SUDX_DROME
ID SUDX_DROME Reviewed; 949 AA.
AC Q9Y0H4; A4UZZ3; Q0E8U5; Q8T0C8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=E3 ubiquitin-protein ligase Su(dx);
DE EC=2.3.2.26;
DE AltName: Full=HECT-type E3 ubiquitin transferase Su(dx);
DE AltName: Full=Protein suppressor of deltex;
GN Name=Su(dx); ORFNames=CG4244;
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], AND TISSUE SPECIFICITY.
RX PubMed=10353900; DOI=10.1093/genetics/152.2.567;
RA Cornell M., Evans D.A.P., Mann R., Fostier M., Flasza M., Monthatong M.,
RA Artavanis-Tsakonas S., Baron M.;
RT "The Drosophila melanogaster Suppressor of deltex gene, a regulator of the
RT Notch receptor signaling pathway, is an E3 class ubiquitin ligase.";
RL Genetics 152:567-576(1999).
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;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 387-949.
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 [6]
RP FUNCTION.
RX PubMed=12648496; DOI=10.1016/s0012-1606(02)00086-6;
RA Mazaleyrat S.L., Fostier M., Wilkin M.B., Aslam H., Evans D.A.P.,
RA Cornell M., Baron M.;
RT "Down-regulation of Notch target gene expression by Suppressor of deltex.";
RL Dev. Biol. 255:363-372(2003).
RN [7]
RP FUNCTION, AND INTERACTION WITH N.
RX PubMed=15620650; DOI=10.1016/j.cub.2004.11.030;
RA Wilkin M.B., Carbery A.-M., Fostier M., Aslam H., Mazaleyrat S.L.,
RA Higgs J., Myat A., Evans D.A.P., Cornell M., Baron M.;
RT "Regulation of notch endosomal sorting and signaling by Drosophila Nedd4
RT family proteins.";
RL Curr. Biol. 14:2237-2244(2004).
RN [8]
RP STRUCTURE BY NMR OF 474-545.
RX PubMed=15173166; DOI=10.1074/jbc.m404987200;
RA Fedoroff O.Y., Townson S.A., Golovanov A.P., Baron M., Avis J.M.;
RT "The structure and dynamics of tandem WW domains in a negative regulator of
RT notch signaling, Suppressor of deltex.";
RL J. Biol. Chem. 279:34991-35000(2004).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates. Down-regulates
CC Notch/N signaling pathway, probably by promoting Notch ubiquitination,
CC endocytosis and degradation. Involved in wing growth and leg joint
CC formation. {ECO:0000269|PubMed:12648496, ECO:0000269|PubMed:15620650}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with N. {ECO:0000269|PubMed:15620650}.
CC -!- INTERACTION:
CC Q9Y0H4; Q24276: Cdc37; NbExp=3; IntAct=EBI-89929, EBI-167469;
CC -!- TISSUE SPECIFICITY: Expressed in pupal wings, at the boundary between
CC vein and intervein territories. {ECO:0000269|PubMed:10353900}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL39551.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF152865; AAD38975.1; -; mRNA.
DR EMBL; AE014134; AAF51311.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10440.1; -; Genomic_DNA.
DR EMBL; BT021390; AAX33538.1; -; mRNA.
DR EMBL; AY069406; AAL39551.1; ALT_INIT; mRNA.
DR RefSeq; NP_001259898.1; NM_001272969.1.
DR RefSeq; NP_001259899.1; NM_001272970.1.
DR RefSeq; NP_476753.1; NM_057405.3.
DR RefSeq; NP_722753.1; NM_164448.2.
DR RefSeq; NP_722754.1; NM_164449.2.
DR PDB; 1TK7; NMR; -; A=474-554.
DR PDB; 2JMF; NMR; -; A=515-557.
DR PDBsum; 1TK7; -.
DR PDBsum; 2JMF; -.
DR AlphaFoldDB; Q9Y0H4; -.
DR SMR; Q9Y0H4; -.
DR BioGRID; 59611; 22.
DR IntAct; Q9Y0H4; 16.
DR STRING; 7227.FBpp0077495; -.
DR PaxDb; Q9Y0H4; -.
DR PRIDE; Q9Y0H4; -.
DR DNASU; 33379; -.
DR EnsemblMetazoa; FBtr0077822; FBpp0077495; FBgn0003557.
DR EnsemblMetazoa; FBtr0077823; FBpp0077496; FBgn0003557.
DR EnsemblMetazoa; FBtr0077824; FBpp0077497; FBgn0003557.
DR EnsemblMetazoa; FBtr0334778; FBpp0306832; FBgn0003557.
DR EnsemblMetazoa; FBtr0339529; FBpp0308612; FBgn0003557.
DR GeneID; 33379; -.
DR KEGG; dme:Dmel_CG4244; -.
DR UCSC; CG4244-RC; d. melanogaster.
DR CTD; 33379; -.
DR FlyBase; FBgn0003557; Su(dx).
DR VEuPathDB; VectorBase:FBgn0003557; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000154635; -.
DR HOGENOM; CLU_002173_0_1_1; -.
DR InParanoid; Q9Y0H4; -.
DR OMA; ANQGYHQ; -.
DR OrthoDB; 167687at2759; -.
DR PhylomeDB; Q9Y0H4; -.
DR Reactome; R-DME-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-DME-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-DME-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-DME-5632684; Hedgehog 'on' state.
DR Reactome; R-DME-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-DME-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-DME-9013420; RHOU GTPase cycle.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9Y0H4; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 33379; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Su(dx); fly.
DR EvolutionaryTrace; Q9Y0H4; -.
