P84022 (SMAD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SMAD3
Synonyms:	MADH3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	425 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. Ref.13 Ref.14 Ref.15 Ref.20 Ref.21 Ref.22 Ref.29 Ref.33 Ref.35 Ref.40 Ref.42
Subunit structure	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 and WWP1. Interacts (via MH2 domain) with CITED2 (via C-terminus) By similarity. Interacts with NEDD4L; the interaction requires TGF-beta stimulation By similarity. 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 syngernistic 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). Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.40 Ref.41 Ref.44 Ref.49
Subcellular location	Cytoplasm. Nucleus. Note: Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4. Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1. Co-localizes with LEMD3 at the nucleus inner membrane. MAPK-mediated phosphorylation appears to have no effect on nuclear import. PDPK1 prevents its nuclear translocation in response to TGF-beta. Ref.22 Ref.23 Ref.26 Ref.29 Ref.33 Ref.40 Ref.42
Domain	The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding. Ref.21 The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import. Ref.21 The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain. Ref.21
Post-translational modification	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. Ref.1 Ref.11 Ref.17 Ref.20 Ref.21 Ref.22 Ref.29 Ref.33 Ref.37 Ref.38 Ref.39 Ref.42 Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta. Ubiquitinated. Ref.37
Involvement in disease	Defects in SMAD3 may be a cause of colorectal cancer (CRC) [MIM:114500]. Defects in SMAD3 are the cause of Loeys-Dietz syndrome type 1C (LDS1C) [MIM:613795]. LDS1C is an 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 LDS1C also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation. Ref.51
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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Aortic aneurysm Disease mutation
Ligand	DNA-binding Metal-binding Zinc
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	SMAD protein complex assembly Inferred from direct assay. Source: BHF-UCL activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype. Source: BHF-UCL cell cycle arrest Inferred from mutant phenotype. Source: BHF-UCL cell-cell junction organization Inferred from mutant phenotype. Source: BHF-UCL evasion of host defenses by virus Inferred from direct assay. Source: BHF-UCL immune response Inferred from mutant phenotype. Source: BHF-UCL induction of apoptosis Inferred from mutant phenotype. Source: BHF-UCL negative regulation of cell growth Inferred from direct assay Ref.1. Source: BHF-UCL negative regulation of mitotic cell cycle Inferred from mutant phenotype. Source: BHF-UCL negative regulation of protein catabolic process Inferred from mutant phenotype. Source: BHF-UCL negative regulation of protein phosphorylation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.1. Source: BHF-UCL positive regulation of canonical Wnt receptor signaling pathway Inferred from mutant phenotype. Source: BHF-UCL positive regulation of catenin import into nucleus Inferred from mutant phenotype. Source: BHF-UCL positive regulation of epithelial to mesenchymal transition Inferred from mutant phenotype. Source: BHF-UCL positive regulation of transcription factor import into nucleus Inferred from direct assay Ref.26. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB primary miRNA processing Traceable author statement. Source: BHF-UCL protein stabilization Inferred from mutant phenotype. Source: BHF-UCL regulation of transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype Ref.1. Source: BHF-UCL regulation of transforming growth factor beta2 production Inferred from mutant phenotype. Source: BHF-UCL response to hypoxia Inferred from mutant phenotype. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from direct assay Ref.13. Source: BHF-UCL transport Inferred from direct assay Ref.26. Source: BHF-UCL wound healing Traceable author statement. Source: BHF-UCL
Cellular component	SMAD protein complex Inferred from direct assay. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nuclear inner membrane Inferred from direct assay Ref.25. Source: UniProtKB receptor complex Inferred from mutant phenotype Ref.1. Source: BHF-UCL
Molecular function	R-SMAD binding Inferred from physical interaction Ref.8. Source: BHF-UCL RNA polymerase II activating transcription factor binding Inferred from physical interaction. Source: BHF-UCL beta-catenin binding Inferred from physical interaction. Source: BHF-UCL co-SMAD binding Inferred from physical interaction Ref.1Ref.8Ref.13. Source: BHF-UCL core promoter proximal region sequence-specific DNA binding Inferred from direct assay. Source: UniProtKB phosphatase binding Inferred from physical interaction Ref.29. Source: UniProtKB protein homodimerization activity Inferred from physical interaction Ref.1. Source: BHF-UCL protein kinase binding Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay Ref.13. Source: BHF-UCL transforming growth factor beta receptor binding Inferred from physical interaction Ref.8. Source: BHF-UCL transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Inferred from direct assay. Source: BHF-UCL ubiquitin binding Inferred from direct assay Ref.37. Source: UniProtKB ubiquitin protein ligase binding Inferred from physical interaction. Source: BHF-UCL zinc ion binding Inferred from direct assay Ref.48. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACTB	P60709	3	EBI-347161,EBI-353944
CHRD	Q9H2X0	2	EBI-347161,EBI-947551
DOCK9	Q9BZ29	3	EBI-347161,EBI-2695893
MYD88	Q99836	3	EBI-347161,EBI-447677
PCK2	Q16822	2	EBI-347161,EBI-2825219
PPP1R12C	Q9BZL4	2	EBI-347161,EBI-721802
PRTN3	P24158	2	EBI-347161,EBI-465028
RNF31	Q96EP0	2	EBI-347161,EBI-948111
SETD2	Q9BYW2	2	EBI-347161,EBI-945869
SMAD2	Q15796	2	EBI-347161,EBI-1040141
SMAD4	Q13485	9	EBI-347161,EBI-347263
SQSTM1	Q13501	3	EBI-347161,EBI-307104
SREBF2	Q12772	3	EBI-347161,EBI-465059
SRY	Q05066	3	EBI-347161,EBI-464987
TSC22D4	Q9Y3Q8	2	EBI-347161,EBI-739485
USP7	Q93009	2	EBI-347161,EBI-302474
WWP2	O00308	4	EBI-347161,EBI-743923
ZC3H12A	Q5D1E8	2	EBI-347161,EBI-747793

