SMAD1
entrez
4086
canonical
uniprot
Q15797
canonical
ensembl
ENSG00000170365
resolver
ensp
ENSP00000305769
resolver
ensp
ENSP00000377652
resolver
ensp
ENSP00000426568
resolver
ensp
ENSP00000555739
resolver
ensp
ENSP00000555740
resolver
ensp
ENSP00000555747
resolver
ensp
ENSP00000555748
resolver
ensp
ENSP00000589746
resolver
genesymbol
SMAD1
resolver
genesymbol_syn
BSP1
resolver
genesymbol_syn
MADH1
resolver
genesymbol_syn
MADR1
resolver
hgnc
HGNC:6767
resolver
uniprot
A8KAJ0
resolver
uniprot
D3DNZ9
resolver
uniprot
Q16636
resolver
uniprot
Q9UFT8
resolver
uniprot_entry
SMAD1_HUMAN
resolver
uniprot_sec
A8KAJ0
resolver
uniprot_sec
D3DNZ9
resolver
uniprot_sec
Q16636
resolver
uniprot_sec
Q9UFT8
resolver
amino_acid_sequence
MNVTSLFSFTSPAVKRLLGWKQGDEEEKWAEKAVDALVKKLKKKKGAMEELEKALSCPGQPSNCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVESPVLPPVLVPRHSEYNPQHSLLAQFRNLGQNEPHMPLNATFPDSFQQPNSHPFPHSPNSSYPNSPGSSSSTYPHSPTSSDPGSPFQMPADTPPPAYLPPEDPMTQDGSQPMDTNMMAPPLPSEINRGDVQAVAYEEPKHWCSIVYYELNNRVGEAFHASSTSVLVDGFTDPSNNKNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECLSDSSIFVQSRNCNYHHGFHPTTVCKIPSGCSLKIFNNQEFAQLLAQSVNHGFETVYELTKMCTIRMSFVKGWGAEYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS
uniprot
proteins
disease_involvement
DISEASE: Note=SMAD1 variants may be associated with susceptibility to pulmonary hypertension, a disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs. {ECO:0000269|PubMed:21898662}.
uniprot
proteins
function
FUNCTION: Transcriptional modulator that plays a role in various cellular processes, including embryonic development, cell differentiation, and tissue homeostasis (PubMed:9335504). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form a heteromeric complex which translocates into the nucleus acting as transcription factor (PubMed:33667543). In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:33667543). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Positively regulates BMP4-induced expression of odontogenic development regulator MSX1 following IPO7-mediated nuclear import (By similarity). {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:33667543, ECO:0000269|PubMed:9335504}.
uniprot
proteins
mass_dalton
52260
uniprot
proteins
mutagenesis
MUTAGEN 297; /note="D->H: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 317; /note="V->D: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 373; /note="K->S: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 418; /note="K->S: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 419; /note="G->S: Loss of phosphorylation."; /evidence="ECO:0000269|PubMed:8653785"; MUTAGEN 424; /note="Y->F: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 426; /note="R->S: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 448; /note="D->H: Reduced trimerization."; /evidence="ECO:0000269|PubMed:11779505"; MUTAGEN 461; /note="I->D: Abolishes the formation of the CHIP-SMAD1 complex."; /evidence="ECO:0000269|PubMed:21454478"; MUTAGEN 463..465; /note="SVS->AVA: Increases interaction with RANBPL3."; /evidence="ECO:0000269|PubMed:25755279"; MUTAGEN 463..465; /note="SVS->DVD: Decreases interaction with RANBPL3."; /evidence="ECO:0000269|PubMed:25755279"; MUTAGEN 464; /note="V->D: Abolishes the formation of the CHIP-SMAD1 complex."; /evidence="ECO:0000269|PubMed:21454478
uniprot
proteins
post_translational_modification
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. Phosphorylation by ERK2 MAP kinase in response to EGF or HGF prevents SMAD1 nuclear accumulation and transcriptional activity in response to BMP (PubMed:9335504). Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (By similarity). Dephosphorylation is inhibited by association with EGR1 (By similarity). Phosphorylation by CDK8/9 creates binding sites for YAP1, and subsequent phosphorylation by GSK3 switches off YAP1 binding and adds binding sites for SMURF1 (PubMed:21685363). {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:11779505, ECO:0000269|PubMed:21685363, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:9136927, ECO:0000269|PubMed:9335504}.; 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. Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (By similarity). Phospho-SMAD1 is ubiquitinated by CHIP leading to disruption of the SMAD1-SMAD4 complex (PubMed:21454478). {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:21454478, ECO:0000269|PubMed:21947082}.
uniprot
proteins
protein_family
Dwarfin/SMAD family
uniprot
proteins
pubmed
10647776
uniprot
proteins
pubmed
10660046
uniprot
proteins
pubmed
10708948
uniprot
proteins
pubmed
10708949
uniprot
proteins
pubmed
11779505
uniprot
proteins
pubmed
12097147
uniprot
proteins
pubmed
14630787
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15647271
uniprot
proteins
pubmed
17292623
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21454478
uniprot
proteins
pubmed
21685363
uniprot
proteins
pubmed
21690388
uniprot
proteins
pubmed
21898662
uniprot
proteins
pubmed
21947082
uniprot
proteins
pubmed
22781750
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23150675
uniprot
proteins
pubmed
24554596
uniprot
proteins
pubmed
25755279
uniprot
proteins
pubmed
29789297
uniprot
proteins
pubmed
33667543
uniprot
proteins
pubmed
8637600
uniprot
proteins
pubmed
8653785
uniprot
proteins
pubmed
8663601
uniprot
proteins
pubmed
8673135
uniprot
proteins
pubmed
8774881
uniprot
proteins
pubmed
9136927
uniprot
proteins
pubmed
9335504
uniprot
proteins
pubmed
9759503
uniprot
proteins
sequence_length
465
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15647271, ECO:0000269|PubMed:9335504}. Nucleus {ECO:0000269|PubMed:15647271, ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:9335504}. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4 (PubMed:15647271). Co-localizes with LEMD3 at the nucleus inner membrane (PubMed:15647271). Exported from the nucleus to the cytoplasm when dephosphorylated (By similarity). {ECO:0000250|UniProtKB:P70340, ECO:0000269|PubMed:15647271}.
uniprot
proteins