Sentrin-specific protease 8 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q96LD8 (SENP8_HUMAN)

Last modified June 16, 2009. Version 65. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Sentrin-specific protease 8
    EC=3.4.22.-
Alternative name(s):
    Sentrin/SUMO-specific protease SENP8
    Protease, cysteine 2
    NEDD8-specific protease 1
    Deneddylase-1

Gene names

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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	212 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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
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. K_M=51 nM for Nedd8-AMC

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Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.9 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
NEDD8	Q15843	1	EBI-1041210,EBI-716247

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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

Active site

119

Active site

163

Nucleophile

Natural variations

Natural variant

207

T → A: dbSNP rs930871. Ref.1 Ref.4

VAR_023705

Experimental info

Mutagenesis

D → A: No effect on activity. Ref.8

Mutagenesis

W → A: Strongly reduces activity. Ref.8

Mutagenesis

D → A or N: Abolishes activity. Ref.8

Mutagenesis

V → A: No effect on activity. Ref.8

Mutagenesis

F → A: No effect on activity. Ref.8

Mutagenesis

P → A: No effect on activity. Ref.8

Mutagenesis

N → A: Abolishes activity. Ref.8

Mutagenesis

102

H → N: Abolishes activity. Ref.8

Mutagenesis

103

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

Mutagenesis

119

D → A or N: Abolishes activity. Ref.8

Mutagenesis

157

Q → A: No effect on activity. Ref.8

Mutagenesis

163

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

Sequence conflict

R → W in AAL06294. Ref.3

Secondary structure

212

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q96LD8-1 [UniParc].

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

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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: 12730221] [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: 15489334] [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: 12759363] [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: 12759362] [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: 15242646] [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: 15775960] [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: 15567417] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NEDD8.

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Cross-references

Sequence databases

AY008293 mRNA. Translation: AAG21828.1.
AF308450 mRNA. Translation: AAL06294.1.
BC031411 mRNA. Translation: AAH31411.1.

IPI

IPI00165616.

RefSeq

NP_660205.2.

UniGene

Hs.513002

3D structure databases

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	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96LD8. 1 interaction.

Protein family/group databases

MEROPS

C48.011.

Proteomic databases

PRIDE

Q96LD8.

Genome annotation databases

Ensembl

ENSG00000166192. Homo sapiens. [Contig view]

GeneID

123228.

KEGG

hsa:123228.

Organism-specific databases

GeneCards

GC15P070197.

H-InvDB

HIX0012402.

HGNC

HGNC:22992. SENP8.

MIM

608659. gene.

PharmGKB

PA134866772.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96LD8.

HOVERGEN

Q96LD8.

OMA

Q96LD8. NSVHAKQ.

Gene expression databases

ArrayExpress

Q96LD8.

Bgee

Q96LD8.

CleanEx

HS_SENP8.

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 Resources

NextBio

81089.

SOURCE

Search...

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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:	June 16, 2009
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 15

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents