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Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (SMAD family member 1) (SMAD 1) (Smad1)

 SMAD1_RAT               Reviewed;         468 AA.
P97588; O70520;
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
01-MAY-1997, sequence version 1.
02-DEC-2020, entry version 160.
RecName: Full=Mothers against decapentaplegic homolog 1;
Short=MAD homolog 1;
Short=Mothers against DPP homolog 1;
AltName: Full=SMAD family member 1;
Short=SMAD 1;
Short=Smad1;
Name=Smad1; Synonyms=Mad1, Madh1;
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 [MRNA].
TISSUE=Brain;
PubMed=8917532; DOI=10.1073/pnas.93.23.12992;
Chen Y., Lebrun J.-J., Vale W.W.;
"Regulation of transforming growth factor beta- and activin-induced
transcription by mammalian Mad proteins.";
Proc. Natl. Acad. Sci. U.S.A. 93:12992-12997(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Intestine;
PubMed=9989785;
DOI=10.1002/(sici)1097-4652(199903)178:3<387::aid-jcp13>3.0.co;2-8;
Yue J., Hartsough M.T., Frey R.S., Frielle T., Mulder K.M.;
"Cloning and expression of a rat Smad1: regulation by TGFbeta and
modulation by the Ras/MEK pathway.";
J. Cell. Physiol. 178:387-396(1999).
-!- FUNCTION: Transcriptional modulator activated by BMP (bone
morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-
regulated SMAD (R-SMAD). Has been shown to be also activated by TGF-
beta (transforming growth factor) type I receptor kinase in rat
intestinal epithelial cells (IEC 4-1). SMAD1/OAZ1/PSMB4 complex
mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act
synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-
mediated cardiac-specific gene expression (By similarity).
{ECO:0000250|UniProtKB:Q15797}.
-!- SUBUNIT: Found in a complex with SMAD4 and YY1. Upon C-terminus
phosphorylation: forms trimers with another SMAD1 and the co-SMAD
SMAD4. Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP),
NANOG, p300, SMURF1, SMURF2, HOXC8, USP15 and HGS. Associates with
ZNF423 or ZNF521 in response to BMP2 leading to activate transcription
of BMP target genes. Interacts with SKOR1 and ZCCHC12. Interacts (via
MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial
reduction of receptor-mediated phosphorylation. Forms a ternary complex
with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S
proteasome. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in
a SMAD4-independent manner. Interacts with ZC3H3. Interacts with
TMEM119. Interacts (via MH1 and MH2 domains) with ZNF8 (By similarity).
Interacts with RANBP3L; the interaction increases when SMAD1 is not
phosphorylated and mediates SMAD1 nuclear export (By similarity).
{ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15797}. Nucleus
{ECO:0000250|UniProtKB:Q15797}. Note=In the cytoplasm in the absence of
ligand. Migration to the nucleus when complexed with SMAD4. Colocalizes
with LEMD3 at the nucleus inner membrane. Exported from the nucleus to
the cytoplasm when dephosphorylated (By similarity).
{ECO:0000250|UniProtKB:P70340, ECO:0000250|UniProtKB:Q15797}.
-!- TISSUE SPECIFICITY: Ubiquitous; present in liver, lung, stomach and
spleen with lower level in heart, testes and skeletal muscle.
-!- DOMAIN: The MH2 domain mediates phosphorylation-dependent trimerization
through L3 loop binding of phosphoserines in the adjacent subunit.
{ECO:0000250|UniProtKB:Q15797}.
-!- PTM: Phosphorylation of the C-terminal SVS motif by BMP type 1 receptor
kinase activates SMAD1 by promoting dissociation from the receptor and
trimerization with SMAD4 (By similarity). Dephosphorylation, probably
by PPM1A, induces its export from the nucleus to the cytoplasm (By
similarity). {ECO:0000250|UniProtKB:P70340,
ECO:0000250|UniProtKB:Q15797}.
-!- PTM: Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading
to its degradation. Monoubiquitinated, leading to prevent DNA-binding.
