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    SENP6 SUMO specific peptidase 6 [ Homo sapiens (human) ]

    Gene ID: 26054, updated on 5-Mar-2024

    Summary

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    Official Symbol
    SENP6provided by HGNC
    Official Full Name
    SUMO specific peptidase 6provided by HGNC
    Primary source
    HGNC:HGNC:20944
    See related
    Ensembl:ENSG00000112701 MIM:605003; AllianceGenome:HGNC:20944
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SSP1; SUSP1
    Summary
    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]
    Expression
    Ubiquitous expression in thyroid (RPKM 14.2), testis (RPKM 12.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    6q14.1
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (75601880..75718281)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (76778738..76895148)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (76311596..76427997)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:76311385-76311934 Neighboring gene RNA, U6 small nuclear 1338, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17341 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24759 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:76313673-76314202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:76316827-76317327 Neighboring gene LSM14A, SCD6 homolog A (S. cerevisiae) pseudogene Neighboring gene H3 histone pseudogene 27 Neighboring gene RNA, U6 small nuclear 1016, pseudogene Neighboring gene RN7SK pseudogene 163 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:76397423-76397924 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:76397925-76398424 Neighboring gene oocyte-secreted protein 4B-like Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24760 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24761 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17342 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:76466141-76466640 Neighboring gene RNA, U6 small nuclear 155, pseudogene Neighboring gene myosin VI

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Single Cell RNA-Seq Identifies Immune-Related Prognostic Model and Key Signature-SPP1 in Pancreatic Ductal Adenocarcinoma. Chen K, et al. Genes (Basel), 2022 Sep 29. PMID 36292645, Free PMC Article
    2. Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin. Mitra S, et al. Nat Commun, 2020 Jan 24. PMID 31980633, Free PMC Article
    3. The SUMO Isopeptidase SENP6 Functions as a Rheostat of Chromatin Residency in Genome Maintenance and Chromosome Dynamics. Wagner K, et al. Cell Rep, 2019 Oct 8. PMID 31597105
    4. The poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation. Liebelt F, et al. Nat Commun, 2019 Sep 4. PMID 31485003, Free PMC Article
    5. SENP6-mediated M18BP1 deSUMOylation regulates CENP-A centromeric localization. Fu H, et al. Cell Res, 2019 Mar. PMID 30631152, Free PMC Article

    See all (57) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy].
      Title: [Interaction of SENP6 with PINK1 Promotes Temozolomide Resistance in Neuroglioma Cells via Inducing the Mitophagy].
    2. SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis.
      Title: SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis.
    3. Single Cell RNA-Seq Identifies Immune-Related Prognostic Model and Key Signature-SPP1 in Pancreatic Ductal Adenocarcinoma.
      Title: Single Cell RNA-Seq Identifies Immune-Related Prognostic Model and Key Signature-SPP1 in Pancreatic Ductal Adenocarcinoma.
    4. Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma.
      Title: Genetic alterations of the SUMO isopeptidase SENP6 drive lymphomagenesis and genetic instability in diffuse large B-cell lymphoma.
    5. The SUMO Isopeptidase SENP6 Functions as a Rheostat of Chromatin Residency in Genome Maintenance and Chromosome Dynamics.
      Title: The SUMO Isopeptidase SENP6 Functions as a Rheostat of Chromatin Residency in Genome Maintenance and Chromosome Dynamics.
    6. SENP6 and FEM1C gene expression in liver transplantation predicts transplantation tolerance.
      Title: Tolerance Biomarkers in Liver Transplantation: Independent External Validation of the Predictive Strength of SENP6 and FEM1C Gene Expression.
    7. The authors conclude that SENP6, a factor important for CENP-A maintenance and assembly, functions in protecting a portion of M18BP1 from PIAS4-mediated SUMOylation and subsequent SUMOylation-dependent ubiquitination and degradation.
      Title: SENP6-mediated M18BP1 deSUMOylation regulates CENP-A centromeric localization.
    8. SENP6 activity is required throughout the cell cycle, suggesting that a dynamic SUMO cycle underlies a continuous surveillance of the centromere complex.
      Title: Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin.
    9. SUMO specific peptidase 6 (SENP6) deficient cells are severely compromised for proliferation, accumulate in G2/M and frequently form micronuclei.
      Title: The poly-SUMO2/3 protease SENP6 enables assembly of the constitutive centromere-associated network by group deSUMOylation.
    10. LANA could bind to the promoter region of the SENP6 gene and inhibit SENP6 expression while the regulated SENP6 could in turn modulate the abundance of LANA through desumoylation.
      Title: The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Inhibits Expression of SUMO/Sentrin-Specific Peptidase 6 To Facilitate Establishment of Latency.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ11355, FLJ11887, KIAA0389, KIAA0797

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SUMO-specific endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables SUMO-specific endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in protein desumoylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein desumoylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein modification by small protein removal IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein sumoylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of kinetochore assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of kinetochore assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of spindle assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of spindle assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    sentrin-specific protease 6
    Names
    2810017C20Rik
    SUMO-1-specific protease 1
    SUMO1/sentrin specific peptidase 6
    SUMO1/sentrin specific protease 6
    sentrin/SUMO-specific protease SENP6
    NP_001093879.1
    NP_001291721.1
    NP_056386.2

    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)

    1. NM_001100409.3 → NP_001093879.1  sentrin-specific protease 6 isoform 2

      See identical proteins and their annotated locations for NP_001093879.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AF307849, AK021417, AL109897, AL356057, BC028583, CR990444
      Consensus CDS
      CCDS43483.1
      UniProtKB/TrEMBL
      B3KX86
      Related
      ENSP00000359027.2, ENST00000370010.6
      Conserved Domains (2) summary
      COG5160
      Location:656 → 767
      ULP1; Protease, Ulp1 family [Posttranslational modification, protein turnover, chaperones]
      cl23802
      Location:966 → 1042
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    2. NM_001304792.2 → NP_001291721.1  sentrin-specific protease 6 isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) lacks an exon in the 5' coding region and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 3 which has a shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AA768785, AF306508, AK096455, AL356057, AL589656
      Consensus CDS
      CCDS78158.1
      UniProtKB/TrEMBL
      F8W6D9, H0Y4F4
      Related
      ENSP00000321820.8, ENST00000327284.12
      Conserved Domains (1) summary
      COG5160
      Location:656 → 685
      ULP1; Protease, Ulp1 family [Posttranslational modification, protein turnover, chaperones]

    3. NM_015571.4 → NP_056386.2  sentrin-specific protease 6 isoform 1

      See identical proteins and their annotated locations for NP_056386.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AF307849, AK021417, AL109897, AL356057, CR990444
      Consensus CDS
      CCDS47454.1
      UniProtKB/Swiss-Prot
      A6NNY9, O94891, Q5VUL3, Q5VUL4, Q8TBY4, Q9GZR1, Q9UJV5
      UniProtKB/TrEMBL
      B3KX86
      Related
      ENSP00000402527.2, ENST00000447266.7
      Conserved Domains (1) summary
      cl23802
      Location:680 → 825
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      75601880..75718281
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      76778738..76895148
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9GZR1.2 GenPept UniProtKB/Swiss-Prot:Q9GZR1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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