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 27-MAR-2024, entry version 239. 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 FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=9335504; DOI=10.1038/39348; RA Kretzschmar M., Doody J., Massague J.; RT "Opposing BMP and EGF signalling pathways converge on the TGF-beta family RT mediator Smad1."; RL Nature 389:618-622(1997). RN [13] 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 [14] 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 [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] RP FUNCTION, AND INTERACTION WITH SMAD4 AND SMAD6. RX PubMed=33667543; DOI=10.1016/j.jbc.2021.100496; RA Wu J., Chen X., Sehgal P., Zhang T., Jackson-Weaver O., Gou Y., Bautch V., RA Frenkel B., Sun H., Xu J.; RT "Arginine methylation of R81 in Smad6 confines BMP-induced Smad1 RT signaling."; RL J. Biol. Chem. 296:100496-100496(2021). RN [32] 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). RN [33] {ECO:0007744|PDB:2LAW, ECO:0007744|PDB:2LAX, ECO:0007744|PDB:2LAY, ECO:0007744|PDB:2LAZ, ECO:0007744|PDB:2LB0, ECO:0007744|PDB:2LB1} RP STRUCTURE BY NMR OF 220-233, PHOSPHORYLATION, FUNCTION, AND INTERACTION RP WITH YAP1. RX PubMed=21685363; DOI=10.1101/gad.2060811; RA Aragon E., Goerner N., Zaromytidou A.I., Xi Q., Escobedo A., Massague J., RA Macias M.J.; RT "A Smad action turnover switch operated by WW domain readers of a RT phosphoserine code."; RL Genes Dev. 25:1275-1288(2011). RN [34] {ECO:0007744|PDB:3Q47, ECO:0007744|PDB:3Q4A} RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 456-465, FUNCTION, RP UBIQUITINATION, MUTAGENESIS OF ILE-461 AND VAL-464, AND INTERACTION WITH RP SMAD4. RX PubMed=21454478; DOI=10.1074/jbc.m110.201814; RA Wang L., Liu Y.T., Hao R., Chen L., Chang Z., Wang H.R., Wang Z.X., RA Wu J.W.; RT "Molecular mechanism of the negative regulation of Smad1/5 protein by RT carboxyl terminus of Hsc70-interacting protein (CHIP)."; RL J. Biol. Chem. 286:15883-15894(2011). CC -!- FUNCTION: Transcriptional modulator that plays a role in various CC cellular processes, including embryonic development, cell CC differentiation, and tissue homeostasis (PubMed:9335504). Upon BMP CC ligand binding to their receptors at the cell surface, is CC phosphorylated by activated type I BMP receptors (BMPRIs) and CC associates with SMAD4 to form an heteromeric complex which translocates CC into the nucleus acting as transcription factor (PubMed:33667543). In CC turn, the hetero-trimeric complex recognizes cis-regulatory elements CC containing Smad Binding Elements (SBEs) to modulate the outcome of the CC signaling network (PubMed:33667543). SMAD1/OAZ1/PSMB4 complex mediates CC the degradation of the CREBBP/EP300 repressor SNIP1. Positively CC regulates BMP4-induced expression of odontogenic development regulator CC MSX1 following IPO7-mediated nuclear import (By similarity). CC {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:12097147, CC ECO:0000269|PubMed:33667543, ECO:0000269|PubMed:9335504}. 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 CC (PubMed:21454478, PubMed:33667543). Interacts with PEBP2-alpha subunit, CC CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. CC Associates with ZNF423 or ZNF521 in response to BMP2 leading to CC activate transcription of BMP target genes. Interacts with SKOR1. CC Interacts (via MH2 domain) with LEMD3. Binding to LEMD3 results in at CC least a partial reduction of receptor-mediated phosphorylation. Forms a CC ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into CC the 20S proteasome. Found in a macromolecular complex with FAM83G. CC Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4- CC independent manner. Interacts with ZC3H3 (By similarity). Interacts CC with TMEM119 (By similarity). Interacts (via MH1 and MH2 domains) with CC ZNF8 (By similarity). Interacts with RANBP3L; the interaction increases CC when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export CC (PubMed:25755279). Interacts with EGR1; this interaction inhibits SMAD1 CC dephosphorylation (By similarity). Interacts with SMAD6 CC (PubMed:33667543). Interacts with YAP1 (PubMed:21685363). CC {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:10660046, CC ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:12097147, CC ECO:0000269|PubMed:14630787, ECO:0000269|PubMed:15647271, CC ECO:0000269|PubMed:17292623, ECO:0000269|PubMed:21685363, CC ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:24554596, CC ECO:0000269|PubMed:25755279, ECO:0000269|PubMed:33667543}. 