Q9VVR1 (NOT_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase nonstop
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme nonstop
Ubiquitin thioesterase nonstop
Ubiquitin-specific-processing protease nonstop

Gene names

Name:	not
ORF Names:	CG4166

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	735 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complex SAGA. Catalyzes the deubiquitination of histone H2B, thereby acting as a coactivator in a large subset of genes. Required to counteract heterochromatin silencing. Controls the development of neuronal connectivity in visual system by being required for accurate axon targeting in the optic lobe. Required for expression of ecdysone-induced genes such as br/broad. Ref.1 Ref.5 Ref.6
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Subunit structure	Component of the SAGA transcription coactivator-HAT complex, at least composed of Ada2b, not/nonstop, Pcaf/Gcn5, Sgf11 and Spt3. Ref.5
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in the optic lobe and central brain. Highly expressed in the lamina precursor cells but not in differentiated lamina neurons. Also expressed in marginal, epithelial and medulla glial cells adjacent to the lamina plexus. Ref.1
Disruption phenotype	Defects in the number and migration of glial cells located within the lamina plexus of the developing eye; the lack of glial cells causing mistargeting of the R1-R6 axons in the optic lobe. Lamina neuron development is normal. Ref.1 Ref.5
Sequence similarities	Belongs to the peptidase C19 family. UBP8 subfamily. Contains 1 UBP-type zinc finger.
Sequence caution	The sequence AAF49249.2 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAL13936.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Activator Chromatin regulator Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Inferred from mutant phenotype PubMed 18516287. Source: FlyBase axon target recognition Inferred from mutant phenotype Ref.5PubMed 7857635. Source: FlyBase glial cell development Inferred from mutant phenotype Ref.1. Source: FlyBase glial cell migration Inferred from mutant phenotype Ref.1. Source: FlyBase histone deubiquitination Inferred from mutant phenotype Ref.5. Source: FlyBase positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.6. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process Inferred from genetic interaction Ref.1. Source: FlyBase
Cellular_component	SAGA complex Inferred from direct assay Ref.5PubMed 21764853. Source: FlyBase
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 735	735	Ubiquitin carboxyl-terminal hydrolase nonstop		PRO_0000367514
Regions
	Zinc finger	283 – 342	60	UBP-type
Sites
	Active site	406	1	Nucleophile By similarity
	Active site	689	1	Proton acceptor By similarity
Experimental info
	Sequence conflict	190	1	A → T in AAD53181. Ref.1
	Sequence conflict	199	1	H → N in AAD53181. Ref.1
	Sequence conflict	235	1	A → D in AAD53181. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9VVR1 [UniParc]. Last modified April 14, 2009. Version 3. Checksum: EAE3F4B1DBFF850F	FASTA	735	82,458
	10 20 30 40 50 60 MFQYSYIRKI PMPTSEYDFA TGHTDSCLLP THMRACVCVC VQCEIETRKA SEKSQKFTKK 70 80 90 100 110 120 KPNYFQNWAA RRRTAKVAKI RRKQRKCDKA FVPLQSSAKR AKTKENSVDS NTSVFSSSSS 130 140 150 160 170 180 SSSGRSFGRG TERWAVGAEA GRGTAENETL AVAAAAATTT NAGRFITADL IKTVNSDKQR 190 200 210 220 230 240 DRVAKGHRDA KNPLDATKHL RLSDCLRTVQ KLAIELESAD AGSDASAQAN ASADASSAVM 250 260 270 280 290 300 SETGCRHYQS YVKEHSYDTF RVIDAYFAAC VNRDARERKA IHCNCFECGS YGIQLYACLH 310 320 330 340 350 360 CIYFGCRGAH ITSHLRSKKH NVALELSHGT LYCYACRDFI YDARSREYAL INRKLEAKDL 370 380 390 400 410 420 QKSIGWVPWV PTTKETNLLL ANARRRLVRP NQTIGLRGLL NLGATCFMNC IVQALVHTPL 430 440 450 460 470 480 LSDYFMSDRH DCGSKSSHKC LVCEVSRLFQ EFYSGSRSPL SLHRLLHLIW NHAKHLAGYE 490 500 510 520 530 540 QQDAHEFFIA TLDVLHRHCV KAKAEHESKS NSSGSGSGTN SSNSSSSHCY GQCNCIIDQI 550 560 570 580 590 600 FTGMLQSDVV CQACNGVSTT YDPFWDISLD LGETTTHGGV TPKTLIDCLE RYTRAEHLGS 610 620 630 640 650 660 AAKIKCSTCK SYQESTKQFS LRTLPSVVSF HLKRFEHSAL IDRKISSFIQ FPVEFDMTPF 670 680 690 700 710 720 MSEKKNAYGD FRFSLYAVVN HVGTIDTGHY TAYVRHQKDT WVKCDDHVIT MASLKQVLDS 730 EGYLLFYHKN VLEYE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Glial cells mediate target layer selection of retinal axons in the developing visual system of Drosophila." Poeck B., Fischer S., Gunning D., Zipursky S.L., Salecker I. Neuron 29:99-113(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[2]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[3]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[4]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 27-735. Strain: Berkeley. Tissue: Embryo.
[5]	"SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system." Weake V.M., Lee K.K., Guelman S., Lin C.-H., Seidel C., Abmayr S.M., Workman J.L. EMBO J. 27:394-405(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, IDENTIFICATION IN THE SAGA COMPLEX, INTERACTION WITH SGF11.
[6]	"A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing." Zhao Y., Lang G., Ito S., Bonnet J., Metzger E., Sawatsubashi S., Suzuki E., Le Guezennec X., Stunnenberg H.G., Krasnov A., Georgieva S.G., Schuele R., Takeyama K., Kato S., Tora L., Devys D. Mol. Cell 29:92-101(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF179590 Genomic DNA. Translation: AAD53181.1. AE014296 Genomic DNA. Translation: AAF49249.2. Sequence problems. AY058707 mRNA. Translation: AAL13936.1. Different initiation.
RefSeq	NP_524140.2. NM_079416.4.
UniGene	Dm.2731.
3D structure databases
HSSP	HSSP built from PDB template 2AYN based on UniProtKB P54578.
ProteinModelPortal	Q9VVR1.
SMR	Q9VVR1. Positions 296-727.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9VVR1. 1 interaction.
MINT	MINT-6179419.
STRING	7227.FBpp0288698.
Protein family/group databases
MEROPS	C19.095.
Proteomic databases
PaxDb	Q9VVR1.
PRIDE	Q9VVR1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	40030.
KEGG	dme:Dmel_CG4166.
UCSC	CG4166-RB. d. melanogaster.
Organism-specific databases
CTD	40030.
FlyBase	FBgn0013717. not.
Phylogenomic databases
eggNOG	COG5533.
InParanoid	Q9U6Q9.
KO	K11366.
OrthoDB	EOG4M37QR.
Gene expression databases
Bgee	Q9VVR1.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR015880. Znf_C2H2-like. IPR013083. Znf_RING/FYVE/PHD. IPR001607. Znf_UBP. [Graphical view]
Pfam	PF00443. UCH. 1 hit. PF02148. zf-UBP. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 2 hits. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS50271. ZF_UBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	40030.
NextBio	816633.

Entry information

Entry name

NOT_DROME

Accession

Primary (citable) accession number: Q9VVR1
Secondary accession number(s): Q95TK9, Q9U6Q9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 14, 2009
Last sequence update:	April 14, 2009
Last modified:	May 1, 2013
This is version 102 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project