O15105 (SMAD7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mothers against decapentaplegic homolog 7
Short name=MAD homolog 7
Short name=Mothers against DPP homolog 7

Alternative name(s):
Mothers against decapentaplegic homolog 8
Short name=MAD homolog 8
Short name=Mothers against DPP homolog 8
SMAD family member 7
Short name=SMAD 7
Short name=Smad7
Short name=hSMAD7

Gene names

Name:	SMAD7
Synonyms:	MADH7, MADH8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	426 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator By similarity. Ref.10 Ref.13 Ref.16 Ref.19 Ref.23
Subunit structure	Interacts with WWP1 By similarity. Interacts with COPS5. Interacts with NEDD4L. Interacts with STAMBP. Interacts with RNF111, AXIN1 and AXIN2. Interacts with PPP1R15A. Interacts (via MH2 domain) with EP300. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its degradation. Interacts with PDPK1 (via PH domain). Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23
Subcellular location	Nucleus. Cytoplasm. Note: Interaction with NEDD4L or RNF111 or induces translocation from the nucleus to the cytoplasm. TGF-beta stimulates its translocation from the nucleus to the cytoplasm. PDPK1 inhibits its translocation from the nucleus to the cytoplasm in response to TGF-beta. Ref.18 Ref.22 Ref.23
Tissue specificity	Ubiquitous with higher expression in the lung and vascular endothelium.
Induction	By TGFB1.
Post-translational modification	Phosphorylation on Ser-249 does not affect its stability, nuclear localization or inhibitory function in TGFB signaling; however it affects its ability to regulate transcription By similarity. Phosphorylated by PDPK1. Ref.23 Ubiquitinated by WWP1 By similarity. Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation. In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation. Ref.15 Ref.17 Ref.18 Ref.22 Acetylation prevents ubiquitination and degradation mediated by SMURF1.
Involvement in disease	Colorectal cancer 3 (CRCS3) [MIM:612229]: A 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. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.25
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	Alternative splicing
Ligand	DNA-binding Metal-binding Zinc
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Traceable author statement. Source: Reactome adherens junction assembly Inferred from mutant phenotype PubMed 18593713. Source: BHF-UCL artery morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL cellular protein complex localization Inferred from direct assay PubMed 18593713. Source: BHF-UCL intracellular signal transduction Inferred from electronic annotation. Source: Compara negative regulation of BMP signaling pathway Inferred from direct assay PubMed 17438144. Source: BHF-UCL negative regulation of apoptotic process Traceable author statement PubMed 19018011. Source: BHF-UCL negative regulation of cell migration Traceable author statement PubMed 19018011. Source: BHF-UCL negative regulation of epithelial to mesenchymal transition Traceable author statement PubMed 19018011. Source: BHF-UCL negative regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 17438144. Source: BHF-UCL negative regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 18593713. Source: BHF-UCL negative regulation of peptidyl-threonine phosphorylation Inferred from direct assay PubMed 18593713. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 17438144. Source: BHF-UCL negative regulation of transcription by competitive promoter binding Inferred from direct assay PubMed 17438144. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 17438144. Source: BHF-UCL negative regulation of transforming growth factor beta receptor signaling pathway Inferred from direct assay PubMed 12151385PubMed 17438144PubMed 18762808. Source: BHF-UCL negative regulation of ubiquitin-protein ligase activity Inferred from direct assay PubMed 18593713. Source: BHF-UCL pathway-restricted SMAD protein phosphorylation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell-cell adhesion Inferred from direct assay PubMed 18593713. Source: BHF-UCL positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.15. Source: BHF-UCL positive regulation of protein ubiquitination Inferred from direct assay PubMed 16720724. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome protein stabilization Inferred from direct assay PubMed 18593713. Source: BHF-UCL regulation of activin receptor signaling pathway Inferred from direct assay PubMed 16720724. Source: BHF-UCL regulation of cardiac muscle contraction Inferred from sequence or structural similarity. Source: BHF-UCL regulation of ventricular cardiac muscle cell membrane depolarization Inferred by curator PubMed 18952608. Source: BHF-UCL response to laminar fluid shear stress Inferred from expression pattern Ref.2. Source: BHF-UCL transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome ureteric bud development Inferred from electronic annotation. Source: Compara ventricular cardiac muscle tissue morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL ventricular septum morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay PubMed 12151385. Source: BHF-UCL transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transcription regulatory region DNA binding Inferred from direct assay PubMed 17438144. Source: BHF-UCL transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity Inferred from direct assay Ref.2. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COPS5	Q92905	10	EBI-3861591,EBI-594661
WWP2	O00308	5	EBI-3861591,EBI-743923

