ID DESI2_HUMAN Reviewed; 194 AA. AC Q9BSY9; B1APK6; Q5VVC6; Q9NYS2; Q9Y3E4; DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-NOV-2024, entry version 157. DE RecName: Full=Deubiquitinase DESI2 {ECO:0000305}; DE EC=3.4.19.12 {ECO:0000269|PubMed:28483520}; DE AltName: Full=Desumoylating isopeptidase 2; DE Short=DeSI-2; DE AltName: Full=PPPDE peptidase domain-containing protein 1 {ECO:0000303|PubMed:28483520}; DE AltName: Full=Palmitoyl protein thioesterase DESI2; DE EC=3.1.2.22 {ECO:0000269|PubMed:35427157}; DE AltName: Full=Protein FAM152A; DE AltName: Full=S-depalmitoylase DESI2; GN Name=DESI2; GN Synonyms=C1orf121, FAM152A, PPPDE1 {ECO:0000303|PubMed:28483520}; GN ORFNames=CGI-146, PNAS-4; 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 [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Promyelocytic leukemia; RA Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F., Yan W., RA Yang H., Zhao Z.-L.; RT "Human acute promyelocytic leukemia cell line NB4's apoptosis related RT genes."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP MUTAGENESIS OF CYS-108, INTERACTION WITH RPS7, FUNCTION, ACTIVE SITE, AND RP CATALYTIC ACTIVITY. RX PubMed=28483520; DOI=10.1016/j.bbrc.2017.04.161; RA Xie X., Wang X., Jiang D., Wang J., Fei R., Cong X., Wei L., Wang Y., RA Chen H.; RT "PPPDE1 is a novel deubiquitinase belonging to a cysteine isopeptidase RT family."; RL Biochem. Biophys. Res. Commun. 488:291-296(2017). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=35427157; DOI=10.1126/sciadv.abj8633; RA Luebben A.V., Bender D., Becker S., Crowther L.M., Erven I., Hofmann K., RA Soeding J., Klemp H., Bellotti C., Staeuble A., Qiu T., Kathayat R.S., RA Dickinson B.C., Gaertner J., Sheldrick G.M., Kraetzner R., Steinfeld R.; RT "Cln5 represents a new type of cysteine-based S-depalmitoylase linked to RT neurodegeneration."; RL Sci. Adv. 8:eabj8633-eabj8633(2022). CC -!- FUNCTION: Has deubiquitinating activity towards 'Lys-48'- and 'Lys-63'- CC linked polyubiquitin chains. Deubiquitinates 'Lys-48'-linked CC polyubiquitination of RPS7 leading to its stabilization CC (PubMed:28483520). Exhibits palmitoyl protein thioesterase (S- CC depalmitoylation) activity towards synthetic substrates 4- CC methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside and S- CC depalmitoylation probe 5 (DPP-5) (PubMed:35427157). CC {ECO:0000269|PubMed:28483520, ECO:0000269|PubMed:35427157}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:28483520}; CC -!- CATALYTIC ACTIVITY: CC Reaction=S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl- CC [protein] + hexadecanoate + H(+); Xref=Rhea:RHEA:19233, Rhea:RHEA- CC COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:7896, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, CC ChEBI:CHEBI:74151; EC=3.1.2.22; CC Evidence={ECO:0000269|PubMed:35427157}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19234; CC Evidence={ECO:0000305|PubMed:35427157}; CC -!- ACTIVITY REGULATION: Palmostatin B inhibits its palmitoyl protein CC thioesterase activity. {ECO:0000269|PubMed:35427157}. CC -!- SUBUNIT: Interacts with RPS7. {ECO:0000269|PubMed:28483520}. CC -!- INTERACTION: CC Q9BSY9; P53367: ARFIP1; NbExp=3; IntAct=EBI-12878374, EBI-2808808; CC Q9BSY9; Q12982: BNIP2; NbExp=3; IntAct=EBI-12878374, EBI-752094; CC Q9BSY9; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-12878374, EBI-745535; CC Q9BSY9; Q9HB07: MYG1; NbExp=3; IntAct=EBI-12878374, EBI-709754; CC Q9BSY9; Q9UMS0: NFU1; NbExp=3; IntAct=EBI-12878374, EBI-725252; CC Q9BSY9; Q96AL5: PBX3; NbExp=3; IntAct=EBI-12878374, EBI-741171; CC Q9BSY9; Q99541: PLIN2; NbExp=3; IntAct=EBI-12878374, EBI-2115275; CC Q9BSY9; Q9NS98: SEMA3G; NbExp=3; IntAct=EBI-12878374, EBI-17574989; CC Q9BSY9; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-12878374, EBI-2623095; CC Q9BSY9; Q8N0X7: SPART; NbExp=3; IntAct=EBI-12878374, EBI-2643803; CC Q9BSY9; Q9BT49: THAP7; NbExp=3; IntAct=EBI-12878374, EBI-741350; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9D291}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BSY9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BSY9-2; Sequence=VSP_011422; CC -!- SIMILARITY: Belongs to the DeSI family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD34141.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAF42919.