SMAD1_HUMAN
ID SMAD1_HUMAN Reviewed; 465 AA.
AC Q15797; A8KAJ0; D3DNZ9; Q16636; Q9UFT8;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Mothers against decapentaplegic homolog 1;
DE Short=MAD homolog 1;
DE Short=Mothers against DPP homolog 1;
DE AltName: Full=JV4-1;
DE AltName: Full=Mad-related protein 1;
DE AltName: Full=SMAD family member 1;
DE Short=SMAD 1;
DE Short=Smad1;
DE Short=hSMAD1;
DE AltName: Full=Transforming growth factor-beta-signaling protein 1;
DE Short=BSP-1;
GN Name=SMAD1; Synonyms=BSP1, MADH1, MADR1;
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).
RX PubMed=8673135; DOI=10.1038/ng0796-347;
RA Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E.,
RA Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W.,
RA Vogelstein B.V.;
RT "Mad-related genes in the human.";
RL Nat. Genet. 13:347-349(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=8637600; DOI=10.1038/381620a0;
RA Liu F., Hata A., Baker J.C., Doody J., Carcamo J., Harland R.M.,
RA Massague J.;
RT "A human Mad protein acting as a BMP-regulated transcriptional activator.";
RL Nature 381:620-623(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF GLY-419.
RX PubMed=8653785; DOI=10.1016/s0092-8674(00)81250-7;
RA Hoodless P.A., Haerry T., Abdollah S., Stapleton M., O'Connor M.B.,
RA Attisano L., Wrana J.L.;
RT "MADR1, a MAD-related protein that functions in BMP2 signaling pathways.";
RL Cell 85:489-500(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary carcinoma;
RX PubMed=8663601; DOI=10.1074/jbc.271.30.17617;
RA Lechleider R.J., de Caestecker M.P., Dehejia A., Polymeropoulos M.H.,
RA Roberts A.B.;
RT "Serine phosphorylation, chromosomal localization, and transforming growth
RT factor-beta signal transduction by human bsp-1.";
RL J. Biol. Chem. 271:17617-17620(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=8774881; DOI=10.1038/383168a0;
RA Zhang Y., Feng X.-H., Wu R.-Y., Derynck R.;
RT "Receptor-associated Mad homologues synergize as effectors of the TGF-beta
RT response.";
RL Nature 383:168-172(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [11]
RP PROTEIN SEQUENCE OF 1-15; 33-39; 129-157; 283-306 AND 309-319, ACETYLATION
RP AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lempens A., Norman J.C.;
RL Submitted (OCT-2009) to UniProtKB.
RN [12]
RP PHOSPHORYLATION AT SER-463 AND SER-465.
RX PubMed=9136927; DOI=10.1101/gad.11.8.984;
RA Kretzschmar M., Liu F., Hata A., Doody J., Massague J.;
RT "The TGF-beta family mediator Smad1 is phosphorylated directly and
RT activated functionally by the BMP receptor kinase.";
RL Genes Dev. 11:984-995(1997).
RN [13]
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 [14]
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 [15]
RP INTERACTION WITH ZNF423.
RX PubMed=10660046; DOI=10.1016/s0092-8674(00)81561-5;
RA Hata A., Seoane J., Lagna G., Montalvo E., Hemmati-Brivanlou A.,
RA Massague J.;
RT "OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-
RT Smad and Olf signaling pathways.";
RL Cell 100:229-240(2000).
RN [16]
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 [17]
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 [18]
RP IDENTIFICATION IN A COMPLEX WITH PSMB4 AND OAZ1, AND FUNCTION.
RX PubMed=12097147; DOI=10.1186/1471-2121-3-15;
RA Lin Y., Martin J., Gruendler C., Farley J., Meng X., Li B.-Y.,
RA Lechleider R., Huff C., Kim R.H., Grasser W.A., Paralkar V., Wang T.;
RT "A novel link between the proteasome pathway and the signal transduction
RT pathway of the bone morphogenetic proteins (BMPs).";
RL BMC Cell Biol. 3:15-15(2002).
RN [19]
RP INTERACTION WITH ZNF521.
