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UniProtKB - Q13485 (SMAD4_HUMAN)

Protein

Mothers against decapentaplegic homolog 4

Gene

SMAD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi71ZincBy similarity1
Metal bindingi115ZincBy similarity1
Metal bindingi127ZincBy similarity1
Metal bindingi132ZincBy similarity1
Sitei515Necessary for heterotrimerization1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1181150 Signaling by NODAL
R-HSA-1502540 Signaling by Activin
R-HSA-201451 Signaling by BMP
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-3311021 SMAD4 MH2 Domain Mutants in Cancer
R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-5689880 Ub-specific processing proteases
R-HSA-8941326 RUNX2 regulates bone development
R-HSA-8941855 RUNX3 regulates CDKN1A transcription
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
SignaLinkiQ13485
SIGNORiQ13485

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 4
Short name:
MAD homolog 4
Short name:
Mothers against DPP homolog 4
Alternative name(s):
Deletion target in pancreatic carcinoma 4
SMAD family member 4
Short name:
SMAD 4
Short name:
Smad4
Short name:
hSMAD4
Gene namesi
Name:SMAD4
Synonyms:DPC4, MADH4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000141646.13
HGNCiHGNC:6770 SMAD4
MIMi600993 gene
neXtProtiNX_Q13485

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Pancreatic cancer (PNCA)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
See also OMIM:260350
Juvenile polyposis syndrome (JPS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers.
See also OMIM:174900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022833330E → G in JPS. 1 PublicationCorresponds to variant dbSNP:rs281875324EnsemblClinVar.1
Natural variantiVAR_019572361R → C in JPS. 1 PublicationCorresponds to variant dbSNP:rs80338963EnsemblClinVar.1
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionJP/HHT syndrome phenotype consists of the coexistence of juvenile polyposis (JIP) and hereditary hemorrhagic telangiectasia (HHT) [MIM:187300] in a single individual. JIP and HHT are autosomal dominant disorders with distinct and non-overlapping clinical features. The former, an inherited gastrointestinal malignancy predisposition, is caused by mutations in SMAD4 or BMPR1A, and the latter is a vascular malformation disorder caused by mutations in ENG or ACVRL1. All four genes encode proteins involved in the transforming-growth-factor-signaling pathway. Although there are reports of patients and families with phenotypes of both disorders combined, the genetic etiology of this association is unknown.
See also OMIM:175050
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019573386G → D in JP/HHT. 1 PublicationCorresponds to variant dbSNP:rs121912580EnsemblClinVar.1
Colorectal cancer (CRC)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also OMIM:114500
SMAD4 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.1 Publication
Myhre syndrome (MYHRS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by pre- and postnatal growth deficiency, mental retardation, generalized muscle hypertrophy and striking muscular build, decreased joint mobility, cryptorchidism, and unusual facies. Dysmorphic facial features include microcephaly, midface hypoplasia, prognathism, and blepharophimosis. Typical skeletal anomalies are short stature, square body shape, broad ribs, iliac hypoplasia, brachydactyly, flattened vertebrae, and thickened calvaria. Other features, such as congenital heart disease, may also occur.
See also OMIM:139210
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067602500I → M in MYHRS. 1 PublicationCorresponds to variant dbSNP:rs281875320EnsemblClinVar.1
Natural variantiVAR_067603500I → T in MYHRS; there is an enhanced levels of SMAD4 protein with lower levels of ubiquitinated SMAD4 fibroblasts compared to controls suggesting stabilization of the mutant protein; 8-fold increase in phosphorylated SMAD2 and SMAD3; 11-fold increase in phosphorylated SMAD1, SMAD5 and SMAD8 in cell nuclei compared to controls. 2 PublicationsCorresponds to variant dbSNP:rs281875321EnsemblClinVar.1
Natural variantiVAR_067604500I → V in MYHRS. 2 PublicationsCorresponds to variant dbSNP:rs281875322EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi416R → S: No effect on heterotrimerization. Partially diminished transcriptional activation. 1 Publication1
Mutagenesisi496R → S: No effect on heterotrimerization. Partially diminished transcriptional activation. 1
Mutagenesisi502R → S: No effect on heterotrimerization. Greatly reduced transcriptional activation. 1 Publication1
Mutagenesisi515R → S: Reduced heterotrimerization. 1 Publication1
Mutagenesisi519K → R: Abolishes ubiquitination. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4089
GeneReviewsiSMAD4
MalaCardsiSMAD4
MIMi114500 phenotype
139210 phenotype
174900 phenotype
175050 phenotype
260350 phenotype
OpenTargetsiENSG00000141646
Orphaneti1333 Familial pancreatic carcinoma
329971 Generalized juvenile polyposis/juvenile polyposis coli
774 Hereditary hemorrhagic telangiectasia
2588 Myhre syndrome
PharmGKBiPA30527

