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   10-FEB-2021, entry version 138.
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=Protein FAM152A;
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).
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). {ECO:0000269|PubMed:28483520}.
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   -!- 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};
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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   SMR; Q9BSY9; -.
DR   BioGRID; 119235; 18.
DR   IntAct; Q9BSY9; 11.
DR   STRING; 9606.ENSP00000306528; -.
DR   MEROPS; C97.002; -.
DR   iPTMnet; Q9BSY9; -.
DR   PhosphoSitePlus; Q9BSY9; -.
DR   SwissPalm; Q9BSY9; -.
DR   BioMuta; DESI2; -.
DR   DMDM; 51827943; -.
DR   EPD; Q9BSY9; -.
DR   jPOST; Q9BSY9; -.
DR   MassIVE; Q9BSY9; -.
DR   MaxQB; Q9BSY9; -.
DR   PaxDb; Q9BSY9; -.
DR   PeptideAtlas; Q9BSY9; -.
DR   PRIDE; Q9BSY9; -.
DR   ProteomicsDB; 78934; -. [Q9BSY9-1]
DR   ProteomicsDB; 78935; -. [Q9BSY9-2]
DR   Antibodypedia; 34714; 111 antibodies.
DR   DNASU; 51029; -.
DR   Ensembl; ENST00000263831; ENSP00000263831; ENSG00000121644. [Q9BSY9-2]
DR   Ensembl; ENST00000302550; ENSP00000306528; ENSG00000121644. [Q9BSY9-1]
DR   GeneID; 51029; -.
DR   KEGG; hsa:51029; -.
DR   UCSC; uc001iao.4; human. [Q9BSY9-1]
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:ENSG00000121644.18; -.
DR   eggNOG; KOG0324; Eukaryota.
DR   GeneTree; ENSGT00730000111005; -.
DR   HOGENOM; CLU_069001_5_1_1; -.
DR   InParanoid; Q9BSY9; -.
DR   OMA; CVVPRDW; -.
DR   OrthoDB; 1300278at2759; -.
DR   PhylomeDB; Q9BSY9; -.
DR   TreeFam; TF313188; -.
DR   PathwayCommons; Q9BSY9; -.
DR   BioGRID-ORCS; 51029; 6 hits in 869 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 female reproductive system and 255 other tissues.
DR   ExpressionAtlas; Q9BSY9; baseline and differential.
DR   Genevisible; Q9BSY9; HS.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IMP:UniProtKB.
DR   GO; GO:0061578; F:Lys63-specific deubiquitinase activity; IMP:UniProtKB.
DR   GO; GO:0004843; F:thiol-dependent ubiquitin-specific protease activity; IDA:FlyBase.
DR   GO; GO:0101005; F:ubiquitinyl hydrolase activity; IBA:GO_Central.
DR   GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR   GO; GO:0070646; P:protein modification by small protein removal; IBA:GO_Central.
DR   Gene3D; 3.90.1720.30; -; 1.
DR   InterPro; IPR008580; PPPDE_dom.
DR   InterPro; IPR042266; PPPDE_sf.
DR   PANTHER; PTHR12378; PTHR12378; 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; Reference proteome;
KW   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   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
//