DR GenomeRNAi; 33379; -.
DR PRO; PR:Q9Y0H4; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0003557; Expressed in adult midgut (Drosophila) and 27 other tissues.
DR ExpressionAtlas; Q9Y0H4; baseline and differential.
DR Genevisible; Q9Y0H4; DM.
DR GO; GO:0005938; C:cell cortex; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:FlyBase.
DR GO; GO:0016348; P:imaginal disc-derived leg joint morphogenesis; IMP:UniProtKB.
DR GO; GO:0008587; P:imaginal disc-derived wing margin morphogenesis; IGI:FlyBase.
DR GO; GO:0008586; P:imaginal disc-derived wing vein morphogenesis; IMP:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IDA:FlyBase.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IGI:FlyBase.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IMP:FlyBase.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IGI:FlyBase.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0006622; P:protein targeting to lysosome; IGI:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; ISS:FlyBase.
DR GO; GO:0035209; P:pupal development; IMP:UniProtKB.
DR GO; GO:0045463; P:R8 cell development; IGI:FlyBase.
DR GO; GO:0031623; P:receptor internalization; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:FlyBase.
DR GO; GO:0048190; P:wing disc dorsal/ventral pattern formation; IMP:UniProtKB.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 4.
DR Gene3D; 2.60.40.150; -; 1.
DR IDEAL; IID50161; -.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR024928; E3_ub_ligase_SMURF1.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00397; WW; 4.
DR PIRSF; PIRSF001569; E3_ub_ligase_SMURF1; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 4.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 3.
DR PROSITE; PS50020; WW_DOMAIN_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Notch signaling pathway;
KW Reference proteome; Repeat; Transferase; Ubl conjugation pathway.
FT CHAIN 1..949
FT /note="E3 ubiquitin-protein ligase Su(dx)"
FT /id="PRO_0000120331"
FT DOMAIN 30..146
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 363..396
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 395..428
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 477..510
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 521..554
FT /note="WW 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 615..949
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..240
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..358
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 917
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000305"
FT STRAND 477..482
FT /evidence="ECO:0007829|PDB:1TK7"
FT STRAND 485..488
FT /evidence="ECO:0007829|PDB:1TK7"
FT TURN 489..491
FT /evidence="ECO:0007829|PDB:1TK7"
FT STRAND 492..497
FT /evidence="ECO:0007829|PDB:1TK7"
FT TURN 498..501
FT /evidence="ECO:0007829|PDB:1TK7"
FT STRAND 502..507
FT /evidence="ECO:0007829|PDB:1TK7"
FT TURN 511..513
FT /evidence="ECO:0007829|PDB:1TK7"
FT HELIX 516..519
FT /evidence="ECO:0007829|PDB:1TK7"
FT STRAND 528..532
FT /evidence="ECO:0007829|PDB:1TK7"
FT TURN 533..535
FT /evidence="ECO:0007829|PDB:1TK7"
FT STRAND 536..541
FT /evidence="ECO:0007829|PDB:1TK7"
FT TURN 542..545
FT /evidence="ECO:0007829|PDB:1TK7"
FT STRAND 546..552
FT /evidence="ECO:0007829|PDB:1TK7"
SQ SEQUENCE 949 AA; 107966 MW; 74B17A8B05AC6E6B CRC64;
MADGNGLPAG AASGGMEAGQ TVNGAGSASP TPTSSSGAGA SGSANQGYHQ LSVTIEEASL
RNNGFLKPNP YVELLIDSKS KRKTDLVKNS YLPKWNEEFT VLITPNSTLH FKVLDHSSFR
KDAMLGERII NLAHILQHYN GRCEFLELTI DLFVTSKSDN RQTKSGELVA ILNGLKLDMS
KLQIQPVAGQ QNGNPPVQAV NPSVVSDAAA GRSCMIYGGV RARMRLRSSS GNSNGGETRS
PLPNGGGDHR RSTQAPPVWE QQQQQSQNQQ QPLRMVNGSG AAVPQTAPYP QQPPAPALAR
PLTQVYGALP ENTQPAAVYL PAGGGAAVGP PGVAGPPIEQ PGVGLPVSQS TDPQLQTQPA
DDEPLPAGWE IRLDQYGRRY YVDHNTRSTY WEKPTPLPPG WEIRKDGRGR VYYVDHNTRK
TTWQRPNSER LMHFQHWQGQ RAHVVSQGNQ RYLYSQQQQQ PTAVTAQVTQ DDEDALGPLP
DGWEKKIQSD NRVYFVNHKN RTTQWEDPRT QGQEVSLINE GPLPPGWEIR YTAAGERFFV
DHNTRRTTFE DPRPGAPKGA KGVYGVPRAY ERSFRWKLSQ FRYLCQSNAL PSHIKITVTR
QTLFEDSYHQ IMRLPAYELR RRLYIIFRGE EGLDYGGVSR EWFFLLSHEV LNPMYCLFEY
ANKNNYSLQI NPASYVNPDH LQYFKFIGRF IAMALYHGRF IYSGFTMPFY KRMLNKKLTI
KDIETIDPEF YNSLIWVKDN NIDECGLELW FSVDFEVLGQ IIHHELKENG EKERVTEENK
EEYITLMTEW RMTRGIEQQT KTFLEGFNEV VPLEWLKYFD ERELELILCG MQDVDVEDWQ
RNTIYRHYNR NSKQVVWFWQ FVRETDNEKR ARLLQFVTGT CRVPVGGFAE LMGSNGPQRF
CIEKVGKETW LPRSHTCFNR LDLPPYKSYD QLVEKLTFAI EETEGFCQE