Polymorphism and mutation databases

BioMutaiSMAD4
DMDMi13959561

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000908611 – 552Mothers against decapentaplegic homolog 4Add BLAST552

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei37N6-acetyllysineCombined sources1
Cross-linki113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei428N6-acetyllysineCombined sources1
Modified residuei507N6-acetyllysineCombined sources1
Cross-linki519Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Phosphorylated by PDPK1.1 Publication
Monoubiquitinated on Lys-519 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination by USP9X restores its competence to mediate TGF-beta signaling.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13485
MaxQBiQ13485
PaxDbiQ13485
PeptideAtlasiQ13485
PRIDEiQ13485
ProteomicsDBi59479

PTM databases

iPTMnetiQ13485
PhosphoSitePlusiQ13485

Expressioni

Gene expression databases

BgeeiENSG00000141646 Expressed in 224 organ(s), highest expression level in kidney
CleanExiHS_SMAD4
ExpressionAtlasiQ13485 baseline and differential
GenevisibleiQ13485 HS

Organism-specific databases

HPAiHPA019154

Interactioni

Subunit structurei

Found in a complex with SMAD1 and YY1 (By similarity). Interacts with CITED2 (By similarity). Monomer; in the absence of TGF-beta activation. Heterodimer; on TGF-beta activation. Composed of two molecules of a C-terminally phosphorylated R-SMAD molecule, SMAD2 or SMAD3, and one molecule of SMAD4 to form the transcriptional active SMAD2/SMAD3-SMAD4 complex. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Interacts with ZNF423; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with ZNF521; the interaction takes place in response to BMP2 leading to activation of transcription of BMP target genes. Interacts with USP9X. Interacts (via the MH1 and MH2 domains) with RBPMS. Interacts with WWTR1 (via coiled-coil domain). Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. Interacts with CITED1. Interacts with PDPK1 (via PH domain) (By similarity). Interacts with VPS39; this interaction affects heterodimer formation with SMAD3, but not with SMAD2, and leads to inhibition of SMAD3-dependent transcription activation. Interactions with VPS39 and SMAD2 may be mutually exclusive. Interacts with ZC3H3 (By similarity). Interacts (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with NUP93 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (PubMed:26878725). Interacts with CREB3L1, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in the assembly of collagen extracellular matrix (PubMed:25310401). Interacts with DLX1 (PubMed:14671321). Interacts with ZBTB7A; the interaction is direct and stimulated by TGFB1 (PubMed:25514493). Interacts with CREBBP; the recruitment of this transcriptional coactivator is negatively regulated by ZBTB7A (PubMed:25514493). Interacts with EP300; the interaction with this transcriptional coactivator is negatively regulated by ZBTB7A (PubMed:25514493). Interacts with HDAC1 (PubMed:25514493).By similarity22 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi110264, 226 interactors
ComplexPortaliCPX-1 SMAD2-SMAD3-SMAD4 complex
CPX-3208 SMAD2-SMAD4 complex
CPX-3252 SMAD3-SMAD4 complex
CPX-54 SMAD1-SMAD4 complex
CORUMiQ13485
DIPiDIP-31512N
IntActiQ13485, 122 interactors
MINTiQ13485
STRINGi9606.ENSP00000341551

Structurei

Secondary structure

1552
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00464
ProteinModelPortaliQ13485
SMRiQ13485
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13485

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 142MH1PROSITE-ProRule annotationAdd BLAST125
Domaini323 – 552MH2PROSITE-ProRule annotationAdd BLAST230

