Full text data of SENP8
SENP8
(DEN1, NEDP1, PRSC2)
[Confidence: low (only semi-automatic identification from reviews)]
Sentrin-specific protease 8; 3.4.22.68 (Deneddylase-1; NEDD8-specific protease 1; Protease, cysteine 2; Sentrin/SUMO-specific protease SENP8)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Sentrin-specific protease 8; 3.4.22.68 (Deneddylase-1; NEDD8-specific protease 1; Protease, cysteine 2; Sentrin/SUMO-specific protease SENP8)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96LD8
ID SENP8_HUMAN Reviewed; 212 AA.
AC Q96LD8; Q96QA4;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-2001, sequence version 1.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=Sentrin-specific protease 8;
DE EC=3.4.22.68;
DE AltName: Full=Deneddylase-1;
DE AltName: Full=NEDD8-specific protease 1;
DE AltName: Full=Protease, cysteine 2;
DE AltName: Full=Sentrin/SUMO-specific protease SENP8;
GN Name=SENP8; Synonyms=DEN1, NEDP1, PRSC2; ORFNames=FKSG8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-207, TISSUE SPECIFICITY,
RP MUTAGENESIS OF CYS-163, AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=12730221; DOI=10.1074/jbc.M212948200;
RA Mendoza H.M., Shen L.-N., Botting C., Lewis A., Chen J., Ink B.,
RA Hay R.T.;
RT "NEDP1, a highly conserved cysteine protease that deneddylates
RT cullins.";
RL J. Biol. Chem. 278:25637-25643(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Gong L., Yeh E.T.H.;
RT "Identification of SENP8, a novel member of the sentrin-specific
RT protease family.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Wang Y.-G.;
RT "Identification of FKSG8, a novel gene encoding a protein with
RT cysteine protease activity.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-207.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 181-197, INTERACTION WITH NEDD8, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=12759363; DOI=10.1074/jbc.M302888200;
RA Wu K., Yamoah K., Dolios G., Gan-Erdene T., Tan P., Chen A.,
RA Lee C.-G., Wei N., Wilkinson K.D., Wang R., Pan Z.-Q.;
RT "DEN1 is a dual function protease capable of processing the C-terminus
RT of Nedd8 and deconjugating hyper-neddylated CUL1.";
RL J. Biol. Chem. 278:28882-28891(2003).
RN [6]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12759362; DOI=10.1074/jbc.M302890200;
RA Gan-Erdene T., Nagamalleswari K., Yin L., Wu K., Pan Z.-Q.,
RA Wilkinson K.D.;
RT "Identification and characterization of DEN1, a deneddylase of the ULP
RT family.";
RL J. Biol. Chem. 278:28892-28900(2003).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF CYS-163.
RX PubMed=15242646; DOI=10.1016/j.cell.2004.06.016;
RA Xirodimas D.P., Saville M.K., Bourdon J.-C., Hay R.T., Lane D.P.;
RT "Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional
RT activity.";
RL Cell 118:83-97(2004).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NEDD8,
RP MUTAGENESIS OF ASP-10; TRP-26; ASP-29; VAL-58; PHE-74; PRO-77; ASN-91;
RP HIS-102; TRP-103; ASP-119; GLN-157 AND CYS-163, AND FUNCTION.
RX PubMed=15775960; DOI=10.1038/sj.emboj.7600628;
RA Shen L.-N., Liu H., Dong C., Xirodimas D.P., Naismith J.H., Hay R.T.;
RT "Structural basis of NEDD8 ubiquitin discrimination by the
RT deneddylating enzyme NEDP1.";
RL EMBO J. 24:1341-1351(2005).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NEDD8.
RX PubMed=15567417; DOI=10.1016/j.jmb.2004.10.022;
RA Reverter D., Wu K., Erdene T.G., Pan Z.-Q., Wilkinson K.D., Lima C.D.;
RT "Structure of a complex between Nedd8 and the Ulp/Senp protease family
RT member Den1.";
RL J. Mol. Biol. 345:141-151(2005).
