ID SMUF1_HUMAN Reviewed; 757 AA.
AC Q9HCE7; A4D279; B7ZMB6; B9EGV3; O75853; Q547Q3; Q9UJT8;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2001, sequence version 2.
DT 27-MAR-2024, entry version 210.
DE RecName: Full=E3 ubiquitin-protein ligase SMURF1;
DE Short=hSMURF1;
DE EC=2.3.2.26 {ECO:0000269|PubMed:19937093};
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; Synonyms=KIAA1625;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liang M., Lin X., Feng X.-H.;
RT "Smurf1-beta, an alternatively spliced variant of Smad-ubiquitin E3 ligase
RT Smurf1.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Brain, and Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-731 (ISOFORM SHORT), AND FUNCTION.
RX PubMed=10458166; DOI=10.1038/23293;
RA Zhu H., Kavsak P., Abdollah S., Wrana J.L., Thomsen G.H.;
RT "A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic
RT pattern formation.";
RL Nature 400:687-693(1999).
RN [8]
RP INTERACTION WITH SMAD7 AND TGFBR1.
RX PubMed=11163210; DOI=10.1016/s1097-2765(00)00134-9;
RA Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H.,
RA Wrana J.L.;
RT "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF-
RT beta receptor for degradation.";
RL Mol. Cell 6:1365-1375(2000).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-725, AND INTERACTION WITH
RP TRAF4.
RX PubMed=19937093; DOI=10.1007/s11010-009-0315-y;
RA Li S., Lu K., Wang J., An L., Yang G., Chen H., Cui Y., Yin X., Xie P.,
RA Xing G., He F., Zhang L.;
RT "Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination
RT and degradation.";
RL Mol. Cell. Biochem. 338:11-17(2010).
RN [10]
RP SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-381 AND LYS-383, INTERACTION
RP WITH FBXL15, AND MUTAGENESIS OF LYS-350; LYS-381; LYS-383 AND CYS-725.
RX PubMed=21572392; DOI=10.1038/emboj.2011.155;
RA Cui Y., He S., Xing C., Lu K., Wang J., Xing G., Meng A., Jia S., He F.,
RA Zhang L.;
RT "SCF(FBXL15) regulates BMP signalling by directing the degradation of HECT-
RT type ubiquitin ligase Smurf1.";
RL EMBO J. 30:2675-2689(2011).
RN [11]
RP FUNCTION.
RX PubMed=21791611; DOI=10.1128/mcb.05448-11;
RA Yan X., Zhang J., Pan L., Wang P., Xue H., Zhang L., Gao X., Zhao X.,
RA Ning Y., Chen Y.G.;
RT "TSC-22 promotes transforming growth factor beta-mediated cardiac
RT myofibroblast differentiation by antagonizing Smad7 activity.";
RL Mol. Cell. Biol. 31:3700-3709(2011).
RN [12]
RP FUNCTION, INTERACTION WITH MAVS, AND AUTO-UBIQUITINATION.
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).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23999003; DOI=10.1016/j.jdermsci.2013.07.010;
RA Yoo J.C., Lim T.Y., Park J.S., Hah Y.S., Park N., Hong S.G., Park J.Y.,
RA Yoon T.J.;
RT "SYT14L, especially its C2 domain, is involved in regulating melanocyte
RT differentiation.";
RL J. Dermatol. Sci. 72:246-251(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 13-140, FUNCTION, DOMAIN C2,
RP INTERACTION WITH RHOA, AND MUTAGENESIS OF LYS-28 AND LYS-85.
RX PubMed=21402695; DOI=10.1074/jbc.m110.211979;
RA Lu K., Li P., Zhang M., Xing G., Li X., Zhou W., Bartlam M., Zhang L.,
RA Rao Z., He F.;
RT "Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate
RT selection.";
RL J. Biol. Chem. 286:16861-16870(2011).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator
CC of BMP signaling pathway. Mediates ubiquitination and degradation of
CC SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP
CC pathway. Promotes ubiquitination and subsequent proteasomal degradation
CC of TRAF family members and RHOA. Promotes ubiquitination and subsequent
CC proteasomal degradation of MAVS (PubMed:23087404). Acts as an
CC antagonist of TGF-beta signaling by ubiquitinating TGFBR1 and targeting
CC it for degradation (PubMed:21791611). Plays a role in dendrite
CC formation by melanocytes (PubMed:23999003).
