UFD4_DROME
ID UFD4_DROME Reviewed; 2727 AA.
AC Q9VL06; Q6NR00;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=E3 ubiquitin-protein ligase Ufd4 {ECO:0000303|PubMed:27552662};
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:Q69ZR2};
DE AltName: Full=Ubiquitin fusion-degradation 4-like {ECO:0000312|FlyBase:FBgn0032208};
GN Name=Ufd4 {ECO:0000303|PubMed:27552662, ECO:0000312|FlyBase:FBgn0032208};
GN ORFNames=CG5604 {ECO:0000312|FlyBase:FBgn0032208};
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 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
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] {ECO:0000312|EMBL:AAQ23602.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAQ23602.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=27552662; DOI=10.1371/journal.pbio.1002539;
RA Ashton-Beaucage D., Lemieux C., Udell C.M., Sahmi M., Rochette S.,
RA Therrien M.;
RT "The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of
RT the N-end Rule ligase POE/UBR4 in Drosophila.";
RL PLoS Biol. 14:E1002539-E1002539(2016).
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 (By
CC similarity). Involved in the negative regulation of the Ras/MAPK
CC signaling pathway in the wing by acting with the E2 enzyme Unc6 and the
CC putative E3 ligases poe and Kcmf1 to mediate the ubiquitination and
CC proteasomal degradation of rl/MAPK (PubMed:27552662).
CC {ECO:0000250|UniProtKB:Q69ZR2, ECO:0000269|PubMed:27552662}.
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; Evidence={ECO:0000250|UniProtKB:Q69ZR2};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q69ZR2}.
CC -!- SIMILARITY: Belongs to the UPL family. K-HECT subfamily. {ECO:0000305}.
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DR EMBL; AE014134; AAF52899.1; -; Genomic_DNA.
DR EMBL; BT010284; AAQ23602.1; -; mRNA.
DR RefSeq; NP_609369.1; NM_135525.2.
DR SMR; Q9VL06; -.
DR IntAct; Q9VL06; 5.
DR STRING; 7227.FBpp0079663; -.
DR PaxDb; Q9VL06; -.
DR PRIDE; Q9VL06; -.
DR EnsemblMetazoa; FBtr0080074; FBpp0079663; FBgn0032208.
DR GeneID; 34378; -.
DR KEGG; dme:Dmel_CG5604; -.
DR UCSC; CG5604-RA; d. melanogaster.
DR CTD; 34378; -.
DR FlyBase; FBgn0032208; Ufd4.
DR VEuPathDB; VectorBase:FBgn0032208; -.
DR eggNOG; KOG4276; Eukaryota.
DR GeneTree; ENSGT00940000156572; -.
DR HOGENOM; CLU_000869_0_0_1; -.
DR InParanoid; Q9VL06; -.
DR OMA; INHTLTM; -.
DR OrthoDB; 34110at2759; -.
DR PhylomeDB; Q9VL06; -.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 34378; 0 hits in 1 CRISPR screen.
DR ChiTaRS; CG5604; fly.
DR GenomeRNAi; 34378; -.
DR PRO; PR:Q9VL06; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0032208; Expressed in second segment of antenna (Drosophila) and 28 other tissues.
DR Genevisible; Q9VL06; DM.
DR GO; GO:0016607; C:nuclear speck; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:FlyBase.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IGI:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:FlyBase.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:FlyBase.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR045322; HECTD1/TRIP12-like.
DR InterPro; IPR010606; Mib_Herc2.
DR InterPro; IPR037252; Mib_Herc2_sf.
DR InterPro; IPR012919; SUN_dom.
DR PANTHER; PTHR45670; PTHR45670; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF06701; MIB_HERC2; 1.
DR Pfam; PF07738; Sad1_UNC; 1.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF159034; SSF159034; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS51416; MIB_HERC2; 1.
PE 2: Evidence at transcript level;
KW ANK repeat; Reference proteome; Repeat; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..2727
FT /note="E3 ubiquitin-protein ligase Ufd4"
FT /id="PRO_0000442701"
FT REPEAT 422..451
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 453..482
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 486..518
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT DOMAIN 1322..1392