CC -!- FUNCTION: Protease that catalyzes two essential functions in the
CC NEDD8 pathway: processing of full-length NEDD8 to its mature form
CC and deconjugation of NEDD8 from targeted proteins such as cullins
CC or p53.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of the alpha-linked peptide bond in
CC the sequence Gly-Gly-|-Ala-Thr-Tyr at the C-terminal end of the
CC small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to
CC the mature form of the protein. A second reaction involves the
CC cleavage of an epsilon-linked peptide bond between the C-terminal
CC glycine of the mature SUMO and the lysine epsilon-amino group of
CC the target protein.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=51 nM for Nedd8-AMC;
CC Note=KM for Ub-AMC exceeds 5uM;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in
CC kidney and pancreas.
CC -!- SIMILARITY: Belongs to the peptidase C48 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AY008293; AAG21828.1; -; mRNA.
DR EMBL; AF308450; AAL06294.1; -; mRNA.
DR EMBL; BC031411; AAH31411.1; -; mRNA.
DR RefSeq; NP_001159812.1; NM_001166340.1.
DR RefSeq; NP_001165580.1; NM_001172109.1.
DR RefSeq; NP_001165581.1; NM_001172110.1.
DR RefSeq; NP_001165582.1; NM_001172111.1.
DR RefSeq; NP_660205.3; NM_145204.3.
DR RefSeq; XP_005254214.1; XM_005254157.1.
DR UniGene; Hs.513002; -.
DR PDB; 1XT9; X-ray; 2.20 A; A=1-212.
DR PDB; 2BKQ; X-ray; 2.00 A; A/B/C/D=1-212.
DR PDB; 2BKR; X-ray; 1.90 A; A=1-212.
DR PDBsum; 1XT9; -.
DR PDBsum; 2BKQ; -.
DR PDBsum; 2BKR; -.
DR ProteinModelPortal; Q96LD8; -.
DR SMR; Q96LD8; 1-211.
DR IntAct; Q96LD8; 2.
DR MINT; MINT-3055530; -.
DR STRING; 9606.ENSP00000340505; -.
DR BindingDB; Q96LD8; -.
DR ChEMBL; CHEMBL1741207; -.
DR GuidetoPHARMACOLOGY; 2417; -.
DR MEROPS; C48.011; -.
DR PhosphoSite; Q96LD8; -.
DR DMDM; 26006881; -.
DR PaxDb; Q96LD8; -.
DR PRIDE; Q96LD8; -.
DR DNASU; 123228; -.
DR Ensembl; ENST00000340912; ENSP00000340505; ENSG00000166192.
DR Ensembl; ENST00000542035; ENSP00000446057; ENSG00000166192.
DR Ensembl; ENST00000544171; ENSP00000439415; ENSG00000166192.
DR Ensembl; ENST00000544411; ENSP00000441753; ENSG00000166192.
DR GeneID; 123228; -.
DR KEGG; hsa:123228; -.
DR UCSC; uc002atp.3; human.
DR CTD; 123228; -.
DR GeneCards; GC15P072410; -.
DR HGNC; HGNC:22992; SENP8.
DR HPA; HPA036273; -.
DR MIM; 608659; gene.
DR neXtProt; NX_Q96LD8; -.
DR PharmGKB; PA134866772; -.
DR eggNOG; NOG251510; -.
DR HOGENOM; HOG000005740; -.
DR HOVERGEN; HBG054214; -.
DR InParanoid; Q96LD8; -.
DR KO; K08597; -.
DR OMA; SWLNDHI; -.
DR OrthoDB; EOG747PM3; -.
DR PhylomeDB; Q96LD8; -.
DR EvolutionaryTrace; Q96LD8; -.
DR GeneWiki; SENP8; -.
DR GenomeRNAi; 123228; -.
DR NextBio; 81089; -.
DR PRO; PR:Q96LD8; -.
DR ArrayExpress; Q96LD8; -.
DR Bgee; Q96LD8; -.
DR CleanEx; HS_SENP8; -.
DR Genevestigator; Q96LD8; -.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR003653; Peptidase_C48.
DR Pfam; PF02902; Peptidase_C48; 1.
DR PROSITE; PS50600; ULP_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome;
KW Direct protein sequencing; Hydrolase; Polymorphism; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1 212 Sentrin-specific protease 8.
