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Reviewed, UniProtKB/Swiss-Prot Q13485 (SMAD4_HUMAN)

Last modified January 19, 2010. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Mothers against decapentaplegic homolog 4
      Short name=Mothers against DPP homolog 4
Alternative name(s):
    SMAD 4
    hSMAD4
    Deletion target in pancreatic carcinoma 4
Gene names
Name: SMAD4
Synonyms: DPC4, MADH4
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length552 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. May act as a tumor suppressor. Ref.7

Subunit structure

May form trimers with receptor-regulated SMAD (R-SMAD). Found in a ternary complex composed of SMAD4, STK11 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11, STK11IP and TRIM33. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X. Interacts with RBPMS; the interaction is direct. Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16

Subcellular location

Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with R-SMAD.

Domain

The MH1 and MH2 domains are necessary for interaction with RBPMS.

Post-translational modification

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.

Involvement in disease

Defects in SMAD4 are a cause of pancreatic carcinoma [MIM:260350]. Ref.1

Defects in SMAD4 are a cause of juvenile polyposis syndrome (JPS) [MIM:174900]; also known as juvenile intestinal polyposis (JIP). JPS is an autosomal 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. Ref.25 Ref.26

Defects in SMAD4 are a cause of juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT) [MIM:175050]. JP/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.

Defects in SMAD4 may be a cause of colorectal cancer (CRC) [MIM:114500].

Sequence similarities

Belongs to the dwarfin/SMAD family.

Contains 1 MH1 (MAD homology 1) domain.

Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processBMP signaling pathway Ref.7

Inferred from direct assay. Source: UniProtKB

SMAD protein complex assembly

Inferred from direct assay. Source: UniProtKB

SMAD protein signal transduction

Inferred from direct assay. Source: UniProtKB

negative regulation of cell growth Ref.2

Inferred from direct assay. Source: UniProtKB

negative regulation of transcription, DNA-dependent Ref.2

Inferred from direct assay. Source: UniProtKB

palate development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of SMAD protein nuclear translocation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from direct assay. Source: UniProtKB

regulation of transforming growth factor-beta2 production

Inferred from mutant phenotype. Source: UniProtKB

response to hypoxia

Inferred from mutant phenotype. Source: UniProtKB

transcription

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway Ref.7

Inferred from direct assay. Source: UniProtKB

   Cellular componentactivin responsive factor complex Ref.7

Inferred from direct assay. Source: UniProtKB

cytosol

Inferred from Experiment. Source: Reactome

   Molecular functionR-SMAD binding Ref.2

Inferred from physical interaction. Source: UniProtKB

promoter binding

Inferred from direct assay. Source: UniProtKB

protein homodimerization activity Ref.2

Inferred from physical interaction. Source: UniProtKB

transcription factor activity

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta receptor, common-partner cytoplasmic mediator activity Ref.7

Inferred from direct assay. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 552552Mothers against decapentaplegic homolog 4
PRO_0000090861

Regions

Domain18 – 142125MH1
Domain323 – 552230MH2
Region275 – 32046SAD
Compositional bias451 – 46616Poly-Ala

Amino acid modifications

Modified residue371N6-acetyllysine Ref.17
Modified residue4281N6-acetyllysine Ref.17
Modified residue5071N6-acetyllysine Ref.17
Cross-link519Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Natural variant1011W → G: dbSNP rs2229083.
VAR_052022
Natural variant1301P → S in a colorectal cancer sample; somatic mutation. Ref.28
VAR_036475
Natural variant3301E → G in JPS. Ref.26
VAR_022833
Natural variant3511D → N in a colorectal cancer sample; somatic mutation. Ref.28
VAR_036476
Natural variant3521G → R in JP/HHT and JPS. Ref.26 Ref.27
VAR_019571
Natural variant3611R → C in JPS. Ref.25
VAR_019572
Natural variant3611R → H in a colorectal cancer sample; somatic mutation. Ref.28
VAR_036477
Natural variant3861G → D in JP/HHT. dbSNP rs28936393. Ref.27
VAR_019573
Natural variant4931D → H in pancreatic carcinoma. dbSNP rs28936392. Ref.1
VAR_011380

