Q96LD8 (SENP8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SENP8
Synonyms:	DEN1, NEDP1, PRSC2
ORF Names:	FKSG8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	212 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8
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 process	Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 212

212

Sentrin-specific protease 8

PRO_0000101727

Regions

Region

11 – 174

164

Protease

Sites

Active site

102

1

Active site

119

1

Active site

163

1

Nucleophile

Natural variations

Natural variant

207

1

T → A. Ref.1 Ref.4
Corresponds to variant rs930871 [ dbSNP | Ensembl ].

VAR_023705

Experimental info

Mutagenesis

10

1

D → A: No effect on activity. Ref.8

Mutagenesis

26

1

W → A: Strongly reduces activity. Ref.8

Mutagenesis

29

1

D → A or N: Abolishes activity. Ref.8

Mutagenesis

58

1

V → A: No effect on activity. Ref.8

Mutagenesis

74

1

F → A: No effect on activity. Ref.8

Mutagenesis

77

1

P → A: No effect on activity. Ref.8

Mutagenesis

91

1

N → A: Abolishes activity. Ref.8

Mutagenesis

102

1

H → N: Abolishes activity. Ref.8

Mutagenesis

103

1

W → A or H: Strongly reduces activity. Ref.8

Mutagenesis

119

1

D → A or N: Abolishes activity. Ref.8

Mutagenesis

157

1

Q → A: No effect on activity. Ref.8

Mutagenesis

163

1

C → A: Abolishes activity. Ref.1 Ref.7 Ref.8

Sequence conflict

14

1

R → W in AAL06294. Ref.3

Secondary structure

1

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212

Helix Strand Turn

Details...

Beta strand

4 – 8

5

Beta strand

11 – 14

4

Helix

15 – 19

5

Helix

29 – 41

13

Turn

42 – 44

3

Helix

45 – 47

3

Turn

48 – 50

3

Beta strand

51 – 54

4

Helix

56 – 64

9

Helix

68 – 75

8

Helix

76 – 78

3

Helix

80 – 82

3

Beta strand

84 – 91

8

Beta strand

95 – 99

5

Beta strand

103 – 109

7

Helix

110 – 112

3

Beta strand

114 – 118

5

Turn

122 – 125

4

Helix

126 – 140

15

Beta strand

149 – 151

3

Beta strand

158 – 161

4

Helix

163 – 179

17

Helix

186 – 189

4

Helix

192 – 210

19

Sequences

	Sequence		Length	Mass (Da)
	Q96LD8 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 680D93B85EF6028C	FASTA	212	24,107
	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

References

	« Hide 'large scale' referencesShow '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]	"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.
[9]	"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.

IPI

IPI00165616.

RefSeq

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.

UniGene

Hs.513002.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q96LD8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96LD8. 1 interaction.

MINT

MINT-3055530.

STRING

9606.ENSP00000340505.

Protein family/group databases

MEROPS

C48.011.

PTM databases

PhosphoSite

Q96LD8.

Polymorphism databases

DMDM

26006881.

Proteomic databases

PaxDb

Q96LD8.

PRIDE

Q96LD8.

Protocols and materials databases

DNASU

123228.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340912; ENSP00000340505; ENSG00000166192.
ENST00000542035; ENSP00000446057; ENSG00000166192.
ENST00000544171; ENSP00000439415; ENSG00000166192.
ENST00000544411; ENSP00000441753; ENSG00000166192.

GeneID

123228.

KEGG

hsa:123228.

UCSC

uc002atp.3. human.

Organism-specific databases

CTD

123228.

GeneCards

GC15P072410.

HGNC

HGNC:22992. SENP8.

HPA

HPA036273.

MIM

608659. gene.

neXtProt

NX_Q96LD8.

PharmGKB

PA134866772.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG251510.

HOGENOM

HOG000005740.

HOVERGEN

HBG054214.

InParanoid

Q96LD8.

KO

K08597.

OMA

NDHIIGF.

OrthoDB

EOG4HDSVF.

PhylomeDB

Q96LD8.

Gene expression databases

ArrayExpress

Q96LD8.

Bgee

Q96LD8.

CleanEx

HS_SENP8.

Genevestigator

Q96LD8.

GermOnline

ENSG00000166192. Homo sapiens.

Family and domain databases

InterPro

IPR003653. Peptidase_C48.
[Graphical view]

Pfam

PF02902. Peptidase_C48. 1 hit.
[Graphical view]

PROSITE

PS50600. ULP_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q96LD8.

ChEMBL

CHEMBL1741207.

EvolutionaryTrace

Q96LD8.

GenomeRNAi

123228.

NextBio

81089.

SOURCE

Search...

Entry information

Entry name

SENP8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.