FT /FTId=PRO_0000101727.
FT REGION 11 174 Protease.
FT ACT_SITE 102 102
FT ACT_SITE 119 119
FT ACT_SITE 163 163 Nucleophile.
FT MOD_RES 1 1 N-acetylmethionine.
FT VARIANT 207 207 T -> A (in dbSNP:rs930871).
FT /FTId=VAR_023705.
FT MUTAGEN 10 10 D->A: No effect on activity.
FT MUTAGEN 26 26 W->A: Strongly reduces activity.
FT MUTAGEN 29 29 D->A,N: Abolishes activity.
FT MUTAGEN 58 58 V->A: No effect on activity.
FT MUTAGEN 74 74 F->A: No effect on activity.
FT MUTAGEN 77 77 P->A: No effect on activity.
FT MUTAGEN 91 91 N->A: Abolishes activity.
FT MUTAGEN 102 102 H->N: Abolishes activity.
FT MUTAGEN 103 103 W->A,H: Strongly reduces activity.
FT MUTAGEN 119 119 D->A,N: Abolishes activity.
FT MUTAGEN 157 157 Q->A: No effect on activity.
FT MUTAGEN 163 163 C->A: Abolishes activity.
FT CONFLICT 14 14 R -> W (in Ref. 3; AAL06294).
FT STRAND 4 8
FT STRAND 11 14
FT HELIX 15 19
FT HELIX 29 41
FT TURN 42 44
FT HELIX 45 47
FT TURN 48 50
FT STRAND 51 54
FT HELIX 56 64
FT HELIX 68 75
FT HELIX 76 78
FT HELIX 80 82
FT STRAND 84 91
FT STRAND 95 99
FT STRAND 103 109
FT HELIX 110 112
FT STRAND 114 118
FT TURN 122 125
FT HELIX 126 140
FT STRAND 149 151
FT STRAND 158 161
FT HELIX 163 179
FT HELIX 186 189
FT HELIX 192 210
SQ SEQUENCE 212 AA; 24107 MW; 680D93B85EF6028C CRC64;
MDPVVLSYMD SLLRQSDVSL LDPPSWLNDH IIGFAFEYFA NSQFHDCSDH VSFISPEVTQ
FIKCTSNPAE IAMFLEPLDL PNKRVVFLAI NDNSNQAAGG THWSLLVYLQ DKNSFFHYDS
HSRSNSVHAK QVAEKLEAFL GRKGDKLAFV EEKAPAQQNS YDCGMYVICN TEALCQNFFR
QQTESLLQLL TPAYITKKRG EWKDLITTLA KK
//
ID SENP8_HUMAN Reviewed; 212 AA.
AC Q96LD8; Q96QA4;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-2001, sequence version 1.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=Sentrin-specific protease 8;
DE EC=3.4.22.68;
DE AltName: Full=Deneddylase-1;
DE AltName: Full=NEDD8-specific protease 1;
DE AltName: Full=Protease, cysteine 2;
DE AltName: Full=Sentrin/SUMO-specific protease SENP8;
GN Name=SENP8; Synonyms=DEN1, NEDP1, PRSC2; ORFNames=FKSG8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-207, TISSUE SPECIFICITY,
RP MUTAGENESIS OF CYS-163, AND FUNCTION.
RC TISSUE=Kidney;
RX PubMed=12730221; DOI=10.1074/jbc.M212948200;
RA Mendoza H.M., Shen L.-N., Botting C., Lewis A., Chen J., Ink B.,
RA Hay R.T.;
RT "NEDP1, a highly conserved cysteine protease that deneddylates
RT cullins.";
RL J. Biol. Chem. 278:25637-25643(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Gong L., Yeh E.T.H.;
RT "Identification of SENP8, a novel member of the sentrin-specific
RT protease family.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Wang Y.-G.;
RT "Identification of FKSG8, a novel gene encoding a protein with
RT cysteine protease activity.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-207.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 181-197, INTERACTION WITH NEDD8, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=12759363; DOI=10.1074/jbc.M302888200;
RA Wu K., Yamoah K., Dolios G., Gan-Erdene T., Tan P., Chen A.,
RA Lee C.-G., Wei N., Wilkinson K.D., Wang R., Pan Z.-Q.;
RT "DEN1 is a dual function protease capable of processing the C-terminus
RT of Nedd8 and deconjugating hyper-neddylated CUL1.";
RL J. Biol. Chem. 278:28882-28891(2003).