Experimental info

Mutagenesis5191K → R: Abolishes ubiquitination. Ref.16

Secondary structure

....................................... 552
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13485-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 7EE3C4647712DA90

FASTA55260,439
        10         20         30         40         50         60 
MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK KDELDSLITA 

        70         80         90        100        110        120 
ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR WPDLHKNELK HVKYCQYAFD 

       130        140        150        160        170        180 
LKCDSVCVNP YHYERVVSPG IDLSGLTLQS NAPSSMMVKD EYVHDFEGQP SLSTEGHSIQ 

       190        200        210        220        230        240 
TIQHPPSNRA STETYSTPAL LAPSESNATS TANFPNIPVA STSQPASILG GSHSEGLLQI 

       250        260        270        280        290        300 
ASGPQPGQQQ NGFTGQPATY HHNSTTTWTG SRTAPYTPNL PHHQNGHLQH HPPMPPHPGH 

       310        320        330        340        350        360 
YWPVHNELAF QPPISNHPAP EYWCSIAYFE MDVQVGETFK VPSSCPIVTV DGYVDPSGGD 

       370        380        390        400        410        420 
RFCLGQLSNV HRTEAIERAR LHIGKGVQLE CKGEGDVWVR CLSDHAVFVQ SYYLDREAGR 

       430        440        450        460        470        480 
APGDAVHKIY PSAYIKVFDL RQCHRQMQQQ AATAQAAAAA QAAAVAGNIP GPGSVGGIAP 

       490        500        510        520        530        540 
AISLSAAAGI GVDDLRRLCI LRMSFVKGWG PDYPRQSIKE TPCWIEIHLH RALQLLDEVL 

