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Q96LD8

- SENP8_HUMAN

UniProt

Q96LD8 - SENP8_HUMAN

Protein

Sentrin-specific protease 8

Gene

SENP8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    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

    1. cysteine-type peptidase activity Source: UniProtKB-KW

    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: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:22992. SENP8.

    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.

    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

    ArrayExpressiQ96LD8.
    BgeeiQ96LD8.
    CleanExiHS_SENP8.
    GenevestigatoriQ96LD8.

    Organism-specific databases

    HPAiHPA036273.

    Interactioni

    Protein-protein interaction databases

    BioGridi125819. 18 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 – 85
    Beta strandi11 – 144
    Helixi15 – 195
    Helixi29 – 4113
    Turni42 – 443
    Helixi45 – 473
    Turni48 – 503
    Beta strandi51 – 544
    Helixi56 – 649
    Helixi68 – 758
    Helixi76 – 783
    Helixi80 – 823
    Beta strandi84 – 918
    Beta strandi95 – 995
    Beta strandi103 – 1097
    Helixi110 – 1123
    Beta strandi114 – 1185
    Turni122 – 1254
    Helixi126 – 14015
    Beta strandi149 – 1513
    Beta strandi158 – 1614
    Helixi163 – 17917
    Helixi186 – 1894
    Helixi192 – 21019

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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

    MDPVVLSYMD SLLRQSDVSL LDPPSWLNDH IIGFAFEYFA NSQFHDCSDH    50
    VSFISPEVTQ FIKCTSNPAE IAMFLEPLDL PNKRVVFLAI NDNSNQAAGG 100
    THWSLLVYLQ DKNSFFHYDS HSRSNSVHAK QVAEKLEAFL GRKGDKLAFV 150
    EEKAPAQQNS YDCGMYVICN TEALCQNFFR QQTESLLQLL TPAYITKKRG 200
    EWKDLITTLA KK 212
    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. 1 PublicationCurated

    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:
    EMBL
    GenBank
    DDBJ
    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_005254157.1.
    UniGeneiHs.513002.

    Genome annotation databases

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

    Polymorphism databases

    DMDMi26006881.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY008293 mRNA. Translation: AAG21828.1 .
    AF308450 mRNA. Translation: AAL06294.1 .
    BC031411 mRNA. Translation: AAH31411.1 .
    CCDSi CCDS10240.1.
    RefSeqi NP_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_005254157.1.
    UniGenei Hs.513002.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1XT9 X-ray 2.20 A 1-212 [» ]
    2BKQ X-ray 2.00 A/B/C/D 1-212 [» ]
    2BKR X-ray 1.90 A 1-212 [» ]
    ProteinModelPortali Q96LD8.
    SMRi Q96LD8. Positions 1-211.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 125819. 18 interactions.
    IntActi Q96LD8. 2 interactions.
    MINTi MINT-3055530.
    STRINGi 9606.ENSP00000340505.

    Chemistry

    BindingDBi Q96LD8.
    ChEMBLi CHEMBL1741207.
    GuidetoPHARMACOLOGYi 2417.

    Protein family/group databases

    MEROPSi C48.011.

    PTM databases

    PhosphoSitei Q96LD8.

    Polymorphism databases

    DMDMi 26006881.

    Proteomic databases

    MaxQBi Q96LD8.
    PaxDbi Q96LD8.
    PRIDEi Q96LD8.

    Protocols and materials databases

    DNASUi 123228.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000340912 ; ENSP00000340505 ; ENSG00000166192 .
    ENST00000542035 ; ENSP00000446057 ; ENSG00000166192 .
    GeneIDi 123228.
    KEGGi hsa:123228.
    UCSCi uc002atp.3. human.

    Organism-specific databases

    CTDi 123228.
    GeneCardsi GC15P072410.
    HGNCi HGNC:22992. SENP8.
    HPAi HPA036273.
    MIMi 608659. gene.
    neXtProti NX_Q96LD8.
    PharmGKBi PA134866772.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG251510.
    HOGENOMi HOG000005740.
    HOVERGENi HBG054214.
    InParanoidi Q96LD8.
    KOi K08597.
    OMAi SWLNDHI.
    OrthoDBi EOG747PM3.
    PhylomeDBi Q96LD8.
    TreeFami TF351057.

    Miscellaneous databases

    EvolutionaryTracei Q96LD8.
    GeneWikii SENP8.
    GenomeRNAii 123228.
    NextBioi 81089.
    PROi Q96LD8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96LD8.
    Bgeei Q96LD8.
    CleanExi HS_SENP8.
    Genevestigatori Q96LD8.

    Family and domain databases

    InterProi IPR003653. Peptidase_C48.
    [Graphical view ]
    Pfami PF02902. Peptidase_C48. 1 hit.
    [Graphical view ]
    PROSITEi PS50600. ULP_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 114 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