RX PubMed=14630787; DOI=10.1182/blood-2003-07-2388;
RA Bond H.M., Mesuraca M., Carbone E., Bonelli P., Agosti V., Amodio N.,
RA De Rosa G., Di Nicola M., Gianni A.M., Moore M.A., Hata A., Grieco M.,
RA Morrone G., Venuta S.;
RT "Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse
RT Evi3, is highly expressed in primitive human hematopoietic cells.";
RL Blood 103:2062-2070(2004).
RN [20]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LEMD3.
RX PubMed=15647271; DOI=10.1074/jbc.m411234200;
RA Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S.,
RA Luo K.;
RT "The integral inner nuclear membrane protein MAN1 physically interacts with
RT the R-Smad proteins to repress signaling by the transforming growth
RT factor-{beta} superfamily of cytokines.";
RL J. Biol. Chem. 280:15992-16001(2005).
RN [21]
RP INTERACTION WITH SKOR1.
RX PubMed=17292623; DOI=10.1016/j.mcn.2007.01.002;
RA Arndt S., Poser I., Moser M., Bosserhoff A.-K.;
RT "Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling.";
RL Mol. Cell. Neurosci. 34:603-611(2007).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP PHOSPHORYLATION AT THR-322.
RX PubMed=21690388; DOI=10.1073/pnas.1104128108;
RA Kaneko S., Chen X., Lu P., Yao X., Wright T.G., Rajurkar M., Kariya K.,
RA Mao J., Ip Y.T., Xu L.;
RT "Smad inhibition by the Ste20 kinase Misshapen.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11127-11132(2011).
RN [24]
RP UBIQUITINATION, DEUBIQUITINATION BY USP15, DNA-BINDING, AND INTERACTION
RP WITH USP15.
RX PubMed=21947082; DOI=10.1038/ncb2346;
RA Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., Enzo E.,
RA Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.;
RT "USP15 is a deubiquitylating enzyme for receptor-activated SMADs.";
RL Nat. Cell Biol. 13:1368-1375(2011).
RN [25]
RP 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 [26]
RP POSSIBLE INVOLVEMENT IN PULMONARY HYPERTENSION, VARIANT ALA-3, AND
RP CHARACTERIZATION OF VARIANT ALA-3.
RX PubMed=21898662; DOI=10.1002/humu.21605;
RA Nasim M.T., Ogo T., Ahmed M., Randall R., Chowdhury H.M., Snape K.M.,
RA Bradshaw T.Y., Southgate L., Lee G.J., Jackson I., Lord G.M., Gibbs J.S.,
RA Wilkins M.R., Ohta-Ogo K., Nakamura K., Girerd B., Coulet F., Soubrier F.,
RA Humbert M., Morrell N.W., Trembath R.C., Machado R.D.;
RT "Molecular genetic characterization of SMAD signaling molecules in
RT pulmonary arterial hypertension.";
RL Hum. Mutat. 32:1385-1389(2011).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [28]
RP INTERACTION WITH FAM83G.
RX PubMed=24554596; DOI=10.1098/rsob.130210;
RA Vogt J., Dingwell K.S., Herhaus L., Gourlay R., Macartney T., Campbell D.,
RA Smith J.C., Sapkota G.P.;
RT "Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I
RT bone morphogenetic protein receptors and modulates bone morphogenetic
RT protein signalling.";
RL Open Biol. 4:130210-130210(2014).
RN [29]
RP INTERACTION WITH RANBP3L, AND MUTAGENESIS OF 463-SER--SER-465.
RX PubMed=25755279; DOI=10.1128/mcb.00121-15;
RA Chen F., Lin X., Xu P., Zhang Z., Chen Y., Wang C., Han J., Zhao B.,
RA Xiao M., Feng X.H.;
RT "Nuclear export of Smads by RanBP3L regulates bone morphogenetic protein
RT signaling and mesenchymal stem cell differentiation.";
RL Mol. Cell. Biol. 35:1700-1711(2015).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 248-465, PHOSPHORYLATION AT
RP SER-463 AND SER-465, SUBUNIT, AND MUTAGENESIS OF ASP-297; VAL-317; LYS-373;
RP LYS-418; TYR-424; ARG-426 AND ASP-448.
