DPP8 Gene

Name	dipeptidyl-peptidase 8
Description	This gene encodes a member of the peptidase S9B family, a small family of dipeptidyl peptidases that are able to cleave peptide substrates at a prolyl bond. The encoded protein shares similarity with dipeptidyl peptidase IV in that it is ubiquitously expressed, and hydrolyzes the same substrates. These similarities suggest that, like dipeptidyl peptidase IV, this protein may play a role in T-cell activation and immune function. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dipeptidyl peptidase 8 (DPP8) is an intracellular serine protease belonging to the dipeptidyl peptidase IV (DPPIV) family that displays post‐proline dipeptidyl cleavage activity. It shares extensive structural and functional similarities with its close homolog DPP9 and, like DPP9, is localized exclusively in the cytoplasm (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " A number of studies indicate that DPP8 participates in the regulation of immune and inflammatory responses. Inhibition of DPP8, frequently in combination with DPP9 inhibition, triggers activation of inflammasomes (notably those based on NLRP1 and CARD8) via proteasomal degradation of inhibitory N‐terminal domains, thereby releasing the C‐terminal fragments that initiate caspase‐1 activation and pyroptosis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, DPP8 is capable of processing select chemokines – cleaving two N‐terminal residues from mediators such as CXCL10, CXCL11, and SDF‐1 – and this proteolytic modification may profoundly alter receptor binding and cellular trafficking (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond immune modulation, functional studies have implicated DPP8 in the regulation of cell–extracellular matrix interactions, where its overexpression can impair cell adhesion, migration, and wound healing while enhancing apoptosis. Proteomic analyses have also uncovered a broad substrate repertoire for DPP8 that connects its activity to the maintenance of cellular metabolism and homeostasis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Mutagenesis and structural investigations have identified key residues in the C‐terminal regions that are absolutely required for DPP8’s optimal enzymatic activity and have delineated a substrate specificity that is distinct from that of DPPIV, further emphasizing its unique functional role within the DPPIV family (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the field of metabolism, DPP8 helps regulate adipogenesis: inhibition or knockdown of DPP8 markedly impairs the induction of PPARγ2 and subsequent adipocyte differentiation, suggesting that the enzyme could be a therapeutic target for metabolic disorders (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, aberrant expression of DPP8 has been reported in certain cancers and hematological malignancies – with upregulation in chronic lymphocytic leukemia and variable expression in solid tumors – pointing to potential roles in tumorigenesis and disease progression (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, the design and evaluation of selective inhibitors have underscored the importance of distinguishing DPP8 from other DPP enzymes, particularly given the off‐target effects observed with clinically used DPPIV inhibitors. Cell‐based models overexpressing DPP8 (and DPP9) have proven useful for dissecting inhibitor specificity and evaluating potential toxicities (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies suggest that DPP8 is a multifunctional enzyme critically involved in peptide processing that modulates immune responses, cell adhesion and migration, as well as adipogenesis, with its dysregulation potentially contributing to tumorigenesis and other pathophysiological conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shu Y Qi, Pierre J Riviere, Jerzy Trojnar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20021914"}], "href": "https://doi.org/10.1042/BJ20021914"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12662155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12662155"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katerina Ajami, Catherine A Abbott, Geoffrey W McCaughan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dipeptidyl peptidase 9 has two forms, a broad tissue distribution, cytoplasmic localization and DPIV-like peptidase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbaexp.2004.03.010"}], "href": "https://doi.org/10.1016/j.bbaexp.2004.03.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15245913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15245913"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ashley J Chui, Marian C Okondo, Sahana D Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-terminal degradation activates the NLRP1B inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aau1208"}], "href": "https://doi.org/10.1126/science.aau1208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30872531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30872531"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "L Wagner, C Klemann, M Stephan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cei.12757"}], "href": "https://doi.org/10.1111/cei.12757"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26671446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26671446"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Katerina Ajami, Melissa R Pitman, Claire H Wilson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stromal cell-derived factors 1alpha and 1beta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2008.02.005"}], "href": "https://doi.org/10.1016/j.febslet.2008.02.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18275857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18275857"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Denise M T Yu, Xin M Wang, Geoffrey W McCaughan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extraenzymatic functions of the dipeptidyl peptidase IV-related proteins DP8 and DP9 in cell adhesion, migration and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2006.05253.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2006.05253.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16704418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16704418"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Claire H Wilson, Dono Indarto, Alain Doucet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identifying natural substrates for dipeptidyl peptidases 8 and 9 using terminal amine isotopic labeling of substrates (TAILS) reveals in vivo roles in cellular homeostasis and energy metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.445841"}], "href": "https://doi.org/10.1074/jbc.M112.445841"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23519473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23519473"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hong-Jen Lee, Yuan-Shou Chen, Chi-Yuan Chou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M603895200"}], "href": "https://doi.org/10.1074/jbc.M603895200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17040910"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17040910"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sebastiaan Van Goethem, Veerle Matheeussen, Jurgen Joossens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 9 (DPP8, DPP9): is DPP8-selectivity an attainable goal?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/jm200383j"}], "href": "https://doi.org/10.1021/jm200383j"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21711053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21711053"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ruijun Han, Xinying Wang, William Bachovchin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep12348"}], "href": "https://doi.org/10.1038/srep12348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26242871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26242871"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Melanie L Sulda, Catherine A Abbott, Peter J Macardle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and prognostic assessment of dipeptidyl peptidase IV and related enzymes in B-cell chronic lymphocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cbt.10.2.12168"}], "href": "https://doi.org/10.4161/cbt.10.2.12168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20534982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20534982"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Claire H Wilson, Catherine A Abbott "}, {"type": "b", "children": [{"type": "t", "text": "Expression profiling of dipeptidyl peptidase 8 and 9 in breast and ovarian carcinoma cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2012.1522"}], "href": "https://doi.org/10.3892/ijo.2012.1522"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22736146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22736146"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yi Huan, Qian Jiang, Jing-long Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Establishment of a dipeptidyl peptidases (DPP) 8/9 expressing cell model for evaluating the selectivity of DPP4 inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Toxicol Methods (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.vascn.2014.11.002"}], "href": "https://doi.org/10.1016/j.vascn.2014.11.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25464020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25464020"}]}]}]}
Synonyms	DPRP1, MSTP097, MST097, MSTP141, DP8, MSTP135, DPRP-1
Proteins	DPP8_HUMAN
NCBI Gene ID	54878
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DPP8 has 6,276 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 108 datasets.

Click the + buttons to view associations for DPP8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 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 DPP8 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DPP8 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 DPP8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DPP8 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DPP8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DPP8 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 DPP8 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DPP8 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DPP8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DPP8 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DPP8 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 DPP8 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 DPP8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DPP8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DPP8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DPP8 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 DPP8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DPP8 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 DPP8 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 DPP8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DPP8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DPP8 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DPP8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DPP8 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing DPP8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DPP8 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DPP8 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing DPP8 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of DPP8 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of DPP8 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of DPP8 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.