       550 
HTMPIADPQP LD 

« Hide

References

« Hide 'large scale' references
[1]"DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1."
Hahn S.A., Schutte M., Shamsul Hoque A.T.M., Moskaluk C.A., da Costa L.T., Rozenblum E., Weinstein C.L., Fischer A., Yeo C.J., Hruban R.H., Kern S.E.
Science 271:350-353(1996) [PubMed: 8553070] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT PANCREATIC CARCINOMA HIS-493.
Tissue: Fetal brain.
[2]"Receptor-associated Mad homologues synergize as effectors of the TGF-beta response."
Zhang Y., Feng X.-H., Wu R.-Y., Derynck R.
Nature 383:168-172(1996) [PubMed: 8774881] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Genomic sequencing of DPC4 in the analysis of familial pancreatic carcinoma."
Moskaluk C.A., Hruban R.H., Schutte M., Lietman A.S., Smyrk T., Fusaro L., Fusaro R., Lynch J., Yeo C.J., Jackson C.E., Lynch H.T., Kern S.E.
Diagn. Mol. Pathol. 6:85-90(1997) [PubMed: 9098646] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Muscle.
[7]"Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes."
Liu F., Pouponnot C., Massague J.
Genes Dev. 11:3157-3167(1997) [PubMed: 9389648] [Abstract]
Cited for: FUNCTION.
[8]"OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways."
Hata A., Seoane J., Lagna G., Montalvo E., Hemmati-Brivanlou A., Massague J.
Cell 100:229-240(2000) [PubMed: 10660046] [Abstract]
Cited for: INTERACTION WITH ZNF423.
[9]"The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain."
de Caestecker M.P., Yahata T., Wang D., Parks W.T., Huang S., Hill C.S., Shioda T., Roberts A.B., Lechleider R.J.
J. Biol. Chem. 275:2115-2122(2000) [PubMed: 10636916] [Abstract]
Cited for: CHARACTERIZATION OF SAD DOMAIN.
[10]"LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1."
Smith D.P., Rayter S.I., Niederlander C., Spicer J., Jones C.M., Ashworth A.
Hum. Mol. Genet. 10:2869-2877(2001) [PubMed: 11741830] [Abstract]
Cited for: IDENTIFICATION IN A TERNARY COMPLEX COMPOSED OF STK11 AND STK11IP, INTERACTION WITH STK11 AND STK11IP.
[11]"Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation."
Wan M., Cao X., Wu Y., Bai S., Wu L., Shi X., Wang N., Cao X.
EMBO Rep. 3:171-176(2002) [PubMed: 11818334] [Abstract]
Cited for: INTERACTION WITH COPS5.
[12]"DACH1 inhibits transforming growth factor-beta signaling through binding Smad4."
Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K., Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G.
J. Biol. Chem. 278:51673-51684(2003) [PubMed: 14525983] [Abstract]
Cited for: INTERACTION WITH DACH1.
[13]"Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells."
Bond H.M., Mesuraca M., Carbone E., Bonelli P., Agosti V., Amodio N., De Rosa G., Di Nicola M., Gianni A.M., Moore M.A., Hata A., Grieco M., Morrone G., Venuta S.
Blood 103:2062-2070(2004) [PubMed: 14630787] [Abstract]
Cited for: INTERACTION WITH ZNF521.
[14]"Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase."
Dupont S., Zacchigna L., Cordenonsi M., Soligo S., Adorno M., Rugge M., Piccolo S.
Cell 121:87-99(2005) [PubMed: 15820681] [Abstract]
Cited for: INTERACTION WITH TRIM33.
[15]"Potentiation of Smad-mediated transcriptional activation by the RNA-binding protein RBPMS."
Sun Y., Ding L., Zhang H., Han J., Yang X., Yan J., Zhu Y., Li J., Song H., Ye Q.
Nucleic Acids Res. 34:6314-6326(2006) [PubMed: 17099224] [Abstract]
Cited for: INTERACTION WITH RBPMS.
[16]"FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination."
Dupont S., Mamidi A., Cordenonsi M., Montagner M., Zacchigna L., Adorno M., Martello G., Stinchfield M.J., Soligo S., Morsut L., Inui M., Moro S., Modena N., Argenton F., Newfeld S.J., Piccolo S.
Cell 136:123-135(2009) [PubMed: 19135894] [Abstract]
Cited for: INTERACTION WITH USP9X, UBIQUITINATION, MUTAGENESIS OF LYS-519.
[17]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-37; LYS-428 AND LYS-507, MASS SPECTROMETRY.
[18]"A structural basis for mutational inactivation of the tumour suppressor Smad4."
Shi Y., Hata A., Lo R.S., Massague J., Pavletich N.P.
Nature 388:87-93(1997) [PubMed: 9214508] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 319-543.
[19]"Crystal structure of a transcriptionally active Smad4 fragment."
Qin B., Lam S.S., Lin K.
Structure 7:1493-1503(1999) [PubMed: 10647180] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 285-552.
[20]"The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization."
Chacko B.M., Qin B., Correia J.J., Lam S.S., de Caestecker M.P., Lin K.
Nat. Struct. Biol. 8:248-253(2001) [PubMed: 11224571] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3 ANGSTROMS) OF 273-552.
[21]"TGF-beta signal transduction."
Massague J.
Annu. Rev. Biochem. 67:753-791(1998) [PubMed: 9759503] [Abstract]
Cited for: REVIEW.
[22]"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
Verschueren K., Huylebroeck D.
Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed: 10647776] [Abstract]
Cited for: REVIEW.
[23]"The Smad pathway."
Wrana J.L., Attisano L.
Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed: 10708948] [Abstract]
Cited for: REVIEW.
[24]"TGF-beta signaling by Smad proteins."
Miyazono K.
Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed: 10708949] [Abstract]
Cited for: REVIEW.
[25]"Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases."
Houlston R., Bevan S., Williams A., Young J., Dunlop M., Rozen P., Eng C., Markie D., Woodford-Richens K., Rodriguez-Bigas M.A., Leggett B., Neale K., Phillips R., Sheridan E., Hodgson S., Iwama T., Eccles D., Bodmer W., Tomlinson I.
Hum. Mol. Genet. 7:1907-1912(1998) [PubMed: 9811934] [Abstract]
Cited for: VARIANT JPS CYS-361.
[26]"Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis."
Sayed M.G., Ahmed A.F., Ringold J.R., Anderson M.E., Bair J.L., Mitros F.A., Lynch H.T., Tinley S.T., Petersen G.M., Giardiello F.M., Vogelstein B., Howe J.R.
Ann. Surg. Oncol. 9:901-906(2002) [PubMed: 12417513] [Abstract]
Cited for: VARIANTS JPS GLY-330 AND ARG-352.
[27]"A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4)."
Gallione C.J., Repetto G.M., Legius E., Rustgi A.K., Schelley S.L., Tejpar S., Mitchell G., Drouin E., Westermann C.J.J., Marchuk D.A.
Lancet 363:852-859(2004) [PubMed: 15031030] [Abstract]
Cited for: VARIANTS JP/HHT ARG-352 AND ASP-386.
[28]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-130; ASN-351 AND HIS-361.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF045447 expand/collapse EMBL AC list , 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.
IPIIPI00013404.
PIRS71811.
RefSeqNP_005350.1.
UniGeneHs.75862

