ID   UBP36_DROME             Reviewed;        1038 AA.
AC   Q9VRP5; M9NE30; Q7YTX7; Q86NM9; Q8IQ57; Q8IQ58; Q8IQ59; Q8IQ60; Q960Q4;
DT   07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 3.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 36;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 36;
DE   AltName: Full=Protein scrawny;
DE   AltName: Full=Ubiquitin thioesterase 36;
DE   AltName: Full=Ubiquitin-specific-processing protease 36;
GN   Name=scny; Synonyms=Usp36; ORFNames=CG5505;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC   STRAIN=Berkeley; TISSUE=Embryo;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS C AND D).
RC   STRAIN=Berkeley; TISSUE=Testis;
RA   Stapleton M., Brokstein P., Hong L., Agbayani A., Booth B., Carlson J.W.,
RA   Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E.,
RA   George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G.,
RA   Miranda A., Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S.,
RA   Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M.,
RA   Celniker S.E.;
RL   Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-513; SER-515; THR-658;
RP   THR-662; SER-672; SER-674; SER-747; SER-779; THR-782; SER-785; SER-819;
RP   THR-825; SER-843 AND THR-846, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Embryo;
RX   PubMed=18327897; DOI=10.1021/pr700696a;
RA   Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT   "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL   J. Proteome Res. 7:1675-1682(2008).
RN   [6]
RP   FUNCTION, INTERACTION WITH IMD, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP   AND MUTAGENESIS OF CYS-181 AND HIS-439.
RX   PubMed=19837371; DOI=10.1016/j.chom.2009.09.007;
RA   Thevenon D., Engel E., Avet-Rochex A., Gottar M., Bergeret E., Tricoire H.,
RA   Benaud C., Baudier J., Taillebourg E., Fauvarque M.O.;
RT   "The Drosophila ubiquitin-specific protease dUSP36/Scny targets IMD to
RT   prevent constitutive immune signaling.";
RL   Cell Host Microbe 6:309-320(2009).
RN   [7]
RP   FUNCTION, INTERACTION WITH ATMS, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP   CYS-181.
RX   PubMed=19039105; DOI=10.1126/science.1165678;
RA   Buszczak M., Paterno S., Spradling A.C.;
RT   "Drosophila stem cells share a common requirement for the histone H2B
RT   ubiquitin protease scrawny.";
RL   Science 323:248-251(2009).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22622177; DOI=10.4161/auto.19381;
RA   Taillebourg E., Gregoire I., Viargues P., Jacomin A.C., Thevenon D.,
RA   Faure M., Fauvarque M.O.;
RT   "The deubiquitinating enzyme USP36 controls selective autophagy activation
RT   by ubiquitinated proteins.";
RL   Autophagy 8:767-779(2012).
RN   [9]
RP   FUNCTION.
RX   PubMed=25027767; DOI=10.1186/s12964-014-0041-2;
RA   Engel E., Viargues P., Mortier M., Taillebourg E., Coute Y., Thevenon D.,
RA   Fauvarque M.O.;
RT   "Identifying USPs regulating immune signals in Drosophila: USP2
RT   deubiquitinates Imd and promotes its degradation by interacting with the
RT   proteasome.";
RL   Cell Commun. Signal. 12:41-41(2014).
CC   -!- FUNCTION: Hydrolase that deubiquitinates polyubiquitinated target
CC       proteins including imd (PubMed:19837371, PubMed:19039105). Required for
CC       preventing the constitutive activation of the imd/NF-kappa-B (Imd)
CC       signaling cascade under unchalleneged conditions (PubMed:19837371,
CC       PubMed:25027767). Deubiquitinates imd linked 'Lys-63' chains which
CC       leads its proteasomal degradation and consequently down-regulation of
CC       the Imd signaling cascade (PubMed:19837371). Removal of the activating
CC       'Lys-63'-linked chains is likely to enable their replacement with 'Lys-
CC       48'-linked chains which act as 'tags' the for proteasomal degradation
CC       of imd (PubMed:19837371). Required for maintaining multiple types of
CC       adult stem cells, including male and female germline, epithelial
CC       follicle cell and intestinal stem cells (PubMed:19039105). May function
CC       as a transcriptional repressor by continually deubiquiting histone H2B
CC       at the promoters of genes critical for cellular differentiation,
CC       thereby preventing histone H3 'Lys-4' trimethylation (H3K4me3)
CC       (PubMed:19039105). Controls selective autophagy activation by
CC       ubiquitinated proteins (PubMed:22622177). {ECO:0000269|PubMed:19039105,
CC       ECO:0000269|PubMed:19837371, ECO:0000269|PubMed:22622177,
CC       ECO:0000269|PubMed:25027767}.
