SENP6 Gene

Name	SUMO1/sentrin specific peptidase 6
Description	Ubiquitin-like molecules (UBLs), such as SUMO1 (UBL1; MIM 601912), are structurally related to ubiquitin (MIM 191339) and can be ligated to target proteins in a similar manner as ubiquitin. However, covalent attachment of UBLs does not result in degradation of the modified proteins. SUMO1 modification is implicated in the targeting of RANGAP1 (MIM 602362) to the nuclear pore complex, as well as in stabilization of I-kappa-B-alpha (NFKBIA; MIM 164008) from degradation by the 26S proteasome. Like ubiquitin, UBLs are synthesized as precursor proteins, with 1 or more amino acids following the C-terminal glycine-glycine residues of the mature UBL protein. Thus, the tail sequences of the UBL precursors need to be removed by UBL-specific proteases, such as SENP6, prior to their conjugation to target proteins (Kim et al., 2000 [PubMed 10799485]). SENPs also display isopeptidase activity for deconjugation of SUMO-conjugated substrates (Lima and Reverter, 2008 [PubMed 18799455]).[supplied by OMIM, Jun 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSENP6 is a divergent member of the SUMO-specific protease family that preferentially targets SUMO2/3 modifications and poly‐SUMO chains. Structural and biochemical studies have revealed that unique elements—such as an insertion in the catalytic domain—provide SENP6 with its distinctive substrate specificity, enabling the efficient disassembly of SUMO chains and fine‐tuning of protein SUMOylation dynamics. This specialized activity distinguishes SENP6 from other SUMO proteases by ensuring accurate deconjugation of mixed SUMO chains, a feature critical for multiple downstream signaling events."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its catalytic precision, SENP6 plays a pivotal role in preserving chromatin integrity and genomic stability. Its activity underpins the proper assembly of centromeres and kinetochores by modulating the SUMOylation status of key inner kinetochore proteins, such as the CENP-H/I/K complex, and by antagonizing the ubiquitin ligase RNF4 that targets hyper‐SUMOylated substrates for degradation. Additionally, SENP6 contributes to the organization of promyelocytic leukemia nuclear bodies by regulating the balance of SUMO conjugates, and it is actively involved in controlling cohesin complex association and ATR–Chk1–mediated DNA damage responses. Loss or depletion of SENP6 is associated with aberrant protein SUMOylation, defective spindle assembly, and ultimately genomic instability that can promote tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSENP6 also influences a range of signaling pathways that interface with cellular stress responses and disease pathogenesis. Viral regulatory proteins, exemplified by the KSHV latency-associated nuclear antigen (LANA), target the SENP6 promoter to repress its expression, thereby modulating the SUMOylation status of viral proteins and influencing the establishment of latency. In parallel, SENP6 regulates intracellular receptor trafficking; for instance, by deSUMOylating VEGFR2, it governs the transit of the receptor from the Golgi apparatus to the plasma membrane, a process critical for pathological angiogenesis. Moreover, by interacting with mitophagy effectors such as PINK1 and reducing their SUMO2 modification, SENP6 has been implicated in promoting mitophagy that contributes to temozolomide resistance in glioma cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christopher D Lima, David Reverter "}, {"type": "b", "children": [{"type": "t", "text": "Structure of the human SENP7 catalytic domain and poly-SUMO deconjugation activities for SENP6 and SENP7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M805655200"}], "href": "https://doi.org/10.1074/jbc.M805655200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18799455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18799455"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kamela O Alegre, David Reverter "}, {"type": "b", "children": [{"type": "t", "text": "Swapping small ubiquitin-like modifier (SUMO) isoform specificity of SUMO proteases SENP6 and SENP7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.268847"}], "href": "https://doi.org/10.1074/jbc.M111.268847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21878624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21878624"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kamela O Alegre, David Reverter "}, {"type": "b", "children": [{"type": "t", "text": "Structural insights into the SENP6 Loop1 structure in complex with SUMO2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.2425"}], "href": "https://doi.org/10.1002/pro.2425"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24424631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24424631"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Debaditya Mukhopadhyay, Alexei Arnaoutov, Mary Dasso "}, {"type": "b", "children": [{"type": "t", "text": "The SUMO protease SENP6 is essential for inner kinetochore assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200909008"}], "href": "https://doi.org/10.1083/jcb.200909008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20212317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20212317"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Neil Hattersley, Linnan Shen, Ellis G Jaffray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SUMO protease SENP6 is a direct regulator of PML nuclear bodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E10-06-0504"}], "href": "https://doi.org/10.1091/mbc.E10-06-0504"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21148299"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21148299"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Frauke Liebelt, Nicolette S Jansen, Sumit Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-11773-x"}], "href": "https://doi.org/10.1038/s41467-019-11773-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31485003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31485003"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kristina Wagner, Kathrin Kunz, Tanja Piller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SUMO Isopeptidase SENP6 Functions as a Rheostat of Chromatin Residency in Genome Maintenance and Chromosome Dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.08.106"}], "href": "https://doi.org/10.1016/j.celrep.2019.08.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31597105"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31597105"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sreyoshi Mitra, Dani L Bodor, Ana F David, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-14276-x"}], "href": "https://doi.org/10.1038/s41467-019-14276-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31980633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31980633"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Markus Schick, Le Zhang, Sabine Maurer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-27704-8"}], "href": "https://doi.org/10.1038/s41467-021-27704-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35022408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35022408"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiaoxi Lin, Rui Sun, Fang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Inhibits Expression of SUMO/Sentrin-Specific Peptidase 6 To Facilitate Establishment of Latency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00806-17"}], "href": "https://doi.org/10.1128/JVI.00806-17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28615201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28615201"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Qi He, Zhenfeng Chen, Jieyu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms24032544"}], "href": "https://doi.org/10.3390/ijms24032544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36768878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36768878"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Y W Wang, K G Jia, H J Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol (Mosk) (2024)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38062972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38062972"}]}]}]}
Synonyms	SSP1, SUSP1
Proteins	SENP6_HUMAN
NCBI Gene ID	26054
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SENP6 has 7,544 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

Click the + buttons to view associations for SENP6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SENP6 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SENP6 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 SENP6 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 SENP6 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 SENP6 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 SENP6 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 SENP6 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 SENP6 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 SENP6 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 SENP6 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 SENP6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SENP6 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 SENP6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SENP6 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SENP6 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 SENP6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SENP6 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 SENP6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SENP6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SENP6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SENP6 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 SENP6 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 SENP6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SENP6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SENP6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SENP6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SENP6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SENP6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SENP6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SENP6 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 SENP6 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 SENP6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SENP6 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 SENP6 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 SENP6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SENP6 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 SENP6 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 SENP6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with SENP6 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 SENP6 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of SENP6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.