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Protein

Sentrin-specific protease 8

Gene

SENP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53.5 Publications

Kineticsi

KM for Ub-AMC exceeds 5 µM.
  1. KM=51 nM for Nedd8-AMC1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei1021
    Active sitei1191
    Active sitei163Nucleophile1

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase, Protease, Thiol protease
    Biological processUbl conjugation pathway

    Enzyme and pathway databases

    ReactomeiR-HSA-5689603 UCH proteinases
    R-HSA-8951664 Neddylation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sentrin-specific protease 8 (EC:3.4.22.-)
    Alternative name(s):
    Deneddylase-1
    NEDD8-specific protease 1
    Protease, cysteine 2
    Sentrin/SUMO-specific protease SENP8
    Gene namesi
    Name:SENP8
    Synonyms:DEN1, NEDP1, PRSC2
    ORF Names:FKSG8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000166192.14
    HGNCiHGNC:22992 SENP8
    MIMi608659 gene
    neXtProtiNX_Q96LD8

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi10D → A: No effect on activity. 1 Publication1
    Mutagenesisi26W → A: Strongly reduces activity. 1 Publication1
    Mutagenesisi29D → A or N: Abolishes activity. 1 Publication1
    Mutagenesisi58V → A: No effect on activity. 1 Publication1
    Mutagenesisi74F → A: No effect on activity. 1 Publication1
    Mutagenesisi77P → A: No effect on activity. 1 Publication1
    Mutagenesisi91N → A: Abolishes activity. 1 Publication1
    Mutagenesisi102H → N: Abolishes activity. 1 Publication1
    Mutagenesisi103W → A or H: Strongly reduces activity. 1 Publication1
    Mutagenesisi119D → A or N: Abolishes activity. 1 Publication1
    Mutagenesisi157Q → A: No effect on activity. 1 Publication1
    Mutagenesisi163C → A: Abolishes activity. 3 Publications1

    Organism-specific databases

    DisGeNETi123228
    OpenTargetsiENSG00000166192
    PharmGKBiPA134866772

    Chemistry databases

    ChEMBLiCHEMBL1741207
    GuidetoPHARMACOLOGYi2417

    Polymorphism and mutation databases

    BioMutaiSENP8
    DMDMi26006881

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001017271 – 212Sentrin-specific protease 8Add BLAST212

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ96LD8
    MaxQBiQ96LD8
    PaxDbiQ96LD8
    PeptideAtlasiQ96LD8
    PRIDEiQ96LD8
    ProteomicsDBi77207

    PTM databases

    iPTMnetiQ96LD8
    PhosphoSitePlusiQ96LD8

    Expressioni

    Tissue specificityi

    Broadly expressed, with highest levels in kidney and pancreas.1 Publication

    Gene expression databases

    BgeeiENSG00000166192 Expressed in 137 organ(s), highest expression level in sperm
    CleanExiHS_SENP8
    ExpressionAtlasiQ96LD8 baseline and differential
    GenevisibleiQ96LD8 HS

    Organism-specific databases

    HPAiHPA036273

    Interactioni

    Protein-protein interaction databases

    BioGridi125819, 17 interactors
    IntActiQ96LD8, 3 interactors
    MINTiQ96LD8
    STRINGi9606.ENSP00000340505

    Chemistry databases

    BindingDBiQ96LD8

    Structurei

    Secondary structure

    1212
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliQ96LD8
    SMRiQ96LD8
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96LD8

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni11 – 174ProteaseAdd BLAST164

    Sequence similaritiesi

    Belongs to the peptidase C48 family.Curated

    Phylogenomic databases

    eggNOGiKOG3246 Eukaryota
    ENOG4111G37 LUCA
    GeneTreeiENSGT00390000014038
    HOGENOMiHOG000005740
    HOVERGENiHBG054214
    InParanoidiQ96LD8
    KOiK08597
    OMAiPPNWLND
    OrthoDBiEOG091G0UXY
    PhylomeDBiQ96LD8
    TreeFamiTF351057

    Family and domain databases

    InterProiView protein in InterPro
    IPR038765 Papain_like_cys_pep_sf
    IPR003653 Peptidase_C48_C
    PfamiView protein in Pfam
    PF02902 Peptidase_C48, 1 hit
    SUPFAMiSSF54001 SSF54001, 1 hit
    PROSITEiView protein in PROSITE
    PS50600 ULP_PROTEASE, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

    Q96LD8-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MDPVVLSYMD SLLRQSDVSL LDPPSWLNDH IIGFAFEYFA NSQFHDCSDH
    60 70 80 90 100
    VSFISPEVTQ FIKCTSNPAE IAMFLEPLDL PNKRVVFLAI NDNSNQAAGG
    110 120 130 140 150
    THWSLLVYLQ DKNSFFHYDS HSRSNSVHAK QVAEKLEAFL GRKGDKLAFV
    160 170 180 190 200
    EEKAPAQQNS YDCGMYVICN TEALCQNFFR QQTESLLQLL TPAYITKKRG
    210
    EWKDLITTLA KK
    Length:212
    Mass (Da):24,107
    Last modified:December 1, 2001 - v1
    Checksum:i680D93B85EF6028C
    GO