RN [6]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12759362; DOI=10.1074/jbc.M302890200;
RA Gan-Erdene T., Nagamalleswari K., Yin L., Wu K., Pan Z.-Q.,
RA Wilkinson K.D.;
RT "Identification and characterization of DEN1, a deneddylase of the ULP
RT family.";
RL J. Biol. Chem. 278:28892-28900(2003).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF CYS-163.
RX PubMed=15242646; DOI=10.1016/j.cell.2004.06.016;
RA Xirodimas D.P., Saville M.K., Bourdon J.-C., Hay R.T., Lane D.P.;
RT "Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional
RT activity.";
RL Cell 118:83-97(2004).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NEDD8,
RP MUTAGENESIS OF ASP-10; TRP-26; ASP-29; VAL-58; PHE-74; PRO-77; ASN-91;
RP HIS-102; TRP-103; ASP-119; GLN-157 AND CYS-163, AND FUNCTION.
RX PubMed=15775960; DOI=10.1038/sj.emboj.7600628;
RA Shen L.-N., Liu H., Dong C., Xirodimas D.P., Naismith J.H., Hay R.T.;
RT "Structural basis of NEDD8 ubiquitin discrimination by the
RT deneddylating enzyme NEDP1.";
RL EMBO J. 24:1341-1351(2005).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NEDD8.
RX PubMed=15567417; DOI=10.1016/j.jmb.2004.10.022;
RA Reverter D., Wu K., Erdene T.G., Pan Z.-Q., Wilkinson K.D., Lima C.D.;
RT "Structure of a complex between Nedd8 and the Ulp/Senp protease family
RT member Den1.";
RL J. Mol. Biol. 345:141-151(2005).
CC -!- FUNCTION: Protease that catalyzes two essential functions in the
CC NEDD8 pathway: processing of full-length NEDD8 to its mature form
CC and deconjugation of NEDD8 from targeted proteins such as cullins
CC or p53.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of the alpha-linked peptide bond in
CC the sequence Gly-Gly-|-Ala-Thr-Tyr at the C-terminal end of the
CC small ubiquitin-like modifier (SUMO) propeptide, Smt3, leading to
CC the mature form of the protein. A second reaction involves the
CC cleavage of an epsilon-linked peptide bond between the C-terminal
CC glycine of the mature SUMO and the lysine epsilon-amino group of
CC the target protein.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=51 nM for Nedd8-AMC;
CC Note=KM for Ub-AMC exceeds 5uM;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in
CC kidney and pancreas.
CC -!- SIMILARITY: Belongs to the peptidase C48 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AY008293; AAG21828.1; -; mRNA.
DR EMBL; AF308450; AAL06294.1; -; mRNA.
DR EMBL; BC031411; AAH31411.1; -; mRNA.
DR RefSeq; NP_001159812.1; NM_001166340.1.
DR RefSeq; NP_001165580.1; NM_001172109.1.
DR RefSeq; NP_001165581.1; NM_001172110.1.
DR RefSeq; NP_001165582.1; NM_001172111.1.
DR RefSeq; NP_660205.3; NM_145204.3.
DR RefSeq; XP_005254214.1; XM_005254157.1.
DR UniGene; Hs.513002; -.
DR PDB; 1XT9; X-ray; 2.20 A; A=1-212.
DR PDB; 2BKQ; X-ray; 2.00 A; A/B/C/D=1-212.
DR PDB; 2BKR; X-ray; 1.90 A; A=1-212.
DR PDBsum; 1XT9; -.
DR PDBsum; 2BKQ; -.
DR PDBsum; 2BKR; -.
DR ProteinModelPortal; Q96LD8; -.
DR SMR; Q96LD8; 1-211.
DR IntAct; Q96LD8; 2.
DR MINT; MINT-3055530; -.
DR STRING; 9606.ENSP00000340505; -.
DR BindingDB; Q96LD8; -.
