UniProtKB - Q13485 (SMAD4_HUMAN)
Mothers against decapentaplegic homolog 4
SMAD4
Functioni
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 71 | ZincBy similarity | 1 | |
Metal bindingi | 115 | ZincBy similarity | 1 | |
Metal bindingi | 127 | ZincBy similarity | 1 | |
Metal bindingi | 132 | ZincBy similarity | 1 | |
Sitei | 515 | Necessary for heterotrimerization | 1 |
GO - Molecular functioni
- chromatin binding Source: Ensembl
- collagen binding Source: Ensembl
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- identical protein binding Source: IntAct
- I-SMAD binding Source: BHF-UCL
- metal ion binding Source: UniProtKB-KW
- protein homodimerization activity Source: BHF-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II transcription factor binding Source: Ensembl
- R-SMAD binding Source: BHF-UCL
- sulfate binding Source: CAFA
- transcription coactivator binding Source: UniProtKB
- transcription factor binding Source: GO_Central
- transcription regulatory region sequence-specific DNA binding Source: BHF-UCL
- ubiquitin protein ligase binding Source: GO_Central
GO - Biological processi
- anatomical structure morphogenesis Source: GO_Central
- atrioventricular canal development Source: BHF-UCL
- atrioventricular valve formation Source: BHF-UCL
- axon guidance Source: Ensembl
- BMP signaling pathway Source: BHF-UCL
- brainstem development Source: Ensembl
- branching involved in ureteric bud morphogenesis Source: Ensembl
- cell differentiation Source: GO_Central
- cell population proliferation Source: Ensembl
- cellular iron ion homeostasis Source: BHF-UCL
- cellular response to BMP stimulus Source: BHF-UCL
- developmental growth Source: Ensembl
- embryonic digit morphogenesis Source: Ensembl
- endocardial cell differentiation Source: BHF-UCL
- endoderm development Source: Ensembl
- endothelial cell activation Source: Ensembl
- epithelial to mesenchymal transition involved in endocardial cushion formation Source: Ensembl
- female gonad morphogenesis Source: Ensembl
- formation of anatomical boundary Source: Ensembl
- gastrulation with mouth forming second Source: Ensembl
- interleukin-6-mediated signaling pathway Source: BHF-UCL
- intracellular signal transduction Source: CACAO
- in utero embryonic development Source: Ensembl
- left ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
- mesoderm development Source: Ensembl
- metanephric mesenchyme morphogenesis Source: Ensembl
- negative regulation of cardiac muscle hypertrophy Source: BHF-UCL
- negative regulation of cardiac myofibril assembly Source: BHF-UCL
- negative regulation of cell death Source: Ensembl
- negative regulation of cell growth Source: BHF-UCL
- negative regulation of cell population proliferation Source: Ensembl
- negative regulation of ERK1 and ERK2 cascade Source: BHF-UCL
- negative regulation of transcription, DNA-templated Source: BHF-UCL
- negative regulation of transcription by RNA polymerase II Source: BHF-UCL
- nephrogenic mesenchyme morphogenesis Source: Ensembl
- neural crest cell differentiation Source: Ensembl
- neuron fate commitment Source: Ensembl
- outflow tract septum morphogenesis Source: BHF-UCL
- ovarian follicle development Source: Ensembl
- positive regulation of BMP signaling pathway Source: BHF-UCL
- positive regulation of cell proliferation involved in heart valve morphogenesis Source: BHF-UCL
- positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
- positive regulation of follicle-stimulating hormone secretion Source: Ensembl
- positive regulation of histone H3-K4 methylation Source: BHF-UCL
- positive regulation of histone H3-K9 acetylation Source: BHF-UCL
- positive regulation of luteinizing hormone secretion Source: Ensembl
- positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: Ensembl
- positive regulation of SMAD protein signal transduction Source: BHF-UCL
