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Mothers against decapentaplegic homolog 7 (MAD homolog 7) (Mothers against DPP homolog 7) (SMAD family member 7) (SMAD 7) (Smad7)

 SMAD7_RAT               Reviewed;         426 AA.
O88406; Q9QUG1;
04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
04-MAY-2001, sequence version 2.
26-FEB-2020, entry version 161.
RecName: Full=Mothers against decapentaplegic homolog 7;
Short=MAD homolog 7;
Short=Mothers against DPP homolog 7;
AltName: Full=SMAD family member 7;
Short=SMAD 7;
Short=Smad7;
Name=Smad7; Synonyms=Madh7;
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 [GENOMIC DNA / MRNA].
PubMed=10656934; DOI=10.1007/s003350010032;
Stopa M., Benes V., Ansorge W., Gressner A.M., Dooley S.;
"Genomic locus and promoter region of rat Smad7, an important antagonist of
TGFbeta signaling.";
Mamm. Genome 11:169-176(2000).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=11181520; DOI=10.1210/endo.142.3.8028;
Bilezikjian L.M., Corrigan A.Z., Blount A.L., Chen Y., Vale W.W.;
"Regulation and actions of Smad7 in the modulation of activin, inhibin, and
transforming growth factor-beta signaling in anterior pituitary cells.";
Endocrinology 142:1065-1072(2001).
-!- FUNCTION: Antagonist of signaling by TGF-beta (transforming growth
factor) type 1 receptor superfamily members; has been shown to inhibit
TGF-beta (Transforming growth factor) and activin signaling by
associating with their receptors thus preventing SMAD2 access.
Functions as an adapter to recruit SMURF2 to the TGF-beta receptor
complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1,
which promotes its dephosphorylation. Positively regulates PDPK1 kinase
activity by stimulating its dissociation from the 14-3-3 protein YWHAQ
which acts as a negative regulator. {ECO:0000250|UniProtKB:O15105}.
-!- SUBUNIT: Interacts with COPS5. Interacts with STAMBP. Interacts with
NEDD4L. Interacts with RNF111, AXIN1 and AXIN2. Interacts with
PPP1R15A. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7
recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its
degradation. Interacts with WWP1 (By similarity). Interacts with PDPK1
(via PH domain) (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15105}. Cytoplasm
{ECO:0000250|UniProtKB:O15105}. Note=Interaction with NEDD4L or RNF111
induces translocation from the nucleus to the cytoplasm. TGF-beta
stimulates its translocation from the nucleus to the cytoplasm. PDPK1
inhibits its translocation from the nucleus to the cytoplasm in
response to TGF-beta. {ECO:0000250|UniProtKB:O15105}.
-!- TISSUE SPECIFICITY: Ubiquitous.
-!- PTM: Phosphorylation on Ser-249 does not affect its stability, nuclear
localization or inhibitory function in TGFB signaling; however it
affects its ability to regulate transcription (By similarity).
Phosphorylated by PDPK1 (By similarity). {ECO:0000250|UniProtKB:O15105,
ECO:0000250|UniProtKB:O35253}.
-!- PTM: Ubiquitinated by WWP1 (By similarity). Polyubiquitinated by
RNF111, which is enhanced by AXIN1 and promotes proteasomal
degradation. In response to TGF-beta, ubiquitinated by SMURF1; which
promotes its degradation (By similarity).
{ECO:0000250|UniProtKB:O15105, ECO:0000250|UniProtKB:O35253}.
-!- PTM: Acetylation prevents ubiquitination and degradation mediated by
SMURF1. {ECO:0000250|UniProtKB:O15105}.
-!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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EMBL; AF156730; AAF00608.1; -; Genomic_DNA.
EMBL; AF156727; AAF00608.1; JOINED; Genomic_DNA.
EMBL; AF156728; AAF00608.1; JOINED; Genomic_DNA.
EMBL; AF156729; AAF00608.1; JOINED; Genomic_DNA.
EMBL; AF159626; AAD41130.1; -; mRNA.
EMBL; AF042499; AAC25062.1; -; mRNA.
RefSeq; NP_110485.1; NM_030858.1.
SMR; O88406; -.
BioGrid; 249513; 3.
IntAct; O88406; 1.
MINT; O88406; -.
STRING; 10116.ENSRNOP00000024831; -.
PhosphoSitePlus; O88406; -.
PaxDb; O88406; -.
PRIDE; O88406; -.
GeneID; 81516; -.
KEGG; rno:81516; -.
CTD; 4092; -.
RGD; 69314; Smad7.
eggNOG; KOG3701; Eukaryota.
eggNOG; ENOG410XQKU; LUCA.
InParanoid; O88406; -.
KO; K19631; -.
OrthoDB; 395665at2759; -.
PhylomeDB; O88406; -.
TreeFam; TF314923; -.
Reactome; R-RNO-201451; Signaling by BMP.
Reactome; R-RNO-2173788; Downregulation of TGF-beta receptor signaling.
Reactome; R-RNO-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
Reactome; R-RNO-5689880; Ub-specific processing proteases.
PRO; PR:O88406; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005737; C:cytoplasm; ISO:RGD.
GO; GO:0005634; C:nucleus; ISO:RGD.
GO; GO:0005886; C:plasma membrane; ISO:RGD.
GO; GO:0032991; C:protein-containing complex; ISO:RGD.
GO; GO:0005667; C:transcription factor complex; IEA:InterPro.
GO; GO:0048185; F:activin binding; ISO:RGD.
GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
GO; GO:0005518; F:collagen binding; ISO:RGD.
GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0044212; F:transcription regulatory region DNA binding; ISO:RGD.
GO; GO:0030617; F:transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity; ISO:RGD.
GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISO:RGD.
GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
GO; GO:0034333; P:adherens junction assembly; ISO:RGD.
GO; GO:0048844; P:artery morphogenesis; ISO:RGD.
GO; GO:0034629; P:cellular protein-containing complex localization; ISO:RGD.
GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:RGD.
GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISO:RGD.
GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD.
GO; GO:0002725; P:negative regulation of T cell cytokine production; ISO:RGD.
GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; ISO:RGD.
GO; GO:2000317; P:negative regulation of T-helper 17 type immune response; ISO:RGD.
GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; ISO:RGD.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEP:RGD.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISO:RGD.
GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISO:RGD.
GO; GO:0022409; P:positive regulation of cell-cell adhesion; ISO:RGD.
GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:RGD.
GO; GO:0050821; P:protein stabilization; ISO:RGD.
GO; GO:0032925; P:regulation of activin receptor signaling pathway; ISO:RGD.
GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:RGD.
GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISO:RGD.
GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IDA:RGD.
GO; GO:0034616; P:response to laminar fluid shear stress; ISO:RGD.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
GO; GO:0001657; P:ureteric bud development; ISO:RGD.
GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
GO; GO:0060412; P:ventricular septum morphogenesis; ISO: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; Isopeptide bond; Metal-binding;
Nucleus; Phosphoprotein; Reference proteome; Transcription;
Transcription regulation; Ubl conjugation; Zinc.
CHAIN 1..426
/note="Mothers against decapentaplegic homolog 7"
/id="PRO_0000090874"
DOMAIN 64..207
/note="MH1"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
DOMAIN 261..426
/note="MH2"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
REGION 208..217
/note="Important for interaction with SMURF2"
/evidence="ECO:0000250"
MOTIF 208..211
/note="PY-motif"
/evidence="ECO:0000250"
COMPBIAS 27..36
/note="Poly-Gly"
COMPBIAS 49..56
/note="Poly-Gly"
COMPBIAS 206..209
/note="Poly-Pro"
METAL 125
/note="Zinc"
/evidence="ECO:0000250"
METAL 180
/note="Zinc"
/evidence="ECO:0000250"
METAL 192
/note="Zinc"
/evidence="ECO:0000250"
METAL 197
/note="Zinc"
/evidence="ECO:0000250"
MOD_RES 64
/note="N6-acetyllysine; alternate"
/evidence="ECO:0000250|UniProtKB:O15105"
MOD_RES 70
/note="N6-acetyllysine; alternate"
/evidence="ECO:0000250|UniProtKB:O15105"
MOD_RES 249
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:O35253,
ECO:0000255|PROSITE-ProRule:PRU00439"
CROSSLNK 64
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin); alternate"
/evidence="ECO:0000250|UniProtKB:O15105"
CROSSLNK 70
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in ubiquitin); alternate"
/evidence="ECO:0000250|UniProtKB:O15105"
CONFLICT 36
/note="G -> D (in Ref. 2; AAF00608/AAD41130)"
/evidence="ECO:0000305"
CONFLICT 193
/note="Missing (in Ref. 1; AAC25062)"
/evidence="ECO:0000305"
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


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Pathways :
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP32: Translation Factors
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP1596: Iron Homeostasis
WP1045: TGF-beta Receptor Signaling Pathway
WP1161: TGF-beta Receptor Signaling Pathway
WP1370: TGF Beta Signaling Pathway
WP362: TGF-beta Receptor Signaling Pathway
WP809: TGF-beta Receptor Signaling Pathway
WP1780: ABC-family proteins mediated transport
WP1909: Signal regulatory protein (SIRP) family interactions
WP930: TGF Beta Signaling Pathway
WP230: TGF Beta Signaling Pathway
WP258: TGF-beta Receptor Signaling Pathway
WP113: TGF Beta Signaling Pathway
WP1367: TGF-beta Receptor Signaling Pathway
WP341: Nodal signaling pathway
WP560: TGF Beta Signaling Pathway
WP1834: Interactions of the immunoglobulin superfamily (IgSF) member proteins
WP926: TGF-beta Receptor Signaling Pathway
WP211: BMP signaling pathway
WP1048: TGF Beta Signaling Pathway
WP1164: TGF Beta Signaling Pathway
WP339: ESC Pluripotency Pathways
WP505: TGF Beta Signaling Pathway

Related Genes :
[SMAD7 MADH7 MADH8] Mothers against decapentaplegic homolog 7 (MAD homolog 7) (Mothers against DPP homolog 7) (Mothers against decapentaplegic homolog 8) (MAD homolog 8) (Mothers against DPP homolog 8) (SMAD family member 7) (SMAD 7) (Smad7) (hSMAD7)
[Smad7 Madh7 Madh8] Mothers against decapentaplegic homolog 7 (MAD homolog 7) (Mothers against DPP homolog 7) (Mothers against decapentaplegic homolog 8) (MAD homolog 8) (Mothers against DPP homolog 8) (SMAD family member 7) (SMAD 7) (Smad7)
[Smad7 Madh7] Mothers against decapentaplegic homolog 7 (MAD homolog 7) (Mothers against DPP homolog 7) (SMAD family member 7) (SMAD 7) (Smad7)
[SMAD6 MADH6] Mothers against decapentaplegic homolog 6 (MAD homolog 6) (Mothers against DPP homolog 6) (SMAD family member 6) (SMAD 6) (Smad6) (hSMAD6)
[SMAD4 DPC4 MADH4] Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (Deletion target in pancreatic carcinoma 4) (SMAD family member 4) (SMAD 4) (Smad4) (hSMAD4)
[Smad1 Madh1 Madr1] Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (Dwarfin-A) (Dwf-A) (Mothers-against-DPP-related 1) (Mad-related protein 1) (mMad1) (SMAD family member 1) (SMAD 1) (Smad1)
