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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 5uM.

  1. KM=51 nM for Nedd8-AMC1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei102 – 1021
    Active sitei119 – 1191
    Active sitei163 – 1631Nucleophile

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Ubl conjugation pathway

    Protein family/group databases

    MEROPSiC48.011.

    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
    ProteomesiUP000005640 Componenti: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:22992. SENP8.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi10 – 101D → A: No effect on activity. 1 Publication
    Mutagenesisi26 – 261W → A: Strongly reduces activity. 1 Publication
    Mutagenesisi29 – 291D → A or N: Abolishes activity. 1 Publication
    Mutagenesisi58 – 581V → A: No effect on activity. 1 Publication
    Mutagenesisi74 – 741F → A: No effect on activity. 1 Publication
    Mutagenesisi77 – 771P → A: No effect on activity. 1 Publication
    Mutagenesisi91 – 911N → A: Abolishes activity. 1 Publication
    Mutagenesisi102 – 1021H → N: Abolishes activity. 1 Publication
    Mutagenesisi103 – 1031W → A or H: Strongly reduces activity. 1 Publication
    Mutagenesisi119 – 1191D → A or N: Abolishes activity. 1 Publication
    Mutagenesisi157 – 1571Q → A: No effect on activity. 1 Publication
    Mutagenesisi163 – 1631C → A: Abolishes activity. 3 Publications

    Organism-specific databases

    PharmGKBiPA134866772.

    Polymorphism and mutation databases

    BioMutaiSENP8.
    DMDMi26006881.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 212212Sentrin-specific protease 8PRO_0000101727Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine2 Publications

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ96LD8.
    PaxDbiQ96LD8.
    PRIDEiQ96LD8.

    PTM databases

    PhosphoSiteiQ96LD8.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiQ96LD8.
    CleanExiHS_SENP8.
    ExpressionAtlasiQ96LD8. baseline and differential.
    GenevisibleiQ96LD8. HS.

    Organism-specific databases

    HPAiHPA036273.

    Interactioni

    Protein-protein interaction databases

    BioGridi125819. 13 interactions.
    IntActiQ96LD8. 2 interactions.
    MINTiMINT-3055530.
    STRINGi9606.ENSP00000340505.

    Structurei

    Secondary structure

    1
    212
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi4 – 85Combined sources
    Beta strandi11 – 144Combined sources
    Helixi15 – 195Combined sources
    Helixi29 – 4113Combined sources
    Turni42 – 443Combined sources
    Helixi45 – 473Combined sources
    Turni48 – 503Combined sources
    Beta strandi51 – 544Combined sources
    Helixi56 – 649Combined sources
    Helixi68 – 758Combined sources
    Helixi76 – 783Combined sources
    Helixi80 – 823Combined sources
    Beta strandi84 – 918Combined sources
    Beta strandi95 – 995Combined sources
    Beta strandi103 – 1097Combined sources
    Helixi110 – 1123Combined sources
    Beta strandi114 – 1185Combined sources
    Turni122 – 1254Combined sources
    Helixi126 – 14015Combined sources
    Beta strandi149 – 1513Combined sources
    Beta strandi158 – 1614Combined sources
    Helixi163 – 17917Combined sources
    Helixi186 – 1894Combined sources
    Helixi192 – 21019Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1XT9X-ray2.20A1-212[»]
    2BKQX-ray2.00A/B/C/D1-212[»]
    2BKRX-ray1.90A1-212[»]
    ProteinModelPortaliQ96LD8.
    SMRiQ96LD8. Positions 1-211.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ96LD8.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni11 – 174164ProteaseAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C48 family.Curated

    Phylogenomic databases

    eggNOGiNOG251510.
    GeneTreeiENSGT00390000014038.
    HOGENOMiHOG000005740.
    HOVERGENiHBG054214.
    InParanoidiQ96LD8.
    KOiK08597.
    OMAiSWLNDHI.
    OrthoDBiEOG747PM3.
    PhylomeDBiQ96LD8.
    TreeFamiTF351057.

    Family and domain databases

    InterProiIPR003653. Peptidase_C48.
    [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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti14 – 141R → W in AAL06294 (Ref. 3) Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti207 – 2071T → A.2 Publications
    Corresponds to variant rs930871 [ dbSNP | Ensembl ].
    VAR_023705

    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_005254157.2.
    UniGeneiHs.513002.

