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Q96LD8 (SENP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SENP8
Synonyms:DEN1, NEDP1, PRSC2
ORF Names:FKSG8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length212 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5 Ref.6 Ref.7 Ref.10

Catalytic activity

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.

Tissue specificity

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

Sequence similarities

Belongs to the peptidase C48 family.

Biophysicochemical properties

Kinetic parameters:

KM for Ub-AMC exceeds 5uM.

KM=51 nM for Nedd8-AMC Ref.6

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Coding sequence diversityPolymorphism
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processproteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functioncysteine-type peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 212212Sentrin-specific protease 8
PRO_0000101727

Regions

Region11 – 174164Protease

Sites

Active site1021
Active site1191
Active site1631Nucleophile

Amino acid modifications

Modified residue11N-acetylmethionine Ref.8 Ref.9

Natural variations

Natural variant2071T → A. Ref.1 Ref.4
Corresponds to variant rs930871 [ dbSNP | Ensembl ].
VAR_023705

Experimental info

Mutagenesis101D → A: No effect on activity. Ref.10
Mutagenesis261W → A: Strongly reduces activity. Ref.10
Mutagenesis291D → A or N: Abolishes activity. Ref.10
Mutagenesis581V → A: No effect on activity. Ref.10
Mutagenesis741F → A: No effect on activity. Ref.10
Mutagenesis771P → A: No effect on activity. Ref.10
Mutagenesis911N → A: Abolishes activity. Ref.10
Mutagenesis1021H → N: Abolishes activity. Ref.10
Mutagenesis1031W → A or H: Strongly reduces activity. Ref.10
Mutagenesis1191D → A or N: Abolishes activity. Ref.10
Mutagenesis1571Q → A: No effect on activity. Ref.10
Mutagenesis1631C → A: Abolishes activity. Ref.1 Ref.7 Ref.10
Sequence conflict141R → W in AAL06294. Ref.3

Secondary structure

......................................... 212
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96LD8 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 680D93B85EF6028C

FASTA21224,107
        10         20         30         40         50         60 
MDPVVLSYMD SLLRQSDVSL LDPPSWLNDH IIGFAFEYFA NSQFHDCSDH VSFISPEVTQ 

        70         80         90        100        110        120 
FIKCTSNPAE IAMFLEPLDL PNKRVVFLAI NDNSNQAAGG THWSLLVYLQ DKNSFFHYDS 

       130        140        150        160        170        180 
HSRSNSVHAK QVAEKLEAFL GRKGDKLAFV EEKAPAQQNS YDCGMYVICN TEALCQNFFR 

       190        200        210 
QQTESLLQLL TPAYITKKRG EWKDLITTLA KK 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY008293 mRNA. Translation: AAG21828.1.
AF308450 mRNA. Translation: AAL06294.1.
BC031411 mRNA. Translation: AAH31411.1.
RefSeqNP_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.
UniGeneHs.513002.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XT9X-ray2.20A1-212[»]
2BKQX-ray2.00A/B/C/D1-212[»]
2BKRX-ray1.90A1-212[»]
ProteinModelPortalQ96LD8.
SMRQ96LD8. Positions 1-211.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125819. 17 interactions.
IntActQ96LD8. 2 interactions.
MINTMINT-3055530.
STRING9606.ENSP00000340505.

Chemistry

BindingDBQ96LD8.
ChEMBLCHEMBL1741207.
GuidetoPHARMACOLOGY2417.

Protein family/group databases

MEROPSC48.011.

PTM databases

PhosphoSiteQ96LD8.

Polymorphism databases

DMDM26006881.

Proteomic databases

PaxDbQ96LD8.
PRIDEQ96LD8.

Protocols and materials databases

DNASU123228.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340912; ENSP00000340505; ENSG00000166192.
ENST00000542035; ENSP00000446057; ENSG00000166192.
ENST00000544171; ENSP00000439415; ENSG00000166192.
ENST00000544411; ENSP00000441753; ENSG00000166192.
GeneID123228.
KEGGhsa:123228.
UCSCuc002atp.3. human.

Organism-specific databases

CTD123228.
GeneCardsGC15P072410.
HGNCHGNC:22992. SENP8.
HPAHPA036273.
MIM608659. gene.
neXtProtNX_Q96LD8.
PharmGKBPA134866772.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG251510.
HOGENOMHOG000005740.
HOVERGENHBG054214.
InParanoidQ96LD8.
KOK08597.
OMASWLNDHI.
OrthoDBEOG747PM3.
PhylomeDBQ96LD8.
TreeFamTF351057.

Gene expression databases

ArrayExpressQ96LD8.
BgeeQ96LD8.
CleanExHS_SENP8.
GenevestigatorQ96LD8.

Family and domain databases

InterProIPR003653. Peptidase_C48.
[Graphical view]
PfamPF02902. Peptidase_C48. 1 hit.
[Graphical view]
PROSITEPS50600. ULP_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96LD8.
GeneWikiSENP8.
GenomeRNAi123228.
NextBio81089.
PROQ96LD8.
SOURCESearch...

Entry information

Entry nameSENP8_HUMAN
AccessionPrimary (citable) accession number: Q96LD8
Secondary accession number(s): Q96QA4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2002
Last sequence update: December 1, 2001
Last modified: March 19, 2014
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM