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 24-JAN-2024, entry version 172. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 30. 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; 9606-ENSP00000340505; -. DR PeptideAtlas; Q96LD8; -. DR ProteomicsDB; 77207; -. DR Pumba; Q96LD8; -. DR Antibodypedia; 26582; 321 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 AGR; HGNC:22992; -. 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; GFYFEYL; -. DR OrthoDB; 49695at2759; -. 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; 31 hits in 1158 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 125 other cell types or tissues. DR ExpressionAtlas; Q96LD8; baseline and differential. 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:0006508; P:proteolysis; IEA:UniProtKB-KW. DR InterPro; IPR044613; Nep1/2-like. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR003653; Peptidase_C48_C. DR PANTHER; PTHR46468; SENTRIN-SPECIFIC PROTEASE 8; 1. DR PANTHER; PTHR46468:SF1; SENTRIN-SPECIFIC PROTEASE 8; 1. DR Pfam; PF02902; Peptidase_C48; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS50600; ULP_PROTEASE; 1. DR Genevisible; Q96LD8; HS. 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 //