SMUF1_MOUSE
ID SMUF1_MOUSE Reviewed; 731 AA.
AC Q9CUN6; Q3U412; Q8K300;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 180.
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=SMAD ubiquitination regulatory factor 1;
DE AltName: Full=SMAD-specific E3 ubiquitin-protein ligase 1;
GN Name=Smurf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND INTERACTION WITH MAVS.
RX PubMed=23087404; DOI=10.4049/jimmunol.1201445;
RA Wang Y., Tong X., Ye X.;
RT "Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing
RT E3 ligase Smurf1-mediated MAVS degradation.";
RL J. Immunol. 189:5304-5313(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
CC of BMP signaling pathway (By similarity). Mediates ubiquitination and
CC degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for
CC the BMP pathway (By similarity). Promotes ubiquitination and subsequent
CC proteasomal degradation of TRAF family members and RHOA (By
CC similarity). Promotes ubiquitination and subsequent proteasomal
CC degradation of MAVS (PubMed:23087404). Plays a role in dendrite
CC formation by melanocytes (By similarity).
CC {ECO:0000250|UniProtKB:Q9HCE7, ECO:0000269|PubMed:23087404}.
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 TRAF4 (By similarity). Interacts (via HECT
CC domain) with FBXL15 (via LRR repeats) (By similarity). Interacts with
CC SMAD7 and TGFBR1; SMAD7 recruits SMURF1 to TGFBR1 and regulates TGF-
CC beta receptor degradation (By similarity). Interacts with MAVS; the
CC interaction is mediated by NDFIP1 (PubMed:23087404).
CC {ECO:0000250|UniProtKB:Q9HCE7, ECO:0000269|PubMed:23087404}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}.
CC -!- DOMAIN: The C2 domain mediates membrane localization and substrate
CC selection. {ECO:0000250}.
CC -!- PTM: Auto-ubiquitinated in presence of NDFIP1. Ubiquitinated by the
CC SCF(FBXL15) complex at Lys-355 and Lys-357, leading to its degradation
CC by the proteasome. Lys-357 is the primary ubiquitination site.
CC {ECO:0000250|UniProtKB:Q9HCE7}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB29770.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK015264; BAB29770.2; ALT_INIT; mRNA.
DR EMBL; AK154491; BAE32623.1; -; mRNA.
DR EMBL; BC029097; AAH29097.1; -; mRNA.
DR CCDS; CCDS39380.1; -.
DR RefSeq; NP_001033716.1; NM_001038627.1.
DR RefSeq; NP_083714.3; NM_029438.3.
DR AlphaFoldDB; Q9CUN6; -.
DR BMRB; Q9CUN6; -.
DR SMR; Q9CUN6; -.
DR BioGRID; 217743; 20.
DR CORUM; Q9CUN6; -.
DR IntAct; Q9CUN6; 3.
DR MINT; Q9CUN6; -.
DR STRING; 10090.ENSMUSP00000082827; -.
DR iPTMnet; Q9CUN6; -.
DR PhosphoSitePlus; Q9CUN6; -.
DR MaxQB; Q9CUN6; -.
DR PaxDb; Q9CUN6; -.
DR PRIDE; Q9CUN6; -.
DR ProteomicsDB; 257528; -.
DR Antibodypedia; 30289; 415 antibodies from 37 providers.
DR DNASU; 75788; -.
DR Ensembl; ENSMUST00000085684; ENSMUSP00000082827; ENSMUSG00000038780.
DR GeneID; 75788; -.
DR KEGG; mmu:75788; -.
DR UCSC; uc009alv.1; mouse.
DR CTD; 57154; -.
DR MGI; MGI:1923038; Smurf1.
DR VEuPathDB; HostDB:ENSMUSG00000038780; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000158690; -.
DR HOGENOM; CLU_002173_1_1_1; -.
DR InParanoid; Q9CUN6; -.
DR PhylomeDB; Q9CUN6; -.
DR TreeFam; TF323658; -.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR Reactome; R-MMU-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-MMU-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR Reactome; R-MMU-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 75788; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Smurf1; mouse.
