SMAD7_HUMAN
ID SMAD7_HUMAN Reviewed; 426 AA.
AC O15105; B7Z773; K7EQ10; O14740; Q6DK23;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Mothers against decapentaplegic homolog 7;
DE Short=MAD homolog 7;
DE Short=Mothers against DPP homolog 7;
DE AltName: Full=Mothers against decapentaplegic homolog 8;
DE Short=MAD homolog 8;
DE Short=Mothers against DPP homolog 8;
DE AltName: Full=SMAD family member 7;
DE Short=SMAD 7;
DE Short=Smad7;
DE Short=hSMAD7;
GN Name=SMAD7; Synonyms=MADH7, MADH8;
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 [MRNA] (ISOFORM 1), AND MUTAGENESIS OF
RP 409-ARG--ARG-426.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=9215638; DOI=10.1016/s0092-8674(00)80303-7;
RA Hayashi H., Abdollah S., Qiu Y., Cai J., Xu Y.-Y., Grinnell B.W.,
RA Richardson M.A., Topper J.N., Gimbrone M.A. Jr., Wrana J.L., Falb D.;
RT "The MAD-related protein Smad7 associates with the TGFbeta receptor and
RT functions as an antagonist of TGFbeta signaling.";
RL Cell 89:1165-1173(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=9256479; DOI=10.1073/pnas.94.17.9314;
RA Topper J.N., Cai J., Qui Y., Anderson K.R., Xu Y.-Y., Deeds J.D.,
RA Feeley R., Gimeno C.J., Woolf E.A., Tayber O., Mays G.G., Sampson B.A.,
RA Schoen F.J., Gimbrone M.A. Jr., Falb D.;
RT "Vascular MADs: two novel MAD-related genes selectively inducible by flow
RT in human vascular endothelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9314-9319(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9335507; DOI=10.1038/39369;
RA Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J.L., Heuchel R.,
RA Itoh S., Kawabata M., Heldin N.-E., Heldin C.-H., ten Dijke P.;
RT "Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta
RT signalling.";
RL Nature 389:631-635(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Hagiwara K., Yang K., McMenamin M.G., Freeman A.H., Bennett W.P.,
RA Nagashima M., Minter A.R., Miyazono K., Takenoshita S., Harris C.C.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 98-271 (ISOFORM 3).
RC TISSUE=Pulmonary artery;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [8]
RP REVIEW.
RX PubMed=9759503; DOI=10.1146/annurev.biochem.67.1.753;
RA Massague J.;
RT "TGF-beta signal transduction.";
RL Annu. Rev. Biochem. 67:753-791(1998).
RN [9]
RP REVIEW.
RX PubMed=10647776; DOI=10.1016/s1359-6101(99)00012-x;
RA Verschueren K., Huylebroeck D.;
RT "Remarkable versatility of Smad proteins in the nucleus of transforming
RT growth factor-beta activated cells.";
RL Cytokine Growth Factor Rev. 10:187-199(1999).
RN [10]
RP INTERACTION WITH ACVR1B, AND FUNCTION.
RX PubMed=9892009; DOI=10.1210/mend.13.1.0218;
RA Lebrun J.J., Takabe K., Chen Y., Vale W.;
RT "Roles of pathway-specific and inhibitory Smads in activin receptor
RT signaling.";
RL Mol. Endocrinol. 13:15-23(1999).
RN [11]
RP REVIEW.
RX PubMed=10708948; DOI=10.1016/s1359-6101(99)00024-6;
RA Wrana J.L., Attisano L.;
RT "The Smad pathway.";
RL Cytokine Growth Factor Rev. 11:5-13(2000).
RN [12]
RP REVIEW.
RX PubMed=10708949; DOI=10.1016/s1359-6101(99)00025-8;
RA Miyazono K.;
RT "TGF-beta signaling by Smad proteins.";
RL Cytokine Growth Factor Rev. 11:15-22(2000).
RN [13]
RP FUNCTION, MUTAGENESIS OF TYR-211 AND 207-PRO--TYR-211, AND INTERACTION WITH
RP SMURF2 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 [14]
RP INTERACTION WITH STAMBP.
RX PubMed=11483516; DOI=10.1093/emboj/20.15.4132;
RA Itoh F., Asao H., Sugamura K., Heldin C.-H., ten Dijke P., Itoh S.;
RT "Promoting bone morphogenetic protein signaling through negative regulation
RT of inhibitory Smads.";
RL EMBO J. 20:4132-4142(2001).
RN [15]
RP INTERACTION WITH SMURF1 AND TGFBR1, AND UBIQUITINATION.
RX PubMed=11278251; DOI=10.1074/jbc.c100008200;
RA Ebisawa T., Fukuchi M., Murakami G., Chiba T., Tanaka K., Imamura T.,
RA Miyazono K.;
RT "Smurf1 interacts with transforming growth factor-beta type I receptor
RT through Smad7 and induces receptor degradation.";
RL J. Biol. Chem. 276:12477-12480(2001).
RN [16]
RP INTERACTION WITH ACVR1B, AND FUNCTION.
RX PubMed=12023024; DOI=10.1016/s0014-5793(02)02718-7;
RA Liu X., Nagarajan R.P., Vale W., Chen Y.;
RT "Phosphorylation regulation of the interaction between Smad7 and activin
RT type I receptor.";
RL FEBS Lett. 519:93-98(2002).
RN [17]
RP INTERACTION WITH EP300, ACETYLATION AT LYS-64 AND LYS-70, UBIQUITINATION AT
RP LYS-64 AND LYS-70, AND MUTAGENESIS OF LYS-64 AND LYS-70.
RX PubMed=12408818; DOI=10.1016/s1097-2765(02)00639-1;
RA Gronroos E., Hellman U., Heldin C.H., Ericsson J.;
RT "Control of Smad7 stability by competition between acetylation and
RT ubiquitination.";
RL Mol. Cell 10:483-493(2002).
RN [18]
RP INTERACTION WITH RNF111, UBIQUITINATION, AND SUBCELLULAR LOCATION.
RX PubMed=14657019; DOI=10.1093/emboj/cdg632;
RA Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A.,
RA Ebina M., Nukiwa T., Miyazawa K., Imamura T., Miyazono K.;
RT "Arkadia amplifies TGF-beta superfamily signaling through degradation of
RT Smad7.";
RL EMBO J. 22:6458-6470(2003).
RN [19]
RP FUNCTION, AND INTERACTION WITH PPP1R15A.
RX PubMed=14718519; DOI=10.1083/jcb.200307151;
RA Shi W., Sun C., He B., Xiong W., Shi X., Yao D., Cao X.;
RT "GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor.";
RL J. Cell Biol. 164:291-300(2004).
RN [20]
RP INTERACTION WITH COPS5.
RX PubMed=14993265; DOI=10.1128/mcb.24.6.2251-2262.2004;
RA Kim B.-C., Lee H.-J., Park S.H., Lee S.R., Karpova T.S., McNally J.G.,
RA Felici A., Lee D.K., Kim S.-J.;
RT "Jab1/CSN5, a component of the COP9 signalosome, regulates transforming
RT growth factor beta signaling by binding to Smad7 and promoting its
RT degradation.";
RL Mol. Cell. Biol. 24:2251-2262(2004).
RN [21]
RP INTERACTION WITH SMURF2.
RX PubMed=16061177; DOI=10.1016/j.molcel.2005.06.028;
RA Ogunjimi A.A., Briant D.J., Pece-Barbara N., Le Roy C., Di Guglielmo G.M.,
RA Kavsak P., Rasmussen R.K., Seet B.T., Sicheri F., Wrana J.L.;
RT "Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the
RT HECT domain.";
RL Mol. Cell 19:297-308(2005).
RN [22]
RP INTERACTION WITH AXIN1 AND AXIN2, UBIQUITINATION, AND SUBCELLULAR LOCATION.
RX PubMed=16601693; DOI=10.1038/sj.emboj.7601057;
RA Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S.,
RA Chan S.C., Chen Y.-G., Han J., Lin S.-C.;
RT "Axin is a scaffold protein in TGF-beta signaling that promotes degradation
RT of Smad7 by Arkadia.";
RL EMBO J. 25:1646-1658(2006).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, AND INTERACTION
RP WITH PDPK1.
RX PubMed=17327236; DOI=10.1074/jbc.m609279200;
RA Seong H.A., Jung H., Kim K.T., Ha H.;
RT "3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth
RT factor-beta-induced signaling in a kinase-dependent manner through physical
RT interaction with Smad proteins.";
RL J. Biol. Chem. 282:12272-12289(2007).
RN [24]
RP STRUCTURE BY NMR OF 203-217 IN COMPLEX WITH SMURF2.
RX PubMed=16641086; DOI=10.1074/jbc.m601493200;
RA Chong P.A., Lin H., Wrana J.L., Forman-Kay J.D.;
RT "An expanded WW domain recognition motif revealed by the interaction
RT between Smad7 and the E3 ubiquitin ligase Smurf2.";
RL J. Biol. Chem. 281:17069-17075(2006).
RN [25]
RP INVOLVEMENT IN CRCS3.
RX PubMed=17934461; DOI=10.1038/ng.2007.18;
RG Members of the CORGI consortium;
RA Broderick P., Carvajal-Carmona L., Pittman A.M., Webb E., Howarth K.,
RA Rowan A., Lubbe S., Spain S., Sullivan K., Fielding S., Jaeger E.,
RA Vijayakrishnan J., Kemp Z., Gorman M., Chandler I., Papaemmanuil E.,
RA Penegar S., Wood W., Sellick G., Qureshi M., Teixeira A., Domingo E.,
RA Barclay E., Martin L., Sieber O., Kerr D., Gray R., Peto J., Cazier J.-B.,
RA Tomlinson I., Houlston R.S.;
RT "A genome-wide association study shows that common alleles of SMAD7
RT influence colorectal cancer risk.";
RL Nat. Genet. 39:1315-1317(2007).
CC -!- FUNCTION: Antagonist of signaling by TGF-beta (transforming growth
CC factor) type 1 receptor superfamily members; has been shown to inhibit
CC TGF-beta (Transforming growth factor) and activin signaling by
CC associating with their receptors thus preventing SMAD2 access.
CC Functions as an adapter to recruit SMURF2 to the TGF-beta receptor
CC complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1,
CC which promotes its dephosphorylation. Positively regulates PDPK1 kinase
CC activity by stimulating its dissociation from the 14-3-3 protein YWHAQ
CC which acts as a negative regulator. {ECO:0000269|PubMed:11163210,
CC ECO:0000269|PubMed:12023024, ECO:0000269|PubMed:14718519,
CC ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:9892009}.
CC -!- SUBUNIT: Interacts with WWP1 (By similarity). Interacts with COPS5.
CC Interacts with NEDD4L. Interacts with STAMBP. Interacts with RNF111,
CC AXIN1 and AXIN2. Interacts with PPP1R15A. Interacts (via MH2 domain)
CC with EP300. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7
CC recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its
CC degradation. Interacts with PDPK1 (via PH domain). {ECO:0000250,
CC ECO:0000269|PubMed:11163210, ECO:0000269|PubMed:11278251,
CC ECO:0000269|PubMed:11483516, ECO:0000269|PubMed:12023024,
CC ECO:0000269|PubMed:12408818, ECO:0000269|PubMed:14657019,
CC ECO:0000269|PubMed:14718519, ECO:0000269|PubMed:14993265,
CC ECO:0000269|PubMed:16061177, ECO:0000269|PubMed:16601693,
CC ECO:0000269|PubMed:16641086, ECO:0000269|PubMed:17327236,
CC ECO:0000269|PubMed:9892009}.
CC -!- INTERACTION:
CC O15105; P36896: ACVR1B; NbExp=2; IntAct=EBI-3861591, EBI-1384128;
CC O15105; O15169: AXIN1; NbExp=8; IntAct=EBI-3861591, EBI-710484;
CC O15105; Q92905: COPS5; NbExp=10; IntAct=EBI-3861591, EBI-594661;
CC O15105; P62942: FKBP1A; NbExp=3; IntAct=EBI-3861591, EBI-1027571;
CC O15105; Q96PU5-5: NEDD4L; NbExp=3; IntAct=EBI-3861591, EBI-7196393;
CC O15105; Q9HCE7-1: SMURF1; NbExp=4; IntAct=EBI-3861591, EBI-15884081;
CC O15105; Q9HAU4: SMURF2; NbExp=7; IntAct=EBI-3861591, EBI-396727;
CC O15105; O00308: WWP2; NbExp=5; IntAct=EBI-3861591, EBI-743923;
CC O15105; P46937: YAP1; NbExp=7; IntAct=EBI-3861591, EBI-1044059;
CC O15105; Q99ML9: Rnf111; Xeno; NbExp=2; IntAct=EBI-3861591, EBI-646015;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14657019,
CC ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17327236}. Cytoplasm
CC {ECO:0000269|PubMed:14657019, ECO:0000269|PubMed:16601693,
CC ECO:0000269|PubMed:17327236}. Note=Interaction with NEDD4L or RNF111
CC induces translocation from the nucleus to the cytoplasm
CC (PubMed:16601693). TGF-beta stimulates its translocation from the
CC nucleus to the cytoplasm. PDPK1 inhibits its translocation from the
CC nucleus to the cytoplasm in response to TGF-beta (PubMed:17327236).
CC {ECO:0000269|PubMed:16601693, ECO:0000269|PubMed:17327236}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O15105-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15105-2; Sequence=VSP_045197;
CC Name=3;
CC IsoId=O15105-3; Sequence=VSP_047540;
CC -!- TISSUE SPECIFICITY: Ubiquitous with higher expression in the lung and
CC vascular endothelium.
CC -!- INDUCTION: By TGFB1.
CC -!- PTM: Phosphorylation on Ser-249 does not affect its stability, nuclear
CC localization or inhibitory function in TGFB signaling; however it
CC affects its ability to regulate transcription (By similarity).
CC Phosphorylated by PDPK1. {ECO:0000250|UniProtKB:O35253,
CC ECO:0000269|PubMed:17327236}.
CC -!- PTM: Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by
CC RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation
CC (PubMed:14657019, PubMed:16601693). In response to TGF-beta,
CC ubiquitinated by SMURF1; which promotes its degradation
CC (PubMed:11278251). {ECO:0000250|UniProtKB:O35253,
CC ECO:0000269|PubMed:11278251, ECO:0000269|PubMed:14657019,
CC ECO:0000269|PubMed:16601693}.
CC -!- PTM: Acetylation prevents ubiquitination and degradation mediated by
CC SMURF1. {ECO:0000269|PubMed:12408818}.
CC -!- DISEASE: Colorectal cancer 3 (CRCS3) [MIM:612229]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. {ECO:0000269|PubMed:17934461}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; AF010193; AAB81246.1; -; mRNA.
DR EMBL; AF015261; AAB81354.1; -; mRNA.
DR EMBL; AF026559; AAL68977.1; -; Genomic_DNA.
DR EMBL; AF026556; AAL68977.1; JOINED; Genomic_DNA.
DR EMBL; AF026557; AAL68977.1; JOINED; Genomic_DNA.
DR EMBL; AF026558; AAL68977.1; JOINED; Genomic_DNA.
DR EMBL; AK301535; BAH13509.1; -; mRNA.
DR EMBL; DA882147; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC114684; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074818; AAH74818.2; -; mRNA.
DR EMBL; BC074819; AAH74819.2; -; mRNA.
