ID NOT_DROME Reviewed; 496 AA.
AC Q9VVR1; Q95TK9; Q9U6Q9; X2JCK7;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 4.
DT 27-MAR-2024, entry version 173.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase nonstop;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme nonstop;
DE AltName: Full=Ubiquitin thioesterase nonstop;
DE AltName: Full=Ubiquitin-specific-processing protease nonstop;
GN Name=not; ORFNames=CG4166;
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 [MRNA], FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=11182084; DOI=10.1016/s0896-6273(01)00183-0;
RA Poeck B., Fischer S., Gunning D., Zipursky S.L., Salecker I.;
RT "Glial cells mediate target layer selection of retinal axons in the
RT developing visual system of Drosophila.";
RL Neuron 29:99-113(2001).
RN [2]
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 [3]
RP GENOME REANNOTATION.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP FUNCTION, DISRUPTION PHENOTYPE, IDENTIFICATION IN THE SAGA COMPLEX, AND
RP INTERACTION WITH SGF11.
RX PubMed=18188155; DOI=10.1038/sj.emboj.7601966;
RA Weake V.M., Lee K.K., Guelman S., Lin C.-H., Seidel C., Abmayr S.M.,
RA Workman J.L.;
RT "SAGA-mediated H2B deubiquitination controls the development of neuronal
RT connectivity in the Drosophila visual system.";
RL EMBO J. 27:394-405(2008).
RN [6]
RP FUNCTION.
RX PubMed=18206972; DOI=10.1016/j.molcel.2007.12.011;
RA Zhao Y., Lang G., Ito S., Bonnet J., Metzger E., Sawatsubashi S.,
RA Suzuki E., Le Guezennec X., Stunnenberg H.G., Krasnov A., Georgieva S.G.,
RA Schuele R., Takeyama K., Kato S., Tora L., Devys D.;
RT "A TFTC/STAGA module mediates histone H2A and H2B deubiquitination,
RT coactivates nuclear receptors, and counteracts heterochromatin silencing.";
RL Mol. Cell 29:92-101(2008).
CC -!- FUNCTION: Histone deubiquitinating component of the transcription
CC regulatory histone acetylation (HAT) complex SAGA. Catalyzes the
CC deubiquitination of histone H2B, thereby acting as a coactivator in a
CC large subset of genes. Required to counteract heterochromatin
CC silencing. Controls the development of neuronal connectivity in visual
CC system by being required for accurate axon targeting in the optic lobe.
CC Required for expression of ecdysone-induced genes such as br/broad.
CC {ECO:0000269|PubMed:11182084, ECO:0000269|PubMed:18188155,
CC ECO:0000269|PubMed:18206972}.
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: Component of the SAGA transcription coactivator-HAT complex,
CC at least composed of Ada2b, not/nonstop, Pcaf/Gcn5, Sgf11 and Spt3.
CC {ECO:0000269|PubMed:18188155}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the optic lobe and central brain.
CC Highly expressed in the lamina precursor cells but not in
CC differentiated lamina neurons. Also expressed in marginal, epithelial
CC and medulla glial cells adjacent to the lamina plexus.
CC {ECO:0000269|PubMed:11182084}.
CC -!- DISRUPTION PHENOTYPE: Defects in the number and migration of glial
CC cells located within the lamina plexus of the developing eye; the lack
CC of glial cells causing mistargeting of the R1-R6 axons in the optic
CC lobe. Lamina neuron development is normal.
CC {ECO:0000269|PubMed:11182084, ECO:0000269|PubMed:18188155}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. UBP8 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD53181.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAL13936.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF179590; AAD53181.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AE014296; AAF49249.2; -; Genomic_DNA.
DR EMBL; AE014296; AHN58131.1; -; Genomic_DNA.
DR EMBL; AY058707; AAL13936.1; ALT_INIT; mRNA.
DR RefSeq; NP_001287106.1; NM_001300177.1.
DR RefSeq; NP_524140.2; NM_079416.4.
DR AlphaFoldDB; Q9VVR1; -.
