SMUF1_DROME
ID SMUF1_DROME Reviewed; 1061 AA.
AC Q9V853; Q9U3W2;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 3.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=E3 ubiquitin-protein ligase Smurf1;
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:Q9HCE7};
DE AltName: Full=HECT-type E3 ubiquitin transferase Smurf1;
DE AltName: Full=Lethal with a checkpoint kinase protein;
DE AltName: Full=SMAD ubiquitination regulatory factor 1 homolog;
DE Short=DSmurf;
GN Name=Smurf {ECO:0000303|PubMed:11703946}; Synonyms=lack, Smurf1;
GN ORFNames=CG4943 {ECO:0000312|FlyBase:FBgn0029006};
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, INTERACTION WITH MAD, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=11703946; DOI=10.1016/s1534-5807(01)00057-0;
RA Podos S.D., Hanson K.K., Wang Y.-C., Ferguson E.L.;
RT "The DSmurf ubiquitin-protein ligase restricts BMP signaling spatially and
RT temporally during Drosophila embryogenesis.";
RL Dev. Cell 1:567-578(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH MAD, AND MUTAGENESIS
RP OF TRP-541; PRO-544 AND CYS-1029.
RX PubMed=12754252; DOI=10.1074/jbc.c300028200;
RA Liang Y.-Y., Lin X., Liang M., Brunicardi F.C., ten Dijke P., Chen Z.,
RA Choi K.-W., Feng X.-H.;
RT "DSmurf selectively degrades decapentaplegic-activated MAD, and its
RT overexpression disrupts imaginal disc development.";
RL J. Biol. Chem. 278:26307-26310(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Laurencon A., Hawley S.;
RT "Molecular cloning of a type E3 Ubiquitin ligase.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-262; THR-412 AND SER-416, AND
RP 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).
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 Dpp signaling after gastrulation by promoting MAD ubiquitination and
CC subsequent degradation. {ECO:0000269|PubMed:11703946,
CC ECO:0000269|PubMed:12754252}.
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:Q9HCE7};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with phosphorylated MAD.
CC {ECO:0000269|PubMed:11703946, ECO:0000269|PubMed:12754252}.
CC -!- INTERACTION:
CC Q9V853; P23647: fu; NbExp=5; IntAct=EBI-133520, EBI-165536;
CC Q9V853; Q95SI0: tkv; NbExp=2; IntAct=EBI-133520, EBI-3401975;
CC -!- DEVELOPMENTAL STAGE: Uniformly expressed at blastoderm stage. Weakly
CC but broadly expressed at later stages of embryogenesis.
CC {ECO:0000269|PubMed:11703946}.
CC -!- DISRUPTION PHENOTYPE: Flies exhibit lethal defects in hindgut
CC morphogenesis. {ECO:0000269|PubMed:11703946}.
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DR EMBL; AF416571; AAL09691.1; -; mRNA.
DR EMBL; AF464851; AAM09646.1; -; mRNA.
DR EMBL; AF216521; AAF21125.1; -; mRNA.
DR EMBL; AE013599; AAF57824.3; -; Genomic_DNA.
DR EMBL; BT021410; AAX33558.1; -; mRNA.
DR RefSeq; NP_001261061.1; NM_001274132.1.
DR RefSeq; NP_523779.1; NM_079055.3.
DR AlphaFoldDB; Q9V853; -.
DR SMR; Q9V853; -.
DR BioGRID; 62687; 15.
DR ComplexPortal; CPX-1897; Fused-Smurf ubiquitin ligase complex.
DR IntAct; Q9V853; 8.
DR STRING; 7227.FBpp0305371; -.
DR iPTMnet; Q9V853; -.
DR PaxDb; Q9V853; -.
DR PRIDE; Q9V853; -.
DR EnsemblMetazoa; FBtr0086833; FBpp0086011; FBgn0029006.
DR EnsemblMetazoa; FBtr0333168; FBpp0305371; FBgn0029006.
DR GeneID; 36999; -.
DR KEGG; dme:Dmel_CG4943; -.
DR CTD; 36999; -.
DR FlyBase; FBgn0029006; Smurf.
DR VEuPathDB; VectorBase:FBgn0029006; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000155563; -.
DR HOGENOM; CLU_002173_1_1_1; -.
DR InParanoid; Q9V853; -.
DR OMA; ASNGWTQ; -.
DR OrthoDB; 167687at2759; -.
DR PhylomeDB; Q9V853; -.
DR Reactome; R-DME-201451; Signaling by BMP.
DR Reactome; R-DME-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-DME-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-DME-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-DME-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-DME-4641257; Degradation of AXIN.
DR Reactome; R-DME-5632684; Hedgehog 'on' state.
DR Reactome; R-DME-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9V853; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 36999; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Smurf; fly.