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15105-1)

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.

Isoform 2 (identifier: O15105-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-215: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 426

426

Mothers against decapentaplegic homolog 7

PRO_0000090872

Regions

Domain

64 – 207

144

MH1

Domain

261 – 426

166

MH2

Region

208 – 217

10

Important for interaction with SMURF2

Motif

208 – 211

4

PY-motif

Compositional bias

27 – 35

9

Poly-Gly

Compositional bias

49 – 56

8

Poly-Gly

Compositional bias

207 – 210

4

Poly-Pro

Sites

Metal binding

125

1

Zinc By similarity

Metal binding

180

1

Zinc By similarity

Metal binding

192

1

Zinc By similarity

Metal binding

197

1

Zinc By similarity

Amino acid modifications

Modified residue

64

1

N6-acetyllysine; alternate Ref.17

Modified residue

70

1

N6-acetyllysine; alternate Ref.17

Modified residue

249

1

Phosphoserine By similarity

Cross-link

64

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate Ref.17

Cross-link

70

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate Ref.17

Natural variations

Alternative sequence

1 – 215

215

Missing in isoform 2.

VSP_045197

Experimental info

Mutagenesis

64

1

K → A: Loss of acetylation, and of SMURF1-dependent degradation; when associated with A-70. Ref.17

Mutagenesis

70

1

K → A: Loss of acetylation, and of SMURF1-dependent degradation; when associated with A-64. Ref.17

Mutagenesis

207 – 211

5

Missing: Diminishes interaction with SMURF2. Ref.13

Mutagenesis

211

1

Y → A: Diminishes interaction with SMURF2 and reduces inhibition of TGF-beta signaling. Ref.13

Mutagenesis

409 – 426

18

Missing: 90% reduction in TGF-beta receptor binding. Ref.1

Sequence conflict

71

1

G → C in AAB81354. Ref.3

Secondary structure

1

.

.

.

.

.

426

Helix Strand Turn

Details...