CC {ECO:0000269|PubMed:10458166, ECO:0000269|PubMed:19937093,
CC ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:21791611,
CC ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23999003}.
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:0000269|PubMed:19937093};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with TRAF4. Interacts (via HECT domain) with FBXL15
CC (via LRR repeats). Interacts with SMAD7 and TGFBR1; SMAD7 recruits
CC SMURF1 to TGFBR1 and regulates TGF-beta receptor degradation. Interacts
CC with MAVS; the interaction is mediated by NDFIP1 (PubMed:23087404).
CC {ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:19937093,
CC ECO:0000269|PubMed:21402695, ECO:0000269|PubMed:21572392,
CC ECO:0000269|PubMed:23087404}.
CC -!- INTERACTION:
CC Q9HCE7; Q9H469: FBXL15; NbExp=6; IntAct=EBI-976466, EBI-6144096;
CC Q9HCE7; Q9Y5W3: KLF2; NbExp=2; IntAct=EBI-976466, EBI-9846663;
CC Q9HCE7; Q53GL0: PLEKHO1; NbExp=2; IntAct=EBI-976466, EBI-949945;
CC Q9HCE7; P61289: PSME3; NbExp=5; IntAct=EBI-976466, EBI-355546;
CC Q9HCE7; Q15797: SMAD1; NbExp=2; IntAct=EBI-976466, EBI-1567153;
CC Q9HCE7-1; O15105: SMAD7; NbExp=4; IntAct=EBI-15884081, EBI-3861591;
CC Q9HCE7-2; O14757: CHEK1; NbExp=4; IntAct=EBI-9845742, EBI-974488;
CC Q9HCE7-2; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-9845742, EBI-25840379;
CC Q9HCE7-2; P28799: GRN; NbExp=3; IntAct=EBI-9845742, EBI-747754;
CC Q9HCE7-2; P42858: HTT; NbExp=6; IntAct=EBI-9845742, EBI-466029;
CC Q9HCE7-2; Q9H160: ING2; NbExp=3; IntAct=EBI-9845742, EBI-389787;
CC Q9HCE7-2; Q9Y5W3: KLF2; NbExp=4; IntAct=EBI-9845742, EBI-9846663;
CC Q9HCE7-2; Q53GL0: PLEKHO1; NbExp=4; IntAct=EBI-9845742, EBI-949945;
CC Q9HCE7-2; O60260-5: PRKN; NbExp=3; IntAct=EBI-9845742, EBI-21251460;
CC Q9HCE7-2; P61586: RHOA; NbExp=2; IntAct=EBI-9845742, EBI-446668;
CC Q9HCE7-2; P62745: RHOB; NbExp=3; IntAct=EBI-9845742, EBI-602647;
CC Q9HCE7-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-9845742, EBI-396669;
CC Q9HCE7-2; Q15797: SMAD1; NbExp=2; IntAct=EBI-9845742, EBI-1567153;
CC Q9HCE7-2; P37840: SNCA; NbExp=3; IntAct=EBI-9845742, EBI-985879;
CC Q9HCE7-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-9845742, EBI-5235340;
CC Q9HCE7-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-9845742, EBI-372899;
CC Q9HCE7-2; Q9BUZ4: TRAF4; NbExp=4; IntAct=EBI-9845742, EBI-3650647;
CC Q9HCE7-2; O76024: WFS1; NbExp=3; IntAct=EBI-9845742, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21572392}. Cell
CC membrane {ECO:0000269|PubMed:21572392}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21572392}; Cytoplasmic side
CC {ECO:0000269|PubMed:21572392}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q9HCE7-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q9HCE7-2; Sequence=VSP_006812;
CC -!- TISSUE SPECIFICITY: Expressed in melanocytes (PubMed:23999003).
CC {ECO:0000269|PubMed:23999003}.
CC -!- DOMAIN: The C2 domain mediates membrane localization and substrate
CC selection. {ECO:0000269|PubMed:21402695}.
CC -!- PTM: Auto-ubiquitinated in presence of NDFIP1 (PubMed:23087404).
CC Ubiquitinated by the SCF(FBXL15) complex at Lys-381 and Lys-383,
CC leading to its degradation by the proteasome. Lys-383 is the primary
CC ubiquitination site. {ECO:0000269|PubMed:21572392,
CC ECO:0000269|PubMed:23087404}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13451.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB046845; BAB13451.1; ALT_INIT; mRNA.
DR EMBL; AC004893; AAC62434.1; -; Genomic_DNA.
DR EMBL; AF464850; AAM90910.1; -; mRNA.
DR EMBL; AC073468; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236956; EAL23885.1; -; Genomic_DNA.
DR EMBL; CH236956; EAL23886.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76687.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76688.1; -; Genomic_DNA.
DR EMBL; BC136804; AAI36805.1; -; mRNA.
DR EMBL; BC144414; AAI44415.1; -; mRNA.
DR EMBL; BC152468; AAI52469.1; -; mRNA.
DR EMBL; AF199364; AAF08298.2; -; mRNA.
DR CCDS; CCDS34689.1; -. [Q9HCE7-2]
DR CCDS; CCDS34690.1; -. [Q9HCE7-1]
DR RefSeq; NP_001186776.1; NM_001199847.1.
DR RefSeq; NP_065162.1; NM_020429.2. [Q9HCE7-1]
DR RefSeq; NP_851994.1; NM_181349.2. [Q9HCE7-2]
DR PDB; 2LAZ; NMR; -; A=235-267.
DR PDB; 2LB0; NMR; -; A=235-267.
DR PDB; 2LB1; NMR; -; A=305-340.
DR PDB; 2LTX; NMR; -; A=306-340.
DR PDB; 3PYC; X-ray; 1.96 A; A=13-140.
DR PDBsum; 2LAZ; -.
DR PDBsum; 2LB0; -.
DR PDBsum; 2LB1; -.
DR PDBsum; 2LTX; -.
DR PDBsum; 3PYC; -.
DR AlphaFoldDB; Q9HCE7; -.
DR BMRB; Q9HCE7; -.
DR SMR; Q9HCE7; -.
DR BioGRID; 121411; 557.
DR CORUM; Q9HCE7; -.
DR DIP; DIP-36709N; -.
DR IntAct; Q9HCE7; 37.
DR MINT; Q9HCE7; -.
DR STRING; 9606.ENSP00000354621; -.
DR BindingDB; Q9HCE7; -.
DR ChEMBL; CHEMBL3879859; -.
DR iPTMnet; Q9HCE7; -.
DR PhosphoSitePlus; Q9HCE7; -.
DR SwissPalm; Q9HCE7; -.
DR BioMuta; SMURF1; -.
DR DMDM; 17865625; -.
DR EPD; Q9HCE7; -.
DR jPOST; Q9HCE7; -.
DR MassIVE; Q9HCE7; -.
DR MaxQB; Q9HCE7; -.
DR PaxDb; 9606-ENSP00000354621; -.
DR PeptideAtlas; Q9HCE7; -.
DR ProteomicsDB; 81693; -. [Q9HCE7-1]
DR ProteomicsDB; 81694; -. [Q9HCE7-2]
DR Pumba; Q9HCE7; -.
DR ABCD; Q9HCE7; 2 sequenced antibodies.
DR Antibodypedia; 30289; 447 antibodies from 37 providers.
DR DNASU; 57154; -.
DR Ensembl; ENST00000361125.1; ENSP00000354621.1; ENSG00000198742.10. [Q9HCE7-1]
DR Ensembl; ENST00000361368.7; ENSP00000355326.2; ENSG00000198742.10. [Q9HCE7-2]
DR GeneID; 57154; -.
DR KEGG; hsa:57154; -.
DR MANE-Select; ENST00000361368.7; ENSP00000355326.2; NM_181349.3; NP_851994.1. [Q9HCE7-2]
DR UCSC; uc003upu.3; human. [Q9HCE7-1]
DR AGR; HGNC:16807; -.
DR CTD; 57154; -.
DR DisGeNET; 57154; -.
DR GeneCards; SMURF1; -.
DR HGNC; HGNC:16807; SMURF1.
DR HPA; ENSG00000198742; Low tissue specificity.
DR MIM; 605568; gene.
DR neXtProt; NX_Q9HCE7; -.
DR OpenTargets; ENSG00000198742; -.
DR PharmGKB; PA134987175; -.
DR VEuPathDB; HostDB:ENSG00000198742; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000158690; -.
DR HOGENOM; CLU_002173_1_1_1; -.
DR InParanoid; Q9HCE7; -.
DR OMA; QWDRPRH; -.
DR OrthoDB; 5480520at2759; -.
DR PhylomeDB; Q9HCE7; -.
DR TreeFam; TF323658; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q9HCE7; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-HSA-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9HCE7; -.
DR SIGNOR; Q9HCE7; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 57154; 35 hits in 1206 CRISPR screens.
DR ChiTaRS; SMURF1; human.
DR EvolutionaryTrace; Q9HCE7; -.
DR GeneWiki; SMURF1; -.
DR GenomeRNAi; 57154; -.
DR Pharos; Q9HCE7; Tchem.
DR PRO; PR:Q9HCE7; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9HCE7; Protein.
DR Bgee; ENSG00000198742; Expressed in popliteal artery and 100 other cell types or tissues.
DR Genevisible; Q9HCE7; HS.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0070697; F:activin receptor binding; IPI:BHF-UCL.
DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0005543; F:phospholipid binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0070412; F:R-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IPI:BHF-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:BHF-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IDA:UniProtKB.
DR GO; GO:0007398; P:ectoderm development; TAS:UniProtKB.
DR GO; GO:0061736; P:engulfment of target by autophagosome; IMP:ParkinsonsUK-UCL.
DR GO; GO:0032926; P:negative regulation of activin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045773; P:positive regulation of axon extension; IEA:Ensembl.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IDA:UniProtKB.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IMP:CACAO.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0006611; P:protein export from nucleus; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0071211; P:protein targeting to vacuole involved in autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0032801; P:receptor catabolic process; IDA:BHF-UCL.
DR GO; GO:0061753; P:substrate localization to autophagosome; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; TAS:Reactome.
DR CDD; cd08382; C2_Smurf-like; 1.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 2.
DR Gene3D; 2.20.70.10; -; 1.
DR Gene3D; 2.60.40.150; C2 domain; 1.
DR Gene3D; 3.30.2160.10; Hect, E3 ligase catalytic domain; 1.
DR Gene3D; 3.30.2410.10; Hect, E3 ligase catalytic domain; 1.
DR Gene3D; 3.90.1750.10; Hect, E3 ligase catalytic domains; 1.
DR IDEAL; IID00328; -.
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 PANTHER; PTHR11254:SF293; E3 UBIQUITIN-PROTEIN LIGASE SMURF1; 1.
DR PANTHER; PTHR11254; HECT DOMAIN UBIQUITIN-PROTEIN LIGASE; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00397; WW; 2.
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; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 1.
DR SUPFAM; SSF51045; WW domain; 2.
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 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Differentiation; Isopeptide bond; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..757
FT /note="E3 ubiquitin-protein ligase SMURF1"
FT /id="PRO_0000120326"
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 306..339
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 420..757
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 193..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 198..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 725
FT /note="Glycyl thioester intermediate"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 381
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21572392"
FT CROSSLNK 383
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21572392"
FT VAR_SEQ 269..294
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10458166,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_006812"
FT VARIANT 466
FT /note="S -> Y (in dbSNP:rs13246077)"
FT /id="VAR_052959"
FT MUTAGEN 28
FT /note="K->A: Fails to ubiquitinate RHOA; when associated
FT with A-85."
FT /evidence="ECO:0000269|PubMed:21402695"
FT MUTAGEN 85
FT /note="K->A: Fails to ubiquitinate RHOA; when associated
FT with A-28."