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
- positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
- protein deubiquitination Source: Reactome
- regulation of binding Source: Ensembl
- regulation of hair follicle development Source: Ensembl
- regulation of transforming growth factor beta2 production Source: BHF-UCL
- regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
- response to hypoxia Source: BHF-UCL
- response to transforming growth factor beta Source: UniProtKB
- sebaceous gland development Source: Ensembl
- secondary palate development Source: BHF-UCL
- seminiferous tubule development Source: Ensembl
- single fertilization Source: Ensembl
- SMAD protein complex assembly Source: BHF-UCL
- SMAD protein signal transduction Source: BHF-UCL
- somatic stem cell population maintenance Source: Reactome
- somite rostral/caudal axis specification Source: Ensembl
- spermatogenesis Source: Ensembl
- transforming growth factor beta receptor signaling pathway Source: BHF-UCL
- uterus development Source: Ensembl
- ventricular septum morphogenesis Source: BHF-UCL
Keywordsi
Molecular function | DNA-binding |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q13485 |
Reactomei | R-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 R-HSA-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes R-HSA-9617828, FOXO-mediated transcription of cell cycle genes |
SignaLinki | Q13485 |
SIGNORi | Q13485 |
Names & Taxonomyi
Protein namesi | Recommended name: Mothers against decapentaplegic homolog 4Short 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000141646.13 |
HGNCi | HGNC:6770, SMAD4 |
MIMi | 600993, gene |
neXtProti | NX_Q13485 |
Subcellular locationi
Cytoskeleton
- centrosome Source: HPA
Cytosol
- cytosol Source: HPA
Nucleus
- heteromeric SMAD protein complex Source: GO_Central
- nuclear chromatin Source: BHF-UCL
- nucleoplasm Source: HPA
- nucleus Source: BHF-UCL
Other locations
- activin responsive factor complex Source: BHF-UCL
- cytoplasm Source: BHF-UCL
- SMAD protein complex Source: UniProtKB
- transcription regulator complex Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Pancreatic cancer (PNCA)1 Publication
Juvenile polyposis syndrome (JPS)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022833 | 330 | E → G in JPS. 1 PublicationCorresponds to variant dbSNP:rs281875324EnsemblClinVar. | 1 | |
Natural variantiVAR_019571 | 352 | G → R in JP/HHT and JPS. 2 PublicationsCorresponds to variant dbSNP:rs121912581EnsemblClinVar. | 1 | |
Natural variantiVAR_019572 | 361 | R → C in JPS. 1 PublicationCorresponds to variant dbSNP:rs80338963EnsemblClinVar. | 1 |
Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019571 | 352 | G → R in JP/HHT and JPS. 2 PublicationsCorresponds to variant dbSNP:rs121912581EnsemblClinVar. | 1 | |
Natural variantiVAR_019573 | 386 | G → D in JP/HHT. 1 PublicationCorresponds to variant dbSNP:rs121912580EnsemblClinVar. | 1 |
Colorectal cancer (CRC)1 Publication
Myhre syndrome (MYHRS)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_067602 | 500 | I → M in MYHRS. 1 PublicationCorresponds to variant dbSNP:rs281875320EnsemblClinVar. | 1 | |
Natural variantiVAR_067603 | 500 | I → 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_067604 | 500 | I → V in MYHRS. 2 PublicationsCorresponds to variant dbSNP:rs281875322EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 416 | R → S: No effect on heterotrimerization. Partially diminished transcriptional activation. 1 Publication | 1 | |
Mutagenesisi | 496 | R → S: No effect on heterotrimerization. Partially diminished transcriptional activation. | 1 | |
Mutagenesisi | 502 | R → S: No effect on heterotrimerization. Greatly reduced transcriptional activation. 1 Publication | 1 | |
Mutagenesisi | 515 | R → S: Reduced heterotrimerization. 1 Publication | 1 | |
Mutagenesisi | 519 | K → R: Abolishes ubiquitination. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 4089 |