DR CCDS; CCDS11936.1; -. [O15105-1]
DR CCDS; CCDS54186.1; -. [O15105-2]
DR CCDS; CCDS59317.1; -. [O15105-3]
DR RefSeq; NP_001177750.1; NM_001190821.1. [O15105-3]
DR RefSeq; NP_001177751.1; NM_001190822.1. [O15105-2]
DR RefSeq; NP_001177752.1; NM_001190823.1.
DR RefSeq; NP_005895.1; NM_005904.3. [O15105-1]
DR PDB; 2DJY; NMR; -; B=203-217.
DR PDB; 2KXQ; NMR; -; B=203-217.
DR PDB; 2LTV; NMR; -; B=206-217.
DR PDB; 2LTW; NMR; -; B=205-217.
DR PDB; 2LTX; NMR; -; B=203-217.
DR PDB; 2LTY; NMR; -; B=203-217.
DR PDB; 2LTZ; NMR; -; B=203-217.
DR PDBsum; 2DJY; -.
DR PDBsum; 2KXQ; -.
DR PDBsum; 2LTV; -.
DR PDBsum; 2LTW; -.
DR PDBsum; 2LTX; -.
DR PDBsum; 2LTY; -.
DR PDBsum; 2LTZ; -.
DR AlphaFoldDB; O15105; -.
DR BMRB; O15105; -.
DR SMR; O15105; -.
DR BioGRID; 110267; 110.
DR CORUM; O15105; -.
DR DIP; DIP-42252N; -.
DR IntAct; O15105; 30.
DR MINT; O15105; -.
DR STRING; 9606.ENSP00000262158; -.
DR iPTMnet; O15105; -.
DR PhosphoSitePlus; O15105; -.
DR BioMuta; SMAD7; -.
DR MassIVE; O15105; -.
DR PaxDb; O15105; -.
DR PeptideAtlas; O15105; -.
DR PRIDE; O15105; -.
DR Antibodypedia; 9268; 536 antibodies from 39 providers.
DR DNASU; 4092; -.
DR Ensembl; ENST00000262158.8; ENSP00000262158.2; ENSG00000101665.10. [O15105-1]
DR Ensembl; ENST00000589634.1; ENSP00000467621.1; ENSG00000101665.10. [O15105-3]
DR Ensembl; ENST00000591805.5; ENSP00000466902.1; ENSG00000101665.10. [O15105-2]
DR GeneID; 4092; -.
DR KEGG; hsa:4092; -.
DR MANE-Select; ENST00000262158.8; ENSP00000262158.2; NM_005904.4; NP_005895.1.
DR UCSC; uc002ldg.3; human. [O15105-1]
DR CTD; 4092; -.
DR DisGeNET; 4092; -.
DR GeneCards; SMAD7; -.
DR HGNC; HGNC:6773; SMAD7.
DR HPA; ENSG00000101665; Low tissue specificity.
DR MalaCards; SMAD7; -.
DR MIM; 602932; gene.
DR MIM; 612229; phenotype.
DR neXtProt; NX_O15105; -.
DR OpenTargets; ENSG00000101665; -.
DR PharmGKB; PA134875286; -.
DR VEuPathDB; HostDB:ENSG00000101665; -.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000159872; -.
DR HOGENOM; CLU_026736_5_0_1; -.
DR InParanoid; O15105; -.
DR OMA; HPELVCC; -.
DR OrthoDB; 395665at2759; -.
DR PhylomeDB; O15105; -.
DR TreeFam; TF314923; -.
DR PathwayCommons; O15105; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; O15105; -.
DR SIGNOR; O15105; -.
DR BioGRID-ORCS; 4092; 25 hits in 1101 CRISPR screens.
DR ChiTaRS; SMAD7; human.
DR EvolutionaryTrace; O15105; -.
DR GeneWiki; Mothers_against_decapentaplegic_homolog_7; -.
DR GenomeRNAi; 4092; -.
DR Pharos; O15105; Tbio.
DR PRO; PR:O15105; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O15105; protein.
DR Bgee; ENSG00000101665; Expressed in popliteal artery and 174 other tissues.