FT /evidence="ECO:0000269|PubMed:21402695"
FT MUTAGEN 350
FT /note="K->R: Abolishes FBXL15-mediated ubiquitination and
FT degradation; when associated with R-381 and R-381."
FT /evidence="ECO:0000269|PubMed:21572392"
FT MUTAGEN 381
FT /note="K->R: Abolishes FBXL15-mediated ubiquitination and
FT degradation; when associated with R-350 and R-383.
FT Abolishes FBXL15-mediated ubiquitination and degradation;
FT when associated with R-383."
FT /evidence="ECO:0000269|PubMed:21572392"
FT MUTAGEN 383
FT /note="K->R: Abolishes FBXL15-mediated ubiquitination and
FT degradation; when associated with R-350 and R-381.
FT Abolishes FBXL15-mediated ubiquitination and degradation;
FT when associated with R-381."
FT /evidence="ECO:0000269|PubMed:21572392"
FT MUTAGEN 725
FT /note="C->A: Loss of enzyme activity, without abolishing
FT FBXL15-mediated ubiquitination."
FT /evidence="ECO:0000269|PubMed:19937093,
FT ECO:0000269|PubMed:21572392"
FT CONFLICT 447
FT /note="W -> G (in Ref. 6; AAI44415)"
FT /evidence="ECO:0000305"
FT CONFLICT 697..699
FT /note="Missing (in Ref. 6; AAI36805/AAI44415)"
FT /evidence="ECO:0000305"
FT STRAND 13..24
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3PYC"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 61..71
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:3PYC"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:3PYC"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:3PYC"
FT HELIX 102..108
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 131..139
FT /evidence="ECO:0007829|PDB:3PYC"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:2LAZ"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:2LAZ"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:2LAZ"
FT TURN 255..258
FT /evidence="ECO:0007829|PDB:2LAZ"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:2LAZ"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:2LB1"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:2LB1"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:2LB1"
FT TURN 327..330
FT /evidence="ECO:0007829|PDB:2LB1"
FT STRAND 331..334
FT /evidence="ECO:0007829|PDB:2LB1"
SQ SEQUENCE 757 AA; 86114 MW; 89A171CFC47B40E9 CRC64;
MSNPGTRRNG SSIKIRLTVL CAKNLAKKDF FRLPDPFAKI VVDGSGQCHS TDTVKNTLDP
KWNQHYDLYV GKTDSITISV WNHKKIHKKQ GAGFLGCVRL LSNAISRLKD TGYQRLDLCK
LNPSDTDAVR GQIVVSLQTR DRIGTGGSVV DCRGLLENEG TVYEDSGPGR PLSCFMEEPA
PYTDSTGAAA GGGNCRFVES PSQDQRLQAQ RLRNPDVRGS LQTPQNRPHG HQSPELPEGY
EQRTTVQGQV YFLHTQTGVS TWHDPRIPSP SGTIPGGDAA FLYEFLLQGH TSEPRDLNSV
NCDELGPLPP GWEVRSTVSG RIYFVDHNNR TTQFTDPRLH HIMNHQCQLK EPSQPLPLPS
EGSLEDEELP AQRYERDLVQ KLKVLRHELS LQQPQAGHCR IEVSREEIFE ESYRQIMKMR
PKDLKKRLMV KFRGEEGLDY GGVAREWLYL LCHEMLNPYY GLFQYSTDNI YMLQINPDSS
INPDHLSYFH FVGRIMGLAV FHGHYINGGF TVPFYKQLLG KPIQLSDLES VDPELHKSLV
WILENDITPV LDHTFCVEHN AFGRILQHEL KPNGRNVPVT EENKKEYVRL YVNWRFMRGI
EAQFLALQKG FNELIPQHLL KPFDQKELEL IIGGLDKIDL NDWKSNTRLK HCVADSNIVR
WFWQAVETFD EERRARLLQF VTGSTRVPLQ GFKALQGSTG AAGPRLFTIH LIDANTDNLP
KAHTCFNRID IPPYESYEKL YEKLLTAVEE TCGFAVE
//