DR PRO; PR:Q9CUN6; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9CUN6; protein.
DR Bgee; ENSMUSG00000038780; Expressed in gastrula and 244 other tissues.
DR ExpressionAtlas; Q9CUN6; baseline and differential.
DR Genevisible; Q9CUN6; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0070411; F:I-SMAD binding; ISO:MGI.
DR GO; GO:0070412; F:R-SMAD binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; ISS:UniProtKB.
DR GO; GO:0061736; P:engulfment of target by autophagosome; ISO:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:MGI.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0006611; P:protein export from nucleus; ISO:MGI.
DR GO; GO:0034394; P:protein localization to cell surface; ISO:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0071211; P:protein targeting to vacuole involved in autophagy; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IMP:MGI.
DR GO; GO:0032801; P:receptor catabolic process; ISO:MGI.
DR GO; GO:0061753; P:substrate localization to autophagosome; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0030579; P:ubiquitin-dependent SMAD protein catabolic process; ISO:MGI.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 2.
DR Gene3D; 2.60.40.150; -; 1.
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; 1.
DR PIRSF; PIRSF001569; E3_ub_ligase_SMURF1; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 2.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 2.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Differentiation; Isopeptide bond; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..731
FT /note="E3 ubiquitin-protein ligase SMURF1"
FT /id="PRO_0000120327"
FT DOMAIN 1..120
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 234..267
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 280..313
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 394..731
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 216..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 699
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HCE7"
FT CROSSLNK 355
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9HCE7"
FT CROSSLNK 357
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9HCE7"
FT CONFLICT 63
FT /note="N -> S (in Ref. 2; AAH29097)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="D -> N (in Ref. 1; BAB29770)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="R -> Q (in Ref. 1; BAB29770)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="R -> Q (in Ref. 1; BAB29770)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="E -> G (in Ref. 1; BAE32623)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="S -> N (in Ref. 1; BAB29770)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="T -> K (in Ref. 1; BAB29770)"
FT /evidence="ECO:0000305"
FT CONFLICT 671..673
FT /note="Missing (in Ref. 1; BAB29770 and 2; AAH29097)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 731 AA; 83356 MW; F0A7A1B019CC9D3E CRC64;
MSNPGTRRNG SSIKIRLTVL CAKNLAKKDF FRLPDPFAKI VVDGSGQCHS TDTVKNTLDP
KWNQHYDLYV GKTDSITISV WNHKKIHKKQ GAGFLGCVRL LSNAISRLKD TGYQRLDLCK
LNPSDTDAVR GQIVVSLQTR DRIGGGGSVV DCRGLLENEG TVYEDSGPGR PLSCLMEEPA
PYTDGTGAAA GGGNCRFVES PSQDQRLLVQ RLRNPEVRGP LQTPQNRPHG HQSPELPEGY
EQRTTVQGQV YFLHTQTGVS TWHDPRIPRD LNSVNCDELG PLPPGWEVRS TVSGRIYFVD
HNNRTTQFTD PRLHHIMNHQ CQLKEPSQPL QLPSEGSVED EELPAQRYER DLVQKLKVLR
HELSLQQPQA GHCRIEVSRE EIFEESYRQI MKMRPKDLKK RLMVKFRGEE GLDYGGVARE
WLYLLCHEML NPYYGLFQYS TDNIYTLQIN PDSSINPDHL SYFHFVGRIM GLAVFHGHYI
NGGFTVPFYK QLLGKPIQLS DLESVDPELH KSLVWILEND ITPVLDHTFC VEHNAFGRIL
QHELKPNGRN VPVTEENKKE YVRLYVNWRF MRGIEAQFLA LQKGFNELIP QHLLKPFDQK
ELELIIGGLD KIDLNDWKSN TRLKHCVADS NIVRWFWQAV ETFDEERRAR LLQFVTGSTR
VPLQGFKALQ GSTGAAGPRL FTIHLIDANT DNLPKAHTCF NRIDIPPYES YEKLYEKLLT
AVEETCGFAV E
