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Protein

Sentrin-specific protease 8

Gene

SENP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Catalytic activityi

Hydrolysis of the alpha-linked peptide bond in the sequence Gly-Gly-|-Ala-Thr-Tyr at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to the mature form of the protein. A second reaction involves the cleavage of an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein.

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

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Ubl conjugation pathway

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000166192-MONOMER.
    ReactomeiR-HSA-5689603. UCH proteinases.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sentrin-specific protease 8 (EC:3.4.22.68)
    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

    HGNCiHGNC:22992. SENP8.

    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.

    PTM databases

    iPTMnetiQ96LD8.
    PhosphoSitePlusiQ96LD8.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiENSG00000166192.
    CleanExiHS_SENP8.
    ExpressionAtlasiQ96LD8. baseline and differential.
    GenevisibleiQ96LD8. HS.

    Organism-specific databases

    HPAiHPA036273.

    Interactioni

    Protein-protein interaction databases

    BioGridi125819. 15 interactors.
    IntActiQ96LD8. 2 interactors.
    MINTiMINT-3055530.
    STRINGi9606.ENSP00000340505.

    Chemistry databases

    BindingDBiQ96LD8.

    Structurei

    Secondary structure

    1212
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi4 – 8Combined sources5
    Beta strandi11 – 14Combined sources4
    Helixi15 – 19Combined sources5
    Helixi29 – 41Combined sources13
    Turni42 – 44Combined sources3
    Helixi45 – 47Combined sources3
    Turni48 – 50Combined sources3
    Beta strandi51 – 54Combined sources4
    Helixi56 – 64Combined sources9
    Helixi68 – 75Combined sources8
    Helixi76 – 78Combined sources3
    Helixi80 – 82Combined sources3
    Beta strandi84 – 91Combined sources8
    Beta strandi95 – 99Combined sources5
    Beta strandi103 – 109Combined sources7
    Helixi110 – 112Combined sources3
    Beta strandi114 – 118Combined sources5
    Turni122 – 125Combined sources4
    Helixi126 – 140Combined sources15
    Beta strandi149 – 151Combined sources3
    Beta strandi158 – 161Combined sources4
    Helixi163 – 179Combined sources17
    Helixi186 – 189Combined sources4
    Helixi192 – 210Combined sources19

    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...

    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.
    OMAiFFHYDSH.
    OrthoDBiEOG091G0UXY.
    PhylomeDBiQ96LD8.
    TreeFamiTF351057.

    Family and domain databases

    InterProiIPR003653. Peptidase_C48_C.
    [Graphical view]
    PfamiPF02902. Peptidase_C48. 1 hit.
    [Graphical view]
    PROSITEiPS50600. ULP_PROTEASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    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

    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 → A.2 PublicationsCorresponds to variant rs930871dbSNPEnsembl.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

    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. 15 interactors.
    IntActiQ96LD8. 2 interactors.
    MINTiMINT-3055530.
    STRINGi9606.ENSP00000340505.

    Chemistry databases

    BindingDBiQ96LD8.
    ChEMBLiCHEMBL1741207.
    GuidetoPHARMACOLOGYi2417.

    PTM databases

    iPTMnetiQ96LD8.
    PhosphoSitePlusiQ96LD8.

    Polymorphism and mutation databases

    BioMutaiSENP8.
    DMDMi26006881.

    Proteomic databases

    EPDiQ96LD8.
    MaxQBiQ96LD8.
    PaxDbiQ96LD8.
    PeptideAtlasiQ96LD8.
    PRIDEiQ96LD8.

    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.
    GeneCardsiSENP8.
    HGNCiHGNC:22992. SENP8.
    HPAiHPA036273.
    MIMi608659. gene.
    neXtProtiNX_Q96LD8.
    OpenTargetsiENSG00000166192.
    PharmGKBiPA134866772.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000166192-MONOMER.
    ReactomeiR-HSA-5689603. UCH proteinases.

    Miscellaneous databases

    EvolutionaryTraceiQ96LD8.
    GeneWikiiSENP8.
    GenomeRNAii123228.
    PROiQ96LD8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000166192.
    CleanExiHS_SENP8.
    ExpressionAtlasiQ96LD8. baseline and differential.
    GenevisibleiQ96LD8. HS.

    Family and domain databases

    InterProiIPR003653. Peptidase_C48_C.
    [Graphical view]
    PfamiPF02902. Peptidase_C48. 1 hit.
    [Graphical view]
    PROSITEiPS50600. ULP_PROTEASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSENP8_HUMAN
    AccessioniPrimary (citable) accession number: Q96LD8
    Secondary accession number(s): Q96QA4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 28, 2002
    Last sequence update: December 1, 2001
    Last modified: November 2, 2016
    This is version 133 of the entry and version 1 of the sequence. [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. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.