    Genome annotation databases

    EnsembliENST00000340912; ENSP00000340505; ENSG00000166192.
    ENST00000542035; ENSP00000446057; ENSG00000166192.
    GeneIDi123228.
    KEGGihsa:123228.
    UCSCiuc002atp.3. 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_005254157.2.
    UniGeneiHs.513002.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1XT9X-ray2.20A1-212[»]
    2BKQX-ray2.00A/B/C/D1-212[»]
    2BKRX-ray1.90A1-212[»]
    ProteinModelPortaliQ96LD8.
    SMRiQ96LD8. Positions 1-211.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi125819. 13 interactions.
    IntActiQ96LD8. 2 interactions.
    MINTiMINT-3055530.
    STRINGi9606.ENSP00000340505.

    Chemistry

    BindingDBiQ96LD8.
    ChEMBLiCHEMBL1741207.
    GuidetoPHARMACOLOGYi2417.

    Protein family/group databases

    MEROPSiC48.011.

    PTM databases

    PhosphoSiteiQ96LD8.

    Polymorphism and mutation databases

    BioMutaiSENP8.
    DMDMi26006881.

    Proteomic databases

    MaxQBiQ96LD8.
    PaxDbiQ96LD8.
    PRIDEiQ96LD8.

    Protocols and materials databases

    DNASUi123228.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000340912; ENSP00000340505; ENSG00000166192.
    ENST00000542035; ENSP00000446057; ENSG00000166192.
    GeneIDi123228.
    KEGGihsa:123228.
    UCSCiuc002atp.3. human.

    Organism-specific databases

    CTDi123228.
    GeneCardsiGC15P072410.
    HGNCiHGNC:22992. SENP8.
    HPAiHPA036273.
    MIMi608659. gene.
    neXtProtiNX_Q96LD8.
    PharmGKBiPA134866772.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG251510.
    GeneTreeiENSGT00390000014038.
    HOGENOMiHOG000005740.
    HOVERGENiHBG054214.
    InParanoidiQ96LD8.
    KOiK08597.
    OMAiSWLNDHI.
    OrthoDBiEOG747PM3.
    PhylomeDBiQ96LD8.
    TreeFamiTF351057.

    Miscellaneous databases

    EvolutionaryTraceiQ96LD8.
    GeneWikiiSENP8.
    GenomeRNAii123228.
    NextBioi81089.
    PROiQ96LD8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ96LD8.
    CleanExiHS_SENP8.
    ExpressionAtlasiQ96LD8. baseline and differential.
    GenevisibleiQ96LD8. HS.

    Family and domain databases

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

    Publicationsi

    « Hide 'large scale' publications
    1. "NEDP1, a highly conserved cysteine protease that deneddylates cullins."
      Mendoza H.M., Shen L.-N., Botting C., Lewis A., Chen J., Ink B., Hay R.T.
      J. Biol. Chem. 278:25637-25643(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-207, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-163, FUNCTION.
      Tissue: Kidney.
    2. "Identification of SENP8, a novel member of the sentrin-specific protease family."
      Gong L., Yeh E.T.H.
      Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    3. "Identification of FKSG8, a novel gene encoding a protein with cysteine protease activity."
      Wang Y.-G.
      Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-207.
      Tissue: Brain.
    5. "DEN1 is a dual function protease capable of processing the C-terminus of Nedd8 and deconjugating hyper-neddylated CUL1."
      Wu K., Yamoah K., Dolios G., Gan-Erdene T., Tan P., Chen A., Lee C.-G., Wei N., Wilkinson K.D., Wang R., Pan Z.-Q.
      J. Biol. Chem. 278:28882-28891(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 181-197, INTERACTION WITH NEDD8, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION.
    6. "Identification and characterization of DEN1, a deneddylase of the ULP family."
      Gan-Erdene T., Nagamalleswari K., Yin L., Wu K., Pan Z.-Q., Wilkinson K.D.
      J. Biol. Chem. 278:28892-28900(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    7. "Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity."
      Xirodimas D.P., Saville M.K., Bourdon J.-C., Hay R.T., Lane D.P.
      Cell 118:83-97(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF CYS-163.
    8. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Structural basis of NEDD8 ubiquitin discrimination by the deneddylating enzyme NEDP1."
      Shen L.-N., Liu H., Dong C., Xirodimas D.P., Naismith J.H., Hay R.T.
      EMBO J. 24:1341-1351(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NEDD8, MUTAGENESIS OF ASP-10; TRP-26; ASP-29; VAL-58; PHE-74; PRO-77; ASN-91; HIS-102; TRP-103; ASP-119; GLN-157 AND CYS-163, FUNCTION.
    11. "Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1."
      Reverter D., Wu K., Erdene T.G., Pan Z.-Q., Wilkinson K.D., Lima C.D.
      J. Mol. Biol. 345:141-151(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NEDD8.

    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: June 24, 2015
    This is version 122 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

    External Data

    Dasty 3

    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 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.