Beta strand

204 – 206

3

Beta strand

212 – 214

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 5B76EC986776C102	FASTA	426	46,426
	10 20 30 40 50 60 MFRTKRSALV RRLWRSRAPG GEDEEEGAGG GGGGGELRGE GATDSRAHGA GGGGPGRAGC 70 80 90 100 110 120 CLGKAVRGAK GHHHPHPPAA GAGAAGGAEA DLKALTHSVL KKLKERQLEL LLQAVESRGG 130 140 150 160 170 180 TRTACLLLPG RLDCRLGPGA PAGAQPAQPP SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC 190 200 210 220 230 240 ESYGKINPEL VCCNPHHLSR LCELESPPPP YSRYPMDFLK PTADCPDAVP SSAETGGTNY 250 260 270 280 290 300 LAPGGLSDSQ LLLEPGDRSH WCVVAYWEEK TRVGRLYCVQ EPSLDIFYDL PQGNGFCLGQ 310 320 330 340 350 360 LNSDNKSQLV QKVRSKIGCG IQLTREVDGV WVYNRSSYPI FIKSATLDNP DSRTLLVHKV 370 380 390 400 410 420 FPGFSIKAFD YEKAYSLQRP NDHEFMQQPW TGFTVQISFV KGWGQCYTRQ FISSCPCWLE VIFNSR
	Isoform 2 [UniParc]. Checksum: 04F71C0D2D257D71	FASTA	211	23,901
	10 20 30 40 50 60 MDFLKPTADC PDAVPSSAET GGTNYLAPGG LSDSQLLLEP GDRSHWCVVA YWEEKTRVGR 70 80 90 100 110 120 LYCVQEPSLD IFYDLPQGNG FCLGQLNSDN KSQLVQKVRS KIGCGIQLTR EVDGVWVYNR 130 140 150 160 170 180 SSYPIFIKSA TLDNPDSRTL LVHKVFPGFS IKAFDYEKAY SLQRPNDHEF MQQPWTGFTV 190 200 210 QISFVKGWGQ CYTRQFISSC PCWLEVIFNS R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling." Hayashi H., Abdollah S., Qiu Y., Cai J., Xu Y.-Y., Grinnell B.W., Richardson M.A., Topper J.N., Gimbrone M.A. Jr., Wrana J.L., Falb D. Cell 89:1165-1173(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF 409-ARG--ARG-426. Tissue: Umbilical vein endothelial cell.
[2]	"Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium." Topper J.N., Cai J., Qui Y., Anderson K.R., Xu Y.-Y., Deeds J.D., Feeley R., Gimeno C.J., Woolf E.A., Tayber O., Mays G.G., Sampson B.A., Schoen F.J., Gimbrone M.A. Jr., Falb D. Proc. Natl. Acad. Sci. U.S.A. 94:9314-9319(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Umbilical vein endothelial cell.
[3]	"Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling." Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J.L., Heuchel R., Itoh S., Kawabata M., Heldin N.-E., Heldin C.-H., ten Dijke P. Nature 389:631-635(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract] 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[8]	"TGF-beta signal transduction." Massague J. Annu. Rev. Biochem. 67:753-791(1998) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"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] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACVR1B, FUNCTION.
[11]	"The Smad pathway." Wrana J.L., Attisano L. Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"TGF-beta signaling by Smad proteins." Miyazono K. Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[13]	"Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF-beta receptor for degradation." Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H., Wrana J.L. Mol. Cell 6:1365-1375(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TYR-211 AND 207-PRO--TYR-211, INTERACTION WITH SMURF2 AND TGFBR1.
[14]	"Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads." Itoh F., Asao H., Sugamura K., Heldin C.-H., ten Dijke P., Itoh S. EMBO J. 20:4132-4142(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STAMBP.
[15]	"Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation." Ebisawa T., Fukuchi M., Murakami G., Chiba T., Tanaka K., Imamura T., Miyazono K. J. Biol. Chem. 276:12477-12480(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMURF1 AND TGFBR1, PROTEASOMAL DEGRADATION.
[16]	"Phosphorylation regulation of the interaction between Smad7 and activin type I receptor." Liu X., Nagarajan R.P., Vale W., Chen Y. FEBS Lett. 519:93-98(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACVR1B, FUNCTION.
[17]	"Control of Smad7 stability by competition between acetylation and ubiquitination." Gronroos E., Hellman U., Heldin C.H., Ericsson J. Mol. Cell 10:483-493(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EP300, ACETYLATION AT LYS-64 AND LYS-70, UBIQUITINATION AT LYS-64 AND LYS-70, MUTAGENESIS OF LYS-64 AND LYS-70.
[18]	"Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7." Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A., Ebina M., Nukiwa T., Miyazawa K., Imamura T., Miyazono K. EMBO J. 22:6458-6470(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF111, UBIQUITINATION, SUBCELLULAR LOCATION.
[19]	"GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor." Shi W., Sun C., He B., Xiong W., Shi X., Yao D., Cao X. J. Cell Biol. 164:291-300(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PPP1R15A.
[20]	"Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation." Kim B.-C., Lee H.-J., Park S.H., Lee S.R., Karpova T.S., McNally J.G., Felici A., Lee D.K., Kim S.-J. Mol. Cell. Biol. 24:2251-2262(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH COPS5.
[21]	"Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain." Ogunjimi A.A., Briant D.J., Pece-Barbara N., Le Roy C., Di Guglielmo G.M., Kavsak P., Rasmussen R.K., Seet B.T., Sicheri F., Wrana J.L. Mol. Cell 19:297-308(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SMURF2.
[22]	"Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia." Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., Chan S.C., Chen Y.-G., Han J., Lin S.-C. EMBO J. 25:1646-1658(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AXIN1 AND AXIN2, UBIQUITINATION, SUBCELLULAR LOCATION.
[23]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, INTERACTION WITH PDPK1.
[24]	"An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2." Chong P.A., Lin H., Wrana J.L., Forman-Kay J.D. J. Biol. Chem. 281:17069-17075(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 203-217 IN COMPLEX WITH SMURF2.
[25]	"A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk." Members of the CORGI consortium Broderick P., Carvajal-Carmona L., Pittman A.M., Webb E., Howarth K., Rowan A., Lubbe S., Spain S., Sullivan K., Fielding S., Jaeger E., Vijayakrishnan J., Kemp Z., Gorman M., Chandler I., Papaemmanuil E., Penegar S., Wood W. , Sellick G., Qureshi M., Teixeira A., Domingo E., Barclay E., Martin L., Sieber O., Kerr D., Gray R., Peto J., Cazier J.-B., Tomlinson I., Houlston R.S. Nat. Genet. 39:1315-1317(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CRCS3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF010193 mRNA. Translation: AAB81246.1.
AF015261 mRNA. Translation: AAB81354.1.
AF026559 , AF026556, AF026557, AF026558 Genomic DNA. Translation: AAL68977.1.
AK301535 mRNA. Translation: BAH13509.1.
AC114684 Genomic DNA. No translation available.
BC074818 mRNA. Translation: AAH74818.2.
BC074819 mRNA. Translation: AAH74819.2.

