li, H K Tiwari, W-Y Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic association analysis of 30 genes related to obesity in a European American population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Obes (Lond) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ijo.2013.140"}], "href": "https://doi.org/10.1038/ijo.2013.140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23900445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23900445"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "J M Ramis, N L W Franssen-van Hal, E Kramer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/pl00012518"}], "href": "https://doi.org/10.1007/pl00012518"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12530526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12530526"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Howard J Edenberg, Daniel L Koller, Xiaoling Xuei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of alcohol dependence implicates a region on chromosome 11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alcohol Clin Exp Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1530-0277.2010.01156.x"}], "href": "https://doi.org/10.1111/j.1530-0277.2010.01156.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20201924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20201924"}]}]}]}
Synonyms	CPH
Proteins	CBPE_HUMAN
NCBI Gene ID	1363
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CPE has 14,336 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

Click the + buttons to view associations for CPE from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CPE Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CPE gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CPE gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CPE gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CPE gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CPE gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CPE gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CPE gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CPE gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CPE gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CPE gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CPE gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CPE gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CPE gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CPE protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CPE gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CPE gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CPE gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CPE gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CPE gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of CPE gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CPE protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CPE gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CPE protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CPE protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CPE protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CPE protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CPE protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CPE protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CPE gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CPE gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CPE gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with CPE gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CPE protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CPE gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CPE gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CPE gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CPE gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CPE gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CPE gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CPE protein from the curated DrugBank Drug Targets dataset.