DR ChEMBL; CHEMBL1741207; -.
DR GuidetoPHARMACOLOGY; 2417; -.
DR MEROPS; C48.011; -.
DR PhosphoSite; Q96LD8; -.
DR DMDM; 26006881; -.
DR PaxDb; Q96LD8; -.
DR PRIDE; Q96LD8; -.
DR DNASU; 123228; -.
DR Ensembl; ENST00000340912; ENSP00000340505; ENSG00000166192.
DR Ensembl; ENST00000542035; ENSP00000446057; ENSG00000166192.
DR Ensembl; ENST00000544171; ENSP00000439415; ENSG00000166192.
DR Ensembl; ENST00000544411; ENSP00000441753; ENSG00000166192.
DR GeneID; 123228; -.
DR KEGG; hsa:123228; -.
DR UCSC; uc002atp.3; human.
DR CTD; 123228; -.
DR GeneCards; GC15P072410; -.
DR HGNC; HGNC:22992; SENP8.
DR HPA; HPA036273; -.
DR MIM; 608659; gene.
DR neXtProt; NX_Q96LD8; -.
DR PharmGKB; PA134866772; -.
DR eggNOG; NOG251510; -.
DR HOGENOM; HOG000005740; -.
DR HOVERGEN; HBG054214; -.
DR InParanoid; Q96LD8; -.
DR KO; K08597; -.
DR OMA; SWLNDHI; -.
DR OrthoDB; EOG747PM3; -.
DR PhylomeDB; Q96LD8; -.
DR EvolutionaryTrace; Q96LD8; -.
DR GeneWiki; SENP8; -.
DR GenomeRNAi; 123228; -.
DR NextBio; 81089; -.
DR PRO; PR:Q96LD8; -.
DR ArrayExpress; Q96LD8; -.
DR Bgee; Q96LD8; -.
DR CleanEx; HS_SENP8; -.
DR Genevestigator; Q96LD8; -.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR003653; Peptidase_C48.
DR Pfam; PF02902; Peptidase_C48; 1.
DR PROSITE; PS50600; ULP_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome;
KW Direct protein sequencing; Hydrolase; Polymorphism; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1 212 Sentrin-specific protease 8.
FT /FTId=PRO_0000101727.
FT REGION 11 174 Protease.
FT ACT_SITE 102 102
FT ACT_SITE 119 119
FT ACT_SITE 163 163 Nucleophile.
FT MOD_RES 1 1 N-acetylmethionine.
FT VARIANT 207 207 T -> A (in dbSNP:rs930871).
FT /FTId=VAR_023705.
FT MUTAGEN 10 10 D->A: No effect on activity.
FT MUTAGEN 26 26 W->A: Strongly reduces activity.
FT MUTAGEN 29 29 D->A,N: Abolishes activity.
FT MUTAGEN 58 58 V->A: No effect on activity.
FT MUTAGEN 74 74 F->A: No effect on activity.
FT MUTAGEN 77 77 P->A: No effect on activity.
FT MUTAGEN 91 91 N->A: Abolishes activity.
FT MUTAGEN 102 102 H->N: Abolishes activity.
FT MUTAGEN 103 103 W->A,H: Strongly reduces activity.
FT MUTAGEN 119 119 D->A,N: Abolishes activity.
FT MUTAGEN 157 157 Q->A: No effect on activity.
FT MUTAGEN 163 163 C->A: Abolishes activity.
FT CONFLICT 14 14 R -> W (in Ref. 3; AAL06294).