DR GenomeRNAi; 36999; -.
DR PRO; PR:Q9V853; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0029006; Expressed in wing disc and 25 other tissues.
DR ExpressionAtlas; Q9V853; baseline and differential.
DR Genevisible; Q9V853; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:FlyBase.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0001700; P:embryonic development via the syncytial blastoderm; IMP:UniProtKB.
DR GO; GO:0048619; P:embryonic hindgut morphogenesis; IMP:UniProtKB.
DR GO; GO:0007293; P:germarium-derived egg chamber formation; IGI:FlyBase.
DR GO; GO:0048232; P:male gamete generation; IMP:FlyBase.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:FlyBase.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IGI:FlyBase.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IMP:FlyBase.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:FlyBase.
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:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0040008; P:regulation of growth; IMP:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 3.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
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; 3.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 3.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 3.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 2.
DR PROSITE; PS50020; WW_DOMAIN_2; 3.
PE 1: Evidence at protein level;
KW Developmental protein; Phosphoprotein; Reference proteome; Repeat;
KW Transferase; Ubl conjugation pathway.
FT CHAIN 1..1061
FT /note="E3 ubiquitin-protein ligase Smurf1"
FT /id="PRO_0000120330"
FT DOMAIN 1..116
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 167..200
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 513..546
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 561..594
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 723..1061
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 143..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 513..602
FT /note="Interaction with MAD"
FT REGION 608..661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..176
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..266
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 267..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..403
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..418
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..460
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..475
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 636..658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1029
FT /note="Glycyl thioester intermediate"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 412
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 541
FT /note="W->F: Abolishes interaction with MAD; when
FT associated with A-544."
FT /evidence="ECO:0000269|PubMed:12754252"
FT MUTAGEN 544
FT /note="P->A: Abolishes interaction with MAD; when
FT associated with F-541."
FT /evidence="ECO:0000269|PubMed:12754252"
FT MUTAGEN 1029
FT /note="C->A: Abolishes enzymatic activity; no change in
FT interaction with MAD."
FT /evidence="ECO:0000269|PubMed:12754252"
SQ SEQUENCE 1061 AA; 115676 MW; 6BBCC550F5129163 CRC64;
MNKLDYPRRN GTHKVRITIL CARNLARKDL FRLPDPFAKV QVDGTGQVYS TEISKSSLDP
KWNAHYDLFL GIGDAITITV WNQRKIHKGS GFLGCVRIPA FNIQSLKGAG FQRLDLGKLS
PDDDELVRGQ IIISLLSKDG PSSGNPLAIV GPSGDVRGPS EDDSSEDSLP EGWEERRTDN
GRVYYVNHAT KSTQWDRPRQ PGVVGSSHAT SPQQRHNTHN GNSGDRQAPA GPTRSTTCTN
LMNNGHRSRD LSVTASDERR HSTEILSSVG KENTSPTTPV SATTTPGKKT SSSNSSSAGG
RTLEQRPTNE PATPTSSTTS ASVRLHSNDN HVKTPKHQTN GHAPPESTPT SPTGQQNYVN
GNAQNGSTSG NGSGQAAQPQ SASNGWTQED AATTTSPSTT TSPPRHSQSP PTPNISPPAS
VTPSANGNVH SPNANSTPAG SGGGSRSYTA ATPGQRSQRR SSRQQGEESS TRRRSSRGTR
NGGTSGGGGG GGSGQRYASA AIAAANQAAR PFLDLPPGYE MRTTQQGQVY FYHIPTGVST
WHDPRIPRDF DTQHLTLDAI GPLPSGWEQR KTASGRVYFV DHNNRTTQFT DPRLSGSILQ
MIRRGTVPPT SAANAGTPAP PSATPATPSA AAAVPPQATP ASNATPTTLT TTTNPPHRIV
PDLPQGLLEG ADLLPKYRRD LVGKLRALRT ELQTMQPQSG HCRLEVSRNE IFEESYRLIM
KMRAKDMRKR LMVKFKGEEG LDYGGVAREW LHLLSREMLN PQYGLFQYSR DDHYTLQINP
DSGVNPDHLS YFHFVGRTLG IAVFHGHCLD GGFTTPFYKQ LLNKPITLGD IEGVDPDLHR
SLTWMLESNI SGIIESTFSV ENNSFGALVV HELKPGGASI PVTEENKREY VKLYVNYRFM
RGIEQQFLAL QKGFCELIPS HLLRPFDERE LELVIGGISS IDVNDWRNNT RLKHCTNETT
QVLWFWQVVE SYSSEMRARL LQFVTGSSRV PLQGFRALQG STGAVGPRLF TIHLTADVPT
QNLPKAHTCF NRIDLPPYET YQLLCDKLTQ AVEETCGFAV E