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 322Mediates interaction with ZBTB7A1 PublicationAdd BLAST322
Regioni275 – 320SADAdd BLAST46

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi451 – 466Poly-AlaAdd BLAST16

Domaini

The MH1 domain is required for DNA binding.
The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

eggNOGiKOG3701 Eukaryota
ENOG410XQKU LUCA
GeneTreeiENSGT00760000119091
HOGENOMiHOG000286019
HOVERGENiHBG053353
InParanoidiQ13485
KOiK04501
OMAiPQMGPGT
OrthoDBiEOG091G05Z9
PhylomeDBiQ13485
TreeFamiTF314923

Family and domain databases

Gene3Di2.60.200.10, 1 hit
3.90.520.10, 1 hit
InterProiView protein in InterPro
IPR013790 Dwarfin
IPR003619 MAD_homology1_Dwarfin-type
IPR013019 MAD_homology_MH1
IPR017855 SMAD-like_dom_sf
IPR001132 SMAD_dom_Dwarfin-type
IPR008984 SMAD_FHA_dom_sf
IPR036578 SMAD_MH1_sf
PANTHERiPTHR13703 PTHR13703, 1 hit
PfamiView protein in Pfam
PF03165 MH1, 1 hit
PF03166 MH2, 1 hit
SMARTiView protein in SMART
SM00523 DWA, 1 hit
SM00524 DWB, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF56366 SSF56366, 1 hit
PROSITEiView protein in PROSITE
PS51075 MH1, 1 hit
PS51076 MH2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 9 potential isoforms that are computationally mapped.Show allAlign All

Q13485-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK 
        60         70         80         90        100
KDELDSLITA ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR 
       110        120        130        140        150
WPDLHKNELK HVKYCQYAFD LKCDSVCVNP YHYERVVSPG IDLSGLTLQS 
       160        170        180        190        200
NAPSSMMVKD EYVHDFEGQP SLSTEGHSIQ TIQHPPSNRA STETYSTPAL 
       210        220        230        240        250
LAPSESNATS TANFPNIPVA STSQPASILG GSHSEGLLQI ASGPQPGQQQ 
       260        270        280        290        300
NGFTGQPATY HHNSTTTWTG SRTAPYTPNL PHHQNGHLQH HPPMPPHPGH 
       310        320        330        340        350
YWPVHNELAF QPPISNHPAP EYWCSIAYFE MDVQVGETFK VPSSCPIVTV 
       360        370        380        390        400
DGYVDPSGGD RFCLGQLSNV HRTEAIERAR LHIGKGVQLE CKGEGDVWVR 
       410        420        430        440        450
CLSDHAVFVQ SYYLDREAGR APGDAVHKIY PSAYIKVFDL RQCHRQMQQQ 
       460        470        480        490        500
AATAQAAAAA QAAAVAGNIP GPGSVGGIAP AISLSAAAGI GVDDLRRLCI 
       510        520        530        540        550
LRMSFVKGWG PDYPRQSIKE TPCWIEIHLH RALQLLDEVL HTMPIADPQP 

LD
Length:552
Mass (Da):60,439
Last modified:November 1, 1996 - v1
Checksum:i7EE3C4647712DA90
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7EIU8K7EIU8_HUMAN
Mothers against decapentaplegic hom...
SMAD4
456Annotation score:
K7ENG8K7ENG8_HUMAN
Mothers against decapentaplegic hom...
SMAD4
151Annotation score:
K7ES96K7ES96_HUMAN
Mothers against decapentaplegic hom...
SMAD4
320Annotation score:
K7EL15K7EL15_HUMAN
Mothers against decapentaplegic hom...
SMAD4
120Annotation score:
K7EIJ2K7EIJ2_HUMAN
Mothers against decapentaplegic hom...
SMAD4
140Annotation score:
K7EL18K7EL18_HUMAN
Mothers against decapentaplegic hom...
SMAD4
126Annotation score:
K7ENG1K7ENG1_HUMAN
Mothers against decapentaplegic hom...
SMAD4
90Annotation score:
K7ELK2K7ELK2_HUMAN
Mothers against decapentaplegic hom...
SMAD4
82Annotation score:
A0A087WUF3A0A087WUF3_HUMAN
Mothers against decapentaplegic hom...
SMAD4
220Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06687013N → S Rare variant; found in a patient with pulmonary hypertension; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs281875323EnsemblClinVar.1
Natural variantiVAR_036475130P → S in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_022833330E → G in JPS. 1 PublicationCorresponds to variant dbSNP:rs281875324EnsemblClinVar.1
Natural variantiVAR_036476351D → N in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_019571352G → R in JP/HHT and JPS. 2 PublicationsCorresponds to variant dbSNP:rs121912581EnsemblClinVar.1
Natural variantiVAR_019572361R → C in JPS. 1 PublicationCorresponds to variant dbSNP:rs80338963EnsemblClinVar.1
Natural variantiVAR_036477361R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs377767347EnsemblClinVar.1
Natural variantiVAR_019573386G → D in JP/HHT. 1 PublicationCorresponds to variant dbSNP:rs121912580EnsemblClinVar.1
Natural variantiVAR_011380493D → H in pancreatic carcinoma. 1 PublicationCorresponds to variant dbSNP:rs121912578EnsemblClinVar.1
Natural variantiVAR_067602500I → M in MYHRS. 1 PublicationCorresponds to variant dbSNP:rs281875320EnsemblClinVar.1
Natural variantiVAR_067603500I → T in MYHRS; there is an enhanced levels of SMAD4 protein with lower levels of ubiquitinated SMAD4 fibroblasts compared to controls suggesting stabilization of the mutant protein; 8-fold increase in phosphorylated SMAD2 and SMAD3; 11-fold increase in phosphorylated SMAD1, SMAD5 and SMAD8 in cell nuclei compared to controls. 2 PublicationsCorresponds to variant dbSNP:rs281875321EnsemblClinVar.1
Natural variantiVAR_067604500I → V in MYHRS. 2 PublicationsCorresponds to variant dbSNP:rs281875322EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045447
, AF045438, AF045439, AF045440, AF045441, AF045442, AF045443, AF045444, AF045445, AF045446 Genomic DNA Translation: AAC03051.1
U44378 mRNA Translation: AAA91041.1
AK290770 mRNA Translation: BAF83459.1
CH471096 Genomic DNA Translation: EAW62985.1
BC002379 mRNA Translation: AAH02379.1
CCDSiCCDS11950.1
PIRiS71811
RefSeqiNP_005350.1, NM_005359.5
UniGeneiHs.75862

Genome annotation databases

EnsembliENST00000342988; ENSP00000341551; ENSG00000141646
ENST00000398417; ENSP00000381452; ENSG00000141646
GeneIDi4089
KEGGihsa:4089
UCSCiuc010xdp.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Mendelian genes SMAD family member 4 (SMAD4)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045447
, AF045438, AF045439, AF045440, AF045441, AF045442, AF045443, AF045444, AF045445, AF045446 Genomic DNA Translation: AAC03051.1
U44378 mRNA Translation: AAA91041.1
AK290770 mRNA Translation: BAF83459.1
CH471096 Genomic DNA Translation: EAW62985.1
BC002379 mRNA Translation: AAH02379.1
CCDSiCCDS11950.1
PIRiS71811
RefSeqiNP_005350.1, NM_005359.5
UniGeneiHs.75862

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DD1X-ray2.62A/B/C285-552[»]
1G88X-ray3.00A/B/C285-552[»]
1MR1X-ray2.85A/B319-552[»]
1U7FX-ray2.60B314-552[»]
1U7VX-ray2.70B314-549[»]
1YGSX-ray2.10A319-552[»]
5C4VX-ray2.60A/C/E314-549[»]
5MEYX-ray2.05A10-140[»]
5MEZX-ray2.98A/B10-140[»]
5MF0X-ray3.03A/B10-140[»]
5UWUX-ray2.24D133-149[»]
DisProtiDP00464
ProteinModelPortaliQ13485
SMRiQ13485
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110264, 226 interactors
ComplexPortaliCPX-1 SMAD2-SMAD3-SMAD4 complex
CPX-3208 SMAD2-SMAD4 complex
CPX-3252 SMAD3-SMAD4 complex
CPX-54 SMAD1-SMAD4 complex
CORUMiQ13485
DIPiDIP-31512N
IntActiQ13485, 122 interactors
MINTiQ13485
STRINGi9606.ENSP00000341551