Deubiquitination by USP15 alleviates inhibition and promotes activation
of TGF-beta target genes (By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; U66478; AAC52943.1; -; mRNA.
EMBL; AF067727; AAC19116.1; -; mRNA.
SMR; P97588; -.
STRING; 10116.ENSRNOP00000025079; -.
jPOST; P97588; -.
PaxDb; P97588; -.
PRIDE; P97588; -.
UCSC; RGD:3030; rat.
RGD; 3030; Smad1.
eggNOG; KOG3701; Eukaryota.
InParanoid; P97588; -.
PhylomeDB; P97588; -.
TreeFam; TF314923; -.
Reactome; R-RNO-201451; Signaling by BMP.
Reactome; R-RNO-5689880; Ub-specific processing proteases.
Reactome; R-RNO-8941326; RUNX2 regulates bone development.
PRO; PR:P97588; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0071144; C:heteromeric SMAD protein complex; IBA:GO_Central.
GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
GO; GO:0005634; C:nucleus; IDA:RGD.
GO; GO:0032991; C:protein-containing complex; ISO:RGD.
GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
GO; GO:0070410; F:co-SMAD binding; ISO:RGD.
GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:RGD.
GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
GO; GO:0070411; F:I-SMAD binding; ISO:RGD.
GO; GO:0042802; F:identical protein binding; ISO:RGD.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0070878; F:primary miRNA binding; ISO:RGD.
GO; GO:0019901; F:protein kinase binding; ISO:RGD.
GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
GO; GO:0008134; F:transcription factor binding; IBA:GO_Central.
GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
GO; GO:0030509; P:BMP signaling pathway; IMP:RGD.
GO; GO:0060348; P:bone development; ISO:RGD.
GO; GO:0060038; P:cardiac muscle cell proliferation; ISO:RGD.
GO; GO:0051216; P:cartilage development; ISO:RGD.
GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
GO; GO:0071773; P:cellular response to BMP stimulus; ISO:RGD.
GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
GO; GO:0007276; P:gamete generation; ISO:RGD.
GO; GO:0030902; P:hindbrain development; ISO:RGD.
GO; GO:0042592; P:homeostatic process; ISO:RGD.
GO; GO:0006954; P:inflammatory response; ISO:RGD.
GO; GO:0001822; P:kidney development; IEP:RGD.
GO; GO:0000165; P:MAPK cascade; IMP:RGD.
GO; GO:0001710; P:mesodermal cell fate commitment; ISO:RGD.
GO; GO:0030901; P:midbrain development; ISO:RGD.
GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IEP:RGD.
GO; GO:0002051; P:osteoblast fate commitment; ISO:RGD.
GO; GO:0061036; P:positive regulation of cartilage development; ISO:RGD.
GO; GO:0045597; P:positive regulation of cell differentiation; IDA:RGD.
GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IEP:RGD.
GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
GO; GO:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; ISO:RGD.
GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:RGD.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISO:RGD.
GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
GO; GO:0042493; P:response to drug; IDA:RGD.
GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
GO; GO:0007183; P:SMAD protein complex assembly; ISO:RGD.
GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IBA:GO_Central.
GO; GO:0001657; P:ureteric bud development; ISO:RGD.
GO; GO:0042060; P:wound healing; IEP: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; Metal-binding; Nucleus;
Phosphoprotein; Reference proteome; Transcription;
Transcription regulation; Ubl conjugation; Zinc.
CHAIN 1..468
/note="Mothers against decapentaplegic homolog 1"
/id="PRO_0000090849"
DOMAIN 12..136
/note="MH1"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
DOMAIN 274..468
/note="MH2"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
REGION 421..431
/note="L3 loop"
/evidence="ECO:0000250|UniProtKB:Q15797"
COMPBIAS 39..45
/note="Poly-Lys"
COMPBIAS 198..201
/note="Poly-Ser"
METAL 64
/note="Zinc"
/evidence="ECO:0000250"
METAL 109
/note="Zinc"
/evidence="ECO:0000250"
METAL 121
/note="Zinc"
/evidence="ECO:0000250"
METAL 126
/note="Zinc"
/evidence="ECO:0000250"
MOD_RES 1
/note="N-acetylmethionine"
/evidence="ECO:0000250|UniProtKB:Q15797"
MOD_RES 325
/note="Phosphothreonine; by MINK1, TNIK and MAP4K4"
/evidence="ECO:0000250|UniProtKB:Q15797"
MOD_RES 466
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:Q15797,
ECO:0000255|PROSITE-ProRule:PRU00439"
MOD_RES 468
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:Q15797,
ECO:0000255|PROSITE-ProRule:PRU00439"
CONFLICT 185..187
/note="AQY -> PQS (in Ref. 2; AAC19116)"
/evidence="ECO:0000305"
CONFLICT 289
/note="R -> A (in Ref. 2; AAC19116)"
/evidence="ECO:0000305"
CONFLICT 406
/note="E -> V (in Ref. 2; AAC19116)"
/evidence="ECO:0000305"
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


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Pathways :
WP32: Translation Factors
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP1596: Iron Homeostasis
WP1048: TGF Beta Signaling Pathway
WP1780: ABC-family proteins mediated transport
WP1909: Signal regulatory protein (SIRP) family interactions
WP113: TGF Beta Signaling Pathway
WP397: Id Signaling Pathway
WP1180: Delta-Notch Signaling Pathway
WP560: TGF Beta Signaling Pathway
WP2006: Squamous cell TarBase
WP2067: Heart Development
WP1382: Delta-Notch Signaling Pathway
WP827: Delta-Notch Signaling Pathway
WP1539: Angiogenesis
WP946: Delta-Notch Signaling Pathway
WP230: TGF Beta Signaling Pathway
WP265: Delta-Notch Signaling Pathway
WP1834: Interactions of the immunoglobulin superfamily (IgSF) member proteins
WP1064: Delta-Notch Signaling Pathway
WP341: Nodal signaling pathway
WP1168: Id Signaling Pathway
WP512: Id Signaling Pathway
WP2004: Lymphocyte TarBase

Related Genes :
[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)
[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)
[SMAD1] Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (SMAD family member 1) (SMAD 1) (Smad1)
[Smad1 Mad1 Madh1] Mothers against decapentaplegic homolog 1 (MAD homolog 1) (Mothers against DPP homolog 1) (SMAD family member 1) (SMAD 1) (Smad1)
[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) (SMAD family member 4) (SMAD 4) (Smad4) (hSMAD4)
[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)
[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 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)
[Smad3 Madh3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (mMad3) (SMAD family member 3) (SMAD 3) (Smad3)
[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)
[SMAD3 MADH3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (SMAD family member 3) (SMAD 3) (Smad3)
[Smad3 Madh3] Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (SMAD family member 3) (SMAD 3) (Smad3)
[Smad7 Madh7] Mothers against decapentaplegic homolog 7 (MAD homolog 7) (Mothers against DPP homolog 7) (SMAD family member 7) (SMAD 7) (Smad7)
[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)
[Dana\GF20979 dana_GLEANR_4213 Dana_GF20979 GF20979] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dvir\GJ18762 Dvir_GJ18762 GJ18762] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dmoj\GI14415 Dmoj_GI14415] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dyak\GE17479 Dyak_GE17479] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dgri\GH24864 Dgri_GH24864] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dper\GL20193 Dper_GL20193] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dsec\GM11208 Dsec_GM11208] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Dere\GG17985 Dere_GG17985] Mothers against decapentaplegic homolog (MAD homolog) (Mothers against DPP homolog) (SMAD family member)
[Aox3 Aoh1] Aldehyde oxidase 3 (EC 1.2.3.1) (Aldehyde oxidase homolog 1) (Azaheterocycle hydroxylase 3) (EC 1.17.3.-)

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