SMAD3_MOUSE
ID SMAD3_MOUSE Reviewed; 425 AA.
AC Q8BUN5; O09064; O09144; O14510; O35273; Q8BX84; Q92940; Q93002; Q9GKR4;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Mothers against decapentaplegic homolog 3;
DE Short=MAD homolog 3;
DE Short=Mad3;
DE Short=Mothers against DPP homolog 3;
DE Short=mMad3;
DE AltName: Full=SMAD family member 3;
DE Short=SMAD 3;
DE Short=Smad3;
GN Name=Smad3; Synonyms=Madh3;
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 [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10331191; DOI=10.1292/jvms.61.213;
RA Kano K., Notani A., Nam S.-Y., Fujisawa M., Kurohmaru M., Hayashi Y.;
RT "Cloning and studies of the mouse cDNA encoding Smad3.";
RL J. Vet. Med. Sci. 61:213-219(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Yang X., Xu X., Shen S., Deng C.;
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Hippocampus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [5]
RP PHOSPHORYLATION AT SER-422; SER-423 AND SER-425.
RX PubMed=9380693; DOI=10.1073/pnas.94.20.10669;
RA Liu X., Sun Y., Constantinescu S.N., Karam E., Weinberg R.A., Lodish H.F.;
RT "Transforming growth factor beta-induced phosphorylation of Smad3 is
RT required for growth inhibition and transcriptional induction in epithelial
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:10669-10674(1997).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10559937; DOI=10.1038/12971;
RA Ashcroft G.S., Yang X., Glick A.B., Weinstein M., Letterio J.L.,
RA Mizel D.E., Anzano M., Greenwell-Wild T., Wahl S.M., Deng C., Roberts A.B.;
RT "Mice lacking Smad3 show accelerated wound healing and an impaired local
RT inflammatory response.";
RL Nat. Cell Biol. 1:260-266(1999).
RN [7]
RP INTERACTION WITH AIP1, AND IDENTIFICATION IN A COMPLEX WITH AIP1; ACVR2A
RP AND ACVR1B.
RX PubMed=10681527; DOI=10.1074/jbc.275.8.5485;
RA Shoji H., Tsuchida K., Kishi H., Yamakawa N., Matsuzaki T., Liu Z.,
RA Nakamura T., Sugino H.;
RT "Identification and characterization of a PDZ protein that interacts with
RT activin types II receptors.";
RL J. Biol. Chem. 275:5485-5492(2000).
RN [8]
RP INTERACTION WITH HGS.
RX PubMed=11094085; DOI=10.1128/mcb.20.24.9346-9355.2000;
RA Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J.,
RA Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K.;
RT "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through
RT cooperation with SARA.";
RL Mol. Cell. Biol. 20:9346-9355(2000).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11585338; DOI=10.1359/jbmr.2001.16.10.1754;
RA Borton A.J., Frederick J.P., Datto M.B., Wang X.F., Weinstein R.S.;
RT "The loss of Smad3 results in a lower rate of bone formation and osteopenia
RT through dysregulation of osteoblast differentiation and apoptosis.";
RL J. Bone Miner. Res. 16:1754-1764(2001).
RN [10]
RP INTERACTION WITH ZNF8.
RX PubMed=12370310; DOI=10.1128/mcb.22.21.7633-7644.2002;
RA Jiao K., Zhou Y., Hogan B.L.M.;
RT "Identification of mZnf8, a mouse Kruppel-like transcriptional repressor,
RT as a novel nuclear interaction partner of Smad1.";
RL Mol. Cell. Biol. 22:7633-7644(2002).
RN [11]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=14617288; DOI=10.1046/j.1524-475x.2003.11614.x;
RA Ashcroft G.S., Mills S.J., Flanders K.C., Lyakh L.A., Anzano M.A.,
RA Gilliver S.C., Roberts A.B.;
RT "Role of Smad3 in the hormonal modulation of in vivo wound healing
RT responses.";
RL Wound Repair Regen. 11:468-473(2003).
RN [12]
RP INTERACTION WITH TGFB1I1.
RX PubMed=14755691; DOI=10.1002/jcb.10754;
RA Shibanuma M., Kim-Kaneyama J.-R., Sato S., Nose K.;
RT "A LIM protein, Hic-5, functions as a potential coactivator for Sp1.";
RL J. Cell. Biochem. 91:633-645(2004).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH PML
RP AND ZFYVE9/SARA.
RX PubMed=15356634; DOI=10.1038/nature02783;
RA Lin H.K., Bergmann S., Pandolfi P.P.;
RT "Cytoplasmic PML function in TGF-beta signalling.";
RL Nature 431:205-211(2004).
RN [14]
RP INTERACTION WITH WWP1.
RX PubMed=15221015; DOI=10.1038/sj.onc.1207885;
RA Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K.,
RA Miyazawa K.;
RT "Negative regulation of transforming growth factor-beta (TGF-beta)
RT signaling by WW domain-containing protein 1 (WWP1).";
RL Oncogene 23:6914-6923(2004).
RN [15]
RP INTERACTION WITH NEDD4L.
RX PubMed=15496141; DOI=10.1042/bj20040738;
RA Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K.,
RA Imamura T.;
RT "NEDD4-2 (neural precursor cell expressed, developmentally down-regulated
RT 4-2) negatively regulates TGF-beta (transforming growth factor-beta)
RT signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta
RT type I receptor.";
RL Biochem. J. 386:461-470(2005).
RN [16]
RP INTERACTION WITH ZC3H3.
RX PubMed=16115198; DOI=10.1111/j.1365-2443.2005.00887.x;
RA Collart C., Remacle J.E., Barabino S., van Grunsven L.A., Nelles L.,
RA Schellens A., Van de Putte T., Pype S., Huylebroeck D., Verschueren K.;
RT "Smicl is a novel Smad interacting protein and cleavage and polyadenylation
RT specificity factor associated protein.";
RL Genes Cells 10:897-906(2005).
RN [17]
RP INTERACTION WITH PRDM16.
RX PubMed=17467076; DOI=10.1016/j.bbamcr.2007.03.016;
RA Warner D.R., Horn K.H., Mudd L., Webb C.L., Greene R.M., Pisano M.M.;
RT "PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic
RT orofacial tissue.";
RL Biochim. Biophys. Acta 1773:814-820(2007).
RN [18]
RP INTERACTION WITH TTRAP.
RX PubMed=18039968; DOI=10.1242/dev.000026;
RA Esguerra C.V., Nelles L., Vermeire L., Ibrahimi A., Crawford A.D.,
RA Derua R., Janssens E., Waelkens E., Carmeliet P., Collen D.,
RA Huylebroeck D.;
RT "Ttrap is an essential modulator of Smad3-dependent Nodal signaling during
RT zebrafish gastrulation and left-right axis determination.";
RL Development 134:4381-4393(2007).
RN [19]
RP INTERACTION WITH FOXL2.
RX PubMed=19106105; DOI=10.1074/jbc.m806676200;
RA Blount A.L., Schmidt K., Justice N.J., Vale W.W., Fischer W.H.,
RA Bilezikjian L.M.;
RT "FoxL2 and Smad3 coordinately regulate follistatin gene transcription.";
RL J. Biol. Chem. 284:7631-7645(2009).
RN [20]
RP INTERACTION WITH YAP1 AND SMAD4, AND SUBCELLULAR LOCATION.
RX PubMed=21145499; DOI=10.1016/j.devcel.2010.11.012;
RA Varelas X., Samavarchi-Tehrani P., Narimatsu M., Weiss A., Cockburn K.,
RA Larsen B.G., Rossant J., Wrana J.L.;
RT "The Crumbs complex couples cell density sensing to Hippo-dependent control
RT of the TGF-beta-SMAD pathway.";
RL Dev. Cell 19:831-844(2010).
RN [21]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21035443; DOI=10.1016/j.yexmp.2010.10.011;
RA Kawakatsu M., Kanno S., Gui T., Gai Z., Itoh S., Tanishima H., Oikawa K.,
RA Muragaki Y.;
RT "Loss of Smad3 gives rise to poor soft callus formation and accelerates
RT early fracture healing.";
RL Exp. Mol. Pathol. 90:107-115(2011).
RN [22]
RP INTERACTION WITH PPP5C, AND SUBCELLULAR LOCATION.
RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003;
RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.;
RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth
RT factor-beta pathway.";
RL Cell. Signal. 24:1999-2006(2012).
RN [23]
RP INTERACTION WITH RNF111, AND UBIQUITINATION.
RX PubMed=17341133; DOI=10.1371/journal.pbio.0050067;
RA Mavrakis K.J., Andrew R.L., Lee K.L., Petropoulou C., Dixon J.E.,
RA Navaratnam N., Norris D.P., Episkopou V.;
RT "Arkadia enhances Nodal/TGF-beta signaling by coupling phospho-Smad2/3
RT activity and turnover.";
RL PLoS Biol. 5:E67-E67(2007).
CC -!- FUNCTION: Receptor-regulated SMAD (R-SMAD) that is an intracellular
CC signal transducer and transcriptional modulator activated by TGF-beta
CC (transforming growth factor) and activin type 1 receptor kinases. Binds
CC the TRE element in the promoter region of many genes that are regulated
CC by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates
CC transcription. Can also form a SMAD3/SMAD4/JUN/FOS complex at the AP-
CC 1/SMAD site to regulate TGF-beta-mediated transcription. Has an
CC inhibitory effect on wound healing probably by modulating both growth
CC and migration of primary keratinocytes and by altering the TGF-mediated
CC chemotaxis of monocytes. This effect on wound healing appears to be
CC hormone-sensitive. Regulator of chondrogenesis and osteogenesis and
CC inhibits early healing of bone fractures. Positively regulates PDPK1
CC kinase activity by stimulating its dissociation from the 14-3-3 protein
CC YWHAQ which acts as a negative regulator (By similarity).
CC {ECO:0000250|UniProtKB:P84022, ECO:0000269|PubMed:10559937,
CC ECO:0000269|PubMed:11585338, ECO:0000269|PubMed:14617288,
CC ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:21035443}.
CC -!- SUBUNIT: Monomer; in the absence of TGF-beta (By similarity).
CC Homooligomer; in the presence of TGF-beta (By similarity).
CC Heterotrimer; forms a heterotrimer in the presence of TGF-beta
CC consisting of two molecules of C-terminally phosphorylated SMAD2 or
CC SMAD3 and one of SMAD4 to form the transcriptionally active
CC SMAD2/SMAD3-SMAD4 complex (PubMed:21145499). Part of a complex
CC consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:15496141). Forms a
CC complex with SMAD2 and TRIM33 upon addition of TGF-beta (By
CC similarity). Found in a complex composed of SMAD3, RAN and XPO4; within
CC the complex interacts directly with XPO4 (By similarity). Component of
CC the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1
CC promoter site; required for synergistic transcriptional activity in
CC response to TGF-beta (By similarity). Interacts (via an N-terminal
CC domain) with JUN (via its basic DNA binding and leucine zipper
CC domains); this interaction is essential for DNA binding and cooperative
CC transcriptional activity in response to TGF-beta (By similarity).
CC Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and
CC SMAD4 (By similarity). Interacts with PPM1A; the interaction
CC dephosphorylates SMAD3 in the C-terminal SXS motif leading to
CC disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination
CC of TGF-beta signaling (By similarity). Interacts (via MH2 domain) with
CC ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway
CC increases the activity of the SMAD3/SMAD4 transcriptional complex (By
CC similarity). Interacts (when phosphorylated) with RNF111; RNF111 acts
CC as an enhancer of the transcriptional responses by mediating
CC ubiquitination and degradation of SMAD3 inhibitors (PubMed:17341133).
CC Interacts (dephosphorylated form via the MH1 and MH2 domains) with
CC RANBP3 (via its C-terminal R domain); the interaction results in the
CC export of dephosphorylated SMAD3 out of the nucleus and termination of
CC the TGF-beta signaling (By similarity). Interacts (via MH2 domain) with
CC LEMD3; the interaction represses SMAD3 transcriptional activity through
CC preventing the formation of the heteromeric complex with SMAD4 and
CC translocation to the nucleus (By similarity). Interacts (via the linker
CC region) with EP300 (C-terminal); the interaction promotes SMAD3
CC acetylation and is enhanced by TGF-beta phosphorylation in the C-
CC terminal of SMAD3 (By similarity). This interaction can be blocked by
CC competitive binding of adenovirus oncoprotein E1A to the same C-
CC terminal site on EP300, which then results in partially inhibited
CC SMAD3/SMAD4 transcriptional activity (By similarity). Interacts with
CC TGFBR1 (By similarity). Interacts with TGFB1I1 (PubMed:14755691).
CC Interacts with PRDM16 (PubMed:17467076). Interacts with SNW1 (By
CC similarity). Interacts (via MH2 domain) with ZFYVE9 (PubMed:15356634).
CC Interacts with HDAC1 (By similarity). Interacts with TGIF2 (By
CC similarity). Interacts with SKOR1 (By similarity). Interacts with SKOR2
CC (By similarity). Interacts with DACH1; the interaction inhibits the
CC TGF-beta signaling (By similarity). Interacts with RBPMS (By
CC similarity). Interacts (via MH2 domain) with MECOM (By similarity).
CC Interacts with WWTR1 (via its coiled-coil domain) (By similarity).
CC Interacts with SKI; the interaction represses SMAD3 transcriptional
CC activity (By similarity). Interacts with MEN1 (By similarity).
CC Interacts with IL1F7 (By similarity). Interaction with CSNK1G2 (By
CC similarity). Interacts with PDPK1 (via PH domain) (By similarity).
CC Interacts with DAB2; the interactions are enhanced upon TGF-beta
CC stimulation (By similarity). Interacts with USP15 (By similarity).
CC Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation
CC and protein levels (PubMed:22781750). Interacts with LDLRAD4 (via the
CC SMAD interaction motif) (By similarity). Interacts with PMEPA1 (By
CC similarity). Interacts with ZNF451 (By similarity). Interacts with
CC ZFHX3 (By similarity). Interacts weakly with ZNF8 (PubMed:12370310).
CC Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (By
CC similarity). Interacts with YAP1 (when phosphorylated at 'Ser-112')
CC (PubMed:21145499). Interacts with AIP1 (PubMed:10681527). Interacts
CC (via MH2 domain) with CITED2 (via C-terminus) (By similarity).
CC Interacts with HGS (PubMed:11094085). Interacts with WWP1
CC (PubMed:15221015). Interacts with TTRAP (PubMed:18039968). Interacts
CC with FOXL2 (PubMed:19106105). Interacts with PML (PubMed:15356634).
CC Interacts with NEDD4L; the interaction requires TGF-beta stimulation
CC (PubMed:15496141). Interacts with ZC3H3 (PubMed:16115198). Interacts
CC with TGIF. Interacts with CREBBP. Interacts with ATF2.
CC {ECO:0000250|UniProtKB:P84022, ECO:0000250|UniProtKB:P84025,
CC ECO:0000269|PubMed:10681527, ECO:0000269|PubMed:11094085,
CC ECO:0000269|PubMed:12370310, ECO:0000269|PubMed:14755691,
CC ECO:0000269|PubMed:15221015, ECO:0000269|PubMed:15356634,
CC ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:16115198,
CC ECO:0000269|PubMed:17341133, ECO:0000269|PubMed:17467076,
CC ECO:0000269|PubMed:18039968, ECO:0000269|PubMed:19106105,
CC ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:22781750}.
CC -!- INTERACTION:
CC Q8BUN5; O35625: Axin1; NbExp=2; IntAct=EBI-2337983, EBI-2365912;
CC Q8BUN5; P20263: Pou5f1; NbExp=13; IntAct=EBI-2337983, EBI-1606219;
CC Q8BUN5; P97471: Smad4; NbExp=6; IntAct=EBI-2337983, EBI-5259270;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15356634,
CC ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:22781750}. Nucleus
CC {ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:21145499,
CC ECO:0000269|PubMed:22781750}. Note=Cytoplasmic and nuclear in the
CC absence of TGF-beta (PubMed:21145499). On TGF-beta stimulation,
CC migrates to the nucleus when complexed with SMAD4 (PubMed:21145499).
CC Through the action of the phosphatase PPM1A, released from the
CC SMAD2/SMAD4 complex, and exported out of the nucleus by interaction
CC with RANBP1 (By similarity). Co-localizes with LEMD3 at the nucleus
CC inner membrane (By similarity). MAPK-mediated phosphorylation appears
CC to have no effect on nuclear import. PDPK1 prevents its nuclear
CC translocation in response to TGF-beta (By similarity). Localized mainly
CC to the nucleus in the early stages of embryo development with
CC expression becoming evident in the cytoplasm of the inner cell mass at
CC the blastocyst stage (PubMed:21145499). {ECO:0000250|UniProtKB:P84022,
CC ECO:0000269|PubMed:21145499}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and ovary. Detected
CC in the pyramidal cells of the hippocampus, granule cells of the dentate
CC gyrus, granular cells of the cerebral cortex and the granulosa cells of
CC the ovary. {ECO:0000269|PubMed:10331191}.
CC -!- DOMAIN: The MH1 domain is required for DNA binding (By similarity).
CC Also binds zinc ions which are necessary for the DNA binding.
CC {ECO:0000250}.
CC -!- DOMAIN: The MH2 domain is required for both homomeric and heteromeric
CC interactions and for transcriptional regulation. Sufficient for nuclear
CC import (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The linker region is required for the TGFbeta-mediated
CC transcriptional activity and acts synergistically with the MH2 domain.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Enhanced
CC phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on
CC EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated
CC phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle
CC dependent manner and inhibits both the transcriptional activity and
CC antiproliferative functions of SMAD3. This phosphorylation is inhibited
CC by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also
CC phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1
CC and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is
CC required for interaction with SMAD4, nuclear location and
CC transactivational activity, and appears to be a prerequisite for the
CC TGF-beta mediated phosphorylation in the linker region.
CC Dephosphorylated in the C-terminal SXS motif by PPM1A. This
CC dephosphorylation disrupts the interaction with SMAD4, promotes nuclear
CC export and terminates TGF-beta-mediated signaling. Phosphorylation at
CC Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and
CC subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-
CC beta responses (By similarity). Phosphorylated by PDPK1 (By
CC similarity). {ECO:0000250|UniProtKB:P84022}.
CC -!- PTM: Acetylation in the nucleus by EP300 in the MH2 domain regulates
CC positively its transcriptional activity and is enhanced by TGF-beta.
CC {ECO:0000250|UniProtKB:P84022}.
CC -!- PTM: Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding.
CC Deubiquitination by USP15 alleviates inhibition and promotes activation
CC of TGF-beta target genes (By similarity). Ubiquitinated by RNF111,
CC leading to its degradation: only SMAD3 proteins that are 'in use' are
CC targeted by RNF111, RNF111 playing a key role in activating SMAD3 and
CC regulating its turnover (PubMed:17341133). Undergoes STUB1-mediated
CC ubiquitination and degradation (By similarity).
CC {ECO:0000250|UniProtKB:P84022, ECO:0000269|PubMed:17341133}.
CC -!- PTM: Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation
CC negatively regulates SMAD3 transcriptional responses during the course
CC of TGF-beta signaling. {ECO:0000250|UniProtKB:P84022}.
CC -!- DISRUPTION PHENOTYPE: SMAD3 null mice exhibit inhibition of
CC proliferation of mammary gland epithelial cells. Fibrobasts are only
CC partially growth inhibited. Defects in osteoblast differentiation are
CC observed. Animals are osteopenic with less cortical and cancellous
CC bone. Facture healing is accelerated. Decreased bone mineral density
CC (BMD) reflects the inability of osteoblasts to balance osteoclast
CC activity. Wound healing is accelerated to about two and a half times
CC that of normal animals. Wound areas are significantly reduced with less
CC quantities of granulation tissue. There is reduced local infiltration
CC of moncytes and keratinocytes show altered patterns of growth and
CC migration. Accelerated wound healing is observed on castration of null
CC male mice, while null female mice exhibited delayed healing following
CC ovariectomy. {ECO:0000269|PubMed:10559937, ECO:0000269|PubMed:11585338,
CC ECO:0000269|PubMed:14617288, ECO:0000269|PubMed:21035443}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB008192; BAA76956.1; -; mRNA.
DR EMBL; AF016189; AAB81755.1; -; mRNA.
DR EMBL; AK048626; BAC33398.1; -; mRNA.
DR EMBL; AK083158; BAC38789.1; -; mRNA.
DR EMBL; BC066850; AAH66850.1; -; mRNA.
DR CCDS; CCDS23272.1; -.
DR RefSeq; NP_058049.3; NM_016769.4.
DR AlphaFoldDB; Q8BUN5; -.
DR SMR; Q8BUN5; -.
DR BioGRID; 201276; 70.
DR ComplexPortal; CPX-10; SMAD2-SMAD3-SMAD4 complex.
DR ComplexPortal; CPX-14; SMAD3 homotrimer.
DR ComplexPortal; CPX-3286; SMAD3-SMAD4 complex.
DR CORUM; Q8BUN5; -.
DR DIP; DIP-29717N; -.
DR IntAct; Q8BUN5; 47.
DR MINT; Q8BUN5; -.
DR STRING; 10090.ENSMUSP00000034973; -.
DR iPTMnet; Q8BUN5; -.
DR PhosphoSitePlus; Q8BUN5; -.
DR SwissPalm; Q8BUN5; -.
DR EPD; Q8BUN5; -.
DR MaxQB; Q8BUN5; -.
DR PaxDb; Q8BUN5; -.
DR PeptideAtlas; Q8BUN5; -.
DR PRIDE; Q8BUN5; -.
DR ProteomicsDB; 257255; -.
DR Antibodypedia; 26224; 2388 antibodies from 44 providers.
DR DNASU; 17127; -.
DR Ensembl; ENSMUST00000034973; ENSMUSP00000034973; ENSMUSG00000032402.
DR GeneID; 17127; -.
DR KEGG; mmu:17127; -.
DR UCSC; uc009qbi.1; mouse.
DR CTD; 4088; -.
DR MGI; MGI:1201674; Smad3.
DR VEuPathDB; HostDB:ENSMUSG00000032402; -.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000153499; -.
DR HOGENOM; CLU_026736_0_0_1; -.
DR InParanoid; Q8BUN5; -.
DR OMA; MKHRLGA; -.
DR OrthoDB; 608001at2759; -.
DR PhylomeDB; Q8BUN5; -.
DR TreeFam; TF314923; -.
DR Reactome; R-MMU-1181150; Signaling by NODAL.
DR Reactome; R-MMU-1502540; Signaling by Activin.
DR Reactome; R-MMU-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-MMU-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-MMU-9617828; FOXO-mediated transcription of cell cycle genes.
DR BioGRID-ORCS; 17127; 3 hits in 77 CRISPR screens.
DR ChiTaRS; Smad3; mouse.
DR PRO; PR:Q8BUN5; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BUN5; protein.
DR Bgee; ENSMUSG00000032402; Expressed in undifferentiated genital tubercle and 249 other tissues.
DR ExpressionAtlas; Q8BUN5; baseline and differential.
DR Genevisible; Q8BUN5; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; ISO:MGI.
DR GO; GO:0005637; C:nuclear inner membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0071141; C:SMAD protein complex; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISS:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:BHF-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0070410; F:co-SMAD binding; ISO:MGI.
DR GO; GO:0005518; F:collagen binding; IPI:MGI.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IPI:ARUK-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:MGI.
DR GO; GO:0031962; F:nuclear mineralocorticoid receptor binding; ISO:MGI.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0019902; F:phosphatase binding; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0070412; F:R-SMAD binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR GO; GO:0032810; F:sterol response element binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0097296; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI.
DR GO; GO:0030325; P:adrenal gland development; ISO:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045216; P:cell-cell junction organization; ISO:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0098586; P:cellular response to virus; IDA:MGI.
DR GO; GO:0048589; P:developmental growth; IGI:MGI.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IGI:MGI.
DR GO; GO:0048617; P:embryonic foregut morphogenesis; IGI:MGI.
DR GO; GO:0009880; P:embryonic pattern specification; IGI:MGI.
DR GO; GO:0007492; P:endoderm development; IGI:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0007369; P:gastrulation; IGI:MGI.
