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Q96LD8

- SENP8_HUMAN

UniProt

Q96LD8 - SENP8_HUMAN

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Protein
Sentrin-specific protease 8
Gene
SENP8, DEN1, NEDP1, PRSC2, FKSG8
Organism
Homo sapiens (Human)
Status
Reviewed - 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. cysteine-type peptidase activity Source: UniProtKB-KW
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.

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 8
PRO_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. 17 interactions.
IntActiQ96LD8. 2 interactions.
MINTiMINT-3055530.
STRINGi9606.ENSP00000340505.

Structurei

Secondary structure

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.

Miscellaneous databases

EvolutionaryTraceiQ96LD8.

Family & Domainsi

Region

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

Sequence similaritiesi

Belongs to the peptidase C48 family.

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

Natural variant

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti14 – 141R → W in AAL06294. 1 Publication

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.
ENST00000544171; ENSP00000439415; ENSG00000166192.
ENST00000544411; ENSP00000441753; 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. 17 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 .
ENST00000544171 ; ENSP00000439415 ; ENSG00000166192 .
ENST00000544411 ; ENSP00000441753 ; 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

« 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: July 9, 2014
This is version 113 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

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