    Computationally mapped potential isoform sequencesi

    There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H3BTK5H3BTK5_HUMAN
    Sentrin-specific protease 8
    SENP8
    130Annotation score:
    H3BS71H3BS71_HUMAN
    Sentrin-specific protease 8
    SENP8
    73Annotation score:
    H3BTJ8H3BTJ8_HUMAN
    Sentrin-specific protease 8
    SENP8
    37Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti14R → W in AAL06294 (Ref. 3) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_023705207T → A2 PublicationsCorresponds to variant dbSNP:rs930871Ensembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY008293 mRNA Translation: AAG21828.1
    AF308450 mRNA Translation: AAL06294.1
    BC031411 mRNA Translation: AAH31411.1
    CCDSiCCDS10240.1
    RefSeqiNP_001159812.1, NM_001166340.1
    NP_001165580.1, NM_001172109.1
    NP_001165581.1, NM_001172110.1
    NP_001165582.1, NM_001172111.1
    NP_660205.3, NM_145204.3
    XP_005254214.1, XM_005254157.3
    XP_011519519.1, XM_011521217.2
    UniGeneiHs.513002

    Genome annotation databases

    EnsembliENST00000340912; ENSP00000340505; ENSG00000166192
    ENST00000542035; ENSP00000446057; ENSG00000166192
    GeneIDi123228
    KEGGihsa:123228
    UCSCiuc002atp.4 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY008293 mRNA Translation: AAG21828.1
    AF308450 mRNA Translation: AAL06294.1
    BC031411 mRNA Translation: AAH31411.1
    CCDSiCCDS10240.1
    RefSeqiNP_001159812.1, NM_001166340.1
    NP_001165580.1, NM_001172109.1
    NP_001165581.1, NM_001172110.1
    NP_001165582.1, NM_001172111.1
    NP_660205.3, NM_145204.3
    XP_005254214.1, XM_005254157.3
    XP_011519519.1, XM_011521217.2
    UniGeneiHs.513002

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1XT9X-ray2.20A1-212[»]
    2BKQX-ray2.00A/B/C/D1-212[»]
    2BKRX-ray1.90A1-212[»]
    ProteinModelPortaliQ96LD8
    SMRiQ96LD8
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi125819, 17 interactors
    IntActiQ96LD8, 3 interactors
    MINTiQ96LD8
    STRINGi9606.ENSP00000340505

    Chemistry databases

    BindingDBiQ96LD8
    ChEMBLiCHEMBL1741207
    GuidetoPHARMACOLOGYi2417

    PTM databases

    iPTMnetiQ96LD8
    PhosphoSitePlusiQ96LD8

    Polymorphism and mutation databases

    BioMutaiSENP8
    DMDMi26006881

    Proteomic databases

    EPDiQ96LD8
    MaxQBiQ96LD8
    PaxDbiQ96LD8
    PeptideAtlasiQ96LD8
    PRIDEiQ96LD8
    ProteomicsDBi77207

    Protocols and materials databases

    DNASUi123228
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000340912; ENSP00000340505; ENSG00000166192
    ENST00000542035; ENSP00000446057; ENSG00000166192
    GeneIDi123228
    KEGGihsa:123228
    UCSCiuc002atp.4 human

    Organism-specific databases

    CTDi123228
    DisGeNETi123228
    EuPathDBiHostDB:ENSG00000166192.14
    GeneCardsiSENP8
    HGNCiHGNC:22992 SENP8
    HPAiHPA036273
    MIMi608659 gene
    neXtProtiNX_Q96LD8
    OpenTargetsiENSG00000166192
    PharmGKBiPA134866772
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3246 Eukaryota
    ENOG4111G37 LUCA
    GeneTreeiENSGT00390000014038
    HOGENOMiHOG000005740
    HOVERGENiHBG054214
    InParanoidiQ96LD8
    KOiK08597
    OMAiPPNWLND
    OrthoDBiEOG091G0UXY
    PhylomeDBiQ96LD8
    TreeFamiTF351057

    Enzyme and pathway databases

    ReactomeiR-HSA-5689603 UCH proteinases
    R-HSA-8951664 Neddylation

    Miscellaneous databases

    EvolutionaryTraceiQ96LD8
    GeneWikiiSENP8
    GenomeRNAii123228
    PROiPR:Q96LD8
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000166192 Expressed in 137 organ(s), highest expression level in sperm
    CleanExiHS_SENP8
    ExpressionAtlasiQ96LD8 baseline and differential
    GenevisibleiQ96LD8 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR038765 Papain_like_cys_pep_sf
    IPR003653 Peptidase_C48_C
    PfamiView protein in Pfam
    PF02902 Peptidase_C48, 1 hit
    SUPFAMiSSF54001 SSF54001, 1 hit
    PROSITEiView protein in PROSITE
    PS50600 ULP_PROTEASE, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSENP8_HUMAN
    AccessioniPrimary (citable) accession number: Q96LD8
    Secondary accession number(s): Q96QA4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2002
    Last sequence update: December 1, 2001
    Last modified: November 7, 2018
    This is version 146 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
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