FT STRAND 4 8
FT STRAND 11 14
FT HELIX 15 19
FT HELIX 29 41
FT TURN 42 44
FT HELIX 45 47
FT TURN 48 50
FT STRAND 51 54
FT HELIX 56 64
FT HELIX 68 75
FT HELIX 76 78
FT HELIX 80 82
FT STRAND 84 91
FT STRAND 95 99
FT STRAND 103 109
FT HELIX 110 112
FT STRAND 114 118
FT TURN 122 125
FT HELIX 126 140
FT STRAND 149 151
FT STRAND 158 161
FT HELIX 163 179
FT HELIX 186 189
FT HELIX 192 210
SQ SEQUENCE 212 AA; 24107 MW; 680D93B85EF6028C CRC64;
MDPVVLSYMD SLLRQSDVSL LDPPSWLNDH IIGFAFEYFA NSQFHDCSDH VSFISPEVTQ
FIKCTSNPAE IAMFLEPLDL PNKRVVFLAI NDNSNQAAGG THWSLLVYLQ DKNSFFHYDS
HSRSNSVHAK QVAEKLEAFL GRKGDKLAFV EEKAPAQQNS YDCGMYVICN TEALCQNFFR
QQTESLLQLL TPAYITKKRG EWKDLITTLA KK
//
MIM
608659
*RECORD*
*FIELD* NO
608659
*FIELD* TI
*608659 SENTRIN-SPECIFIC PROTEASE FAMILY, MEMBER 8; SENP8
;;NEDD8-SPECIFIC PROTEASE 1; NEDP1;;
read moreDENEDDYLASE 1; DEN1
*FIELD* TX
DESCRIPTION
NEDD8 (603171) is a ubiquitin-like protein that becomes conjugated to
the cullin (see CUL1; 603134) subunit of several ubiquitin ligases. This
conjugation, called neddylation, is required for optimal ubiquitin
ligase activity. NEDD8-specific deneddylases, such as NEDP1, or DEN1,
are required to process the NEDD8 propeptide at a C-terminal diglycine
motif and to remove NEDD8 from cullins (Gan-Erdene et al., 2003).
CLONING
By searching a database for sequences similar to yeast Ulp1, followed by
PCR of a kidney cDNA library, Mendoza et al. (2003) cloned NEDP1. The
deduced 212-amino acid protein contains a cysteine protease domain
flanked by short N- and C-terminal extensions. PCR analysis showed wide
expression of NEDP1, with highest expression in kidney and pancreas.
Wu et al. (2003) purified DEN1 from HeLa cells based on its ability to
deneddylate a CUL1 substrate. By searching for sequences similar to a
DEN1 tryptic fragment, followed by PCR of a fetal brain cDNA library,
they cloned DEN1. Western blot analysis detected the purified protein at
an apparent molecular mass of 24 kD.
GENE FUNCTION
Mendoza et al. (2003) confirmed that recombinant NEDP1 expressed in
bacteria processed the NEDD8 precursor protein after the second gly in
the diglycine motif, but it did not process SUMO1 (601912) or ubiquitin
(see 191339). NEDP1 showed no activity against full-length SUMO1, SUMO2
(603042), or SUMO3 (602231). Inhibition and mutagenesis studies
indicated that NEDP1 is a cysteine protease. NEDP1 deconjugated NEDD8
from CUL2 (603135) in vitro and from modified CUL4A (603137) in vivo.
Wu et al. (2003) determined that recombinant DEN1 bound NEDD8 in an in
vitro pull-down assay, but showed much lower binding to SUMO1 and
ubiquitin. They showed that DEN1 processed NEDD8 precursor proteins into
the mature protein and that DEN1 deconjugated hyperneddylated CUL1.
Gan-Erdene et al. (2003) found that DEN1 catalyzed hydrolysis of a NEDD8
substrate at a much higher rate than it did a ubiquitin substrate. It
did not catalyze hydrolysis of a SUMO1 substrate.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NEDP1
gene to chromosome 15 (TMAP SGC33966).
*FIELD* RF
1. Gan-Erdene, T.; Nagamalleswari, K.; Yin, L.; Wu, K.; Pan, Z.-Q.;
Wilkinson, K. D.: Identification and characterization of DEN1, a
deneddylase of the ULP family. J. Biol. Chem. 278: 28882-28900,
2003.
2. Mendoza, H. M.; Shen, L.; Botting, C.; Lewis, A.; Chen, J.; Ink,
B.; Hay, R. T.: NEDP1, a highly conserved cysteine protease that
deNEDDylates cullins. J. Biol. Chem. 278: 25637-25643, 2003.
3. Wu, K.; Yamoah, K.; Dolios, G.; Gan-Erdene, T.; Tan, P.; Chen,
A.; Lee, C.; Wei, N.; Wilkinson, K. D.; Wang, R.; Pan, Z.-Q.: DEN1
is a dual function protease capable of processing the C terminus of
Nedd8 and deconjugating hyper-neddylated CUL1. J. Biol. Chem. 278:
28882-28891, 2003.