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
SMRQ13485. Positions 19-138.
DisProtDP00464.
ModBaseSearch...

Protein-protein interaction databases

IntActQ13485. 11 interactions.
STRINGQ13485.

PTM databases

PhosphoSiteQ13485.

Proteomic databases

PeptideAtlasQ13485.
PRIDEQ13485.

Genome annotation databases

EnsemblENST00000342988; ENSP00000341551; ENSG00000141646; Homo sapiens. [Genome view]
ENST00000398417; ENSP00000381452; ENSG00000141646; Homo sapiens. [Genome view]
GeneID4089.
KEGGhsa:4089.
UCSCuc002lfa.2. human.

Organism-specific databases

CTD4089.
GeneCardsGC18P046810.
H-InvDBHIX0014453.
HGNCHGNC:6770. SMAD4.
HPACAB002312.
HPA019154.
MIM114500. phenotype.
174900. phenotype.
175050. phenotype.
260350. phenotype.
600993. gene.
Orphanet2929. Juvenile gastrointestinal polyposis.
1333. Pancreatic carcinoma, familial.
PharmGKBPA30527.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG10138.
HOGENOMHBG443554.
HOVERGENQ13485.
InParanoidQ13485.
OMAPTEGHSI.
OrthoDBEOG9PCDBB.
PhylomeDBQ13485.

Enzyme and pathway databases

Pathway_Interaction_DBbmppathway. BMP receptor signaling.
wnt_canonical_pathway. Canonical Wnt signaling pathway.
hif1_tfpathway. HIF-1-alpha transcription factor network.
smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
tgfbrpathway. TGF-beta receptor signaling.
ReactomeREACT_12034. Signaling by BMP.
REACT_6844. Signaling by TGF beta.

Gene expression databases

ArrayExpressQ13485.
BgeeQ13485.
CleanExHS_SMAD4.
GenevestigatorQ13485.
GermOnlineENSG00000141646. Homo sapiens.

Family and domain databases

InterProIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
Gene3DG3DSA:3.90.520.10. MAD_MH1. 1 hit.
G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.
PANTHERPTHR13703. Dwarfin. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

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Entry information

Entry nameSMAD4_HUMAN
AccessionPrimary (citable) accession number: Q13485
Secondary accession number(s): A8K405
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: November 1, 1996
Last modified: January 19, 2010
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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