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UniProtKB - P84022 (SMAD3_HUMAN)

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Protein

Mothers against decapentaplegic homolog 3

Gene

SMAD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.11 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei40Required for trimerization1
Sitei41Required for interaction with DNA and JUN and for functional cooperation with JUN1
Metal bindingi64Zinc1
Metal bindingi109Zinc1
Metal bindingi121Zinc1
Metal bindingi126Zinc1

GO - Molecular functioni

  • beta-catenin binding Source: Ensembl
  • bHLH transcription factor binding Source: BHF-UCL
  • chromatin DNA binding Source: Ensembl
  • collagen binding Source: Ensembl
  • core promoter proximal region sequence-specific DNA binding Source: UniProtKB
  • co-SMAD binding Source: BHF-UCL
  • DEAD/H-box RNA helicase binding Source: BHF-UCL
  • enhancer binding Source: BHF-UCL
  • glucocorticoid receptor binding Source: CAFA
  • identical protein binding Source: IntAct
  • mineralocorticoid receptor binding Source: CAFA
  • phosphatase binding Source: UniProtKB
  • primary miRNA binding Source: BHF-UCL
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: BHF-UCL
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • R-SMAD binding Source: UniProtKB
  • sequence-specific DNA binding Source: BHF-UCL
  • transcription factor activity, RNA polymerase II core promoter sequence-specific Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: BHF-UCL
  • transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: BHF-UCL
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: BHF-UCL
  • zinc ion binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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-2173788. Downregulation of TGF-beta receptor signaling.
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-3304356. SMAD2/3 Phosphorylation Motif Mutants in Cancer.
R-HSA-3311021. SMAD4 MH2 Domain Mutants in Cancer.
R-HSA-3315487. SMAD2/3 MH2 Domain Mutants in Cancer.
R-HSA-3656532. TGFBR1 KD Mutants in Cancer.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-8941855. RUNX3 regulates CDKN1A transcription.
R-HSA-8952158. RUNX3 regulates BCL2L11 (BIM) transcription.
SignaLinkiP84022.
SIGNORiP84022.

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 3
Short name:
MAD homolog 3
Short name:
Mad3
Short name:
Mothers against DPP homolog 3
Short name:
hMAD-3
Alternative name(s):
JV15-2
SMAD family member 3
Short name:
SMAD 3
Short name:
Smad3
Short name:
hSMAD3
Gene namesi
Name:SMAD3
Synonyms:MADH3
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 15

Organism-specific databases

HGNCiHGNC:6769. SMAD3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HPA
  • nuclear chromatin Source: BHF-UCL
  • nuclear inner membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • plasma membrane Source: Ensembl
  • receptor complex Source: BHF-UCL
  • SMAD2-SMAD3 protein complex Source: BHF-UCL
  • SMAD protein complex Source: UniProtKB
  • transcription factor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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
Loeys-Dietz syndrome 3 (LDS3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:21778426). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (PubMed:21778426), they have been classified as LDS3 by the OMIM resource.1 Publication
Disease descriptionAn aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation.
See also OMIM:613795
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067051112A → V in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906854Ensembl.1
Natural variantiVAR_067047239E → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906853Ensembl.1
Natural variantiVAR_065578261T → I in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906851Ensembl.1
Natural variantiVAR_067048279R → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906852Ensembl.1
Natural variantiVAR_065579287R → W in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906850Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi8T → V: Reduced phosphorylation, increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-179 and A-213. 1 Publication1
Mutagenesisi33K → R: Slightly decreased monoubiquitination. 1 Publication1
Mutagenesisi40K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-41; A-43 and A-44. 1 Publication1
Mutagenesisi41K → A: Greatly reduced interaction with DNA and JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-44 and A-43. 1 Publication1
Mutagenesisi43K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44. 1 Publication1
Mutagenesisi44K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with JUN; when associated with A-40; A-41 and A-43. 1 Publication1
Mutagenesisi53K → R: Slightly decreased monoubiquitination. 1 Publication1
Mutagenesisi74R → D: Reduced interaction with JUN. Loss of transcriptional activity and cooperation with JUN. 1 Publication1
Mutagenesisi81K → R: Decreased monoubiquitination. 1 Publication1
Mutagenesisi179T → V: Reduced phosphorylation, increased transcriptional and increased antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and A-213. 3 Publications1
Mutagenesisi204S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. 3 Publications1
Mutagenesisi208S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. 3 Publications1
Mutagenesisi213S → A: Reduced phosphorylation. Increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and V-179. 1 Publication1
Mutagenesisi333K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-341; R-378 and R-409. 1 Publication1
Mutagenesisi341K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-378 and R-409. 1 Publication1
Mutagenesisi378K → Q: Increased transcriptional activity. No further increase in transcriptional activity with EP300. 1 Publication1
Mutagenesisi378K → R: Greatly reduced acetylation and 85% reduction in transcriptional activity. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-409. 1 Publication1
Mutagenesisi409K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378. 1 Publication1
Mutagenesisi418S → A: Increased constitutive activity. 1 Publication1
Mutagenesisi418S → D: Decreased activity. 1 Publication1
Mutagenesisi422 – 425SSVS → AAVA: Does not abolish protein nuclear export. Abolishes almost completely acetylation. 3 Publications4
Mutagenesisi422 – 425SSVS → EEVE: Forms heterotrimers. 3 Publications4
Mutagenesisi422 – 425SSVS → RRVR: Diminishes cargo protein export. 3 Publications4

Keywords - Diseasei

Aortic aneurysm, Disease mutation

Organism-specific databases

DisGeNETi4088.
MalaCardsiSMAD3.
MIMi114500. phenotype.
613795. phenotype.
OpenTargetsiENSG00000166949.
Orphaneti284984. Aneurysm - osteoarthritis syndrome.
91387. Familial thoracic aortic aneurysm and aortic dissection.
PharmGKBiPA30526.

Chemistry databases

ChEMBLiCHEMBL1293258.

Polymorphism and mutation databases

BioMutaiSMAD3.
DMDMi51338669.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000908562 – 425Mothers against decapentaplegic homolog 3Add BLAST424

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei8Phosphothreonine; by CDK2 and CDK41 Publication1
Cross-linki33Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki81Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei179Phosphothreonine; by CDK2, CDK4 and MAPK3 Publications1
Modified residuei204Phosphoserine; by GSK3 and MAPKPROSITE-ProRule annotation3 Publications1
Modified residuei208Phosphoserine; by MAPKPROSITE-ProRule annotation3 Publications1
Modified residuei213Phosphoserine; by CDK2 and CDK4PROSITE-ProRule annotation1 Publication1
Modified residuei378N6-acetyllysine1 Publication1
Modified residuei416PhosphoserineCombined sources1
Modified residuei418Phosphoserine; by CK1PROSITE-ProRule annotation1 Publication1
Modified residuei422Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1
Modified residuei423Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1
Modified residuei425Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1

Post-translational modificationi

Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G1/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1.10 Publications
Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.1 Publication
Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.1 Publication
Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding (PubMed:21947082). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover (By similarity). Undergoes STUB1-mediated ubiquitination and degradation (PubMed:24613385).By similarity2 Publications

Keywords - PTMi

Acetylation, ADP-ribosylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP84022.
MaxQBiP84022.
PaxDbiP84022.
PeptideAtlasiP84022.
PRIDEiP84022.

PTM databases

iPTMnetiP84022.
PhosphoSitePlusiP84022.

Expressioni

Gene expression databases

BgeeiENSG00000166949.
CleanExiHS_SMAD3.
ExpressionAtlasiP84022. baseline and differential.
GenevisibleiP84022. HS.

Organism-specific databases

HPAiCAB008094.
CAB069409.
HPA046386.
HPA067203.