FT /note="MIB/HERC2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00749"
FT DOMAIN 2289..2727
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 247..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 365..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 682..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1401..1448
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1483..1512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1570..1592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1845..1871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1905..1930
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2092..2115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1910..1930
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2696
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT CONFLICT 570
FT /note="L -> F (in Ref. 3; AAQ23602)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2727 AA; 302150 MW; 81D7BA87B482BAC1 CRC64;
MGDVDPETLL EWLSMGQGDE RDMQLIALEQ LCMLLLMSDN VDRCFESCPP RTFLPALCKI
FLDELAPENV LEVTARAITY YLDVSAECTR RIVSIDGAIK AICNHLVVAD LSSRTSRDLA
EQCIKVLELI CTREAGAVFE GGGLNCVLSF IRDCGSQVHK DTLHSAMSVV SRLCTKVEPN
TPCIQNCVES LSTLLQHEDP MVSDGALKCF ASVADRFTRK WVDPAPLAEY GLTTELLKRL
QSVGGNTHSS LTAAGTQPTS SSQPAATTNS DAINENVAGT ATISNSTKVK SSDAAASPQS
ISTTISLLST LCRGSPSITH DILRSQLADA LERALQGDER CVLDCMRFAD LLLLLLFEGR
QALNRGSNNP NQGQLAPRPR RNNTNTDRTH RQLIDCIRSK DSEALREAIE SGGIDVNCMD
DVGQTLLNWA SAFGTLEMVE YLCEKGADVN KGQRSSSLHY AACFGRPAIA KILLKFGAYP
DLRDEDGKTP LDKARERLDD GHREVAAILQ SPGEWMSPDH SLLNKDGKKY TLMEPRGDPE
MAPIYLKVLL PIFCRTFLGS MLGSVRRASL ALIKKIVQYA YPTVLQSLSE TSFSEDAAST
SGQNGGNLLI EVIASVLDNE DDGDGHLIVL NIIEEIMCKT QEEFLDHFAR LGVFAKVQAL
MDTDAEELYV QLPGTVEEPA AAQRSSTSVV VAPRPTSDDP MEDAKEILQG KPYHWREWSI
CRGRDCLYVW SDSVALELSN GSNGWFRFII DGKLATMYSS GSPENGNDSS ENRGEFLEKL
MRARSCVIAG VVSQPILPTA SALRLVVGNW VLQSQKTNQL QIHNTEGHQV TVLQDDLPGF
IFESNRGTKH TFSAETVLGP DFASGWSTAK KKRNKSKTEG QKFQVRNLSR EIYNKYFKSA
QIIPRGAVAI LTDIVKQIEL SFEEQHMAPN GNWETTLTDA LMKLSQLIHE DGVVSAYEMH
SSGLVQALVA VLSVNHWETN SPRCKRNKMQ KQRVSVFKKC ILEDNVESAT NKPRTKSTAS
ILIQKLVSVL ESTEKLPVYL YDSPCTGYSL QILQKRLRFR LERAECESTL FDRSGRTLKM
EPLATIGQLS KYLLKMVAKQ WYDLDRSTYF YLKKIREHRT ATVFTHSFDF DEEGLLFYIG
SNAKTCDWVN PAQYGLVQVT SSEGKTLPYG KLEDILSRDS ISLNCHTKDN KKAWFAIDLG
VYIIPTAYTL RHARGYGRSA LRNWLLQGSK DGSTWTTLST HVDDKSLVEP GSTATWPINC
ATDDSVWYRH IRIQQNGRNA SGQTHYLSLS GFEIYGRVVG VADDIGKSVK EAEAKTRRER
RQIRAQLKHM TTGARVIRGV DWRWEEQDGC AEGTITGEIH NGWIDVKWDH GVRNSYRMGA
EGKYDLKLAD CEYLSAFDGN QSMGSASTAA KPSEKGGNTL TSRKSSSTPS LPEATEKNQN
PEGASNQTVS ADNLAWKQTV ETIAENVFAS AKTQIISNQL AMNTSSSREA RAKHKESGTN
QMHKDNISGP SPLSRELEHI SDLSAINNSM PAINSSNVSD LATISENLSL TELSKENICR
VLTPSYKPAE SVTASQSSSH PDVQSSSPRE NDIKNISNIE ENNKMNANNS VNKISKDLLA
NLRTSNIAGC PPVTQLSTEA LEMIDKMRDG VDMIRNMSNS ILSTDTFPVP CTNVPVGGKK
TPKAQALINP DNANQKQIIV TSEEFPTKSS KKPSVTLKPA QQPNAVLSIV DIKEQPISNE
NVSVPSQMSI SVPNLTTTSA SEVPSTSEVA THTGLLETFA AIARRRTSQG TNIQDNQIMN
AEANVNEHGD QNASGSFLGH SVTSLVKLAL SSNFHSGLLS TAQSYPSLSS NNSENIAPSN
PSNTSAGQQS ASTINHTLTM SLTSTSSDSE QVSLEDFLES CRAPALLGDL DDEDDMDEDN
DEEENEDEYE EVGNTLLQVM VSRNLLTFMD DEAMENRLVG VTKRKSWDDE FVLKRQFSAL
IPAFDPRPGR TNVNQTSDLE ISPLGAELPK PQQSGGPETI EQPLLGLKLR GPGIGGIPEV
EIDLSNTDWT IFRAVQELLQ CSQLNKLDKF RKIWEPTYTI VYREVSPEAQ ESTCLESEEF
PQTPDVSSKS GASTLSPNSP MHIGFNVADN NLCSVDDVLE LLTQINGLNQ SEIDSDVKEH
GVSVLSEDLF ISKKITNKLQ QQIQDPLVLA SNALPNWCEN LNQSCPFLFP FETRQLYFNC
TSFGASRSIV CLQSQRDVTV ERQRIPIMSP RRDDHEFRIG RLKHERVKVP RNEDLLMWAM
QVMKTHCNRK SVLEVEFLDE EGTGLGPTLE FYALVAAEIQ RSDLCMWLCD DDLGEDTENS
TQSAEGNSKP VGYYVNRREH GIFPAPLPQN SEICENVLKY FWFFGVFVAK VLQDMRLVDI
PLSTSFLQLL CHNKVLSRNL QKVISDRRNG DLSVVSEDSD IVETCTKLLR TDSNKSNAFG
GILSLENLKE IDPTRYQFLQ EMQNLLLRKQ SIEFDDTISA EKKHELINEL KLQTQNGLEV
SLEDLALTFT YLPSSSIYGY TQAELLPNGS SVNVTIDNLE AYCELLMNFI LQDGIAQQMK
AFSDGFNEVF PLKKLAAFTP SEARMMICGE QFPHWSREDI ISYTEPKLGY NKDSPGFQRF
VNVLLSMSGD ERKAFLQFTT GCSSLPPGGL ANLHPRLTVV RKVDAGVGSY PSVNTCVHYL
KLPDYPTEEI MKERLLTATK EKGFHLN