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 425

425

Mothers against decapentaplegic homolog 3

PRO_0000090856

Regions

Domain

10 – 136

127

MH1

Domain

232 – 425

194

MH2

Region

137 – 231

95

Linker

Region

271 – 324

54

Sufficient for interaction with XPO4

Sites

Metal binding

64

1

Zinc

Metal binding

109

1

Zinc

Metal binding

121

1

Zinc

Metal binding

126

1

Zinc

Site

40

1

Required for trimerization

Site

41

1

Required for interaction with DNA and JUN and for functional cooperation with JUN

Amino acid modifications

Modified residue

8

1

Phosphothreonine; by CDK2 and CDK4 Ref.20 Ref.39

Modified residue

179

1

Phosphothreonine; by CDK2, CDK4 and MAPK Ref.20 Ref.22 Ref.42

Modified residue

204

1

Phosphoserine; by GSK3 and MAPK Ref.20 Ref.22 Ref.42

Modified residue

208

1

Phosphoserine; by MAPK Ref.20 Ref.22 Ref.42

Modified residue

213

1

Phosphoserine; by CDK2 and CDK4 Ref.20

Modified residue

378

1

N6-acetyllysine Ref.35 Ref.43

Modified residue

416

1

Phosphoserine Ref.38

Modified residue

418

1

Phosphoserine; by CK1 Ref.37

Modified residue

423

1

Phosphoserine By similarity

Modified residue

425

1

Phosphoserine By similarity

Natural variations

Natural variant

170

1

I → V.
Corresponds to variant rs35874463 [ dbSNP | Ensembl ].

VAR_052021

Natural variant

261

1

T → I in LDS1C. Ref.51

VAR_065578

Natural variant

287

1

R → W in LDS1C. Ref.51

VAR_065579

Natural variant

393

1

P → L in a colorectal cancer sample; somatic mutation. Ref.50

VAR_036474

Experimental info

Mutagenesis

8

1

T → V: Reduced phosphorylation, increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-179 and A-213. Ref.20

Mutagenesis

40

1

K → 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. Ref.15

Mutagenesis

41

1

K → A: Greatly reduced interaction with DNA and JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-44 and A-43. Ref.15

Mutagenesis

43

1

K → 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. Ref.15

Mutagenesis

44

1

K → A: Little effect on interaction with DNA or JUN. Abolishes interaction with JUN; when associated with A-40; A-41 and A-43. Ref.15

Mutagenesis

74

1

R → D: Reduced interaction with JUN. Loss of transcriptional activity and cooperation with JUN. Ref.15

Mutagenesis

179

1

T → V: Reduced phosphorylation, increased transcriptional and increased antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and A-213. Ref.20 Ref.22 Ref.42

Mutagenesis

204

1

S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. Ref.20 Ref.22 Ref.42

Mutagenesis

208

1

S → A: Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208. Ref.20 Ref.22 Ref.42

Mutagenesis

213

1

S → A: Reduced phosphorylation. Increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and V-179. Ref.20

Mutagenesis

333

1

K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-341; R-378 and R-409. Ref.35

Mutagenesis

341

1

K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-378 and R-409. Ref.35

Mutagenesis

378

1

K → Q: Increased transcriptional activity. No further increase in transcriptional activity with EP300. Ref.35

Mutagenesis

378

1

K → 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. Ref.35

Mutagenesis

409

1

K → R: No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378. Ref.35

Mutagenesis

418

1

S → A: Increased constitutive activity. Ref.37

Mutagenesis

418

1

S → D: Decreased activity. Ref.37

Mutagenesis

422 – 425

4

SSVS → AAVA: Does not abolish protein nuclear export. Abolishes almost completely acetylation. Ref.17 Ref.31 Ref.35

Mutagenesis

422 – 425

4

SSVS → EEVE: Forms heterotrimers. Ref.17 Ref.31 Ref.35

Mutagenesis

422 – 425

4

SSVS → RRVR: Diminishes cargo protein export. Ref.17 Ref.31 Ref.35

Sequence conflict

178

1

E → EVGTWAAQAGL in BAA22032. Ref.3

Secondary structure

1

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425

Helix Strand Turn

Details...