GeneReviewsi | SMAD4 |
MalaCardsi | SMAD4 |
MIMi | 114500, phenotype 139210, phenotype 174900, phenotype 175050, phenotype 260350, phenotype |
OpenTargetsi | ENSG00000141646 |
Orphaneti | 1333, Familial pancreatic carcinoma 91387, Familial thoracic aortic aneurysm and aortic dissection 329971, Generalized juvenile polyposis/juvenile polyposis coli 774, Hereditary hemorrhagic telangiectasia 2588, Myhre syndrome |
PharmGKBi | PA30527 |
Miscellaneous databases
Pharosi | Q13485, Tbio |
Polymorphism and mutation databases
BioMutai | SMAD4 |
DMDMi | 13959561 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000090861 | 1 – 552 | Mothers against decapentaplegic homolog 4Add BLAST | 552 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 37 | N6-acetyllysineCombined sources | 1 | |
Cross-linki | 113 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 428 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 507 | N6-acetyllysineCombined sources | 1 | |
Cross-linki | 519 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-1268 CPTAC-1269 |
EPDi | Q13485 |
jPOSTi | Q13485 |
MassIVEi | Q13485 |
MaxQBi | Q13485 |
PaxDbi | Q13485 |
PeptideAtlasi | Q13485 |
PRIDEi | Q13485 |
ProteomicsDBi | 59479 |
PTM databases
iPTMneti | Q13485 |
MetOSitei | Q13485 |
PhosphoSitePlusi | Q13485 |
SwissPalmi | Q13485 |
Expressioni
Gene expression databases
Bgeei | ENSG00000141646, Expressed in kidney and 238 other tissues |
ExpressionAtlasi | Q13485, baseline and differential |
Genevisiblei | Q13485, HS |
Organism-specific databases
HPAi | ENSG00000141646, Low tissue specificity |
Interactioni
Subunit structurei
Monomer; in the absence of TGF-beta activation (PubMed:9670020). Heterotrimer; on TGF-beta activation (PubMed:15799969). Heterotrimer 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 (PubMed:15799969, PubMed:15350224).
Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP.
Found in a complex with SMAD1 and YY1 (By similarity).
Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267).
Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes.
Interacts with USP9X.
Interacts (via the MH1 and MH2 domains) with RBPMS.
Interacts with WWTR1 (via coiled-coil domain).
Interacts with CITED1 and CITED2.
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 (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (PubMed:24324267).
Interacts with ZC3H3 (By similarity).
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).
Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (PubMed:16777850).
By similarity23 PublicationsBinary interactionsi
Hide detailsQ13485
GO - Molecular functioni
- identical protein binding Source: IntAct
- I-SMAD binding Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- RNA polymerase II transcription factor binding Source: Ensembl
- R-SMAD binding Source: BHF-UCL
- transcription coactivator binding Source: UniProtKB
- transcription factor binding Source: GO_Central
- ubiquitin protein ligase binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 110264, 243 interactors |
ComplexPortali | CPX-1, SMAD2-SMAD3-SMAD4 complex CPX-3208, SMAD2-SMAD4 complex CPX-3252, SMAD3-SMAD4 complex CPX-54, SMAD1-SMAD4 complex |
CORUMi | Q13485 |
DIPi | DIP-31512N |
IntActi | Q13485, 125 interactors |
MINTi | Q13485 |
STRINGi | 9606.ENSP00000341551 |
Miscellaneous databases
RNActi | Q13485, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q13485 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13485 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 18 – 142 | MH1PROSITE-ProRule annotationAdd BLAST | 125 | |
Domaini | 323 – 552 | MH2PROSITE-ProRule annotationAdd BLAST | 230 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 322 | Mediates interaction with ZBTB7A1 PublicationAdd BLAST | 322 | |