*FIELD* CD
Patricia A. Hartz: 5/14/2004
*FIELD* ED
mgross: 05/14/2004
*RECORD*
*FIELD* NO
608659
*FIELD* TI
*608659 SENTRIN-SPECIFIC PROTEASE FAMILY, MEMBER 8; SENP8
;;NEDD8-SPECIFIC PROTEASE 1; NEDP1;;
read moreDENEDDYLASE 1; DEN1
*FIELD* TX
DESCRIPTION
NEDD8 (603171) is a ubiquitin-like protein that becomes conjugated to
the cullin (see CUL1; 603134) subunit of several ubiquitin ligases. This
conjugation, called neddylation, is required for optimal ubiquitin
ligase activity. NEDD8-specific deneddylases, such as NEDP1, or DEN1,
are required to process the NEDD8 propeptide at a C-terminal diglycine
motif and to remove NEDD8 from cullins (Gan-Erdene et al., 2003).
CLONING
By searching a database for sequences similar to yeast Ulp1, followed by
PCR of a kidney cDNA library, Mendoza et al. (2003) cloned NEDP1. The
deduced 212-amino acid protein contains a cysteine protease domain
flanked by short N- and C-terminal extensions. PCR analysis showed wide
expression of NEDP1, with highest expression in kidney and pancreas.
Wu et al. (2003) purified DEN1 from HeLa cells based on its ability to
deneddylate a CUL1 substrate. By searching for sequences similar to a
DEN1 tryptic fragment, followed by PCR of a fetal brain cDNA library,
they cloned DEN1. Western blot analysis detected the purified protein at
an apparent molecular mass of 24 kD.
GENE FUNCTION
Mendoza et al. (2003) confirmed that recombinant NEDP1 expressed in
bacteria processed the NEDD8 precursor protein after the second gly in
the diglycine motif, but it did not process SUMO1 (601912) or ubiquitin
(see 191339). NEDP1 showed no activity against full-length SUMO1, SUMO2
(603042), or SUMO3 (602231). Inhibition and mutagenesis studies
indicated that NEDP1 is a cysteine protease. NEDP1 deconjugated NEDD8
from CUL2 (603135) in vitro and from modified CUL4A (603137) in vivo.
Wu et al. (2003) determined that recombinant DEN1 bound NEDD8 in an in
vitro pull-down assay, but showed much lower binding to SUMO1 and
ubiquitin. They showed that DEN1 processed NEDD8 precursor proteins into
the mature protein and that DEN1 deconjugated hyperneddylated CUL1.
Gan-Erdene et al. (2003) found that DEN1 catalyzed hydrolysis of a NEDD8
substrate at a much higher rate than it did a ubiquitin substrate. It
did not catalyze hydrolysis of a SUMO1 substrate.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NEDP1
gene to chromosome 15 (TMAP SGC33966).
*FIELD* RF
1. Gan-Erdene, T.; Nagamalleswari, K.; Yin, L.; Wu, K.; Pan, Z.-Q.;
Wilkinson, K. D.: Identification and characterization of DEN1, a
deneddylase of the ULP family. J. Biol. Chem. 278: 28882-28900,
2003.
2. Mendoza, H. M.; Shen, L.; Botting, C.; Lewis, A.; Chen, J.; Ink,
B.; Hay, R. T.: NEDP1, a highly conserved cysteine protease that
deNEDDylates cullins. J. Biol. Chem. 278: 25637-25643, 2003.
3. Wu, K.; Yamoah, K.; Dolios, G.; Gan-Erdene, T.; Tan, P.; Chen,
A.; Lee, C.; Wei, N.; Wilkinson, K. D.; Wang, R.; Pan, Z.-Q.: DEN1
is a dual function protease capable of processing the C terminus of
Nedd8 and deconjugating hyper-neddylated CUL1. J. Biol. Chem. 278:
28882-28891, 2003.
*FIELD* CD
Patricia A. Hartz: 5/14/2004
*FIELD* ED
mgross: 05/14/2004