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    SENP8 SUMO peptidase family member, NEDD8 specific [ Homo sapiens (human) ]

    Gene ID: 123228, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SENP8provided by HGNC
    Official Full Name
    SUMO peptidase family member, NEDD8 specificprovided by HGNC
    Primary source
    HGNC:HGNC:22992
    See related
    Ensembl:ENSG00000166192 MIM:608659; AllianceGenome:HGNC:22992
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DEN1; NEDP1; PRSC2
    Summary
    This gene encodes a cysteine protease that is a member of the sentrin-specific protease family. The encoded protein is involved in processing and deconjugation of the ubiquitin-like protein termed, neural precursor cell expressed developmentally downregulated 8. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]
    Expression
    Broad expression in testis (RPKM 2.2), thyroid (RPKM 1.6) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SENP8 in Genome Data Viewer
    Location:
    15q23
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (72114258..72143692)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (69930994..69960429)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (72406599..72436033)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene myosin IXA Neighboring gene eukaryotic translation initiation factor 5A2 pseudogene 1 Neighboring gene RNA, U2 small nuclear 65, pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:72394409-72394919 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9710 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6616 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9711 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9712 Neighboring gene ribosomal protein L21 pseudogene 115 Neighboring gene uncharacterized LOC124903522 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9713 Neighboring gene Sharpr-MPRA regulatory region 4122 Neighboring gene GRAM domain containing 2A Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr15:72485963-72486586 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9714 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6617 Neighboring gene Sharpr-MPRA regulatory region 1213 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9715 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6618 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6619 Neighboring gene pyruvate kinase M1/2

    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. DeSUMOylating enzymes--SENPs. Drag M, et al. IUBMB Life, 2008 Nov. PMID 18666185
    2. The molecular determinants of NEDD8 specific recognition by human SENP8. Shin YC, et al. PLoS One, 2011. PMID 22110750, Free PMC Article
    3. Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1. Reverter D, et al. J Mol Biol, 2005 Jan 7. PMID 15567417
    4. Structural basis of NEDD8 ubiquitin discrimination by the deNEDDylating enzyme NEDP1. Shen LN, et al. EMBO J, 2005 Apr 6. PMID 15775960, Free PMC Article
    5. A time-resolved fluorescence resonance energy transfer-based assay for DEN1 peptidase activity. Engels IH, et al. Anal Biochem, 2009 Jul 1. PMID 19328766

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity.
      Title: The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity.
    2. Impairment of NEDDylation by Ubc12 knockout enhances PCNA ubiquitination and promotes PCNA-poleta interaction, while up-regulation of NEDDylation by NEDD8 overexpression or NEDP1 deletion reduces the excessive accumulation of ubiquitinated PCNA. Moreover, Ubc12 knockout decreases cell sensitivity to H2O2-induced oxidative stress, but NEDP1 deletion aggravates this sensitivity
      Title: NEDDylation antagonizes ubiquitination of proliferating cell nuclear antigen and regulates the recruitment of polymerase η in response to oxidative DNA damage.
    3. Furthermore, the authors characterized SENP8/DEN1 as the protease that counteracts Ubc12 auto-neddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components in SENP8-deficient cells.
      Title: SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function.
    4. In endothelial dysfunction, HDAC2 levels were reciprocally regulated by ectopic expression of NEDD8 and the de-NEDDylating enzyme SENP8.
      Title: NEDDylation promotes endothelial dysfunction: a role for HDAC2.
    5. the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype.
      Title: PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.
    6. Data indicate that overexpression of SENP8, a NEDD8-specific cysteine protease, resulted in deNEDDylation of E2F1 and promoted its transactivation activity at the p73 gene.
      Title: NEDDylation controls the target specificity of E2F1 and apoptosis induction.
    7. We analyzed whether CSN1 alone can increase DEN1 degradation in HeLa cells.these data suggest that the COP9 signalosome supports proteasome-dependent protein degradation of DEN1/DenA in fungi and in human cells.
      Title: Control of multicellular development by the physically interacting deneddylases DEN1/DenA and COP9 signalosome.
    8. A role for SENP8 as a central regulator of the inflammatory process is identified using knockdown and overexpression approaches.
      Title: Central role for endothelial human deneddylase-1/SENP8 in fine-tuning the vascular inflammatory response.
    9. the specificity of NEDD8-specific peptidase SENP8
      Title: The molecular determinants of NEDD8 specific recognition by human SENP8.
    10. Data show that the stability of MDM2 is regulated by NEDD8 pathway and identify NEDP1 that deneddylates MDM2, resulting in MDM2 destabilization concomitant with p53 activation.
      Title: Chemotherapy induces NEDP1-mediated destabilization of MDM2.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cysteine-type peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables deNEDDylase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables deNEDDylase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in post-translational protein modification TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein deneddylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein deubiquitination TAS
    Traceable Author Statement
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    sentrin-specific protease 8
    Names
    NEDD8 specific-protease cysteine 2
    NEDD8-specific protease 1
    SUMO sentrin specific protease family member 8
    SUMO/sentrin peptidase family member, NEDD8 specific
    SUMO/sentrin specific peptidase family member 8
    deneddylase 1
    protease, cysteine 2
    NP_001159812.1
    NP_001165580.1
    NP_001165581.1
    NP_001165582.1
    NP_660205.3
    XP_005254214.1
    XP_011519519.1
    XP_054233238.1
    XP_054233239.1

    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_001166340.2 → NP_001159812.1  sentrin-specific protease 8

      See identical proteins and their annotated locations for NP_001159812.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) and variants 2, 3, 4, and 5 encode the same protein.
      Source sequence(s)
      AC020779, AK097557
      Consensus CDS
      CCDS10240.1
      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Related
      ENSP00000446057.2, ENST00000542035.2
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    2. NM_001172109.1 → NP_001165580.1  sentrin-specific protease 8

      See identical proteins and their annotated locations for NP_001165580.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4 and 5 encode the same protein. An in-frame AUG is located 44 codons upstream of the annotated translation start site but is not being annotated as a start site since it is not conserved and is in a weak Kozak sequence context.
      Source sequence(s)
      AC020779, AY008293, DB048641
      Consensus CDS
      CCDS10240.1
      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    3. NM_001172110.1 → NP_001165581.1  sentrin-specific protease 8

      See identical proteins and their annotated locations for NP_001165581.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4 and 5 encode the same protein. An in-frame AUG is located 44 codons upstream of the annotated translation start site but is not being annotated as a start site since it is not conserved and is in a weak Kozak sequence context.
      Source sequence(s)
      AC020779, AY008293, BP370384
      Consensus CDS
      CCDS10240.1
      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    4. NM_001172111.2 → NP_001165582.1  sentrin-specific protease 8

      See identical proteins and their annotated locations for NP_001165582.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4 and 5 encode the same protein. An in-frame AUG is located 44 codons upstream of the annotated translation start site but is not being annotated as a start site since it is not conserved and is in a weak Kozak sequence context.
      Source sequence(s)
      AC020779, AY008293, CN367895
      Consensus CDS
      CCDS10240.1
      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    5. NM_145204.4 → NP_660205.3  sentrin-specific protease 8

      See identical proteins and their annotated locations for NP_660205.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, 4 and 5 encode the same protein.
      Source sequence(s)
      AC020779, AK292298, AY008293
      Consensus CDS
      CCDS10240.1
      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Related
      ENSP00000340505.4, ENST00000340912.6
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      72114258..72143692
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005254157.4 → XP_005254214.1  sentrin-specific protease 8 isoform X1

      See identical proteins and their annotated locations for XP_005254214.1

      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    2. XM_011521217.3 → XP_011519519.1  sentrin-specific protease 8 isoform X1

      See identical proteins and their annotated locations for XP_011519519.1

      UniProtKB/Swiss-Prot
      Q96LD8, Q96QA4
      UniProtKB/TrEMBL
      A8K8D3
      Conserved Domains (1) summary
      cl23802
      Location:26 → 174
      Peptidase_C48; Ulp1 protease family, C-terminal catalytic domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      69930994..69960429
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377263.1 → XP_054233238.1  sentrin-specific protease 8 isoform X1

    2. XM_054377264.1 → XP_054233239.1  sentrin-specific protease 8 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96LD8.1 GenPept UniProtKB/Swiss-Prot:Q96LD8

    Gene LinkOut

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

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