Helix

10 – 16

7

Helix

25 – 44

20

Helix

48 – 57

10

Beta strand

66 – 68

3

Beta strand

75 – 77

3

Beta strand

80 – 82

3

Helix

84 – 92

9

Helix

100 – 102

3

Beta strand

103 – 105

3

Helix

113 – 115

3

Beta strand

118 – 121

4

Helix

124 – 126

3

Beta strand

127 – 129

3

Beta strand

221 – 225

5

Beta strand

231 – 239

9

Beta strand

242 – 250

9

Beta strand

252 – 258

7

Beta strand

268 – 270

3

Helix

281 – 290

10

Beta strand

294 – 299

6

Beta strand

302 – 307

6

Beta strand

309 – 311

3

Beta strand

313 – 316

4

Helix

318 – 321

4

Beta strand

332 – 334

3

Beta strand

339 – 343

5

Helix

345 – 358

14

Helix

360 – 364

5

Helix

365 – 370

6

Beta strand

371 – 377

7

Beta strand

392 – 400

9

Helix

401 – 413

13

Sequences

	Sequence		Length	Mass (Da)
	P84022 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 46DF5E8B371321AC	FASTA	425	48,081
	10 20 30 40 50 60 MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE LEKAITTQNV 70 80 90 100 110 120 NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELRAMELCE FAFNMKKDEV 130 140 150 160 170 180 CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF PPLDDYSHSI PENTNFPAGI EPQSNIPETP 190 200 210 220 230 240 PPGYLSEDGE TSDHQMNHSM DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL 250 260 270 280 290 300 NQRVGETFHA SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG 310 320 330 340 350 360 GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA LLAQSVNQGF 370 380 390 400 410 420 EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL NGPLQWLDKV LTQMGSPSIR CSSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 [MRNA], PHOSPHORYLATION. Tissue: Placenta.
[2]	"Mad-related genes in the human." Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B.V. Nat. Genet. 13:347-349(1996) [PubMed: 8673135] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Genomic structure of the human Smad3 gene and its infrequent alterations in colorectal cancers." Arai T., Akiyama Y., Okabe S., Ando M., Endo M., Yuasa Y. Cancer Lett. 122:157-163(1998) [PubMed: 9464505] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Colon carcinoma.
[4]	Hagiwara K., Yang K., McMenamin M.G., Freeman A.H., Bennett W.P., Nagashima M., Minter A.R., Miyazono K., Takenoshita S., Harris C.C. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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. , 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].
[6]	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. , 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].
[7]	"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: Pancreas.
[8]	"TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4." Nakao A., Imamura T., Souchelnytskyi S., Kawabata M., Ishisaki A., Oeda E., Tamaki K., Hanai J., Heldin C.H., Miyazono K., ten Dijke P. EMBO J. 16:5353-5362(1997) [PubMed: 9311995] [Abstract] Cited for: INTERACTION WITH TGFBR1.
[9]	"SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor." Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L. Cell 95:779-791(1998) [PubMed: 9865696] [Abstract] Cited for: INTERACTION WITH ZFYVE9.
[10]	"Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors." Kawabata M., Inoue H., Hanyu A., Imamura T., Miyazono K. EMBO J. 17:4056-4065(1998) [PubMed: 9670020] [Abstract] Cited for: SUBUNIT.
[11]	"TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein." Shen X., Hu P.P., Liberati N.T., Datto M.B., Frederick J.P., Wang X.F. Mol. Biol. Cell 9:3309-3319(1998) [PubMed: 9843571] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH EP300.
[12]	"The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3." Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., Yazaki Y., Matsumoto K., Hirai H. Nature 394:92-96(1998) [PubMed: 9665135] [Abstract] Cited for: INTERACTION WITH MECOM.
[13]	"Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription." Zhang Y., Feng X.H., Derynck R. Nature 394:909-913(1998) [PubMed: 9732876] [Abstract] Cited for: IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX, INTERACTION WITH JUN AND FOS, DNA-BINDING, FUNCTION.
[14]	"Roles of pathway-specific and inhibitory Smads in activin receptor signaling." Lebrun J.J., Takabe K., Chen Y., Vale W. Mol. Endocrinol. 13:15-23(1999) [PubMed: 9892009] [Abstract] Cited for: INTERACTION WITH ACVR1B, FUNCTION.
[15]	"Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity." Qing J., Zhang Y., Derynck R. J. Biol. Chem. 275:38802-38812(2000) [PubMed: 10995748] [Abstract] Cited for: INTERACTION WITH JUN IN THE SMAD3/SMAD4/JUN/FOS COMPLEX, DNA-BINDING, FUNCTION, MUTAGENESIS OF LYS-40; LYS-41; LYS-43; LYS-44 AND ARG-74.
[16]	"TGIF2 interacts with histone deacetylase 1 and represses transcription." Melhuish T.A., Gallo C.M., Wotton D. J. Biol. Chem. 276:32109-32114(2001) [PubMed: 11427533] [Abstract] Cited for: INTERACTION WITH TGIF2.
[17]	"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: SUBUNIT, PHOSPHORYLATION, MUTAGENESIS OF 422-SER--SER-425.
[18]	"Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling." Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N. Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001) [PubMed: 11274402] [Abstract] Cited for: INTERACTION WITH MEN1.
[19]	"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.
[20]	"Cyclin-dependent kinases regulate the antiproliferative function of Smads." Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F. Nature 430:226-231(2004) [PubMed: 15241418] [Abstract] Cited for: PHOSPHORYLATION AT THR-8; THR-179; SER-204; SER-208 AND SER-213, FUNCTION, MUTAGENESIS OF THR-8; THR-179; SER-204; SER-208 AND SER-213.
[21]	"The Smad3 linker region contains a transcriptional activation domain." Wang G., Long J., Matsuura I., He D., Liu F. Biochem. J. 386:29-34(2005) [PubMed: 15588252] [Abstract] Cited for: TRANSCRIPTIONAL ACTIVATION DOMAIN, FUNCTION, PHOSPHORYLATION, SUBUNIT, INTERACTION WITH EP300.
[22]	"Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3." Matsuura I., Wang G., He D., Liu F. Biochemistry 44:12546-12553(2005) [PubMed: 16156666] [Abstract] Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-179; SER-204 AND SER-208.
[23]	"MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling." Lin F., Morrison J.M., Wu W., Worman H.J. Hum. Mol. Genet. 14:437-445(2005) [PubMed: 15601644] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH LEMD3.
[24]	"Novel function of androgen receptor-associated protein 55/Hic-5 as a negative regulator of Smad3 signaling." Wang H., Song K., Sponseller T.L., Danielpour D. J. Biol. Chem. 280:5154-5162(2005) [PubMed: 15561701] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[25]	"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines." Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K. J. Biol. Chem. 280:15992-16001(2005) [PubMed: 15647271] [Abstract] Cited for: INTERACTION WITH LEMD3.
[26]	"Nuclear targeting of transforming growth factor-beta-activated Smad complexes." Chen H.B., Rud J.G., Lin K., Xu L. J. Biol. Chem. 280:21329-21336(2005) [PubMed: 15799969] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION.
[27]	"Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues." Arndt S., Poser I., Schubert T., Moser M., Bosserhoff A.-K. Lab. Invest. 85:1330-1341(2005) [PubMed: 16200078] [Abstract] Cited for: INTERACTION WITH SKOR2.
[28]	"Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP." Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S., Kurokawa M., Hirai H. Oncogene 24:6165-6173(2005) [PubMed: 15897867] [Abstract] Cited for: INTERACTION WITH MECOM.
[29]	"PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling." Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., Hu M., Davis C.M., Wang J., Brunicardi F.C., Shi Y., Chen Y.G., Meng A., Feng X.H. Cell 125:915-928(2006) [PubMed: 16751101] [Abstract] Cited for: INTERACTION WITH PPM1A, DEPHOSPHORYLATION, FUNCTION, SUBCELLULAR LOCATION.
[30]	"Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway." He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A., Massague J. Cell 125:929-941(2006) [PubMed: 16751102] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH SMAD2 AND TRIM33, INTERACTION WITH SMAD2 AND TRIM33.
[31]	"The mechanism of nuclear export of Smad3 involves exportin 4 and Ran." Kurisaki A., Kurisaki K., Kowanetz M., Sugino H., Yoneda Y., Heldin C.-H., Moustakas A. Mol. Cell. Biol. 26:1318-1332(2006) [PubMed: 16449645] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4, INTERACTION WITH XPO4, MUTAGENESIS OF 422-SER--SER-425.
[32]	"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.
[33]	"3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins." Seong H.A., Jung H., Kim K.T., Ha H. J. Biol. Chem. 282:12272-12289(2007) [PubMed: 17327236] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, INTERACTION WITH PDPK1.
[34]	"Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling." Arndt S., Poser I., Moser M., Bosserhoff A.-K. Mol. Cell. Neurosci. 34:603-611(2007) [PubMed: 17292623] [Abstract] Cited for: INTERACTION WITH SKOR1.
[35]	"Smad3 is acetylated by p300/CBP to regulate its transactivation activity." Inoue Y., Itoh Y., Abe K., Okamoto T., Daitoku H., Fukamizu A., Onozaki K., Hayashi H. Oncogene 26:500-508(2007) [PubMed: 16862174] [Abstract] Cited for: ACETYLATION AT LYS-378, FUNCTION, MUTAGENESIS OF LYS-333; LYS-341; LYS-378; LYS-409 AND 422-SER--SER-425.
[36]	"TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal." Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M., Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L. Nat. Cell Biol. 10:837-848(2008) [PubMed: 18568018] [Abstract] Cited for: INTERACTION WITH WWTR1.
[37]	"Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling." Guo X., Waddell D.S., Wang W., Wang Z., Liberati N.T., Yong S., Liu X., Wang X.-F. Oncogene 27:7235-7247(2008) [PubMed: 18794808] [Abstract] Cited for: INTERACTION WITH CSNK1G2, UBIQUITINATION, PHOSPHORYLATION AT SER-418 BY CSNK1G2/CK1, MUTAGENESIS OF SER-418.
[38]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[39]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[40]	"Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling." Dai F., Lin X., Chang C., Feng X.H. Dev. Cell 16:345-357(2009) [PubMed: 19289081] [Abstract] Cited for: INTERACTION WITH RANBP3, SUBCELLULAR LOCATION, FUNCTION.
[41]	"SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells." Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M., Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., Imamura T. J. Biol. Chem. 284:3334-3344(2009) [PubMed: 19049980] [Abstract] Cited for: INTERACTION WITH PRDM16; SKI AND HDAC1.
[42]	"Transforming growth factor-{beta}-inducible phosphorylation of Smad3." Wang G., Matsuura I., He D., Liu F. J. Biol. Chem. 284:9663-9673(2009) [PubMed: 19218245] [Abstract] Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-179; SER-204 AND SER-208.
[43]	"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-378, MASS SPECTROMETRY.
[44]	"IL-37 is a fundamental inhibitor of innate immunity." Nold M.F., Nold-Petry C.A., Zepp J.A., Palmer B.E., Bufler P., Dinarello C.A. Nat. Immunol. 11:1014-1022(2010) [PubMed: 20935647] [Abstract] Cited for: INTERACTION WITH IL1F7.
[45]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[46]	"Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-beta signaling." Shi Y., Wang Y.-F., Jayaraman L., Yang H., Massague J., Pavletich N.P. Cell 94:585-594(1998) [PubMed: 9741623] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-144.
[47]	"Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control." Qin B.Y., Lam S.S., Correia J.J., Lin K. Genes Dev. 16:1950-1963(2002) [PubMed: 12154125] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 220-425 IN COMPLEX WITH ZFYVE9.
[48]	"Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding." Chai J., Wu J.W., Yan N., Massague J., Pavletich N.P., Shi Y. J. Biol. Chem. 278:20327-20331(2003) [PubMed: 12686552] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-144 IN COMPLEX WITH DNA, ZINC.
[49]	"Structural basis of heteromeric smad protein assembly in TGF-beta signaling." Chacko B.M., Qin B.Y., Tiwari A., Shi G., Lam S., Hayward L.J., De Caestecker M., Lin K. Mol. Cell 15:813-823(2004) [PubMed: 15350224] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 228-424 IN COMPLEX WITH SMAD4, SUBUNIT.
[50]	"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. , 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: VARIANT [LARGE SCALE ANALYSIS] LEU-393.
[51]	"Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis." van de Laar I.M., Oldenburg R.A., Pals G., Roos-Hesselink J.W., de Graaf B.M., Verhagen J.M., Hoedemaekers Y.M., Willemsen R., Severijnen L.A., Venselaar H., Vriend G., Pattynama P.M., Collee M., Majoor-Krakauer D., Poldermans D., Frohn-Mulder I.M., Micha D., Timmermans J. , Hilhorst-Hofstee Y., Bierma-Zeinstra S.M., Willems P.J., Kros J.M., Oei E.H., Oostra B.A., Wessels M.W., Bertoli-Avella A.M. Nat. Genet. 43:121-126(2011) [PubMed: 21217753] [Abstract] Cited for: VARIANTS LDS1C ILE-261 AND TRP-287.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CH471082 Genomic DNA. Translation: EAW77788.1.
BC050743 mRNA. Translation: AAH50743.1.