DR GO; GO:0001947; P:heart looping; IGI:MGI.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0002520; P:immune system development; IGI:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0007254; P:JNK cascade; IMP:MGI.
DR GO; GO:0070306; P:lens fiber cell differentiation; IMP:MGI.
DR GO; GO:0001889; P:liver development; IGI:MGI.
DR GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0061767; P:negative regulation of lung blood pressure; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IGI:MGI.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IMP:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0061045; P:negative regulation of wound healing; IMP:UniProtKB.
DR GO; GO:0038092; P:nodal signaling pathway; ISO:MGI.
DR GO; GO:0002076; P:osteoblast development; IGI:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0048340; P:paraxial mesoderm morphogenesis; IMP:MGI.
DR GO; GO:0060039; P:pericardium development; IGI:MGI.
DR GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; ISO:MGI.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; ISO:MGI.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0032916; P:positive regulation of transforming growth factor beta3 production; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0051098; P:regulation of binding; IDA:MGI.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0050776; P:regulation of immune response; IMP:UniProtKB.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:MGI.
DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; ISO:MGI.
DR GO; GO:0001501; P:skeletal system development; IGI:MGI.
DR GO; GO:0007183; P:SMAD protein complex assembly; ISO:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IGI:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:MGI.
DR GO; GO:0042110; P:T cell activation; IMP:UniProtKB.
DR GO; GO:0030878; P:thyroid gland development; IGI:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:0060290; P:transdifferentiation; ISO:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:MGI.
DR GO; GO:0001657; P:ureteric bud development; IEP:UniProtKB.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 1.
DR InterPro; IPR013790; Dwarfin.
DR InterPro; IPR003619; MAD_homology1_Dwarfin-type.
DR InterPro; IPR013019; MAD_homology_MH1.
DR InterPro; IPR017855; SMAD-like_dom_sf.
DR InterPro; IPR001132; SMAD_dom_Dwarfin-type.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036578; SMAD_MH1_sf.
DR PANTHER; PTHR13703; PTHR13703; 1.
DR Pfam; PF03165; MH1; 1.
DR Pfam; PF03166; MH2; 1.
DR SMART; SM00523; DWA; 1.
DR SMART; SM00524; DWB; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF56366; SSF56366; 1.
DR PROSITE; PS51075; MH1; 1.
DR PROSITE; PS51076; MH2; 1.
PE 1: Evidence at protein level;
KW Acetylation; ADP-ribosylation; Cytoplasm; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT CHAIN 2..425
FT /note="Mothers against decapentaplegic homolog 3"
FT /id="PRO_0000090857"
FT DOMAIN 10..136
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 232..425
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 137..231
FT /note="Linker"
FT REGION 165..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..324
FT /note="Sufficient for interaction with XPO4"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT SITE 40
FT /note="Required for trimerization"
FT /evidence="ECO:0000250"
FT SITE 41
FT /note="Required for interaction with DNA and JUN and for
FT functional cooperation with JUN"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 8
FT /note="Phosphothreonine; by CDK2 and CDK4"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 179
FT /note="Phosphothreonine; by CDK2, CDK4 and MAPK"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 204
FT /note="Phosphoserine; by GSK3 and MAPK"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 208
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 213
FT /note="Phosphoserine; by CDK2 and CDK4"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 378
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 418
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 422
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:9380693"
FT MOD_RES 423
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:9380693"
FT MOD_RES 425
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:9380693"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT CROSSLNK 81
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT CONFLICT 26
FT /note="Q -> E (in Ref. 3; BAC38789)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="F -> L (in Ref. 2; AAB81755)"
FT /evidence="ECO:0000305"
FT CONFLICT 408
FT /note="D -> V (in Ref. 3; BAC33398)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 48081 MW; 46DF5E8B371321AC CRC64;
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE LEKAITTQNV
NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELRAMELCE FAFNMKKDEV
CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF PPLDDYSHSI PENTNFPAGI EPQSNIPETP
PPGYLSEDGE TSDHQMNHSM DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL
NQRVGETFHA SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA LLAQSVNQGF
EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL NGPLQWLDKV LTQMGSPSIR
CSSVS