Regioni | 275 – 320 | SADAdd BLAST | 46 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 451 – 466 | Poly-AlaAdd BLAST | 16 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3701, Eukaryota |
GeneTreei | ENSGT00940000157435 |
InParanoidi | Q13485 |
OMAi | GPPAHMY |
OrthoDBi | 905048at2759 |
PhylomeDBi | Q13485 |
TreeFami | TF314923 |
Family and domain databases
DisProti | DP00464 |
Gene3Di | 2.60.200.10, 1 hit 3.90.520.10, 1 hit |
IDEALi | IID00132 |
InterProi | View 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 |
PANTHERi | PTHR13703, PTHR13703, 1 hit |
Pfami | View protein in Pfam PF03165, MH1, 1 hit PF03166, MH2, 1 hit |
SMARTi | View protein in SMART SM00523, DWA, 1 hit SM00524, DWB, 1 hit |
SUPFAMi | SSF49879, SSF49879, 1 hit SSF56366, SSF56366, 1 hit |
PROSITEi | View protein in PROSITE PS51075, MH1, 1 hit PS51076, MH2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7EIU8 | K7EIU8_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 456 | Annotation score: | ||
K7ES96 | K7ES96_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 320 | Annotation score: | ||
K7EIJ2 | K7EIJ2_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 140 | Annotation score: | ||
K7EL15 | K7EL15_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 120 | Annotation score: | ||
K7EL18 | K7EL18_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 126 | Annotation score: | ||
K7ENG1 | K7ENG1_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 90 | Annotation score: | ||
A0A087WUF3 | A0A087WUF3_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 220 | Annotation score: | ||
K7ELK2 | K7ELK2_HUMAN | Mothers against decapentaplegic hom... | SMAD4 | 82 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066870 | 13 | N → S Rare variant; found in a patient with pulmonary hypertension; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs281875323EnsemblClinVar. | 1 | |
Natural variantiVAR_036475 | 130 | P → S in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1555685186EnsemblClinVar. | 1 | |
Natural variantiVAR_022833 | 330 | E → G in JPS. 1 PublicationCorresponds to variant dbSNP:rs281875324EnsemblClinVar. | 1 | |
Natural variantiVAR_036476 | 351 | D → N in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1057519739EnsemblClinVar. | 1 | |
Natural variantiVAR_019571 | 352 | G → R in JP/HHT and JPS. 2 PublicationsCorresponds to variant dbSNP:rs121912581EnsemblClinVar. | 1 | |
Natural variantiVAR_019572 | 361 | R → C in JPS. 1 PublicationCorresponds to variant dbSNP:rs80338963EnsemblClinVar. | 1 | |
Natural variantiVAR_036477 | 361 | R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs377767347EnsemblClinVar. | 1 | |
Natural variantiVAR_019573 | 386 | G → D in JP/HHT. 1 PublicationCorresponds to variant dbSNP:rs121912580EnsemblClinVar. | 1 | |
Natural variantiVAR_011380 | 493 | D → H in pancreatic carcinoma. 1 PublicationCorresponds to variant dbSNP:rs121912578EnsemblClinVar. | 1 | |
Natural variantiVAR_067602 | 500 | I → M in MYHRS. 1 PublicationCorresponds to variant dbSNP:rs281875320EnsemblClinVar. | 1 | |
Natural variantiVAR_067603 | 500 | I → 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_067604 | 500 | I → 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 |
CCDSi | CCDS11950.1 |
PIRi | S71811 |
RefSeqi | NP_005350.1, NM_005359.5 |
Genome annotation databases
Ensembli | ENST00000342988; ENSP00000341551; ENSG00000141646 ENST00000398417; ENSP00000381452; ENSG00000141646 |
GeneIDi | 4089 |
KEGGi | hsa:4089 |
UCSCi | uc010xdp.3, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar 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 |
CCDSi | CCDS11950.1 |
PIRi | S71811 |
RefSeqi | NP_005350.1, NM_005359.5 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1DD1 | X-ray | 2.62 | A/B/C | 285-552 | [»] | |
1G88 | X-ray | 3.00 | A/B/C | 285-552 | [»] | |
1MR1 | X-ray | 2.85 | A/B | 319-552 | [»] | |
1U7F | X-ray | 2.60 | B | 314-552 | [»] | |
