Details for: SENP1

Gene ID: 29843

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SENP1

Ensembl ID: ENSG00000079387

Description: SUMO specific peptidase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural crest cell CL0011012
    CSI 6.51
    rCSI 5.15%
    PRS 89.11
  • mesothelial cell CL0000077
    CSI 3.69
    rCSI 14.44%
    PRS 81.73
  • melanocyte CL0000148
    CSI 3.62
    rCSI 2.68%
    PRS 91.7
  • interneuron CL0000099
    CSI 3.26
    rCSI 6.55%
    PRS 89.68
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.24
    rCSI 7.27%
    PRS 84.88
  • naive B cell CL0000788
    CSI 2.99
    rCSI 2.56%
    PRS 96.39
  • cardiac endothelial cell CL0010008
    CSI 2.92
    rCSI 11.77%
    PRS 94.58
  • choroid plexus epithelial cell CL0000706
    CSI 2.92
    rCSI 4.78%
    PRS 88.88
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.81
    rCSI 17.58%
    PRS 89.01
  • lung ciliated cell CL1000271
    CSI 2.79
    rCSI 3.22%
    PRS 89.79
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.63
    rCSI 4.41%
    PRS 84.71
  • common myeloid progenitor CL0000049
    CSI 2.52
    rCSI 2.04%
    PRS 94.81
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 2.49
    rCSI 2.27%
    PRS 98.5
  • hepatic stellate cell CL0000632
    CSI 2.47
    rCSI 9.24%
    PRS 91.22
  • cerebral cortex endothelial cell CL1001602
    CSI 2.42
    rCSI 4.19%
    PRS 90.33
  • retinal bipolar neuron CL0000748
    CSI 2.29
    rCSI 4.29%
    PRS 87.83
  • vascular leptomeningeal cell CL4023051
    CSI 2.29
    rCSI 4.01%
    PRS 91.84
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.09
    rCSI 2.5%
    PRS 84.65
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.02
    rCSI 2.51%
    PRS 82.54
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.95
    rCSI 3.44%
    PRS 84.07
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.94
    rCSI 4.92%
    PRS 90.11
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.9
    rCSI 2.45%
    PRS 85.58
  • ependymal cell CL0000065
    CSI 1.88
    rCSI 3.82%
    PRS 79.6
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.61
    rCSI 2.6%
    PRS 85.59
  • myeloid dendritic cell CL0000782
    CSI 1.55
    rCSI 2.25%
    PRS 98.57
  • glial cell CL0000125
    CSI 1.53
    rCSI 5.82%
    PRS 88.76
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.37
    rCSI 5.35%
    PRS 98.98
  • retinal ganglion cell CL0000740
    CSI 1.11
    rCSI 2.45%
    PRS 86.08
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.89
    rCSI 2.17%
    PRS 82.63
  • blood vessel smooth muscle cell CL0019018
    CSI 0.77
    rCSI 6.25%
    PRS 92.8
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.72
    rCSI 2.24%
    PRS 85.66
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.65
    rCSI 2.02%
    PRS 87.31
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.55
    rCSI 1.98%
    PRS 82.92
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.4
    rCSI 2.33%
    PRS 85.01

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Analyzed for its expression specificity (CSI Z-Score), [SENP1](/details-gene/29843) does not function as a specific marker for any particular cell type. Instead, its broad and uniform expression pattern across diverse cell lineages suggests it plays a fundamental, housekeeping role in post-translational protein modification. As a SUMO-specific protease, it is critical for regulating protein activity, localization, and stability through desumoylation, a process essential for a wide range of core cellular functions, including transcription and apoptosis. ## Cellular Roles and Expression Landscape The expression profile of [SENP1](/details-gene/29843) is most notable for its complete lack of cell-type specificity. In the **Overall** context, the CSI (Z-SCORE) is 0.00 across a wide array of functionally and developmentally distinct cell types. These include cells of neural origin like [interneurons](/details-cell/CL0000099) and [astrocytes of the cerebral cortex](/details-cell/CL0002605), immune cells such as [effector memory CD8-positive, alpha-beta T cells](/details-cell/CL0000913), and structural cells like [regular ventricular cardiac myocytes](/details-cell/CL0002131) and [mesothelial cells](/details-cell/CL0000077). This lack of a significant Z-score, combined with uniformly non-significant p-values (p > 0.46) and a consistent Effect Size of 1.00, strongly indicates that [SENP1](/details-gene/29843) is not a defining marker gene used to distinguish one cell type from another. Rather, its consistent presence across tissues of ectodermal, mesodermal, and endodermal origin points to a ubiquitous and essential function. This is consistent with its known localization in multiple cellular compartments, including the [cytoplasm](/details-link/GO:0005737), [nucleus](/details-link/GO:0005634), and [nuclear membrane](/details-link/GO:0031965), as characterized by Bailey et al. ([PubMed: 14563852](https://pubmed.ncbi.nlm.nih.gov/14563852)), allowing it to regulate processes throughout the cell. ## Pathways and Molecular Function The ubiquitous expression of [SENP1](/details-gene/29843) is entirely consistent with its central role in protein desumoylation, a critical and reversible post-translational modification. Its primary molecular functions are '[desumoylase activity](/details-link/GO:0016929)' and '[SUMO-specific endopeptidase activity](/details-link/GO:0070139)', which are essential for cleaving Small Ubiquitin-like Modifier (SUMO) proteins from their targets. This regulatory role places [SENP1](/details-gene/29843) at the heart of fundamental biological pathways, including '[Metabolism of proteins](/details-link/R-HSA-392499)', '[Post-translational protein modification](/details-link/R-HSA-597592)', and the broader '[Sumoylation](/details-link/R-HSA-2990846)' process. SUMOylation affects nearly every major cellular process by altering protein stability, subcellular localization, and enzymatic activity. Consequently, [SENP1](/details-gene/29843) is implicated in the regulation of critical cellular decisions, such as the '[apoptotic signaling pathway](/details-link/GO:0097190)' and '[positive regulation of transcription by rna polymerase ii](/details-link/GO:0045944)'. For instance, research has shown that [SENP1](/details-gene/29843) enhances androgen receptor-dependent transcription by desumoylating histone deacetylase 1, highlighting its direct impact on gene expression programs ([PubMed: 15199155](https://doi.org/10.1128/mcb.24.13.6021-6028.2004)). ## Research Directions The broad, non-specific expression of [SENP1](/details-gene/29843) suggests that its regulatory impact is not controlled at the level of transcription but rather through its enzymatic activity and interaction with cell-type-specific substrates. Future research should focus on understanding this context-dependent regulation. ### Proposed Testable Hypotheses: 1. **Cell-type specific substrate targeting dictates SENP1 function.** The ubiquitous expression of [SENP1](/details-gene/29843) implies that its functional specificity arises from the unique set of SUMOylated proteins present in different cells. For example, in [glutamatergic synapses](/details-link/GO:0098978), SENP1 may primarily desumoylate synaptic scaffolding proteins, whereas in [common myeloid progenitors](/details-cell/CL0000049), it likely targets key hematopoietic transcription factors. * **Experimental Approach:** Utilize proximity-dependent biotinylation (e.g., BioID) or co-immunoprecipitation followed by mass spectrometry (Co-IP/MS) in purified populations of [interneurons](/details-cell/CL0000099) versus [common myeloid progenitors](/details-cell/CL0000049) to identify and compare the SENP1 interactome and its direct substrates in these distinct lineages. 2. **SENP1 enzymatic activity is a critical rheostat for cellular stress response.** Given its role in apoptosis, the catalytic activity of the constitutively expressed SENP1 protein, rather than its transcript level, may determine cell fate under stress. It is hypothesized that inhibition of SENP1 activity will sensitize cells to stress-induced apoptosis by preventing the desumoylation of pro-apoptotic factors. * **Experimental Approach:** Treat a panel of diverse cell types (e.g., [cardiac endothelial cells](/details-cell/CL0010008), [naive B cells](/details-cell/CL0000788)) with a known stressor (e.g., oxidative stress, DNA damage) in the presence or absence of a specific SENP1 pharmacological inhibitor. Measure global protein SUMOylation levels via western blot and quantify apoptosis using flow cytometry for Annexin V staining. 3. **SENP1 is a key regulator of lineage-specific differentiation through chromatin modification.** While expressed broadly, SENP1's role in desumoylating transcriptional regulators and chromatin-modifying enzymes (like HDAC1) suggests it could be a pivotal factor during cell differentiation. Transient inhibition of SENP1 at specific developmental checkpoints may alter cell fate decisions by shifting the balance of SUMOylation on key lineage-determining factors. * **Experimental Approach:** Employ an in vitro differentiation model, such as directing embryonic stem cells towards a neural crest lineage. Use a temporally-controlled SENP1 inhibitor at different stages of differentiation and perform single-cell RNA sequencing (scRNA-seq) to map how the developmental trajectory is altered compared to untreated controls. ### Therapeutic Potential Due to its ubiquitous expression and fundamental role in protein metabolism, systemic inhibition of [SENP1](/details-gene/29843) would likely lead to high toxicity and significant off-target effects. However, its demonstrated role in modulating the activity of specific transcription factors, such as the androgen receptor ([PubMed: 15199155](https://doi.org/10.1128/mcb.24.13.6021-6028.2004)), makes it a compelling therapeutic target in diseases driven by hyperactivity of specific pathways, like prostate cancer. A viable therapeutic strategy may involve developing allosteric inhibitors or protein-protein interaction disruptors that selectively block SENP1's access to a particular substrate (e.g., the androgen receptor) rather than inhibiting its global catalytic function.

