Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (SMAD family member 1) (SMAD 1) (Smad1)

 SMAD1_RAT               Reviewed;         468 AA.
 P97588; O70520;
 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
 01-MAY-1997, sequence version 1.
 02-DEC-2020, entry version 160.
 RecName: Full=Mothers against decapentaplegic homolog 1;
          Short=MAD homolog 1;
          Short=Mothers against DPP homolog 1;
 AltName: Full=SMAD family member 1;
          Short=SMAD 1;
          Short=Smad1;
 Name=Smad1; Synonyms=Mad1, Madh1;
 Rattus norvegicus (Rat).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
 Murinae; Rattus.
 NCBI_TaxID=10116;
 [1]
 NUCLEOTIDE SEQUENCE [MRNA].
 TISSUE=Brain;
 PubMed=8917532; DOI=10.1073/pnas.93.23.12992;
 Chen Y., Lebrun J.-J., Vale W.W.;
 "Regulation of transforming growth factor beta- and activin-induced
 transcription by mammalian Mad proteins.";
 Proc. Natl. Acad. Sci. U.S.A. 93:12992-12997(1996).
 [2]
 NUCLEOTIDE SEQUENCE [MRNA].
 TISSUE=Intestine;
 PubMed=9989785;
 DOI=10.1002/(sici)1097-4652(199903)178:3<387::aid-jcp13>3.0.co;2-8;
 Yue J., Hartsough M.T., Frey R.S., Frielle T., Mulder K.M.;
 "Cloning and expression of a rat Smad1: regulation by TGFbeta and
 modulation by the Ras/MEK pathway.";
 J. Cell. Physiol. 178:387-396(1999).
 -!- FUNCTION: Transcriptional modulator activated by BMP (bone
     morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-
     regulated SMAD (R-SMAD). Has been shown to be also activated by TGF-
     beta (transforming growth factor) type I receptor kinase in rat
     intestinal epithelial cells (IEC 4-1). SMAD1/OAZ1/PSMB4 complex
     mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act
     synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-
     mediated cardiac-specific gene expression (By similarity).
     {ECO:0000250|UniProtKB:Q15797}.
 -!- SUBUNIT: Found in a complex with SMAD4 and YY1. Upon C-terminus
     phosphorylation: forms trimers with another SMAD1 and the co-SMAD
     SMAD4. Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP),
     NANOG, p300, SMURF1, SMURF2, HOXC8, USP15 and HGS. Associates with
     ZNF423 or ZNF521 in response to BMP2 leading to activate transcription
     of BMP target genes. Interacts with SKOR1 and ZCCHC12. Interacts (via
     MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial
     reduction of receptor-mediated phosphorylation. Forms a ternary complex
     with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S
     proteasome. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in
     a SMAD4-independent manner. Interacts with ZC3H3. Interacts with
     TMEM119. Interacts (via MH1 and MH2 domains) with ZNF8 (By similarity).
     Interacts with RANBP3L; the interaction increases when SMAD1 is not
     phosphorylated and mediates SMAD1 nuclear export (By similarity).
     {ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15797}. Nucleus
     {ECO:0000250|UniProtKB:Q15797}. Note=In the cytoplasm in the absence of
     ligand. Migration to the nucleus when complexed with SMAD4. Colocalizes
     with LEMD3 at the nucleus inner membrane. Exported from the nucleus to
     the cytoplasm when dephosphorylated (By similarity).
     {ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
 -!- TISSUE SPECIFICITY: Ubiquitous; present in liver, lung, stomach and
     spleen with lower level in heart, testes and skeletal muscle.
 -!- DOMAIN: The MH2 domain mediates phosphorylation-dependent trimerization
     through L3 loop binding of phosphoserines in the adjacent subunit.
     {ECO:0000250|UniProtKB:Q15797}.
 -!- PTM: Phosphorylation of the C-terminal SVS motif by BMP type 1 receptor
     kinase activates SMAD1 by promoting dissociation from the receptor and
     trimerization with SMAD4 (By similarity). Dephosphorylation, probably
     by PPM1A, induces its export from the nucleus to the cytoplasm (By
     similarity). {ECO:0000250|UniProtKB:P70340,
     ECO:0000250|UniProtKB:Q15797}.
 -!- PTM: Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading
     to its degradation. Monoubiquitinated, leading to prevent DNA-binding.
     Deubiquitination by USP15 alleviates inhibition and promotes activation
     of TGF-beta target genes (By similarity). {ECO:0000250}.
 -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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 EMBL; U66478; AAC52943.1; -; mRNA.
 EMBL; AF067727; AAC19116.1; -; mRNA.
 SMR; P97588; -.
 STRING; 10116.ENSRNOP00000025079; -.
 jPOST; P97588; -.
 PaxDb; P97588; -.
 PRIDE; P97588; -.
 UCSC; RGD:3030; rat.
 RGD; 3030; Smad1.
 eggNOG; KOG3701; Eukaryota.
 InParanoid; P97588; -.
 PhylomeDB; P97588; -.
 TreeFam; TF314923; -.
 Reactome; R-RNO-201451; Signaling by BMP.
 Reactome; R-RNO-5689880; Ub-specific processing proteases.
 Reactome; R-RNO-8941326; RUNX2 regulates bone development.
 PRO; PR:P97588; -.
 Proteomes; UP000002494; Unplaced.
 GO; GO:0005737; C:cytoplasm; IDA:RGD.
 GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
 GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
 GO; GO:0005634; C:nucleus; IDA:RGD.
 GO; GO:0032991; C:protein-containing complex; ISO:RGD.
 GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
 GO; GO:0070410; F:co-SMAD binding; ISO:RGD.
 GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:RGD.
 GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
 GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
 GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
 GO; GO:0042802; F:identical protein binding; ISO:RGD.
 GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO; GO:0070878; F:primary miRNA binding; ISO:RGD.
 GO; GO:0019901; F:protein kinase binding; ISO:RGD.
 GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
 GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
 GO; GO:0008134; F:transcription factor binding; IBA:GO_Central.
 GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
 GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
 GO; GO:0030509; P:BMP signaling pathway; IMP:RGD.
 GO; GO:0060348; P:bone development; ISO:RGD.
 GO; GO:0060038; P:cardiac muscle cell proliferation; ISO:RGD.
 GO; GO:0051216; P:cartilage development; ISO:RGD.
 GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
 GO; GO:0071773; P:cellular response to BMP stimulus; ISO:RGD.
 GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
 GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
 GO; GO:0007276; P:gamete generation; ISO:RGD.
 GO; GO:0030902; P:hindbrain development; ISO:RGD.
 GO; GO:0042592; P:homeostatic process; ISO:RGD.
 GO; GO:0006954; P:inflammatory response; ISO:RGD.
 GO; GO:0001822; P:kidney development; IEP:RGD.
 GO; GO:0000165; P:MAPK cascade; IMP:RGD.
 GO; GO:0001710; P:mesodermal cell fate commitment; ISO:RGD.
 GO; GO:0030901; P:midbrain development; ISO:RGD.
 GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
 GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IEP:RGD.
 GO; GO:0002051; P:osteoblast fate commitment; ISO:RGD.
 GO; GO:0061036; P:positive regulation of cartilage development; ISO:RGD.
 GO; GO:0045597; P:positive regulation of cell differentiation; IDA:RGD.
 GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IEP:RGD.
 GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
 GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
 GO; GO:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; ISO:RGD.
 GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:RGD.
 GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
 GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISO:RGD.
 GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
 GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
 GO; GO:0042493; P:response to drug; IDA:RGD.
 GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
 GO; GO:0007183; P:SMAD protein complex assembly; ISO:RGD.
 GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
 GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
 GO; GO:0001657; P:ureteric bud development; ISO:RGD.
 GO; GO:0042060; P:wound healing; IEP:RGD.
 Gene3D; 2.60.200.10; -; 1.
 Gene3D; 3.90.520.10; -; 1.
 InterPro; IPR013790; Dwarfin.
 InterPro; IPR003619; MAD_homology1_Dwarfin-type.
 InterPro; IPR013019; MAD_homology_MH1.
 InterPro; IPR017855; SMAD-like_dom_sf.
 InterPro; IPR001132; SMAD_dom_Dwarfin-type.
 InterPro; IPR008984; SMAD_FHA_dom_sf.
 InterPro; IPR036578; SMAD_MH1_sf.
 PANTHER; PTHR13703; PTHR13703; 1.
 Pfam; PF03165; MH1; 1.
 Pfam; PF03166; MH2; 1.
 SMART; SM00523; DWA; 1.
 SMART; SM00524; DWB; 1.
 SUPFAM; SSF49879; SSF49879; 1.
 SUPFAM; SSF56366; SSF56366; 1.
 PROSITE; PS51075; MH1; 1.
 PROSITE; PS51076; MH2; 1.
 2: Evidence at transcript level;
 Acetylation; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
 Phosphoprotein; Reference proteome; Transcription;
 Transcription regulation; Ubl conjugation; Zinc.
 CHAIN           1..468
                 /note="Mothers against decapentaplegic homolog 1"
                 /id="PRO_0000090849"
 DOMAIN          12..136
                 /note="MH1"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
 DOMAIN          274..468
                 /note="MH2"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
 REGION          421..431
                 /note="L3 loop"
                 /evidence="ECO:0000250|UniProtKB:Q15797"
 COMPBIAS        39..45
                 /note="Poly-Lys"
 COMPBIAS        198..201
                 /note="Poly-Ser"
 METAL           64
                 /note="Zinc"
                 /evidence="ECO:0000250"
 METAL           109
                 /note="Zinc"
                 /evidence="ECO:0000250"
 METAL           121
                 /note="Zinc"
                 /evidence="ECO:0000250"
 METAL           126
                 /note="Zinc"
                 /evidence="ECO:0000250"
 MOD_RES         1
                 /note="N-acetylmethionine"
                 /evidence="ECO:0000250|UniProtKB:Q15797"
 MOD_RES         325
                 /note="Phosphothreonine; by MINK1, TNIK and MAP4K4"
                 /evidence="ECO:0000250|UniProtKB:Q15797"
 MOD_RES         466
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q15797,
                 ECO:0000255|PROSITE-ProRule:PRU00439"
 MOD_RES         468
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q15797,
                 ECO:0000255|PROSITE-ProRule:PRU00439"
 CONFLICT        185..187
                 /note="AQY -> PQS (in Ref. 2; AAC19116)"
                 /evidence="ECO:0000305"
 CONFLICT        289
                 /note="R -> A (in Ref. 2; AAC19116)"
                 /evidence="ECO:0000305"
 CONFLICT        406
                 /note="E -> V (in Ref. 2; AAC19116)"
                 /evidence="ECO:0000305"
 SEQUENCE   468 AA;  52713 MW;  66A1ED58A0CE3CD1 CRC64;
 MNVTSLFSFT SPAVKRLLGW KQGDEEEKWA EKAVDALVKK LKKKKGAMEE LEKALSCPGQ
 PSNCVTIPRS LDGRLQVSHR KGLPHVIYCR VWRWPDLQSH HELKPLECCE FPFGSKQKEV
 CINPYHYKRV ESPVLPPVLV PRHSEYNPQH SLLAQFRNLG QNEPHMPLNA TFPDSFQQPH
 SHPFAQYPNS SYPNSPGSSS STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMAQDGSQ
 PMDTNMTNMT APTLPAEINR GDVQAVAYEE PKHWCSIVYY ELNNRVGERF HASSTSVLVD
 GFTDPSNNKN RFCLGLLSNV NRNSTIENTR RHIGKGVHLY YVGGEVYAEC LSDSSIFVQS
 RNCNYHHGFH PTTVCKIPSG CSLKIFNNQE FAQLLAQSVN HGFETEYELT KMCTIRMSFV
 KGWGAEYHRQ DVTSTPCWIE IHLHGPLQWL DKVLTQMGSP HNPISSVS

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