SMAD7_RAT
ID SMAD7_RAT Reviewed; 426 AA.
AC O88406; Q9QUG1;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Mothers against decapentaplegic homolog 7;
DE Short=MAD homolog 7;
DE Short=Mothers against DPP homolog 7;
DE AltName: Full=SMAD family member 7;
DE Short=SMAD 7;
DE Short=Smad7;
GN Name=Smad7; Synonyms=Madh7;
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 [GENOMIC DNA / MRNA].
RX PubMed=10656934; DOI=10.1007/s003350010032;
RA Stopa M., Benes V., Ansorge W., Gressner A.M., Dooley S.;
RT "Genomic locus and promoter region of rat Smad7, an important antagonist of
RT TGFbeta signaling.";
RL Mamm. Genome 11:169-176(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11181520; DOI=10.1210/endo.142.3.8028;
RA Bilezikjian L.M., Corrigan A.Z., Blount A.L., Chen Y., Vale W.W.;
RT "Regulation and actions of Smad7 in the modulation of activin, inhibin, and
RT transforming growth factor-beta signaling in anterior pituitary cells.";
RL Endocrinology 142:1065-1072(2001).
CC -!- FUNCTION: Antagonist of signaling by TGF-beta (transforming growth
CC factor) type 1 receptor superfamily members; has been shown to inhibit
CC TGF-beta (Transforming growth factor) and activin signaling by
CC associating with their receptors thus preventing SMAD2 access.
CC Functions as an adapter to recruit SMURF2 to the TGF-beta receptor
CC complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1,
CC which promotes its dephosphorylation. Positively regulates PDPK1 kinase
CC activity by stimulating its dissociation from the 14-3-3 protein YWHAQ
CC which acts as a negative regulator. {ECO:0000250|UniProtKB:O15105}.
CC -!- SUBUNIT: Interacts with COPS5. Interacts with STAMBP. Interacts with
CC NEDD4L. Interacts with RNF111, AXIN1 and AXIN2. Interacts with
CC PPP1R15A. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7
CC recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its
CC degradation. Interacts with WWP1 (By similarity). Interacts with PDPK1
CC (via PH domain) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15105}. Cytoplasm
CC {ECO:0000250|UniProtKB:O15105}. Note=Interaction with NEDD4L or RNF111
CC induces translocation from the nucleus to the cytoplasm. TGF-beta
CC stimulates its translocation from the nucleus to the cytoplasm. PDPK1
CC inhibits its translocation from the nucleus to the cytoplasm in
CC response to TGF-beta. {ECO:0000250|UniProtKB:O15105}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylation on Ser-249 does not affect its stability, nuclear
CC localization or inhibitory function in TGFB signaling; however it
CC affects its ability to regulate transcription (By similarity).
CC Phosphorylated by PDPK1 (By similarity). {ECO:0000250|UniProtKB:O15105,
CC ECO:0000250|UniProtKB:O35253}.
CC -!- PTM: Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by
CC RNF111, which is enhanced by AXIN1 and promotes proteasomal
CC degradation. In response to TGF-beta, ubiquitinated by SMURF1; which
CC promotes its degradation (By similarity).
CC {ECO:0000250|UniProtKB:O15105, ECO:0000250|UniProtKB:O35253}.
CC -!- PTM: Acetylation prevents ubiquitination and degradation mediated by
CC SMURF1. {ECO:0000250|UniProtKB:O15105}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; AF156730; AAF00608.1; -; Genomic_DNA.
DR EMBL; AF156727; AAF00608.1; JOINED; Genomic_DNA.
DR EMBL; AF156728; AAF00608.1; JOINED; Genomic_DNA.
DR EMBL; AF156729; AAF00608.1; JOINED; Genomic_DNA.
DR EMBL; AF159626; AAD41130.1; -; mRNA.
DR EMBL; AF042499; AAC25062.1; -; mRNA.
DR RefSeq; NP_110485.1; NM_030858.1.
DR AlphaFoldDB; O88406; -.
DR BMRB; O88406; -.
DR SMR; O88406; -.
DR BioGRID; 249513; 3.
DR IntAct; O88406; 1.
DR MINT; O88406; -.
DR STRING; 10116.ENSRNOP00000024831; -.
DR PhosphoSitePlus; O88406; -.
DR PaxDb; O88406; -.
DR PRIDE; O88406; -.
DR GeneID; 81516; -.
DR KEGG; rno:81516; -.
DR CTD; 4092; -.
DR RGD; 69314; Smad7.
DR eggNOG; KOG3701; Eukaryota.
DR InParanoid; O88406; -.
DR OrthoDB; 395665at2759; -.
DR PhylomeDB; O88406; -.
DR TreeFam; TF314923; -.
DR Reactome; R-RNO-201451; Signaling by BMP.
DR Reactome; R-RNO-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-RNO-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR PRO; PR:O88406; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0048185; F:activin binding; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0005518; F:collagen binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISO:RGD.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR GO; GO:0034333; P:adherens junction assembly; ISO:RGD.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0048844; P:artery morphogenesis; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:1902731; P:negative regulation of chondrocyte proliferation; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:RGD.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0002725; P:negative regulation of T cell cytokine production; ISO:RGD.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; ISO:RGD.
DR GO; GO:2000317; P:negative regulation of T-helper 17 type immune response; ISO:RGD.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEP:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:RGD.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; ISO:RGD.
DR GO; GO:1903043; P:positive regulation of chondrocyte hypertrophy; ISO:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0031503; P:protein-containing complex localization; ISO:RGD.
DR GO; GO:0032925; P:regulation of activin receptor signaling pathway; ISO:RGD.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:RGD.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:RGD.
DR GO; GO:0034616; P:response to laminar fluid shear stress; ISO:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
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:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO: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; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..426
FT /note="Mothers against decapentaplegic homolog 7"
FT /id="PRO_0000090874"
FT DOMAIN 64..207
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 261..426
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 14..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..217
FT /note="Important for interaction with SMURF2"
FT /evidence="ECO:0000250"
FT MOTIF 208..211
FT /note="PY-motif"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 64
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O15105"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O15105"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35253,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CROSSLNK 64
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:O15105"
FT CROSSLNK 70
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:O15105"
FT CONFLICT 36
FT /note="G -> D (in Ref. 2; AAF00608/AAD41130)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="Missing (in Ref. 1; AAC25062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 426 AA; 46458 MW; 135B7D34972B455D CRC64;
MFRTKRSALV RRLWRSRAPG GEDEEEGVGG GGGGGGLRGE GATDGRAYGA GGGGAGRAGC
CLGKAVRGAK GHHHPHPPSS GAGAAGGAEA DLKALTHSVL KKLKERQLEL LLQAVESRGG
TRTACLLLPG RLDCRLGPGA PASAQPAQPP SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC
ESYGKINPEL VCCNPHHLSR LCELESPPPP YSRYPMDFLK PTADCPDAVP SSDETGGTNY
LAPGGLSDSQ LLLEPGDRSH WCVVAYWEEK TRVGRLYCVQ EPSLDIFYDL PQGNGFCLGQ
LNSDNKSQLV QKVRSKIGCG IQLTREVDGV WVYNRSSYPI FIKSATLDNP DSRTLLVHKV
FPGFSIKAFD YEKAYSLQRP NDHEFMQQPW TGFTVQISFV KGWGQCYTRQ FISSCPCWLE
VIFNSR
