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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

  1. NEDD8-specific protease activity Source: GO_Central

GO - Biological processi

  1. protein deneddylation Source: GO_Central
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: Chromosome 15

Organism-specific databases

HGNCiHGNC:22992. SENP8.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: GO_Central
  2. nucleus Source: GO_Central
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.

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.
GenevestigatoriQ96LD8.

Organism-specific databases

HPAiHPA036273.

Interactioni

Protein-protein interaction databases

BioGridi125819. 16 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. 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:
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_005254157.1.
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:
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_005254157.1.
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. 16 interactions.
IntActiQ96LD8. 2 interactions.
MINTiMINT-3055530.
STRINGi9606.ENSP00000340505.

Chemistry

BindingDBiQ96LD8.
ChEMBLiCHEMBL1741207.
GuidetoPHARMACOLOGYi2417.

Protein family/group databases

MEROPSiC48.011.

PTM databases

PhosphoSiteiQ96LD8.

Polymorphism databases

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.
GenevestigatoriQ96LD8.

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: February 4, 2015
This is version 118 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.