SMAD6_CHICK
ID SMAD6_CHICK Reviewed; 431 AA.
AC Q9W734;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Mothers against decapentaplegic homolog 6;
DE Short=MAD homolog 6;
DE Short=Mothers against DPP homolog 6;
DE AltName: Full=SMAD family member 6;
DE Short=SMAD 6;
DE Short=Smad6;
GN Name=SMAD6; Synonyms=MADH6;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10525349; DOI=10.1006/dbio.1999.9419;
RA Yamada M., Szendro P.I., Prokscha A., Schwartz R.J., Eichele G.;
RT "Evidence for a role of Smad6 in chick cardiac development.";
RL Dev. Biol. 215:48-61(1999).
CC -!- FUNCTION: Transforming growth factor-beta superfamily receptors
CC signaling occurs through the Smad family of intracellular mediators.
CC SMAD6 is an inhibitory Smad (i-Smad) that negatively regulates
CC signaling downstream of type I transforming growth factor-beta. Acts as
CC a mediator of TGF-beta and BMP anti-inflammatory activities. Suppresses
CC IL1R-TLR signaling through its direct interaction with PEL1, preventing
CC NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated
CC expression of pro-inflammatory genes. Blocks the BMP-SMAD1 signaling
CC pathway by competing with SMAD4 for receptor-activated SMAD1-binding.
CC Binds to regulatory elements in target promoter regions.
CC {ECO:0000250|UniProtKB:O43541}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Developing heart, eyes and limbs.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; AF165889; AAD45160.1; -; mRNA.
DR AlphaFoldDB; Q9W734; -.
DR SMR; Q9W734; -.
DR STRING; 9031.ENSGALP00000041470; -.
DR VEuPathDB; HostDB:geneid_374096; -.
DR eggNOG; KOG3701; Eukaryota.
DR HOGENOM; CLU_026736_2_0_1; -.
DR InParanoid; Q9W734; -.
DR PhylomeDB; Q9W734; -.
DR PRO; PR:Q9W734; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005768; C:endosome; IDA:AgBase.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
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:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IBA:GO_Central.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0031589; P:cell-substrate adhesion; ISS:UniProtKB.
DR GO; GO:0010693; P:negative regulation of alkaline phosphatase activity; IMP:AgBase.
DR GO; GO:1902832; P:negative regulation of cell proliferation in dorsal spinal cord; IMP:AgBase.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IMP:AgBase.
DR GO; GO:1902844; P:positive regulation of spinal cord association neuron differentiation by negative regulation of canonical Wnt signaling pathway; IMP:AgBase.
DR GO; GO:0050767; P:regulation of neurogenesis; IMP:AgBase.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
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; 2.
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 DNA-binding; Metal-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..431
FT /note="Mothers against decapentaplegic homolog 6"
FT /id="PRO_0000090871"
FT DOMAIN 85..209
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 265..431
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..88
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
SQ SEQUENCE 431 AA; 47824 MW; 393185BB00ADA04E CRC64;
MFRSKRSGLV RRLWRSRVIP ERDGGDGNGQ SSERNATAVT AEGQRMAQPR RAQEGEGRPV
RCCLFAERPG PELPPPPPPP PPGGASPPGP GGGEARSRLV LLERELKAVT YALLKRLKER
SLHSLLQAVE SRGGTPGGCV LVARGELRLG AARRPPPHLL LGKLFRWPDL QHPAELKALC
ECQSFGAADG PTVCCNPYHF SRLCGPESPP PPYSRLSPND EQKPLDLSDS TLSYTETEAT
NSPNVTPGEF SDASTSPDAV KRSHWCNVAY WEHRTRVGRL YTVYEQSVSI FYDLPQGNGF
CLGQLNLENR SETVRRTRSK IGYGILLSKE PDGVWAYNRS EHPIFVNSPT LDIPNCRTLI
VRKVMPGYSI KVFDYEKSCL LQHTAELDYA DGPYDPNSVR ISFAKGWGPC YSRQFITSCP
CWLEILLSNN R