IPI

IPI00024305.

PIR

S71798.

RefSeq

NP_001138574.1. NM_001145102.1.
NP_001138575.1. NM_001145103.1.
NP_005893.1. NM_005902.3.

UniGene

Hs.36915.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MHD	X-ray	2.80	A/B	1-132	[»]
1MJS	X-ray	1.91	A	229-425	[»]
1MK2	X-ray	2.74	A	220-425	[»]
1OZJ	X-ray	2.40	A/B	1-144	[»]
1U7F	X-ray	2.60	A/C	228-424	[»]
2LAJ	NMR	-	B	202-211	[»]
2LB2	NMR	-	B	178-189	[»]

ProteinModelPortal

P84022.

SMR

P84022. Positions 7-132, 228-425.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29720N.

IntAct

P84022. 112 interactions.

MINT

MINT-193987.

STRING

P84022.

PTM databases

PhosphoSite

P84022.

Polymorphism databases

DMDM

51338669.

Proteomic databases

PRIDE

P84022.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327367; ENSP00000332973; ENSG00000166949.

GeneID

4088.

KEGG

hsa:4088.

UCSC

uc002aqj.1. human.

Organism-specific databases

CTD

4088.

GeneCards

GC15P067358.

H-InvDB

HIX0012370.

HGNC

HGNC:6769. SMAD3.

HPA

CAB008094.

MIM

114500. phenotype.
603109. gene.
613795. phenotype.

neXtProt

NX_P84022.

Orphanet

60030. Aortic aneurysm syndrome, Loeys-Dietz type.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14839.

HOVERGEN

HBG053353.

InParanoid

P84022.

OMA

HTEIPSE.

OrthoDB

EOG48PMK5.

PhylomeDB

P84022.

Enzyme and pathway databases

Pathway_Interaction_DB

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.
telomerasepathway. Regulation of Telomerase.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P84022.

Bgee

P84022.

CleanEx

HS_SMAD3.

Genevestigator

P84022.

GermOnline

ENSG00000166949. Homo sapiens.

Family and domain databases

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.
[Graphical view]

Gene3D

G3DSA:3.90.520.10. MAD_MH1. 1 hit.
G3DSA:2.60.200.10. MH2_Dwarfin-type. 1 hit.

KO

K04500.

PANTHER

PTHR13703. Dwarfin. 1 hit.

Pfam

PF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]

SMART

SM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]

SUPFAM

SSF56366. MAD_MH1. 1 hit.
SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

16026.

SOURCE

Search...

Entry information

Entry name

SMAD3_HUMAN

Accession

Primary (citable) accession number: P84022
Secondary accession number(s): A8K4B6 , O09064, O09144, O14510, O35273, Q92940, Q93002, Q9GKR4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2004
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.