IPI

IPI00005079.
IPI00922705.

RefSeq

NP_001177750.1. NM_001190821.1.
NP_001177751.1. NM_001190822.1.
NP_001177752.1. NM_001190823.1.
NP_005895.1. NM_005904.3.

UniGene

Hs.465087.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DJY	NMR	-	B	203-217	[»]
2KXQ	NMR	-	B	203-217	[»]
2LTV	NMR	-	B	206-217	[»]
2LTW	NMR	-	B	205-217	[»]
2LTX	NMR	-	B	203-217	[»]
2LTY	NMR	-	B	203-217	[»]
2LTZ	NMR	-	B	203-217	[»]

ProteinModelPortal

O15105.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-42252N.

IntAct

O15105. 3 interactions.

MINT

MINT-1179821.

STRING

9606.ENSP00000262158.

PTM databases

PhosphoSite

O15105.

Proteomic databases

PaxDb

O15105.

PRIDE

O15105.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262158; ENSP00000262158; ENSG00000101665.
ENST00000591805; ENSP00000466902; ENSG00000101665.

GeneID

4092.

KEGG

hsa:4092.

UCSC

uc002ldg.3. human.

Organism-specific databases

CTD

4092.

GeneCards

GC18M046446.

HGNC

HGNC:6773. SMAD7.

HPA

CAB026212.
HPA028897.

MIM

602932. gene.
612229. phenotype.

neXtProt

NX_O15105.

PharmGKB

PA134875286.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG309572.

HOGENOM

HOG000060106.

HOVERGEN

HBG053021.

InParanoid

O15105.

KO

K04677.

OMA

MVRAKIG.

OrthoDB

EOG41G34G.

PhylomeDB

O15105.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.
ifngpathway. IFN-gamma pathway.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
tgfbrpathway. TGF-beta receptor signaling.

Reactome

REACT_111102. Signal Transduction.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

O15105.

Bgee

O15105.

CleanEx

HS_SMAD7.

Genevestigator

O15105.

GermOnline

ENSG00000101665. Homo sapiens.

Family and domain databases

Gene3D

2.60.200.10. 1 hit.
3.90.520.10. 2 hits.

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]

PANTHER

PTHR13703. PTHR13703. 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

EvolutionaryTrace

O15105.

GenomeRNAi

4092.

NextBio

16046.

SOURCE

Search...

Entry information

Entry name

SMAD7_HUMAN

Accession

Primary (citable) accession number: O15105
Secondary accession number(s): B7Z773, O14740, Q6DK23

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 4, 2001
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 138 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.