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=3; IntAct=EBI-1567153, EBI-1044059; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15647271, CC ECO:0000269|PubMed:9335504}. Nucleus {ECO:0000269|PubMed:15647271, CC ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:9335504}. 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. Phosphorylation by ERK2 MAP kinase in CC response to EGF or HGF prevents SMAD1 nuclear accumulation and CC transcriptional activity in response to BMP (PubMed:9335504). CC Dephosphorylation, probably by PPM1A, induces its export from the CC nucleus to the cytoplasm (By similarity). Dephosphorylation is CC inhibited by association with EGR1 (By similarity). Phosphorylation by CC CDK8/9 creates binding sites for YAP1, and subsequent phosphorylation CC by GSK3 switches off YAP1 binding and adds binding sites for SMURF1 CC (PubMed:21685363). {ECO:0000250|UniProtKB:P70340, CC ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:21685363, CC ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9136927, CC ECO:0000269|PubMed:9335504}. 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). Phospho- CC SMAD1 is ubiquitinated by CHIP leading to disruption of the SMAD1-SMAD4 CC complex (PubMed:21454478). {ECO:0000250|UniProtKB:P70340, CC ECO:0000269|PubMed:21454478, 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}. 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; 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; 177. 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.ENSP00000305769; -. 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; 9606-ENSP00000426568; -. DR PeptideAtlas; Q15797; -. DR ProteomicsDB; 60766; -. [Q15797-1] DR Pumba; Q15797; -. DR Antibodypedia; 3950; 1581 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 AGR; HGNC:6767; -. 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; WASVAYY; -. DR OrthoDB; 2891561at2759; -. 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 Reactome; R-HSA-9733709; Cardiogenesis. DR SignaLink; Q15797; -. DR SIGNOR; Q15797; -. DR BioGRID-ORCS; 4086; 6 hits in 1169 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 217 other cell types or tissues. DR ExpressionAtlas; Q15797; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProt. 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:0016020; C: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:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. 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:0006351; P:DNA-templated transcription; IDA:ComplexPortal. 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:0001503; P:ossification; IGI:BHF-UCL. 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; IEA:Ensembl. 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:0031053; P:primary miRNA processing; TAS:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. 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 CDD; cd10490; MH1_SMAD_1_5_9; 1. DR CDD; cd10497; MH2_SMAD_1_5_9; 1. DR DisProt; DP01206; -. DR Gene3D; 2.60.200.10; -; 1. DR Gene3D; 3.90.520.10; SMAD MH1 domain; 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:SF23; MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 1; 1. DR PANTHER; PTHR13703; SMAD; 1. DR Pfam; PF03165; MH1; 1. DR Pfam; PF03166; MH2; 1. DR SMART; SM00523; DWA; 1. DR SMART; SM00524; DWB; 1. DR SUPFAM; SSF56366; SMAD MH1 domain; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR PROSITE; PS51075; MH1; 1. DR PROSITE; PS51076; MH2; 1. DR Genevisible; Q15797; HS. 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; uncertain significance; affects SMAD-mediated FT 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 461 FT /note="I->D: Abolishes the formation of the CHIP-SMAD1 FT complex." FT /evidence="ECO:0000269|PubMed:21454478" 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 MUTAGEN 464 FT /note="V->D: Abolishes the formation of the CHIP-SMAD1 FT complex." FT /evidence="ECO:0000269|PubMed:21454478" 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 //