Genular Protein ID: 2305971876

Symbol: SENP1_HUMAN

Name: Sentrin-specific protease 1

UniProtKB Accession Codes:

Q9P0U3 A8K7P5 Q86XC8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 15 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 10 PDBsum 10 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 2 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10652325

Title: Differential regulation of sentrinized proteins by a novel sentrin-specific protease.

PubMed ID: 10652325

DOI: 10.1074/jbc.275.5.3355

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14563852

Title: Characterization of the localization and proteolytic activity of the SUMO-specific protease, SENP1.

PubMed ID: 14563852

DOI: 10.1074/jbc.m306195200

PubMed ID: 15199155

Title: SENP1 enhances androgen receptor-dependent transcription through desumoylation of histone deacetylase 1.

PubMed ID: 15199155

DOI: 10.1128/mcb.24.13.6021-6028.2004

PubMed ID: 15487983

Title: Mapping residues of SUMO precursors essential in differential maturation by SUMO-specific protease, SENP1.

PubMed ID: 15487983

DOI: 10.1042/bj20041210

PubMed ID: 16253240

Title: Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1.

PubMed ID: 16253240

DOI: 10.1016/j.febslet.2005.10.010

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 21965678

Title: SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor antigen 1 (MTA1) synergistically regulate its transcriptional repressor function.

PubMed ID: 21965678

DOI: 10.1074/jbc.m111.267237

PubMed ID: 21829689

Title: SUMOylation of DEC1 protein regulates its transcriptional activity and enhances its stability.

PubMed ID: 21829689

DOI: 10.1371/journal.pone.0023046

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23160374

Title: CLOCK is a substrate of SUMO and sumoylation of CLOCK upregulates the transcriptional activity of estrogen receptor-alpha.

PubMed ID: 23160374

DOI: 10.1038/onc.2012.518

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 24943844

Title: SUMOylation of GPS2 protein regulates its transcription-suppressing function.

PubMed ID: 24943844

DOI: 10.1091/mbc.e13-12-0733

PubMed ID: 25406032

Title: Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis in response to DNA damage.

PubMed ID: 25406032

DOI: 10.1038/ncomms6483

PubMed ID: 29506078

Title: SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function.

PubMed ID: 29506078

DOI: 10.1093/nar/gky156

PubMed ID: 34048572

Title: Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response.