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AF229834; AAF42919.1; ALT_INIT; mRNA. DR EMBL; AF151904; AAD34141.1; ALT_FRAME; mRNA. DR EMBL; AC099757; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL451007; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471148; EAW77114.1; -; Genomic_DNA. DR EMBL; CH471148; EAW77116.1; -; Genomic_DNA. DR EMBL; BC004485; AAH04485.1; -; mRNA. DR CCDS; CCDS1626.1; -. [Q9BSY9-1] DR CCDS; CCDS73055.1; -. [Q9BSY9-2] DR RefSeq; NP_001284675.1; NM_001297746.1. [Q9BSY9-2] DR RefSeq; NP_057160.2; NM_016076.4. [Q9BSY9-1] DR AlphaFoldDB; Q9BSY9; -. DR SMR; Q9BSY9; -. DR BioGRID; 119235; 20. DR IntAct; Q9BSY9; 14. DR STRING; 9606.ENSP00000306528; -. DR MEROPS; C97.002; -. DR iPTMnet; Q9BSY9; -. DR PhosphoSitePlus; Q9BSY9; -. DR SwissPalm; Q9BSY9; -. DR BioMuta; DESI2; -. DR DMDM; 51827943; -. DR jPOST; Q9BSY9; -. DR MassIVE; Q9BSY9; -. DR PaxDb; 9606-ENSP00000306528; -. DR PeptideAtlas; Q9BSY9; -. DR ProteomicsDB; 78934; -. [Q9BSY9-1] DR ProteomicsDB; 78935; -. [Q9BSY9-2] DR Pumba; Q9BSY9; -. DR Antibodypedia; 34714; 112 antibodies from 30 providers. DR DNASU; 51029; -. DR Ensembl; ENST00000263831.11; ENSP00000263831.7; ENSG00000121644.19. [Q9BSY9-2] DR Ensembl; ENST00000302550.16; ENSP00000306528.11; ENSG00000121644.19. [Q9BSY9-1] DR GeneID; 51029; -. DR KEGG; hsa:51029; -. DR MANE-Select; ENST00000302550.16; ENSP00000306528.11; NM_016076.5; NP_057160.2. DR UCSC; uc001iao.4; human. [Q9BSY9-1] DR AGR; HGNC:24264; -. DR CTD; 51029; -. DR DisGeNET; 51029; -. DR GeneCards; DESI2; -. DR HGNC; HGNC:24264; DESI2. DR HPA; ENSG00000121644; Low tissue specificity. DR MIM; 614638; gene. DR neXtProt; NX_Q9BSY9; -. DR OpenTargets; ENSG00000121644; -. DR PharmGKB; PA164724993; -. DR VEuPathDB; HostDB:ENSG00000121644; -. DR eggNOG; KOG0324; Eukaryota. DR GeneTree; ENSGT00730000111005; -. DR HOGENOM; CLU_069001_5_1_1; -. DR InParanoid; Q9BSY9; -. DR OMA; VYWTKPG; -. DR OrthoDB; 125022at2759; -. DR PhylomeDB; Q9BSY9; -. DR TreeFam; TF313188; -. DR PathwayCommons; Q9BSY9; -. DR SignaLink; Q9BSY9; -. DR BioGRID-ORCS; 51029; 12 hits in 1148 CRISPR screens. DR ChiTaRS; DESI2; human. DR GenomeRNAi; 51029; -. DR Pharos; Q9BSY9; Tbio. DR PRO; PR:Q9BSY9; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9BSY9; protein. DR Bgee; ENSG00000121644; Expressed in secondary oocyte and 220 other cell types or tissues. DR ExpressionAtlas; Q9BSY9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:FlyBase. DR GO; GO:0101005; F:deubiquitinase activity; IBA:GO_Central. DR GO; GO:1990380; F:K48-linked deubiquitinase activity; IMP:UniProtKB. DR GO; GO:0061578; F:K63-linked deubiquitinase activity; IMP:UniProtKB. DR GO; GO:0052816; F:long-chain fatty acyl-CoA hydrolase activity; IDA:UniProtKB. DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IEA:RHEA. DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR FunFam; 3.90.1720.30:FF:000001; desumoylating isopeptidase 2; 1. DR Gene3D; 3.90.1720.30; PPPDE domains; 1. DR InterPro; IPR008580; PPPDE_dom. DR InterPro; IPR042266; PPPDE_sf. DR PANTHER; PTHR12378; DESUMOYLATING ISOPEPTIDASE; 1. DR PANTHER; PTHR12378:SF6; DEUBIQUITINASE DESI2; 1. DR Pfam; PF05903; Peptidase_C97; 1. DR SMART; SM01179; DUF862; 1. DR PROSITE; PS51858; PPPDE; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Hydrolase; Protease; KW Proteomics identification; Reference proteome; Ubl conjugation pathway. FT CHAIN 1..194 FT /note="Deubiquitinase DESI2" FT /id="PRO_0000221630" FT DOMAIN 5..149 FT /note="PPPDE" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01205" FT REGION 165..194 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 30 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01205" FT ACT_SITE 108 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01205, FT ECO:0000269|PubMed:28483520" FT VAR_SEQ 39..71 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_011422" FT MUTAGEN 108 FT /note="C->S: Loss of deubiquitination activity." FT /evidence="ECO:0000269|PubMed:28483520" FT CONFLICT 180 FT /note="A -> V (in Ref. 1; AAF42919)" FT /evidence="ECO:0000305" SQ SEQUENCE 194 AA; 21444 MW; 9EADC1A33642EFFF CRC64; MGANQLVVLN VYDMYWMNEY TSSIGIGVFH SGIEVYGREF AYGGHPYPFS GIFEISPGNA SELGETFKFK EAVVLGSTDF LEDDIEKIVE ELGKEYKGNA YHLMHKNCNH FSSALSEILC GKEIPRWINR LAYFSSCIPF LQSCLPKEWL TPAALQSSVS QELQDELEEA EDAAASASVA STAAGSRPGR HTKL //