P70340 · SMAD1_MOUSE
- ProteinMothers against decapentaplegic homolog 1
- GeneSmad1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids465 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcriptional modulator that plays a role in various cellular processes, including embryonic development, cell differentiation, and tissue homeostasis (PubMed:11566864, PubMed:15329343, PubMed:21420501, PubMed:35594155).
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. In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity).
Positively regulates BMP4-induced expression of odontogenic development regulator MSX1 following IPO7-mediated nuclear import (PubMed:34995814).
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. In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity).
Positively regulates BMP4-induced expression of odontogenic development regulator MSX1 following IPO7-mediated nuclear import (PubMed:34995814).
Features
Showing features for binding site.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMothers against decapentaplegic homolog 1
- Short namesMAD homolog 1; Mothers against DPP homolog 1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP70340
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
SMAD1 deletion results in early embryonic lethality due to failure of the allantois to fuse to the chorion (PubMed:11566864).
Chondrocyte-specific conditional knockout show a delay in calvarial bone mineralization and reduction of postnatal bone formation (PubMed:21420501).
Chondrocyte-specific conditional knockout show a delay in calvarial bone mineralization and reduction of postnatal bone formation (PubMed:21420501).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 23 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000090848 | 1-465 | Mothers against decapentaplegic homolog 1 | |||
Sequence: MNVTSLFSFTSPAVKRLLGWKQGDEEEKWAEKAVDALVKKLKKKKGAMEELEKALSCPGQPSNCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVESPVLPPVLVPRHSEYNPQHSLLAQFRNLGQNEPHMPLNATFPDSFQQPNSHPFPHSPNSSYPNSPGGSSSTYPHSPTSSDPGSPFQMPADTPPPAYLPPEDPMAQDGSQPMDTNMMAPPLPAEISRGDVQAVAYEEPKHWCSIVYYELNNRVGEAFHASSTSVLVDGFTDPSNNKNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECLSDSSIFVQSRNCNYHHGFHPTTVCKIPSGCSLKIFNNQEFAQLLAQSVNHGFETVYELTKMCTIRMSFVKGWGAEYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS | ||||||
Modified residue | 322 | Phosphothreonine; by MINK1, TNIK and MAP4K4 | ||||
Sequence: T | ||||||
Modified residue | 463 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 465 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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 (By similarity).
Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (PubMed:25755279).
Dephosphorylation is inhibited by association with EGR1 (PubMed:35594155).
Phosphorylation by CDK8/9 creates binding sites for YAP1, and subsequent phosphorylation by GSK3 switches off YAP1 binding and adds binding sites for SMURF1 (By similarity).
Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (PubMed:25755279).
Dephosphorylation is inhibited by association with EGR1 (PubMed:35594155).
Phosphorylation by CDK8/9 creates binding sites for YAP1, and subsequent phosphorylation by GSK3 switches off YAP1 binding and adds binding sites for SMURF1 (By similarity).
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 (By similarity).
Phospho-SMAD1 is ubiquitinated by CHIP leading to disruption of the SMAD1-SMAD4 complex (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous.
Developmental stage
Ubiquitously expressed during embryogenesis. Expression starts in some seminiferous tubules at 2 weeks of age. After mid-puberty a stage-specific expression is established. During the cycling of the seminiferous epithelium, expression initiates in the pachytene spermatocytes of stage V seminiferous tubules, peaks at stage X, then decreases as pachytene spermatocytes differentiate into secondary spermatocytes and then round spermatids.
Gene expression databases
Interaction
Subunit
Found in a complex with SMAD4 and YY1. Interacts with HGS, NANOG and ZCCHC12 (PubMed:11094085, PubMed:18160706).
Upon C-terminus phosphorylation: forms trimers with another SMAD1 and the co-SMAD SMAD4 (By similarity).
Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with SKOR1. 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. Found in a macromolecular complex with FAM83G. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts with ZC3H3 (PubMed:16115198).
Interacts with TMEM119 (PubMed:21239498).
Interacts (via MH1 and MH2 domains) with ZNF8 (PubMed:12370310).
Interacts with RANBP3L; the interaction increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export (PubMed:25755279).
Interacts with EGR1; this interaction inhibits SMAD1 dephosphorylation (PubMed:35594155).
Interacts with SMAD6 (By similarity).
Interacts with YAP1 (By similarity).
Interacts with MTMR4; negatively regulates BMP signaling through SMAD1 dephosphorylation and retention in endosomes (By similarity).
Upon C-terminus phosphorylation: forms trimers with another SMAD1 and the co-SMAD SMAD4 (By similarity).
Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with SKOR1. 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. Found in a macromolecular complex with FAM83G. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts with ZC3H3 (PubMed:16115198).
Interacts with TMEM119 (PubMed:21239498).
Interacts (via MH1 and MH2 domains) with ZNF8 (PubMed:12370310).
Interacts with RANBP3L; the interaction increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export (PubMed:25755279).
Interacts with EGR1; this interaction inhibits SMAD1 dephosphorylation (PubMed:35594155).
Interacts with SMAD6 (By similarity).
Interacts with YAP1 (By similarity).
Interacts with MTMR4; negatively regulates BMP signaling through SMAD1 dephosphorylation and retention in endosomes (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P70340 | Map3k7 Q62073 | 3 | EBI-6992047, EBI-1775345 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 12-136 | MH1 | ||||
Sequence: PAVKRLLGWKQGDEEEKWAEKAVDALVKKLKKKKGAMEELEKALSCPGQPSNCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCEFPFGSKQKEVCINPYHYKRVESPVLP | ||||||
Region | 162-246 | Disordered | ||||
Sequence: NEPHMPLNATFPDSFQQPNSHPFPHSPNSSYPNSPGGSSSTYPHSPTSSDPGSPFQMPADTPPPAYLPPEDPMAQDGSQPMDTNM | ||||||
Compositional bias | 171-216 | Polar residues | ||||
Sequence: TFPDSFQQPNSHPFPHSPNSSYPNSPGGSSSTYPHSPTSSDPGSPF | ||||||
Compositional bias | 217-231 | Pro residues | ||||
Sequence: QMPADTPPPAYLPPE | ||||||
Domain | 271-465 | MH2 | ||||
Sequence: WCSIVYYELNNRVGEAFHASSTSVLVDGFTDPSNNKNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECLSDSSIFVQSRNCNYHHGFHPTTVCKIPSGCSLKIFNNQEFAQLLAQSVNHGFETVYELTKMCTIRMSFVKGWGAEYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS | ||||||
Region | 418-428 | L3 loop | ||||
Sequence: KGWGAEYHRQD |
Domain
The MH2 domain mediates phosphorylation-dependent trimerization through L3 loop binding of phosphoserines in the adjacent subunit.
Sequence similarities
Belongs to the dwarfin/SMAD family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length465
- Mass (Da)52,157
- Last updated2011-07-27 v2
- Checksum07A56FBEE79A1C2A
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q8C3Y6 | Q8C3Y6_MOUSE | Smad1 | 428 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 95 | in Ref. 1; AAC52785 and 3; AAG41407 | ||||
Sequence: P → S | ||||||
Sequence conflict | 142 | in Ref. 1; AAC52785 and 3; AAG41407 | ||||
Sequence: R → K | ||||||
Compositional bias | 171-216 | Polar residues | ||||
Sequence: TFPDSFQQPNSHPFPHSPNSSYPNSPGGSSSTYPHSPTSSDPGSPF | ||||||
Sequence conflict | 199-200 | in Ref. 2; AAB18256 | ||||
Sequence: SS → QG | ||||||
Compositional bias | 217-231 | Pro residues | ||||
Sequence: QMPADTPPPAYLPPE | ||||||
Sequence conflict | 393 | in Ref. 2; AAB18256 | ||||
Sequence: A → E |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U58992 EMBL· GenBank· DDBJ | AAC52785.1 EMBL· GenBank· DDBJ | mRNA | ||
U74359 EMBL· GenBank· DDBJ | AAB18256.1 EMBL· GenBank· DDBJ | mRNA | ||
AF295768 EMBL· GenBank· DDBJ | AAG41407.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF295763 EMBL· GenBank· DDBJ | AAG41407.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF295764 EMBL· GenBank· DDBJ | AAG41407.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF295765 EMBL· GenBank· DDBJ | AAG41407.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF295766 EMBL· GenBank· DDBJ | AAG41407.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF295767 EMBL· GenBank· DDBJ | AAG41407.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK017583 EMBL· GenBank· DDBJ | BAB30820.1 EMBL· GenBank· DDBJ | mRNA | ||
AK054104 EMBL· GenBank· DDBJ | BAC35658.1 EMBL· GenBank· DDBJ | mRNA | ||
BC058693 EMBL· GenBank· DDBJ | AAH58693.1 EMBL· GenBank· DDBJ | mRNA |