PubMed ID: 34048572

DOI: 10.1093/nar/gkab415

PubMed ID: 37257451

Title: RBM33 is a unique m6A RNA-binding protein that regulates ALKBH5 demethylase activity and substrate selectivity.

PubMed ID: 37257451

DOI: 10.1016/j.molcel.2023.05.010

PubMed ID: 16553580

Title: The structure of SENP1-SUMO-2 complex suggests a structural basis for discrimination between SUMO paralogues during processing.

PubMed ID: 16553580

DOI: 10.1042/bj20052030

PubMed ID: 16712526

Title: Crystal structure of the SENP1 mutant C603S-SUMO complex reveals the hydrolytic mechanism of SUMO-specific protease.

PubMed ID: 16712526

DOI: 10.1042/bj20060526

PubMed ID: 17099698

Title: SUMO protease SENP1 induces isomerization of the scissile peptide bond.

PubMed ID: 17099698

DOI: 10.1038/nsmb1172

Sequence Information:

  • Length: 644
  • Mass: 73481
  • Checksum: 941951A8B341EC64
  • Sequence:
    • MDDIADRMRM DAGEVTLVNH NSVFKTHLLP QTGFPEDQLS LSDQQILSSR QGHLDRSFTC 
STRSAAYNPS YYSDNPSSDS FLGSGDLRTF GQSANGQWRN STPSSSSSLQ KSRNSRSLYL 
ETRKTSSGLS NSFAGKSNHH CHVSAYEKSF PIKPVPSPSW SGSCRRSLLS PKKTQRRHVS 
TAEETVQEEE REIYRQLLQM VTGKQFTIAK PTTHFPLHLS RCLSSSKNTL KDSLFKNGNS 
CASQIIGSDT SSSGSASILT NQEQLSHSVY SLSSYTPDVA FGSKDSGTLH HPHHHHSVPH 
QPDNLAASNT QSEGSDSVIL LKVKDSQTPT PSSTFFQAEL WIKELTSVYD SRARERLRQI 
EEQKALALQL QNQRLQEREH SVHDSVELHL RVPLEKEIPV TVVQETQKKG HKLTDSEDEF 
PEITEEMEKE IKNVFRNGNQ DEVLSEAFRL TITRKDIQTL NHLNWLNDEI INFYMNMLME 
RSKEKGLPSV HAFNTFFFTK LKTAGYQAVK RWTKKVDVFS VDILLVPIHL GVHWCLAVVD 
FRKKNITYYD SMGGINNEAC RILLQYLKQE SIDKKRKEFD TNGWQLFSKK SQEIPQQMNG 
SDCGMFACKY ADCITKDRPI NFTQQHMPYF RKRMVWEILH RKLL

Genular Protein ID: 3213283373

Symbol: Q7Z3G1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q7Z3G1

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 1 PharmGKB 1 RefSeq 1

Sequence Information:

  • Length: 123
  • Mass: 13575
  • Checksum: 4EC4E27EE1EB5A9F
  • Sequence:
    • MRMDAGEVTL VNHNSVFKTH LLPQTGFPED QLSLSDQQIL SSRQGHLDRS FTCSARSAAY 
NPSYYSGPGL GVLARYSWGK MLTFGGHHGV TLMQIRHMAV AGFSSFINFQ IILPQTVFLA 
QAI

Genular Protein ID: 3719458352

Symbol: Q6N001_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6N001

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 1 PharmGKB 1 ProteomicsDB 1 RefSeq 2

Sequence Information:

  • Length: 162
  • Mass: 17790
  • Checksum: 657C8A42AC76E47C
  • Sequence:
    • MKIPLTATIC LPGSSPPGLC IFAKVSDVKR LEMDDIADRM RMDAGEVTLV NHNSVFKTHL 
LPQTGFPEDQ LSLSDQQILS SRQGHLDRSF TCSTRSAAYN PSYYSGPGLG VLARYSWGKM 
LTFGGHHGVT LMQIRHMAVA GFSSFINFQI ILPQTVFLAQ AI