Interactioni

Subunit structurei

Monomer; in the absence of TGF-beta. Homooligomer; in the presence of TGF-beta. Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with TGFBR1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16, HGS, WWP1 and SNW1. Interacts (via MH2 domain) with CITED2 (via C-terminus). Interacts with NEDD4L; the interaction requires TGF-beta stimulation. Interacts (via the MH2 domain) with ZFYVE9. Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and TGFB1I1. Interacts with DACH1; the interaction inhibits the TGF-beta signaling. Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta. Found in a complex with SMAD3, RAN and XPO4. Interacts in the complex directly with XPO4. Interacts (via the MH2 domain) with LEMD3; the interaction represses SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus. Interacts with RBPMS. Interacts (via MH2 domain) with MECOM. Interacts with WWTR1 (via its coiled-coil domain). Interacts (via the linker region) with EP300 (C-terminal); the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation in the C-terminal of SMAD3. This interaction can be blocked by competitive binding of adenovirus oncoprotein E1A to the same C-terminal site on EP300, which then results in partially inhibited SMAD3/SMAD4 transcriptional activity. Interacts with SKI; the interaction represses SMAD3 transcriptional activity. 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 (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta. Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling. Interacts (dephosphorylated form via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling. Interacts with MEN1. Interacts with IL1F7. Interaction with CSNK1G2. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts with PMEPA1. Interacts with ZC3H3 (By similarity). Interacts with ZNF451 (PubMed:24324267). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts with ZFHX3. Interacts weakly with ZNF8 (PubMed:12370310). Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors (By similarity). Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (PubMed:24613385).By similarity43 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • beta-catenin binding Source: Ensembl
  • bHLH transcription factor binding Source: BHF-UCL
  • collagen binding Source: Ensembl
  • co-SMAD binding Source: BHF-UCL
  • DEAD/H-box RNA helicase binding Source: BHF-UCL
  • glucocorticoid receptor binding Source: CAFA
  • identical protein binding Source: IntAct
  • mineralocorticoid receptor binding Source: CAFA
  • phosphatase binding Source: UniProtKB
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: BHF-UCL
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • R-SMAD binding Source: UniProtKB
  • transcription factor binding Source: BHF-UCL
  • transforming growth factor beta receptor binding Source: BHF-UCL
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: BHF-UCL
Complete GO annotation...

Protein-protein interaction databases

BioGridi110263. 341 interactors.
DIPiDIP-29720N.
IntActiP84022. 179 interactors.
MINTiMINT-193987.
STRINGi9606.ENSP00000332973.

Chemistry databases

BindingDBiP84022.

Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 16Combined sources7
Helixi25 – 44Combined sources20
Helixi48 – 57Combined sources10
Beta strandi60 – 62Combined sources3
Beta strandi66 – 68Combined sources3
Beta strandi75 – 77Combined sources3
Beta strandi80 – 82Combined sources3
Helixi84 – 92Combined sources9
Helixi100 – 102Combined sources3
Beta strandi103 – 105Combined sources3
Helixi113 – 115Combined sources3
Beta strandi118 – 121Combined sources4
Helixi124 – 126Combined sources3
Beta strandi127 – 129Combined sources3
Beta strandi221 – 225Combined sources5
Beta strandi231 – 239Combined sources9
Beta strandi242 – 250Combined sources9
Beta strandi252 – 258Combined sources7
Beta strandi268 – 270Combined sources3
Helixi271 – 273Combined sources3
Helixi281 – 290Combined sources10
Beta strandi294 – 299Combined sources6
Beta strandi302 – 307Combined sources6
Beta strandi309 – 311Combined sources3
Beta strandi313 – 316Combined sources4
Helixi318 – 321Combined sources4
Helixi323 – 325Combined sources3
Beta strandi332 – 334Combined sources3
Beta strandi339 – 343Combined sources5
Helixi345 – 358Combined sources14
Helixi360 – 364Combined sources5
Helixi365 – 370Combined sources6
Beta strandi371 – 377Combined sources7
Beta strandi384 – 386Combined sources3
Helixi389 – 391Combined sources3
Beta strandi392 – 400Combined sources9
Helixi401 – 413Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MHDX-ray2.80A/B1-132[»]
1MJSX-ray1.91A229-425[»]
1MK2X-ray2.74A220-425[»]
1OZJX-ray2.40A/B1-144[»]
1U7FX-ray2.60A/C228-425[»]
2LAJNMR-B202-211[»]
2LB2NMR-B178-189[»]
ProteinModelPortaliP84022.
SMRiP84022.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP84022.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 136MH1PROSITE-ProRule annotationAdd BLAST127
Domaini232 – 425MH2PROSITE-ProRule annotationAdd BLAST194

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni137 – 231LinkerAdd BLAST95
Regioni271 – 324Sufficient for interaction with XPO41 PublicationAdd BLAST54

Domaini

The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding.
The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.
The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiP84022.
KOiK04500.
OMAiSDHQMTH.
OrthoDBiEOG091G082C.
PhylomeDBiP84022.
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_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
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.

