ID SMAD5_HUMAN Reviewed; 465 AA. AC Q99717; O14688; Q15798; Q9UQA1; DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 27-MAR-2024, entry version 224. DE RecName: Full=Mothers against decapentaplegic homolog 5; DE Short=MAD homolog 5; DE Short=Mothers against DPP homolog 5; DE AltName: Full=JV5-1; DE AltName: Full=SMAD family member 5; DE Short=SMAD 5; DE Short=Smad5; DE Short=hSmad5; GN Name=SMAD5; Synonyms=MADH5; 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]. 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 [GENOMIC DNA / MRNA]. RX PubMed=9288787; RA Hejlik D.P., Kottickal L.V., Liang H., Fairman J., Davis T., Janecki T., RA Sexton D., Perry W. III, Tavtigian S.V., Teng D.H., Nagarajan L.; RT "Localization of SMAD5 and its evaluation as a candidate myeloid tumor RT suppressor."; RL Cancer Res. 57:3779-3783(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9264367; DOI=10.1038/sj.leu.2400750; RA Zavadil J., Brezinova J., Svoboda P., Zemanova Z., Michalova K.; RT "Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and RT not mutated in the retained allele in human leukemia cell line HL60."; RL Leukemia 11:1187-1192(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9484787; DOI=10.1038/sj.onc.1201614; RA Gemma A., Hagiwara K., Vincent F., Ke Y., Hancock A.R., Nagashima M., RA Bennett W.P., Harris C.C.; RT "hSmad5 gene, a human hSmad family member: its full length cDNA, genomic RT structure, promoter region and mutation analysis in human tumors."; RL Oncogene 16:951-956(1998). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLY-419, FUNCTION, INTERACTION RP WITH SMAD4, AND SUBCELLULAR LOCATION. RX PubMed=9442019; DOI=10.1074/jbc.273.4.1872; RA Nishimura R., Kato Y., Chen D., Harris S.E., Mundy G.R., Yoneda T.; RT "Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic RT differentiation of the pluripotent mesenchymal precursor cell line C2C12."; RL J. Biol. Chem. 273:1872-1879(1998). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 2-16; 34-40; 130-158; 283-306 AND 309-319, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT THR-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V., Lempens A., Norman J.C.; RL Submitted (OCT-2009) to UniProtKB. 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 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 [11] 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 [12] RP INTERACTION WITH ZNF8. RX PubMed=12370310; DOI=10.1128/mcb.22.21.7633-7644.2002; RA Jiao K., Zhou Y., Hogan B.L.M.; RT "Identification of mZnf8, a mouse Kruppel-like transcriptional repressor, RT as a novel nuclear interaction partner of Smad1."; RL Mol. Cell. Biol. 22:7633-7644(2002). RN [13] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=12064918; DOI=10.1006/bcmd.2002.0487; RA Fuchs O., Simakova O., Klener P., Cmejlova J., Zivny J., Zavadil J., RA Stopka T.; RT "Inhibition of Smad5 in human hematopoietic progenitors blocks erythroid RT differentiation induced by BMP4."; RL Blood Cells Mol. Dis. 28:221-233(2002). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=12849988; DOI=10.1016/s0006-291x(03)01139-2; RA Juellig M., Stott N.S.; RT "Mitochondrial localization of Smad5 in a human chondrogenic cell line."; RL Biochem. Biophys. Res. Commun. 307:108-113(2003). RN [15] RP INTERACTION WITH SUV39H1 AND SUV39H2. RX PubMed=15107829; DOI=10.1038/sj.onc.1207660; RA Frontelo P., Leader J.E., Yoo N., Potocki A.C., Crawford M., Kulik M., RA Lechleider R.J.; RT "Suv39h histone methyltransferases interact with Smads and cooperate in RT BMP-induced repression."; RL Oncogene 23:5242-5251(2004). RN [16] RP 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 [17] RP FUNCTION, INTERACTION WITH HGS, AND SUBCELLULAR LOCATION. RX PubMed=16516194; DOI=10.1016/j.yexcr.2006.01.019; RA Haag J., Chubinskaya S., Aigner T.; RT "Hgs physically interacts with Smad5 and attenuates BMP signaling."; RL Exp. Cell Res. 312:1153-1163(2006). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-465, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). 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 ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [24] 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 [25] RP INTERACTION WITH RANBP3L. 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 [26] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HK1. RX PubMed=28675158; DOI=10.1038/cr.2017.85; RA Fang Y., Liu Z., Chen Z., Xu X., Xiao M., Yu Y., Zhang Y., Zhang X., Du Y., RA Jiang C., Zhao Y., Wang Y., Fan B., Terheyden-Keighley D., Liu Y., Shi L., RA Hui Y., Zhang X., Zhang B., Feng H., Ma L., Zhang Q., Jin G., Yang Y., RA Xiang B., Liu L., Zhang X.; RT "Smad5 acts as an intracellular pH messenger and maintains bioenergetic RT homeostasis."; RL Cell Res. 27:1083-1099(2017). RN [27] {ECO:0007744|PDB:6FZS, ECO:0007744|PDB:6TCE} RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 9-138, SUBUNIT, AND FUNCTION. RX PubMed=33510867; DOI=10.1016/j.csbj.2020.12.044; RA Ruiz L., Kaczmarska Z., Gomes T., Aragon E., Torner C., Freier R., RA Baginski B., Martin-Malpartida P., de Martin Garrido N., Marquez J.A., RA Cordeiro T.N., Pluta R., Macias M.J.; RT "Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes."; RL Comput. Struct. Biotechnol. J. 19:632-646(2021). CC -!- FUNCTION: Transcriptional regulator that plays a role in various CC cellular processes including embryonic development, cell CC differentiation, angiogenesis and tissue homeostasis (PubMed:16516194, CC PubMed:12064918). Upon BMP ligand binding to their receptors at the CC cell surface, is phosphorylated by activated type I BMP receptors CC (BMPRIs) and associates with SMAD4 to form an heteromeric complex which CC translocates into the nucleus acting as transcription factor CC (PubMed:9442019). In turn, the hetero-trimeric complex recognizes cis- CC regulatory elements containing Smad Binding Elements (SBEs) to modulate CC the outcome of the signaling network (PubMed:33510867). Non- CC phosphorylated SMAD5 has a cytoplasmic role in energy metabolism CC regulation by promoting mitochondrial respiration and glycolysis in CC response to cytoplasmic pH changes (PubMed:28675158). Mechanistically, CC interacts with hexokinase 1/HK1 and thereby accelerates glycolysis CC (PubMed:28675158). {ECO:0000269|PubMed:12064918, CC ECO:0000269|PubMed:16516194, ECO:0000269|PubMed:28675158, CC ECO:0000269|PubMed:33510867, ECO:0000269|PubMed:9442019}. CC -!- SUBUNIT: Homodimer (PubMed:33510867). Forms trimers with the co-SMAD CC SMAD4 (PubMed:9442019). Interacts with PEBP2-alpha subunit and SMURF1. CC Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with CC LEMD3. Interacts with WWP1. Interacts with TMEM119 (By similarity). CC Interacts with ZNF8 (PubMed:12370310). Interacts with RANBP3L CC (PubMed:25755279). Interacts with HK1 (PubMed:28675158). Interacts with CC HGS; this interaction attenuates BMP signaling (PubMed:16516194). CC {ECO:0000250|UniProtKB:P97454, ECO:0000269|PubMed:12370310, CC ECO:0000269|PubMed:15107829, ECO:0000269|PubMed:15647271, CC ECO:0000269|PubMed:16516194, ECO:0000269|PubMed:25755279, CC ECO:0000269|PubMed:28675158, ECO:0000269|PubMed:33510867}. CC -!- INTERACTION: CC Q99717; P17844: DDX5; NbExp=3; IntAct=EBI-6391136, EBI-351962; CC Q99717; Q92876: KLK6; NbExp=3; IntAct=EBI-6391136, EBI-2432309; CC Q99717; Q99732: LITAF; NbExp=3; IntAct=EBI-6391136, EBI-725647; CC Q99717; P78424: POU6F2; NbExp=3; IntAct=EBI-6391136, EBI-12029004; CC Q99717; Q969T9: WBP2; NbExp=3; IntAct=EBI-6391136, EBI-727055; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16516194, CC ECO:0000269|PubMed:28675158, ECO:0000269|PubMed:9442019}. Nucleus CC {ECO:0000269|PubMed:28675158, ECO:0000269|PubMed:9442019}. CC Mitochondrion {ECO:0000269|PubMed:12849988}. Note=Cytoplasmic in the CC absence of ligand. Migrates to the nucleus when complexed with SMAD4. CC {ECO:0000269|PubMed:9442019}. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- PTM: Phosphorylated on serine by BMP (bone morphogenetic proteins) type CC 1 receptor kinase. {ECO:0000269|PubMed:12064918}. CC -!- PTM: Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin CC ligase SMURF1. 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; U59913; AAC50791.1; -; mRNA. DR EMBL; AF010601; AAB66353.1; -; mRNA. DR EMBL; AF010607; AAB92396.1; -; Genomic_DNA. DR EMBL; AF010602; AAB92396.1; JOINED; Genomic_DNA. DR EMBL; AF010603; AAB92396.1; JOINED; Genomic_DNA. DR EMBL; AF010604; AAB92396.1; JOINED; Genomic_DNA. DR EMBL; AF010605; AAB92396.1; JOINED; Genomic_DNA. DR EMBL; AF010606; AAB92396.1; JOINED; Genomic_DNA. DR EMBL; U73825; AAB95090.1; -; mRNA. DR EMBL; AF009744; AAB82655.1; -; Genomic_DNA. DR EMBL; AF009739; AAB82655.1; JOINED; Genomic_DNA. DR EMBL; AF009740; AAB82655.1; JOINED; Genomic_DNA. DR EMBL; AF009741; AAB82655.1; JOINED; Genomic_DNA. DR EMBL; AF009742; AAB82655.1; JOINED; Genomic_DNA. DR EMBL; AF009743; AAB82655.1; JOINED; Genomic_DNA. DR EMBL; AF009678; AAB72180.1; -; mRNA. DR EMBL; BC009682; AAH09682.1; -; mRNA. DR CCDS; CCDS75308.1; -. DR RefSeq; NP_001001419.1; NM_001001419.2. DR RefSeq; NP_001001420.1; NM_001001420.2. DR RefSeq; NP_005894.3; NM_005903.6. DR RefSeq; XP_016864959.1; XM_017009470.1. DR PDB; 6FZS; X-ray; 2.31 A; A/B=9-138. DR PDB; 6TCE; X-ray; 2.92 A; A=9-138. DR PDBsum; 6FZS; -. DR PDBsum; 6TCE; -. DR AlphaFoldDB; Q99717; -. DR SASBDB; Q99717; -. DR SMR; Q99717; -. DR BioGRID; 110265; 85. DR DIP; DIP-57571N; -. DR IntAct; Q99717; 44. DR MINT; Q99717; -. DR STRING; 9606.ENSP00000441954; -. DR GlyGen; Q99717; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q99717; -. DR PhosphoSitePlus; Q99717; -. DR BioMuta; SMAD5; -. DR DMDM; 13959566; -. DR EPD; Q99717; -. DR jPOST; Q99717; -. DR MassIVE; Q99717; -. DR MaxQB; Q99717; -. DR PaxDb; 9606-ENSP00000441954; -. DR PeptideAtlas; Q99717; -. DR ProteomicsDB; 78432; -. DR Pumba; Q99717; -. DR Antibodypedia; 7303; 758 antibodies from 41 providers. DR DNASU; 4090; -. DR Ensembl; ENST00000509297.6; ENSP00000426696.2; ENSG00000113658.18. DR Ensembl; ENST00000545279.6; ENSP00000441954.2; ENSG00000113658.18. DR Ensembl; ENST00000545620.5; ENSP00000446474.2; ENSG00000113658.18. DR GeneID; 4090; -. DR KEGG; hsa:4090; -. DR MANE-Select; ENST00000545279.6; ENSP00000441954.2; NM_005903.7; NP_005894.3. DR UCSC; uc032vlw.2; human. DR AGR; HGNC:6771; -. DR CTD; 4090; -. DR DisGeNET; 4090; -. DR GeneCards; SMAD5; -. DR HGNC; HGNC:6771; SMAD5. DR HPA; ENSG00000113658; Low tissue specificity. DR MIM; 603110; gene. DR neXtProt; NX_Q99717; -. DR OpenTargets; ENSG00000113658; -. DR PharmGKB; PA30528; -. DR VEuPathDB; HostDB:ENSG00000113658; -. DR eggNOG; KOG3701; Eukaryota. DR GeneTree; ENSGT00940000155437; -. DR HOGENOM; CLU_026736_0_2_1; -. DR InParanoid; Q99717; -. DR OMA; QPMDTGN; -. DR OrthoDB; 2891561at2759; -. DR PhylomeDB; Q99717; -. DR PathwayCommons; Q99717; -. DR Reactome; R-HSA-201451; Signaling by BMP. DR SignaLink; Q99717; -. DR SIGNOR; Q99717; -. DR BioGRID-ORCS; 4090; 12 hits in 348 CRISPR screens. DR ChiTaRS; SMAD5; human. DR GeneWiki; Mothers_against_decapentaplegic_homolog_5; -. DR GenomeRNAi; 4090; -. DR Pharos; Q99717; Tbio. DR PRO; PR:Q99717; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q99717; Protein. DR Bgee; ENSG00000113658; Expressed in mucosa of paranasal sinus and 201 other cell types or tissues. DR ExpressionAtlas; Q99717; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0071141; C:SMAD protein complex; NAS:BHF-UCL. DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IC:UniProt. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl. DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. 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; ISS: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:0060048; P:cardiac muscle contraction; 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:0030218; P:erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0007281; P:germ cell development; IEA:Ensembl. DR GO; GO:0001880; P:Mullerian duct regression; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:BHF-UCL. DR GO; GO:1902045; P:negative regulation of Fas signaling pathway; IMP:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0001649; P:osteoblast differentiation; IDA:BHF-UCL. DR GO; GO:0002051; P:osteoblast fate commitment; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS: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; ISS:BHF-UCL. 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 CDD; cd10490; MH1_SMAD_1_5_9; 1. DR CDD; cd10497; MH2_SMAD_1_5_9; 1. DR Gene3D; 2.60.200.10; -; 1. DR Gene3D; 3.90.520.10; SMAD MH1 domain; 1. DR InterPro; IPR013790; Dwarfin. DR InterPro; IPR003619; MAD_homology1_Dwarfin-type. DR InterPro; IPR013019; MAD_homology_MH1. DR InterPro; IPR017855; SMAD-like_dom_sf. DR InterPro; IPR001132; SMAD_dom_Dwarfin-type. DR InterPro; IPR008984; SMAD_FHA_dom_sf. DR InterPro; IPR036578; SMAD_MH1_sf. DR PANTHER; PTHR13703:SF36; MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 5; 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; Q99717; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; KW DNA-binding; Metal-binding; Mitochondrion; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:22223895" FT CHAIN 2..465 FT /note="Mothers against decapentaplegic homolog 5" FT /id="PRO_0000090865" FT DOMAIN 13..137 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 163..249 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 163..184 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 185..201 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 232..249 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 65 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P97454" FT BINDING 110 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P97454" FT BINDING 122 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P97454" FT BINDING 127 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P97454" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:22223895" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 465 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MUTAGEN 419 FT /note="G->S: Loss of phosphorylation and interaction with FT SMAD4." FT /evidence="ECO:0000269|PubMed:9442019" FT CONFLICT 175 FT /note="D -> H (in Ref. 1; AAC50791)" FT /evidence="ECO:0000305" FT CONFLICT 237 FT /note="N -> P (in Ref. 1; AAC50791)" FT /evidence="ECO:0000305" FT CONFLICT 293 FT /note="S -> R (in Ref. 1; AAC50791)" FT /evidence="ECO:0000305" FT HELIX 13..20 FT /evidence="ECO:0007829|PDB:6FZS" FT HELIX 26..42 FT /evidence="ECO:0007829|PDB:6FZS" FT HELIX 48..57 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 67..69 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:6FZS" FT HELIX 85..93 FT /evidence="ECO:0007829|PDB:6FZS" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:6FZS" FT HELIX 114..116 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 119..122 FT /evidence="ECO:0007829|PDB:6FZS" FT HELIX 125..127 FT /evidence="ECO:0007829|PDB:6FZS" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:6FZS" SQ SEQUENCE 465 AA; 52258 MW; 4A1FD7EC7BD06728 CRC64; MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP NNTPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP MDTSNNMIPQ IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS //