SMAD1_BOVIN
ID SMAD1_BOVIN Reviewed; 465 AA.
AC Q1JQA2; Q06AL6;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 1.
DT 03-AUG-2022, entry version 119.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang X., Xu S.;
RT "Cloning and bioinformatic analysis of cDNA encoding cattle Smad1 gene.";
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcriptional modulator activated by BMP (bone
CC morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-
CC regulated SMAD (R-SMAD). May act synergistically with SMAD4 and YY1 in
CC bone morphogenetic protein (BMP)-mediated cardiac-specific gene
CC expression. {ECO:0000250|UniProtKB:Q15797}.
CC -!- SUBUNIT: Interacts with HGS, NANOG and ZCCHC12. 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 p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521
CC in response to BMP2 leading to activate transcription of BMP target
CC genes. Interacts with SKOR1. Interacts (via MH2 domain) with LEMD3.
CC Binding to LEMD3 results in at least a partial reduction of receptor-
CC mediated phosphorylation. Found in a complex with SMAD4 and YY1. Found
CC in a macromolecular complex with FAM83G. Interacts (via MH2 domain)
CC with FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts
CC with ZC3H3. Interacts with TMEM119. Interacts (via MH1 and MH2 domains)
CC with ZNF8 (By similarity). Interacts with RANBP3L; the interaction
CC increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear
CC export (By similarity). {ECO:0000250|UniProtKB:P70340,
CC ECO:0000250|UniProtKB:Q15797}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15797}. Nucleus
CC {ECO:0000250|UniProtKB:Q15797}. Note=Cytoplasmic in the absence of
CC ligand. Migrates to the nucleus when complexed with SMAD4. Colocalizes
CC with LEMD3 at the nucleus inner membrane (By similarity). Forms a
CC ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into
CC the 20S proteasome (By similarity). Exported from the nucleus to the
CC cytoplasm when dephosphorylated (By similarity).
CC {ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
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; DQ922947; ABI96185.1; -; mRNA.
DR EMBL; BC116117; AAI16118.1; -; mRNA.
DR RefSeq; NP_001069691.2; NM_001076223.2.
DR RefSeq; XP_005217566.1; XM_005217509.2.
DR RefSeq; XP_005217568.1; XM_005217511.2.
DR RefSeq; XP_010812017.1; XM_010813715.2.
DR RefSeq; XP_010812018.1; XM_010813716.2.
DR AlphaFoldDB; Q1JQA2; -.
DR SMR; Q1JQA2; -.
DR STRING; 9913.ENSBTAP00000003668; -.
DR PaxDb; Q1JQA2; -.
DR PRIDE; Q1JQA2; -.
DR Ensembl; ENSBTAT00000003668; ENSBTAP00000003668; ENSBTAG00000002835.
DR Ensembl; ENSBTAT00000067295; ENSBTAP00000067920; ENSBTAG00000002835.
DR Ensembl; ENSBTAT00000067387; ENSBTAP00000074456; ENSBTAG00000002835.
DR Ensembl; ENSBTAT00000072205; ENSBTAP00000057918; ENSBTAG00000002835.
DR GeneID; 540488; -.
DR KEGG; bta:540488; -.
DR CTD; 4086; -.
DR VEuPathDB; HostDB:ENSBTAG00000002835; -.
DR VGNC; VGNC:34974; SMAD1.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000154391; -.
DR HOGENOM; CLU_026736_0_2_1; -.
DR InParanoid; Q1JQA2; -.
DR OMA; GTPSKCV; -.
DR OrthoDB; 608001at2759; -.
DR TreeFam; TF314923; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000002835; Expressed in abomasum and 104 other tissues.
DR ExpressionAtlas; Q1JQA2; baseline.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
DR GO; GO:0071142; C:homomeric SMAD protein complex; IEA:Ensembl.
DR GO; GO:0005637; C:nuclear inner membrane; IEA:Ensembl.
DR GO; GO:0070410; F:co-SMAD binding; IEA:Ensembl.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070878; F:primary miRNA binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; 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:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0007276; P:gamete generation; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0042592; P:homeostatic process; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0001710; P:mesodermal cell fate commitment; IEA:Ensembl.
DR GO; GO:0030901; P:midbrain development; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0002051; P:osteoblast fate commitment; IEA:Ensembl.
DR GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0007183; P:SMAD protein complex assembly; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
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..465
FT /note="Mothers against decapentaplegic homolog 1"
FT /id="PRO_0000260256"
FT DOMAIN 12..136
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 271..465
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 162..249
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..428
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 322
FT /note="Phosphothreonine; by MINK1, TNIK and MAP4K4"
FT /evidence="ECO:0000250|UniProtKB:Q15797"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15797,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 465
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15797,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CONFLICT 62
FT /note="S -> G (in Ref. 1; ABI96185)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 465 AA; 52250 MW; 7C2E679F72B15C4F CRC64;
MNVTSLFSFT SPAVKRLLGW KQGDEEEKWA EKAVDALVKK LKKKKGAMEE LEKALSCPGQ
PSNCVTIPRS LDGRLQVSHR KGLPHVIYCR VWRWPDLQSH HELKPLECCE FPFGSKQKEV
CINPYHYKRV ESPVLPPVLV PRHSEYNPQH SLLAQFRNLG QNEPHMPLNA TFPDSFQQPN
SHPFPHSPNS SYPNSPGSSS STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMTQDGSQ
PMDTNMMAPS LPSEINRGDV QAVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
DPSNNKNRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC
NYHHGFHPTT VCKIPSGCSL KIFNNQEFAQ LLAQSVNHGF ETVYELTKMC TIRMSFVKGW
GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPHNP ISSVS
