SENP8_HUMAN
ID SENP8_HUMAN Reviewed; 212 AA.
AC Q96LD8; Q96QA4;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Sentrin-specific protease 8;
DE EC=3.4.22.-;
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Hay R.T.;
RT "NEDP1, a highly conserved cysteine protease that deneddylates 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 protease
RT 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 cysteine
RT 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 project:
RT 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 MASS
RP 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., Lee C.-G.,
RA Wei N., Wilkinson K.D., Wang R., Pan Z.-Q.;
RT "DEN1 is a dual function protease capable of processing the C-terminus of
RT 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., 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 IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NEDD8, MUTAGENESIS OF
RP ASP-10; TRP-26; ASP-29; VAL-58; PHE-74; PRO-77; ASN-91; HIS-102; TRP-103;
RP 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 deneddylating
RT enzyme NEDP1.";
RL EMBO J. 24:1341-1351(2005).
RN [11]
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 NEDD8
CC pathway: processing of full-length NEDD8 to its mature form and
CC deconjugation of NEDD8 from targeted proteins such as cullins or p53.
CC {ECO:0000269|PubMed:12730221, ECO:0000269|PubMed:12759362,
CC ECO:0000269|PubMed:12759363, ECO:0000269|PubMed:15242646,
CC ECO:0000269|PubMed:15775960}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=51 nM for Nedd8-AMC {ECO:0000269|PubMed:12759362};
CC Note=KM for Ub-AMC exceeds 5 uM.;
CC -!- INTERACTION:
CC Q96LD8; P52757: CHN2; NbExp=3; IntAct=EBI-1041210, EBI-714925;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in kidney
CC and pancreas. {ECO:0000269|PubMed:12730221}.
CC -!- SIMILARITY: Belongs to the peptidase C48 family. {ECO:0000305}.
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DR EMBL; AY008293; AAG21828.1; -; mRNA.
DR EMBL; AF308450; AAL06294.1; -; mRNA.
DR EMBL; BC031411; AAH31411.1; -; mRNA.
DR CCDS; CCDS10240.1; -.
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_005254157.3.
DR RefSeq; XP_011519519.1; XM_011521217.2.
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 AlphaFoldDB; Q96LD8; -.
DR SMR; Q96LD8; -.
DR BioGRID; 125819; 24.
DR IntAct; Q96LD8; 6.
DR MINT; Q96LD8; -.
DR STRING; 9606.ENSP00000340505; -.
DR BindingDB; Q96LD8; -.
DR ChEMBL; CHEMBL1741207; -.
DR GuidetoPHARMACOLOGY; 2417; -.
DR MEROPS; C48.011; -.
DR iPTMnet; Q96LD8; -.
DR PhosphoSitePlus; Q96LD8; -.
DR BioMuta; SENP8; -.
DR DMDM; 26006881; -.
DR EPD; Q96LD8; -.
DR jPOST; Q96LD8; -.
DR MassIVE; Q96LD8; -.
DR MaxQB; Q96LD8; -.
DR PaxDb; Q96LD8; -.
DR PeptideAtlas; Q96LD8; -.
DR PRIDE; Q96LD8; -.
DR ProteomicsDB; 77207; -.
DR Antibodypedia; 26582; 298 antibodies from 29 providers.
DR DNASU; 123228; -.
DR Ensembl; ENST00000340912.6; ENSP00000340505.4; ENSG00000166192.15.
DR Ensembl; ENST00000542035.2; ENSP00000446057.2; ENSG00000166192.15.
DR GeneID; 123228; -.
DR KEGG; hsa:123228; -.
DR MANE-Select; ENST00000340912.6; ENSP00000340505.4; NM_145204.4; NP_660205.3.
DR UCSC; uc002atp.4; human.
DR CTD; 123228; -.
DR DisGeNET; 123228; -.
DR GeneCards; SENP8; -.
DR HGNC; HGNC:22992; SENP8.
DR HPA; ENSG00000166192; Tissue enhanced (testis).
DR MIM; 608659; gene.
DR neXtProt; NX_Q96LD8; -.
DR OpenTargets; ENSG00000166192; -.
DR PharmGKB; PA134866772; -.
DR VEuPathDB; HostDB:ENSG00000166192; -.
DR eggNOG; KOG3246; Eukaryota.
DR GeneTree; ENSGT00390000014038; -.
DR HOGENOM; CLU_043678_3_1_1; -.
DR InParanoid; Q96LD8; -.
DR OMA; LLDPPNW; -.
DR PhylomeDB; Q96LD8; -.
DR TreeFam; TF351057; -.
DR PathwayCommons; Q96LD8; -.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q96LD8; -.
DR BioGRID-ORCS; 123228; 27 hits in 1079 CRISPR screens.
DR EvolutionaryTrace; Q96LD8; -.
DR GeneWiki; SENP8; -.
DR GenomeRNAi; 123228; -.
DR Pharos; Q96LD8; Tchem.
DR PRO; PR:Q96LD8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96LD8; protein.
DR Bgee; ENSG00000166192; Expressed in sperm and 123 other tissues.
DR ExpressionAtlas; Q96LD8; baseline and differential.
DR Genevisible; Q96LD8; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0019784; F:deNEDDylase activity; IBA:GO_Central.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0000338; P:protein deneddylation; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; TAS:Reactome.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR003653; Peptidase_C48_C.
DR Pfam; PF02902; Peptidase_C48; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50600; ULP_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Hydrolase; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..212
FT /note="Sentrin-specific protease 8"
FT /id="PRO_0000101727"
FT REGION 11..174
FT /note="Protease"
FT ACT_SITE 102
FT ACT_SITE 119
FT ACT_SITE 163
FT /note="Nucleophile"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT VARIANT 207
FT /note="T -> A (in dbSNP:rs930871)"
FT /evidence="ECO:0000269|PubMed:12730221,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_023705"
FT MUTAGEN 10
FT /note="D->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 26
FT /note="W->A: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 29
FT /note="D->A,N: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 58
FT /note="V->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 74
FT /note="F->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 77
FT /note="P->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 91
FT /note="N->A: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 102
FT /note="H->N: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 103
FT /note="W->A,H: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 119
FT /note="D->A,N: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 157
FT /note="Q->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15775960"
FT MUTAGEN 163
FT /note="C->A: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:12730221,
FT ECO:0000269|PubMed:15242646, ECO:0000269|PubMed:15775960"
FT CONFLICT 14
FT /note="R -> W (in Ref. 3; AAL06294)"
FT /evidence="ECO:0000305"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 15..19
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 29..41
FT /evidence="ECO:0007829|PDB:2BKR"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:2BKR"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 56..64
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 68..75
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:2BKR"
FT TURN 122..125
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 126..140
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:2BKR"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 163..179
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:2BKR"
FT HELIX 192..210
FT /evidence="ECO:0007829|PDB:2BKR"
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