DR ExpressionAtlas; O15105; baseline and differential.
DR Genevisible; O15105; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0048185; F:activin binding; IPI:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
DR GO; GO:0005518; F:collagen binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IPI:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
DR GO; GO:0034333; P:adherens junction assembly; IMP:BHF-UCL.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0048844; P:artery morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IMP:BHF-UCL.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030336; P:negative regulation of cell migration; TAS:BHF-UCL.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; TAS:BHF-UCL.
DR GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0002725; P:negative regulation of T cell cytokine production; ISS:BHF-UCL.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; ISS:BHF-UCL.
DR GO; GO:2000317; P:negative regulation of T-helper 17 type immune response; ISS:BHF-UCL.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IDA:BHF-UCL.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:BHF-UCL.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:1903043; P:positive regulation of chondrocyte hypertrophy; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL.
DR GO; GO:0031503; P:protein-containing complex localization; IDA:BHF-UCL.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISS:BHF-UCL.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IC:BHF-UCL.
DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; IC:BHF-UCL.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IEP:BHF-UCL.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 1.
DR IDEAL; IID00135; -.
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 3D-structure; Acetylation; Alternative splicing; Cytoplasm; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc.
FT CHAIN 1..426
FT /note="Mothers against decapentaplegic homolog 7"
FT /id="PRO_0000090872"
FT DOMAIN 64..207
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 261..426
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 13..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..217
FT /note="Important for interaction with SMURF2"
FT MOTIF 208..211
FT /note="PY-motif"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 64
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:12408818"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:12408818"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35253,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CROSSLNK 64
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:12408818"
FT CROSSLNK 70
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:12408818"
FT VAR_SEQ 1..215
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045197"
FT VAR_SEQ 223
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047540"
FT MUTAGEN 64
FT /note="K->A: Loss of acetylation, and of SMURF1-dependent
FT degradation; when associated with A-70."
FT /evidence="ECO:0000269|PubMed:12408818"
FT MUTAGEN 70
FT /note="K->A: Loss of acetylation, and of SMURF1-dependent
FT degradation; when associated with A-64."
FT /evidence="ECO:0000269|PubMed:12408818"
FT MUTAGEN 207..211
FT /note="Missing: Diminishes interaction with SMURF2."
FT /evidence="ECO:0000269|PubMed:11163210"
FT MUTAGEN 211
FT /note="Y->A: Diminishes interaction with SMURF2 and reduces
FT inhibition of TGF-beta signaling."
FT /evidence="ECO:0000269|PubMed:11163210"
FT MUTAGEN 409..426
FT /note="Missing: 90% reduction in TGF-beta receptor
FT binding."
FT /evidence="ECO:0000269|PubMed:9215638"
FT CONFLICT 71
FT /note="G -> C (in Ref. 3; AAB81354)"
FT /evidence="ECO:0000305"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:2DJY"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2DJY"
SQ SEQUENCE 426 AA; 46426 MW; 5B76EC986776C102 CRC64;
MFRTKRSALV RRLWRSRAPG GEDEEEGAGG GGGGGELRGE GATDSRAHGA GGGGPGRAGC
CLGKAVRGAK GHHHPHPPAA GAGAAGGAEA DLKALTHSVL KKLKERQLEL LLQAVESRGG
TRTACLLLPG RLDCRLGPGA PAGAQPAQPP SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC
ESYGKINPEL VCCNPHHLSR LCELESPPPP YSRYPMDFLK PTADCPDAVP SSAETGGTNY
LAPGGLSDSQ LLLEPGDRSH WCVVAYWEEK TRVGRLYCVQ EPSLDIFYDL PQGNGFCLGQ
LNSDNKSQLV QKVRSKIGCG IQLTREVDGV WVYNRSSYPI FIKSATLDNP DSRTLLVHKV
FPGFSIKAFD YEKAYSLQRP NDHEFMQQPW TGFTVQISFV KGWGQCYTRQ FISSCPCWLE
VIFNSR