1U7V | X-ray | 2.70 | B | 314-549 | [»] | |
1YGS | X-ray | 2.10 | A | 319-552 | [»] | |
5C4V | X-ray | 2.60 | A/C/E | 314-549 | [»] | |
5MEY | X-ray | 2.05 | A | 10-140 | [»] | |
5MEZ | X-ray | 2.98 | A/B | 10-140 | [»] | |
5MF0 | X-ray | 3.03 | A/B | 10-140 | [»] | |
5UWU | X-ray | 2.24 | D | 133-149 | [»] | |
SMRi | Q13485 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110264, 243 interactors |
ComplexPortali | CPX-1, SMAD2-SMAD3-SMAD4 complex CPX-3208, SMAD2-SMAD4 complex CPX-3252, SMAD3-SMAD4 complex CPX-54, SMAD1-SMAD4 complex |
CORUMi | Q13485 |
DIPi | DIP-31512N |
IntActi | Q13485, 125 interactors |
MINTi | Q13485 |
STRINGi | 9606.ENSP00000341551 |
PTM databases
iPTMneti | Q13485 |
MetOSitei | Q13485 |
PhosphoSitePlusi | Q13485 |
SwissPalmi | Q13485 |
Polymorphism and mutation databases
BioMutai | SMAD4 |
DMDMi | 13959561 |
Proteomic databases
CPTACi | CPTAC-1268 CPTAC-1269 |
EPDi | Q13485 |
jPOSTi | Q13485 |
MassIVEi | Q13485 |
MaxQBi | Q13485 |
PaxDbi | Q13485 |
PeptideAtlasi | Q13485 |
PRIDEi | Q13485 |
ProteomicsDBi | 59479 |
Protocols and materials databases
Antibodypediai | 3711, 1029 antibodies |
DNASUi | 4089 |
Genome annotation databases
Ensembli | ENST00000342988; ENSP00000341551; ENSG00000141646 ENST00000398417; ENSP00000381452; ENSG00000141646 |
GeneIDi | 4089 |
KEGGi | hsa:4089 |
UCSCi | uc010xdp.3, human |
Organism-specific databases
CTDi | 4089 |
DisGeNETi | 4089 |
EuPathDBi | HostDB:ENSG00000141646.13 |
GeneCardsi | SMAD4 |
GeneReviewsi | SMAD4 |
HGNCi | HGNC:6770, SMAD4 |
HPAi | ENSG00000141646, Low tissue specificity |
MalaCardsi | SMAD4 |
MIMi | 114500, phenotype 139210, phenotype 174900, phenotype 175050, phenotype 260350, phenotype 600993, gene |
neXtProti | NX_Q13485 |
OpenTargetsi | ENSG00000141646 |
Orphaneti | 1333, Familial pancreatic carcinoma 91387, Familial thoracic aortic aneurysm and aortic dissection 329971, Generalized juvenile polyposis/juvenile polyposis coli 774, Hereditary hemorrhagic telangiectasia 2588, Myhre syndrome |
PharmGKBi | PA30527 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3701, Eukaryota |
GeneTreei | ENSGT00940000157435 |
InParanoidi | Q13485 |
OMAi | GPPAHMY |
OrthoDBi | 905048at2759 |
PhylomeDBi | Q13485 |
TreeFami | TF314923 |
Enzyme and pathway databases
PathwayCommonsi | Q13485 |
Reactomei | R-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 R-HSA-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes R-HSA-9617828, FOXO-mediated transcription of cell cycle genes |
SignaLinki | Q13485 |
SIGNORi | Q13485 |
Miscellaneous databases
BioGRID-ORCSi | 4089, 47 hits in 881 CRISPR screens |
ChiTaRSi | SMAD4, human |
EvolutionaryTracei | Q13485 |
GeneWikii | Mothers_against_decapentaplegic_homolog_4 |
GenomeRNAii | 4089 |
Pharosi | Q13485, Tbio |
PROi | PR:Q13485 |
RNActi | Q13485, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000141646, Expressed in kidney and 238 other tissues |
ExpressionAtlasi | Q13485, baseline and differential |
Genevisiblei | Q13485, HS |
Family and domain databases
DisProti | DP00464 |
Gene3Di | 2.60.200.10, 1 hit 3.90.520.10, 1 hit |
IDEALi | IID00132 |
InterProi | View 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 |
PANTHERi | PTHR13703, PTHR13703, 1 hit |
Pfami | View protein in Pfam PF03165, MH1, 1 hit PF03166, MH2, 1 hit |
SMARTi | View protein in SMART SM00523, DWA, 1 hit SM00524, DWB, 1 hit |
SUPFAMi | SSF49879, SSF49879, 1 hit SSF56366, SSF56366, 1 hit |
PROSITEi | View protein in PROSITE PS51075, MH1, 1 hit PS51076, MH2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SMAD4_HUMAN | |
Accessioni | Q13485Primary (citable) accession number: Q13485 Secondary accession number(s): A8K405 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 4, 2001 |
Last sequence update: | November 1, 1996 | |
Last modified: | December 2, 2020 | |
This is version 231 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations