SMAD1_RAT
ID SMAD1_RAT Reviewed; 468 AA.
AC P97588; O70520;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Mothers against decapentaplegic homolog 1;
DE Short=MAD homolog 1;
DE Short=Mothers against DPP homolog 1;
DE AltName: Full=SMAD family member 1;
DE Short=SMAD 1;
DE Short=Smad1;
GN Name=Smad1; Synonyms=Mad1, Madh1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8917532; DOI=10.1073/pnas.93.23.12992;
RA Chen Y., Lebrun J.-J., Vale W.W.;
RT "Regulation of transforming growth factor beta- and activin-induced
RT transcription by mammalian Mad proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12992-12997(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Intestine;
RX PubMed=9989785;
RX DOI=10.1002/(sici)1097-4652(199903)178:3<387::aid-jcp13>3.0.co;2-8;
RA Yue J., Hartsough M.T., Frey R.S., Frielle T., Mulder K.M.;
RT "Cloning and expression of a rat Smad1: regulation by TGFbeta and
RT modulation by the Ras/MEK pathway.";
RL J. Cell. Physiol. 178:387-396(1999).
CC -!- FUNCTION: Transcriptional modulator activated by BMP (bone
CC morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-
CC regulated SMAD (R-SMAD). Has been shown to be also activated by TGF-
CC beta (transforming growth factor) type I receptor kinase in rat
CC intestinal epithelial cells (IEC 4-1). SMAD1/OAZ1/PSMB4 complex
CC mediates the 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q15797}.
CC -!- SUBUNIT: Found in a complex with SMAD4 and YY1. Upon C-terminus
CC phosphorylation: forms trimers with another SMAD1 and the co-SMAD
CC SMAD4. Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP),
CC NANOG, p300, SMURF1, SMURF2, HOXC8, USP15 and HGS. Associates with
CC ZNF423 or ZNF521 in response to BMP2 leading to activate transcription
CC of BMP target genes. Interacts with SKOR1 and ZCCHC12. Interacts (via
CC MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial
CC reduction of receptor-mediated phosphorylation. Forms a ternary complex
CC with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S
CC proteasome. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in
CC a SMAD4-independent manner. Interacts with ZC3H3. Interacts with
CC TMEM119. Interacts (via MH1 and MH2 domains) with ZNF8 (By similarity).
CC Interacts with RANBP3L; the interaction increases when SMAD1 is not
CC phosphorylated and mediates SMAD1 nuclear export (By similarity).
CC {ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15797}. Nucleus
CC {ECO:0000250|UniProtKB:Q15797}. Note=In the cytoplasm in the absence of
CC ligand. Migration to the nucleus when complexed with SMAD4. Colocalizes
CC with LEMD3 at the nucleus inner membrane. Exported from the nucleus to
CC the cytoplasm when dephosphorylated (By similarity).
CC {ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
CC -!- TISSUE SPECIFICITY: Ubiquitous; present in liver, lung, stomach and
CC spleen with lower level in heart, testes 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:0000250|UniProtKB:Q15797}.
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 (By similarity). Dephosphorylation, probably
CC by PPM1A, induces its export from the nucleus to the cytoplasm (By
CC similarity). {ECO:0000250|UniProtKB:P70340,
CC ECO:0000250|UniProtKB:Q15797}.
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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; U66478; AAC52943.1; -; mRNA.
DR EMBL; AF067727; AAC19116.1; -; mRNA.
DR RefSeq; NP_037262.2; NM_013130.2.
DR AlphaFoldDB; P97588; -.
DR SMR; P97588; -.
DR STRING; 10116.ENSRNOP00000025079; -.
DR jPOST; P97588; -.
DR PaxDb; P97588; -.
DR GeneID; 25671; -.
DR KEGG; rno:25671; -.
DR UCSC; RGD:3030; rat.
DR CTD; 4086; -.
DR RGD; 3030; Smad1.
DR eggNOG; KOG3701; Eukaryota.
DR InParanoid; P97588; -.
DR PhylomeDB; P97588; -.
DR TreeFam; TF314923; -.
DR Reactome; R-RNO-201451; Signaling by BMP.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:P97588; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; ISO:RGD.
DR GO; GO:0071142; C:homomeric SMAD protein complex; ISO:RGD.
DR GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0070410; F:co-SMAD binding; ISO:RGD.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070878; F:primary miRNA binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:RGD.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
DR GO; GO:0007276; P:gamete generation; ISO:RGD.
DR GO; GO:0030902; P:hindbrain development; ISO:RGD.
DR GO; GO:0042592; P:homeostatic process; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0000165; P:MAPK cascade; IMP:RGD.
DR GO; GO:0001710; P:mesodermal cell fate commitment; ISO:RGD.
DR GO; GO:0030901; P:midbrain development; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IEP:RGD.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR GO; GO:0002051; P:osteoblast fate commitment; ISO:RGD.
DR GO; GO:0061036; P:positive regulation of cartilage development; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IDA:RGD.
DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IEP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0007183; P:SMAD protein complex assembly; ISO:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 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; 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 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..468
FT /note="Mothers against decapentaplegic homolog 1"
FT /id="PRO_0000090849"
FT DOMAIN 12..136
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 274..468
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 162..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..431
FT /note="L3 loop"
FT /evidence="ECO:0000250|UniProtKB:Q15797"
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:0000250|UniProtKB:Q15797"
FT MOD_RES 325
FT /note="Phosphothreonine; by MINK1, TNIK and MAP4K4"
FT /evidence="ECO:0000250|UniProtKB:Q15797"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15797,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15797,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CONFLICT 185..187
FT /note="AQY -> PQS (in Ref. 2; AAC19116)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="R -> A (in Ref. 2; AAC19116)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="E -> V (in Ref. 2; AAC19116)"
FT /evidence="ECO:0000305"
SQ 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