PTM databases

iPTMnetiQ13485
PhosphoSitePlusiQ13485

Polymorphism and mutation databases

BioMutaiSMAD4
DMDMi13959561

Proteomic databases

EPDiQ13485
MaxQBiQ13485
PaxDbiQ13485
PeptideAtlasiQ13485
PRIDEiQ13485
ProteomicsDBi59479

Protocols and materials databases

DNASUi4089
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342988; ENSP00000341551; ENSG00000141646
ENST00000398417; ENSP00000381452; ENSG00000141646
GeneIDi4089
KEGGihsa:4089
UCSCiuc010xdp.3 human

Organism-specific databases

CTDi4089
DisGeNETi4089
EuPathDBiHostDB:ENSG00000141646.13
GeneCardsiSMAD4
GeneReviewsiSMAD4
HGNCiHGNC:6770 SMAD4
HPAiHPA019154
MalaCardsiSMAD4
MIMi114500 phenotype
139210 phenotype
174900 phenotype
175050 phenotype
260350 phenotype
600993 gene
neXtProtiNX_Q13485
OpenTargetsiENSG00000141646
Orphaneti1333 Familial pancreatic carcinoma
329971 Generalized juvenile polyposis/juvenile polyposis coli
774 Hereditary hemorrhagic telangiectasia
2588 Myhre syndrome
PharmGKBiPA30527
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3701 Eukaryota
ENOG410XQKU LUCA
GeneTreeiENSGT00760000119091
HOGENOMiHOG000286019
HOVERGENiHBG053353
InParanoidiQ13485
KOiK04501
OMAiPQMGPGT
OrthoDBiEOG091G05Z9
PhylomeDBiQ13485
TreeFamiTF314923

Enzyme and pathway databases

ReactomeiR-HSA-1181150 Signaling by NODAL
R-HSA-1502540 Signaling by Activin
R-HSA-201451 Signaling by BMP
R-HSA-2173789 TGF-beta receptor signaling activates SMADs
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-3311021 SMAD4 MH2 Domain Mutants in Cancer
R-HSA-3315487 SMAD2/3 MH2 Domain Mutants in Cancer
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-5689880 Ub-specific processing proteases
R-HSA-8941326 RUNX2 regulates bone development
R-HSA-8941855 RUNX3 regulates CDKN1A transcription
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
SignaLinkiQ13485
SIGNORiQ13485

Miscellaneous databases

ChiTaRSiSMAD4 human
EvolutionaryTraceiQ13485
GeneWikiiMothers_against_decapentaplegic_homolog_4
GenomeRNAii4089
PROiPR:Q13485
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141646 Expressed in 224 organ(s), highest expression level in kidney
CleanExiHS_SMAD4
ExpressionAtlasiQ13485 baseline and differential
GenevisibleiQ13485 HS

Family and domain databases

Gene3Di2.60.200.10, 1 hit
3.90.520.10, 1 hit
InterProiView protein in InterPro
IPR013790 Dwarfin
IPR003619 MAD_homology1_Dwarfin-type
IPR013019 MAD_homology_MH1
IPR017855 SMAD-like_dom_sf
IPR001132 SMAD_dom_Dwarfin-type
IPR008984 SMAD_FHA_dom_sf
IPR036578 SMAD_MH1_sf
PANTHERiPTHR13703 PTHR13703, 1 hit
PfamiView protein in Pfam
PF03165 MH1, 1 hit
PF03166 MH2, 1 hit
SMARTiView protein in SMART
SM00523 DWA, 1 hit
SM00524 DWB, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF56366 SSF56366, 1 hit
PROSITEiView protein in PROSITE
PS51075 MH1, 1 hit
PS51076 MH2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSMAD4_HUMAN
AccessioniPrimary (citable) accession number: Q13485
Secondary accession number(s): A8K405
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 214 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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