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P84022-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE 
        60         70         80         90        100
LEKAITTQNV NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH 
       110        120        130        140        150
HELRAMELCE FAFNMKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF 
       160        170        180        190        200
PPLDDYSHSI PENTNFPAGI EPQSNIPETP PPGYLSEDGE TSDHQMNHSM 
       210        220        230        240        250
DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL NQRVGETFHA 
       260        270        280        290        300
SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG 
       310        320        330        340        350
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA 
       360        370        380        390        400
LLAQSVNQGF EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL 
       410        420 
NGPLQWLDKV LTQMGSPSIR CSSVS
Length:425
Mass (Da):48,081
Last modified:July 5, 2004 - v1
Checksum:i46DF5E8B371321AC
GO
Isoform 2 (identifier: P84022-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: MSSILPFTPP...NVNTKCITIP → MSCLHPRQTWKGAALVHRKAWWMG

Note: No experimental confirmation available.
Show »
Length:381
Mass (Da):43,237
Checksum:iD436B607B2677761
GO
Isoform 3 (identifier: P84022-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.

Show »
Length:320
Mass (Da):35,895
Checksum:iCB3D9B2D53AAC9E9
GO
Isoform 4 (identifier: P84022-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-195: Missing.

Note: No experimental confirmation available.
Show »
Length:230
Mass (Da):25,722
Checksum:iAFC64318B5EC08D1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti178E → EVGTWAAQAGL in BAA22032 (PubMed:9464505).Curated1
Sequence conflicti360F → L in BAH13315 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067051112A → V in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906854Ensembl.1
Natural variantiVAR_052021170I → V. Corresponds to variant dbSNP:rs35874463Ensembl.1
Natural variantiVAR_067047239E → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906853Ensembl.1
Natural variantiVAR_065578261T → I in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906851Ensembl.1
Natural variantiVAR_067048279R → K in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906852Ensembl.1
Natural variantiVAR_065579287R → W in LDS3. 1 PublicationCorresponds to variant dbSNP:rs387906850Ensembl.1
Natural variantiVAR_036474393P → L in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0453481 – 195Missing in isoform 4. 1 PublicationAdd BLAST195
Alternative sequenceiVSP_0437931 – 105Missing in isoform 3. 1 PublicationAdd BLAST105
Alternative sequenceiVSP_0429001 – 68MSSIL…CITIP → MSCLHPRQTWKGAALVHRKA WWMG in isoform 2. 1 PublicationAdd BLAST68

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68019 mRNA. Translation: AAB80960.1.
U76622 mRNA. Translation: AAB18967.1.
AB004930 Genomic DNA. Translation: BAA22032.1.
AF025300
, AF025293, AF025294, AF025295, AF025296, AF025297, AF025298, AF025299 Genomic DNA. Translation: AAL68976.1.
AK290881 mRNA. Translation: BAF83570.1.
AK298139 mRNA. Translation: BAH12731.1.
AK300614 mRNA. Translation: BAH13315.1.
AK316017 mRNA. Translation: BAH14388.1.
AC012568 Genomic DNA. No translation available.
AC087482 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77788.1.
BC050743 mRNA. Translation: AAH50743.1.
CCDSiCCDS10222.1. [P84022-1]
CCDS45288.1. [P84022-2]
CCDS53950.1. [P84022-3]
CCDS53951.1. [P84022-4]
PIRiS71798.
RefSeqiNP_001138574.1. NM_001145102.1. [P84022-3]
NP_001138575.1. NM_001145103.1. [P84022-2]
NP_001138576.1. NM_001145104.1. [P84022-4]
NP_005893.1. NM_005902.3. [P84022-1]
UniGeneiHs.727986.
Hs.742270.

Genome annotation databases

EnsembliENST00000327367; ENSP00000332973; ENSG00000166949. [P84022-1]
ENST00000439724; ENSP00000401133; ENSG00000166949. [P84022-2]
ENST00000537194; ENSP00000445348; ENSG00000166949. [P84022-4]
ENST00000540846; ENSP00000437757; ENSG00000166949. [P84022-3]
GeneIDi4088.
KEGGihsa:4088.
UCSCiuc002aqj.4. human. [P84022-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSMAD3_HUMAN
AccessioniPrimary (citable) accession number: P84022
Secondary accession number(s): A8K4B6
, B7Z4Z5, B7Z6M9, B7Z9Q2, F5H383, O09064, O09144, O14510, O35273, Q92940, Q93002, Q9GKR4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2004
Last sequence update: July 5, 2004
Last modified: June 7, 2017
This is version 162 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. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families