RX PubMed=11779505; DOI=10.1016/s1097-2765(01)00417-8;
RA Qin B.Y., Chacko B.M., Lam S.S., de Caestecker M.P., Correia J.J., Lin K.;
RT "Structural basis of Smad1 activation by receptor kinase phosphorylation.";
RL Mol. Cell 8:1303-1312(2001).
CC -!- FUNCTION: Transcriptional modulator activated by BMP (bone
CC morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-
CC regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the
CC degradation of the CREBBP/EP300 repressor SNIP1. May act
CC synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-
CC mediated cardiac-specific gene expression.
CC {ECO:0000269|PubMed:12097147}.
CC -!- SUBUNIT: Found in a complex with SMAD4 and YY1. Interacts with HGS,
CC NANOG and ZCCHC12 (By similarity). Upon C-terminus phosphorylation:
CC forms trimers with another SMAD1 and the co-SMAD SMAD4. Interacts with
CC PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2,
CC USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2
CC leading to activate transcription of BMP target genes. Interacts with
CC SKOR1. Interacts (via MH2 domain) with LEMD3. Binding to LEMD3 results
CC in at least a partial reduction of receptor-mediated phosphorylation.
CC Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is
CC incorporated into the 20S proteasome. Found in a macromolecular complex
CC with FAM83G. Interacts (via MH2 domain) with FAM83G (via MH2 domain);
CC in a SMAD4-independent manner. Interacts with ZC3H3 (By similarity).
CC Interacts with TMEM119 (By similarity). Interacts (via MH1 and MH2
CC domains) with ZNF8 (By similarity). Interacts with RANBP3L; the
CC interaction increases when SMAD1 is not phosphorylated and mediates
CC SMAD1 nuclear export (PubMed:25755279). {ECO:0000250|UniProtKB:P70340,
CC ECO:0000269|PubMed:10660046, ECO:0000269|PubMed:11779505,
CC ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:14630787,
CC ECO:0000269|PubMed:15647271, ECO:0000269|PubMed:17292623,
CC ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:24554596,
CC ECO:0000269|PubMed:25755279}.
CC -!- INTERACTION:
CC Q15797; P10275: AR; NbExp=6; IntAct=EBI-1567153, EBI-608057;
CC Q15797; Q9GZU7: CTDSP1; NbExp=2; IntAct=EBI-1567153, EBI-751587;
CC Q15797; O14595: CTDSP2; NbExp=2; IntAct=EBI-1567153, EBI-2802973;
CC Q15797; O15194: CTDSPL; NbExp=2; IntAct=EBI-1567153, EBI-12544034;
CC Q15797; P17844: DDX5; NbExp=4; IntAct=EBI-1567153, EBI-351962;
CC Q15797; Q9NRR4: DROSHA; NbExp=3; IntAct=EBI-1567153, EBI-528367;
CC Q15797; O95208-2: EPN2; NbExp=3; IntAct=EBI-1567153, EBI-12135243;
CC Q15797; O15397: IPO8; NbExp=2; IntAct=EBI-1567153, EBI-358808;
CC Q15797; Q9Y2U8: LEMD3; NbExp=4; IntAct=EBI-1567153, EBI-2561428;
CC Q15797; Q96CV9: OPTN; NbExp=3; IntAct=EBI-1567153, EBI-748974;
CC Q15797; P28070: PSMB4; NbExp=4; IntAct=EBI-1567153, EBI-603350;
CC Q15797; Q15797: SMAD1; NbExp=5; IntAct=EBI-1567153, EBI-1567153;
CC Q15797; Q13485: SMAD4; NbExp=12; IntAct=EBI-1567153, EBI-347263;
CC Q15797; O43541: SMAD6; NbExp=4; IntAct=EBI-1567153, EBI-976374;
CC Q15797; Q9HCE7: SMURF1; NbExp=2; IntAct=EBI-1567153, EBI-976466;
CC Q15797; Q9HCE7-2: SMURF1; NbExp=2; IntAct=EBI-1567153, EBI-9845742;
CC Q15797; Q9HAU4: SMURF2; NbExp=6; IntAct=EBI-1567153, EBI-396727;
CC Q15797; P15374: UCHL3; NbExp=2; IntAct=EBI-1567153, EBI-954554;
CC Q15797; P46937: YAP1; NbExp=4; IntAct=EBI-1567153, EBI-1044059;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15647271}. Nucleus
CC {ECO:0000269|PubMed:15647271, ECO:0000269|PubMed:22781750}.
CC Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when
CC complexed with SMAD4 (PubMed:15647271). Co-localizes with LEMD3 at the
CC nucleus inner membrane (PubMed:15647271). Exported from the nucleus to
CC the cytoplasm when dephosphorylated (By similarity).
CC {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:15647271}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15797-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15797-2; Sequence=VSP_057163, VSP_057164, VSP_057165,
CC VSP_057166;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression seen in the heart
CC and skeletal muscle.
CC -!- DOMAIN: The MH2 domain mediates phosphorylation-dependent trimerization
CC through L3 loop binding of phosphoserines in the adjacent subunit.
CC {ECO:0000269|PubMed:11779505}.
CC -!- PTM: Phosphorylation of the C-terminal SVS motif by BMP type 1 receptor
CC kinase activates SMAD1 by promoting dissociation from the receptor and
CC trimerization with SMAD4. {ECO:0000269|PubMed:11779505,
CC ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9136927}.
CC -!- PTM: Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading
CC to its degradation. Monoubiquitinated, leading to prevent DNA-binding.
CC Deubiquitination by USP15 alleviates inhibition and promotes activation
CC of TGF-beta target genes. Dephosphorylation, probably by PPM1A, induces
CC its export from the nucleus to the cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:21947082}.
CC -!- DISEASE: Note=SMAD1 variants may be associated with susceptibility to
CC pulmonary hypertension, a disorder characterized by plexiform lesions
CC of proliferating endothelial cells in pulmonary arterioles. The lesions
CC lead to elevated pulmonary arterial pression, right ventricular
CC failure, and death. The disease can occur from infancy throughout life
CC and it has a mean age at onset of 36 years. Penetrance is reduced.
CC Although familial pulmonary hypertension is rare, cases secondary to
CC known etiologies are more common and include those associated with the
CC appetite-suppressant drugs. {ECO:0000269|PubMed:21898662}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; U59912; AAC50790.1; -; mRNA.
DR EMBL; U59423; AAB06852.1; -; mRNA.
DR EMBL; U54826; AAC50493.1; -; mRNA.
DR EMBL; U57456; AAC50621.1; -; mRNA.
DR EMBL; BT007386; AAP36050.1; -; mRNA.
DR EMBL; AK293055; BAF85744.1; -; mRNA.
DR EMBL; AL117396; CAB55898.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05037.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05038.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05039.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05040.1; -; Genomic_DNA.
DR EMBL; BC001878; AAH01878.1; -; mRNA.
DR CCDS; CCDS3765.1; -. [Q15797-1]
DR PIR; S68987; S68987.
DR RefSeq; NP_001003688.1; NM_001003688.1. [Q15797-1]
DR RefSeq; NP_005891.1; NM_005900.2. [Q15797-1]
DR RefSeq; XP_005263049.1; XM_005262992.3.
DR RefSeq; XP_006714280.1; XM_006714217.2.
DR RefSeq; XP_011530263.1; XM_011531961.1.
DR RefSeq; XP_011530264.1; XM_011531962.1. [Q15797-1]
DR RefSeq; XP_011530265.1; XM_011531963.1.
DR RefSeq; XP_011530266.1; XM_011531964.1. [Q15797-1]
DR PDB; 1KHU; X-ray; 2.50 A; A/B/C/D=248-465.
DR PDB; 2LAW; NMR; -; B=222-233.
DR PDB; 2LAX; NMR; -; B=201-209.
DR PDB; 2LAY; NMR; -; B=201-209.
DR PDB; 2LAZ; NMR; -; B=210-217.
DR PDB; 2LB0; NMR; -; B=208-217.
DR PDB; 2LB1; NMR; -; B=220-233.
DR PDB; 3Q47; X-ray; 1.70 A; C=456-464.
DR PDB; 3Q4A; X-ray; 1.54 A; C=456-465.
DR PDB; 5ZOK; X-ray; 2.85 A; A/C=259-462.
DR PDBsum; 1KHU; -.
DR PDBsum; 2LAW; -.
DR PDBsum; 2LAX; -.
DR PDBsum; 2LAY; -.
DR PDBsum; 2LAZ; -.
DR PDBsum; 2LB0; -.
DR PDBsum; 2LB1; -.
DR PDBsum; 3Q47; -.
DR PDBsum; 3Q4A; -.
DR PDBsum; 5ZOK; -.
DR AlphaFoldDB; Q15797; -.
DR SMR; Q15797; -.
DR BioGRID; 110261; 174.
DR ComplexPortal; CPX-144; SMAD1 homotrimer.
DR ComplexPortal; CPX-54; SMAD1-SMAD4 complex.
DR CORUM; Q15797; -.
DR DIP; DIP-38538N; -.
DR IntAct; Q15797; 90.
DR MINT; Q15797; -.
DR STRING; 9606.ENSP00000426568; -.
DR MoonDB; Q15797; Predicted.
DR iPTMnet; Q15797; -.
DR PhosphoSitePlus; Q15797; -.
DR SwissPalm; Q15797; -.
DR BioMuta; SMAD1; -.
DR DMDM; 13633915; -.
DR EPD; Q15797; -.
DR jPOST; Q15797; -.
DR MassIVE; Q15797; -.
DR MaxQB; Q15797; -.
DR PaxDb; Q15797; -.
DR PeptideAtlas; Q15797; -.
DR PRIDE; Q15797; -.
DR ProteomicsDB; 60766; -. [Q15797-1]
DR Antibodypedia; 3950; 1394 antibodies from 43 providers.
DR DNASU; 4086; -.
DR Ensembl; ENST00000302085.9; ENSP00000305769.4; ENSG00000170365.10. [Q15797-1]
DR Ensembl; ENST00000394092.6; ENSP00000377652.2; ENSG00000170365.10. [Q15797-1]
DR Ensembl; ENST00000515385.1; ENSP00000426568.1; ENSG00000170365.10. [Q15797-1]
DR GeneID; 4086; -.
DR KEGG; hsa:4086; -.
DR MANE-Select; ENST00000302085.9; ENSP00000305769.4; NM_005900.3; NP_005891.1.
DR UCSC; uc003ikc.4; human. [Q15797-1]
DR CTD; 4086; -.
DR DisGeNET; 4086; -.
DR GeneCards; SMAD1; -.
DR HGNC; HGNC:6767; SMAD1.
DR HPA; ENSG00000170365; Low tissue specificity.
DR MIM; 601595; gene.
DR neXtProt; NX_Q15797; -.
DR OpenTargets; ENSG00000170365; -.
DR PharmGKB; PA30524; -.
DR VEuPathDB; HostDB:ENSG00000170365; -.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000154391; -.
DR HOGENOM; CLU_026736_0_2_1; -.
DR InParanoid; Q15797; -.
DR OMA; GTPSKCV; -.
DR PhylomeDB; Q15797; -.
DR TreeFam; TF314923; -.
DR PathwayCommons; Q15797; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8941326; RUNX2 regulates bone development.
DR SignaLink; Q15797; -.
DR SIGNOR; Q15797; -.
DR BioGRID-ORCS; 4086; 6 hits in 1091 CRISPR screens.
DR ChiTaRS; SMAD1; human.
DR EvolutionaryTrace; Q15797; -.
DR GeneWiki; Mothers_against_decapentaplegic_homolog_1; -.
DR GenomeRNAi; 4086; -.
DR Pharos; Q15797; Tbio.
DR PRO; PR:Q15797; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q15797; protein.
DR Bgee; ENSG00000170365; Expressed in secondary oocyte and 215 other tissues.
DR ExpressionAtlas; Q15797; baseline and differential.
DR Genevisible; Q15797; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IPI:ComplexPortal.
DR GO; GO:0071142; C:homomeric SMAD protein complex; IPI:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0071141; C:SMAD protein complex; NAS:BHF-UCL.
DR GO; GO:0070410; F:co-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070878; F:primary miRNA binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
DR GO; GO:0007276; P:gamete generation; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0042592; P:homeostatic process; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0001710; P:mesodermal cell fate commitment; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0002051; P:osteoblast fate commitment; IEA:Ensembl.
DR GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISS:BHF-UCL.
DR GO; GO:0031053; P:primary miRNA processing; TAS:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:BHF-UCL.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:ComplexPortal.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:ComplexPortal.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR DisProt; DP01206; -.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 1.
DR IDEAL; IID00174; -.
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;
KW Direct protein sequencing; DNA-binding; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..465
FT /note="Mothers against decapentaplegic homolog 1"
FT /id="PRO_0000090847"
FT DOMAIN 12..136
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 271..465
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 162..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..428
FT /note="L3 loop"
FT /evidence="ECO:0000269|PubMed:11779505"
FT COMPBIAS 171..216
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..231
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.11"
FT MOD_RES 322
FT /note="Phosphothreonine; by MINK1, TNIK and MAP4K4"
FT /evidence="ECO:0000269|PubMed:21690388"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:9136927"
FT MOD_RES 465
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:9136927"
FT VAR_SEQ 1..12
FT /note="MNVTSLFSFTSP -> MFVLLFFPFLFL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_057163"
FT VAR_SEQ 13..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_057164"
FT VAR_SEQ 220..258
FT /note="ADTPPPAYLPPEDPMTQDGSQPMDTNMMAPPLPSEINRG -> GRLECSVMF
FT CSHIRQCYHSVTEKLGQPAVEGGFQPWYMT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_057165"
FT VAR_SEQ 259..465
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_057166"
FT VARIANT 3
FT /note="V -> A (found in a patient with primary pulmonary
FT hypertension; unknown pathological significance; affects
FT SMAD-mediated signaling; dbSNP:rs587777018)"
FT /evidence="ECO:0000269|PubMed:21898662"
FT /id="VAR_066869"
FT MUTAGEN 297
FT /note="D->H: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 317
FT /note="V->D: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 373
FT /note="K->S: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 418
FT /note="K->S: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 419
FT /note="G->S: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:8653785"
FT MUTAGEN 424
FT /note="Y->F: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 426
FT /note="R->S: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 448
FT /note="D->H: Reduced trimerization."
FT /evidence="ECO:0000269|PubMed:11779505"
FT MUTAGEN 463..465
FT /note="SVS->AVA: Increases interaction with RANBPL3."
FT /evidence="ECO:0000269|PubMed:25755279"
FT MUTAGEN 463..465
FT /note="SVS->DVD: Decreases interaction with RANBPL3."
FT /evidence="ECO:0000269|PubMed:25755279"
FT STRAND 272..278
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:5ZOK"
FT STRAND 291..299
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 305..310
FT /evidence="ECO:0007829|PDB:1KHU"
FT HELIX 321..327
FT /evidence="ECO:0007829|PDB:1KHU"
FT TURN 328..332
FT /evidence="ECO:0007829|PDB:5ZOK"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 340..347
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:1KHU"
FT HELIX 358..363
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:1KHU"
FT HELIX 385..393
FT /evidence="ECO:0007829|PDB:1KHU"
FT TURN 394..398
FT /evidence="ECO:0007829|PDB:1KHU"
FT HELIX 400..404
FT /evidence="ECO:0007829|PDB:1KHU"
FT HELIX 405..410
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 411..417
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 421..425
FT /evidence="ECO:0007829|PDB:5ZOK"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 432..440
FT /evidence="ECO:0007829|PDB:1KHU"
FT HELIX 441..451
FT /evidence="ECO:0007829|PDB:1KHU"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:3Q47"
SQ SEQUENCE 465 AA; 52260 MW; 2DD34B7F434DBC7E CRC64;
MNVTSLFSFT SPAVKRLLGW KQGDEEEKWA EKAVDALVKK LKKKKGAMEE LEKALSCPGQ
PSNCVTIPRS LDGRLQVSHR KGLPHVIYCR VWRWPDLQSH HELKPLECCE FPFGSKQKEV
CINPYHYKRV ESPVLPPVLV PRHSEYNPQH SLLAQFRNLG QNEPHMPLNA TFPDSFQQPN
SHPFPHSPNS SYPNSPGSSS STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMTQDGSQ
PMDTNMMAPP LPSEINRGDV QAVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
DPSNNKNRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC
NYHHGFHPTT VCKIPSGCSL KIFNNQEFAQ LLAQSVNHGF ETVYELTKMC TIRMSFVKGW
GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPHNP ISSVS