DR SMR; Q9VVR1; -.
DR BioGRID; 65311; 20.
DR ComplexPortal; CPX-2644; SAGA complex.
DR IntAct; Q9VVR1; 4.
DR MINT; Q9VVR1; -.
DR STRING; 7227.FBpp0312097; -.
DR MEROPS; C19.095; -.
DR PaxDb; 7227-FBpp0288698; -.
DR DNASU; 40030; -.
DR EnsemblMetazoa; FBtr0290259; FBpp0288698; FBgn0013717.
DR EnsemblMetazoa; FBtr0346438; FBpp0312097; FBgn0013717.
DR GeneID; 40030; -.
DR KEGG; dme:Dmel_CG4166; -.
DR UCSC; CG4166-RB; d. melanogaster.
DR AGR; FB:FBgn0013717; -.
DR CTD; 40030; -.
DR FlyBase; FBgn0013717; not.
DR VEuPathDB; VectorBase:FBgn0013717; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000156623; -.
DR HOGENOM; CLU_008279_11_0_1; -.
DR InParanoid; Q9VVR1; -.
DR OMA; QRDQWFK; -.
DR OrthoDB; 227085at2759; -.
DR PhylomeDB; Q9VVR1; -.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 40030; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Not1; fly.
DR GenomeRNAi; 40030; -.
DR PRO; PR:Q9VVR1; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0013717; Expressed in saliva-secreting gland and 12 other cell types or tissues.
DR Genevisible; Q9VVR1; DM.
DR GO; GO:0071819; C:DUBm complex; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0000124; C:SAGA complex; IDA:FlyBase.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISM:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007412; P:axon target recognition; IMP:FlyBase.
DR GO; GO:0006325; P:chromatin organization; IMP:UniProtKB.
DR GO; GO:0021782; P:glial cell development; IMP:FlyBase.
DR GO; GO:0008347; P:glial cell migration; IMP:FlyBase.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IMP:FlyBase.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IGI:FlyBase.
DR CDD; cd02660; Peptidase_C19D; 1.
DR Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR PANTHER; PTHR21646:SF33; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 22; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SUPFAM; SSF54001; Cysteine proteinases; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW Activator; Chromatin regulator; Hydrolase; Metal-binding; Nucleus;
KW Protease; Reference proteome; Thiol protease; Transcription;
KW Transcription regulation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..496
FT /note="Ubiquitin carboxyl-terminal hydrolase nonstop"
FT /id="PRO_0000367514"
FT DOMAIN 158..491
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ZN_FING 4..120
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT ACT_SITE 167
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ACT_SITE 450
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT BINDING 6
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 8
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 49
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 59
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 62
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 71
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
SQ SEQUENCE 496 AA; 56441 MW; 9EB4690FB968A3DE CRC64;
MSETGCRHYQ SYVKEHSYDT FRVIDAYFAA CVNRDARERK AIHCNCFECG SYGIQLYACL
HCIYFGCRGA HITSHLRSKK HNVALELSHG TLYCYACRDF IYDARSREYA LINRKLEAKD
LQKSIGWVPW VPTTKETNLL LANARRRLVR PNQTIGLRGL LNLGATCFMN CIVQALVHTP
LLSDYFMSDR HDCGSKSSHK CLVCEVSRLF QEFYSGSRSP LSLHRLLHLI WNHAKHLAGY
EQQDAHEFFI ATLDVLHRHC VKAKAEHESK SNSSGSGSGT NSSNSSSSHC YGQCNCIIDQ
IFTGMLQSDV VCQACNGVST TYDPFWDISL DLGETTTHGG VTPKTLIDCL ERYTRAEHLG
SAAKIKCSTC KSYQESTKQF SLRTLPSVVS FHLKRFEHSA LIDRKISSFI QFPVEFDMTP
FMSEKKNAYG DFRFSLYAVV NHVGTIDTGH YTAYVRHQKD TWVKCDDHVI TMASLKQVLD
SEGYLLFYHK NVLEYE
//
