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

Gene ID: 123228, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (72114258..72143692)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (69930994..69960429)
105.20220307 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. The molecular determinants of NEDD8 specific recognition by human SENP8. Shin YC, et al. PLoS One, 2011. PMID 22110750, Free PMC Article
  2. DeSUMOylating enzymes--SENPs. Drag M, et al. IUBMB Life, 2008 Nov. PMID 18666185
  3. Genome-wide CRISPR screens reveal genetic mediators of cereblon modulator toxicity in primary effusion lymphoma. Patil A, et al. Blood Adv, 2019 Jul 23. PMID 31300418, Free PMC Article
  4. Central role for endothelial human deneddylase-1/SENP8 in fine-tuning the vascular inflammatory response. Ehrentraut SF, et al. J Immunol, 2013 Jan 1. PMID 23209320, 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)

Genotypes

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 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_2023_10

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

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