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;
CC   -!- SUBUNIT: Interacts with atms/PAF1, but not with CycT (PubMed:19039105).
CC       Interacts (via C-terminus) with imd (via N-terminus) (PubMed:19837371).
CC       {ECO:0000269|PubMed:19039105, ECO:0000269|PubMed:19837371}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:19039105}.
CC       Cytoplasm {ECO:0000269|PubMed:19837371}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC       Name=D;
CC         IsoId=Q9VRP5-3; Sequence=Displayed;
CC       Name=B;
CC         IsoId=Q9VRP5-2; Sequence=VSP_037591, VSP_037592;
CC       Name=C;
CC         IsoId=Q9VRP5-6; Sequence=VSP_037590, VSP_037593;
CC       Name=G; Synonyms=H;
CC         IsoId=Q9VRP5-7; Sequence=VSP_054032;
CC       Name=I;
CC         IsoId=Q9VRP5-8; Sequence=VSP_037590, VSP_037593, VSP_054032;
CC       Name=J;
CC         IsoId=Q9VRP5-9; Sequence=VSP_037591, VSP_037592, VSP_054032;
CC   -!- DISRUPTION PHENOTYPE: Mutants are lethal at larval stages
CC       (PubMed:19837371, PubMed:22622177). They are significantly smaller
CC       without gross morphological defects and die 5 days after egg laying
CC       (PubMed:22622177). Cells show accumulation of ubiquitinated proteins in
CC       both the nucleus and the cytoplasm, forming dense dots
CC       (PubMed:22622177). Double mutants for ref(2)P and scny die 96 hours
CC       after egg laying (PubMed:22622177). RNAi-mediated knockdown is also
CC       larval lethal (PubMed:19837371). RNAi-mediated knockdown in the fat
CC       body or gut of uninfected adults, results in a significant increase in
CC       the expression of the antimicrobial peptide genes Dpt, AttA and puc
CC       (PubMed:19837371). Adults raised under axenic conditions do not display
CC       any increase in Dpt, AttA and puc expression (PubMed:19837371). No
CC       significant increase in the expression of the antifungal peptide gene
CC       Drs (PubMed:19837371). Double knockdown with imd in the adult fat body,
CC       prevents the enhanced expression of Dpt in uninfected flies
CC       (PubMed:19837371). {ECO:0000269|PubMed:19837371,
CC       ECO:0000269|PubMed:22622177}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR   EMBL; AE014296; AAN12107.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12108.2; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12109.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12110.2; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12111.1; -; Genomic_DNA.
DR   EMBL; AE014296; AFH04310.1; -; Genomic_DNA.
DR   EMBL; AE014296; AFH04311.1; -; Genomic_DNA.
DR   EMBL; AY051916; AAK93340.1; -; mRNA.
DR   EMBL; BT004507; AAO42671.1; -; mRNA.
DR   EMBL; BT010120; AAQ22589.1; -; mRNA.
DR   EMBL; BT046169; ACI47091.1; -; mRNA.
DR   RefSeq; NP_001246639.1; NM_001259710.2. [Q9VRP5-7]
DR   RefSeq; NP_001246640.1; NM_001259711.2. [Q9VRP5-7]
DR   RefSeq; NP_647986.3; NM_139729.3. [Q9VRP5-9]
DR   RefSeq; NP_729092.1; NM_168132.3. [Q9VRP5-3]
DR   RefSeq; NP_729093.2; NM_168133.2. [Q9VRP5-8]
DR   RefSeq; NP_729094.1; NM_168134.2. [Q9VRP5-6]
DR   RefSeq; NP_729095.1; NM_168135.2. [Q9VRP5-2]
DR   AlphaFoldDB; Q9VRP5; -.
DR   SMR; Q9VRP5; -.
DR   BioGRID; 64109; 11.
DR   IntAct; Q9VRP5; 99.
DR   STRING; 7227.FBpp0076806; -.
DR   MEROPS; C19.097; -.
DR   iPTMnet; Q9VRP5; -.
DR   PaxDb; 7227-FBpp0076806; -.
DR   DNASU; 38648; -.
DR   EnsemblMetazoa; FBtr0077100; FBpp0076806; FBgn0260936. [Q9VRP5-3]
DR   EnsemblMetazoa; FBtr0077101; FBpp0076807; FBgn0260936. [Q9VRP5-2]
DR   EnsemblMetazoa; FBtr0077103; FBpp0076809; FBgn0260936. [Q9VRP5-6]
DR   EnsemblMetazoa; FBtr0307975; FBpp0300344; FBgn0260936. [Q9VRP5-7]
DR   EnsemblMetazoa; FBtr0307976; FBpp0300345; FBgn0260936. [Q9VRP5-7]
DR   EnsemblMetazoa; FBtr0330127; FBpp0303160; FBgn0260936. [Q9VRP5-8]
DR   EnsemblMetazoa; FBtr0330128; FBpp0303161; FBgn0260936. [Q9VRP5-9]
DR   GeneID; 38648; -.
DR   KEGG; dme:Dmel_CG5505; -.
DR   AGR; FB:FBgn0260936; -.
DR   CTD; 38648; -.
DR   FlyBase; FBgn0260936; scny.
DR   VEuPathDB; VectorBase:FBgn0260936; -.
DR   eggNOG; KOG1865; Eukaryota.
DR   GeneTree; ENSGT00940000170426; -.
DR   HOGENOM; CLU_006208_0_0_1; -.
DR   InParanoid; Q9VRP5; -.
DR   OMA; KRFSMMG; -.
DR   OrthoDB; 227085at2759; -.
DR   PhylomeDB; Q9VRP5; -.
DR   Reactome; R-DME-5689880; Ub-specific processing proteases.
DR   Reactome; R-DME-9648002; RAS processing.
DR   SignaLink; Q9VRP5; -.
DR   BioGRID-ORCS; 38648; 2 hits in 3 CRISPR screens.
DR   ChiTaRS; scny; fly.
DR   GenomeRNAi; 38648; -.
DR   PRO; PR:Q9VRP5; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0260936; Expressed in saliva-secreting gland and 24 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; HDA:FlyBase.
DR   GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:FlyBase.
DR   GO; GO:0061578; F:K63-linked deubiquitinase activity; IDA:FlyBase.
DR   GO; GO:0030718; P:germ-line stem cell population maintenance; IMP:UniProtKB.
DR   GO; GO:0031507; P:heterochromatin formation; IMP:FlyBase.
DR   GO; GO:0002785; P:negative regulation of antimicrobial peptide production; IMP:FlyBase.
DR   GO; GO:0045824; P:negative regulation of innate immune response; IMP:FlyBase.
DR   GO; GO:0016242; P:negative regulation of macroautophagy; IMP:UniProtKB.
DR   GO; GO:0061060; P:negative regulation of peptidoglycan recognition protein signaling pathway; IMP:FlyBase.
DR   GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IMP:FlyBase.
DR   GO; GO:0016579; P:protein deubiquitination; IMP:UniProtKB.
DR   GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:FlyBase.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0042981; P:regulation of apoptotic process; IMP:FlyBase.
DR   GO; GO:0035019; P:somatic stem cell population maintenance; IMP:UniProtKB.
DR   CDD; cd02661; Peptidase_C19E; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF758; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 36; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; Q9VRP5; DM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein;
KW   Protease; Reference proteome; Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..1038
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 36"
FT                   /id="PRO_0000378498"
FT   DOMAIN          172..480
FT                   /note="USP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT   REGION          22..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          107..148
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          487..794
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          818..881
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          912..985
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1000..1038
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        487..519
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        529..561
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        582..614
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        631..645
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        678..694
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        695..728
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        729..746
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        760..776
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        825..847
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        857..881
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        912..940
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        942..960
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        181
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT                   ECO:0000305|PubMed:19039105, ECO:0000305|PubMed:19837371"
FT   ACT_SITE        439
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093,
FT                   ECO:0000305|PubMed:19837371"
FT   MOD_RES         513
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         515
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         658
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         662
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         672
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         674
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         747
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         779
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         782
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         785
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         819
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         825
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         843
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         846
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   VAR_SEQ         1..90
FT                   /note="Missing (in isoform C and isoform I)"
FT                   /evidence="ECO:0000303|Ref.4"
FT                   /id="VSP_037590"
FT   VAR_SEQ         1..70
FT                   /note="Missing (in isoform B and isoform J)"
FT                   /evidence="ECO:0000303|PubMed:12537569"
FT                   /id="VSP_037591"
FT   VAR_SEQ         71..110
FT                   /note="ESVLENLKSKYIVIKPGNPGAINGFSGKNNTGKLVGANGH -> MTVIMVDG
FT                   FALWLLYKLFLSPCCLLLWHVLKLSTVLFTFA (in isoform B and isoform
FT                   J)"
FT                   /evidence="ECO:0000303|PubMed:12537569"
FT                   /id="VSP_037592"
FT   VAR_SEQ         91..110
FT                   /note="AINGFSGKNNTGKLVGANGH -> MLHSPVPRYNKCVPFPTLRT (in
FT                   isoform C and isoform I)"
FT                   /evidence="ECO:0000303|Ref.4"
FT                   /id="VSP_037593"
FT   VAR_SEQ         911..1038
FT                   /note="ELLVDAREQRQRDIDDDEENEMDRGRQRKVKSGSAKGNNASNSTPGYNPFQE
FT                   YEGQKRWNKNGGGGGFPRFYNQNYRQNFQQRNKFKFNRFGGPGSAKFQQQRALQRHLSA
FT                   GGGFSRRQPSAQQQQQT -> ETFELVCAKRIAGHGSVEGSDIVEGSVAVDAAVTSGSD
FT                   SKDVVVIAVAVTDTTADAPDPDRLTDGR (in isoform G, isoform I and
FT                   isoform J)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_054032"
FT   MUTAGEN         181
FT                   /note="C->S: Loss of H2B deubiquitination. Loss of
FT                   'K-48'- and 'K-63'-linked polyubiquitin chain hydrolysis;
FT                   when associated with N-369."
FT                   /evidence="ECO:0000269|PubMed:19039105,
FT                   ECO:0000269|PubMed:19837371"
FT   MUTAGEN         439
FT                   /note="H->N: Loss of 'K-48'- and 'K-63'-linked
FT                   polyubiquitin chain hydrolysis; when associated with
FT                   S-181."
FT                   /evidence="ECO:0000269|PubMed:19837371"
FT   CONFLICT        115
FT                   /note="A -> T (in Ref. 4; AAQ22589)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        642
FT                   /note="N -> D (in Ref. 4; AAQ22589/AAO42671)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        766
FT                   /note="P -> T (in Ref. 4; AAQ22589)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1038 AA;  114088 MW;  98CECD6993333E22 CRC64;
     MPVSMAVCET ANVVNAALRE SLGGNSSAGS STDQAKSGED TNGSLQNHIV ANAKRILMAK
     IEYEEVPNYH ESVLENLKSK YIVIKPGNPG AINGFSGKNN TGKLVGANGH DNNGARKQAE
     HPNNQSHHIN HHNHQHPTSN PNELPKPKRV LYPRENIRIG WKQSERKWQV GTGMINVGNT
     CYLNSTLQAL LHIPALANWL VSEQAHLADC NVAEPGSGCI ICAMTKTLLA TQSNQSAVRP
     FLIYSKLKQI CKHMVVGRQE DAHEFLRFLV EAMERAYLMR FRNYKELDQL VKETTPLGQI
     FGGYLRSEVR CLSCNHVSIT FQHFQDLLLD IRKADSLEDA FEGHFSRERL EDMGYKCEGC
     KKKVSATKQF SLERAPITLC IQLKRFSMIG NKLTKQISFK SRIDLSKYAA RSQAAQAQPL
     TYRLVSMVTH LGASQHCGHY TAIGSTDTGS FYNFDDSYVR PIAMHSVCNT NAYIMFFELD
     LSQAASPAAN RPNGVRLTNG HSTTPVPAAT VSSPSPTRFI GPQLPAGGAN GYTNGNAQKT
     AIQFKQQNQQ SPQNGLQLGT GKFQDTAKPP LVGAHAKGEA TSAPTANGNK SSSPSSNSSS
     NHKSINQQQY LPISSDDEDI EDEMKPRPTT AQLPSMPNMT ENHTEPKAKS PVKIQVKTPV
     KTPLKSLVPY ESASEEEEAP LPNPRKRPSG EDSSESDQES GQTNGHSKTN GSHTNGSASS
     SVHVNNSKQK TDAIDEIFKS LKKSADSDED DDEEEPSIQL TNGWHPQKQS QSQSKAPPSP
     KTPPSPAVIK SKTGIWKVTR NDEVDAIEDD VDVVVVEGSP VKIPTPNKNH RNPFSSSKPS
     TDSPATPGAK RQKLLNGSAL KSHQQPRVGN GYQSNATSNG STINELLKQS YRGYGSPVLS
     WNGKPAELEK ELLVDAREQR QRDIDDDEEN EMDRGRQRKV KSGSAKGNNA SNSTPGYNPF
     QEYEGQKRWN KNGGGGGFPR FYNQNYRQNF QQRNKFKFNR FGGPGSAKFQ QQRALQRHLS
     AGGGFSRRQP SAQQQQQT
//