[SMAD3 MADH3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (hMAD-3) (JV15-2) (SMAD family member 3) (SMAD 3) (Smad3) (hSMAD3)
[SMAD2 MADH2 MADR2] Mothers against decapentaplegic homolog 2 (MAD homolog 2) (Mothers against DPP homolog 2) (JV18-1) (Mad-related protein 2) (hMAD-2) (SMAD family member 2) (SMAD 2) (Smad2) (hSMAD2)
[Smad4 Dpc4 Madh4] Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (Deletion target in pancreatic carcinoma 4 homolog) (SMAD family member 4) (SMAD 4) (Smad4)
[SMAD4 MADH4] Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (SMAD family member 4) (SMAD 4) (Smad4)
[Smad4 Madh4] Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (SMAD family member 4) (SMAD 4) (Smad4)
[SMAD1 BSP1 MADH1 MADR1] Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (JV4-1) (Mad-related protein 1) (SMAD family member 1) (SMAD 1) (Smad1) (hSMAD1) (Transforming growth factor-beta-signaling protein 1) (BSP-1)
[Smad3 Madh3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (SMAD family member 3) (SMAD 3) (Smad3)
[Smad1 Mad1 Madh1] Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (SMAD family member 1) (SMAD 1) (Smad1)
[Smad3 Madh3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (mMad3) (SMAD family member 3) (SMAD 3) (Smad3)
[SMAD1] Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (SMAD family member 1) (SMAD 1) (Smad1)
[SMAD3 MADH3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (SMAD family member 3) (SMAD 3) (Smad3)
[Smox Dmel\CG2262 DSMAD2 DSmad2 dSMAD2 dSmad2 dsmad2 l(1)G0348 Sad sad Smad SMAD2 Smad2 smad2 SMOX SmoX smox ted tmp CG2262 Dmel_CG2262] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[SMAD4] Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (SMAD family member 4) (SMAD 4) (Smad4)
[Mad CG12399] Protein mothers against dpp
[ZFYVE9 MADHIP SARA SMADIP] Zinc finger FYVE domain-containing protein 9 (Mothers against decapentaplegic homolog-interacting protein) (Madh-interacting protein) (Novel serine protease) (NSP) (Receptor activation anchor) (hSARA) (Smad anchor for receptor activation)
[MAD2L2 MAD2B REV7] Mitotic spindle assembly checkpoint protein MAD2B (Mitotic arrest deficient 2-like protein 2) (MAD2-like protein 2) (REV7 homolog) (hREV7)
[rush EG:80H7.5 CG14782] Pleckstrin homology domain-containing family F member 1 homolog (PH domain-containing family F member 1 homolog) (Protein rush hour)
[ABCG1 ABC8 WHT1] ATP-binding cassette sub-family G member 1 (EC 7.6.2.-) (ATP-binding cassette transporter 8) (White protein homolog)
[ERVK-6 ERVK6] Endogenous retrovirus group K member 6 Rec protein (Central open reading frame) (c-orf) (cORF) (Endogenous retrovirus K protein 6) (HERV-K(C7) Rec protein) (HERV-K(HML-2.HOM) Rec protein) (HERV-K108 Rec protein) (HERV-K_7p22.1 provirus Rec protein) (K-Rev) (Rev-like protein) (Rev/Rex homolog)
[FAT1 CDHF7 FAT] Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form]
[LIN7A MALS1 VELI1] Protein lin-7 homolog A (Lin-7A) (hLin-7) (Mammalian lin-seven protein 1) (MALS-1) (Tax interaction protein 33) (TIP-33) (Vertebrate lin-7 homolog 1) (Veli-1)
[KMT2B HRX2 KIAA0304 MLL2 MLL4 TRX2 WBP7] Histone-lysine N-methyltransferase 2B (Lysine N-methyltransferase 2B) (EC 2.1.1.354) (Myeloid/lymphoid or mixed-lineage leukemia protein 4) (Trithorax homolog 2) (WW domain-binding protein 7) (WBP-7)
[Dana\GF20979 dana_GLEANR_4213 Dana_GF20979 GF20979] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Abcg1 Abc8 Wht1] ATP-binding cassette sub-family G member 1 (EC 7.6.2.-) (ATP-binding cassette transporter 8) (White protein homolog)

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