UniProt ID | SMAD3_HUMAN | |
---|---|---|
UniProt AC | P84022 | |
Protein Name | Mothers against decapentaplegic homolog 3 | |
Gene Name | SMAD3 | |
Organism | Homo sapiens (Human). | |
Sequence Length | 425 | |
Subcellular Localization | Cytoplasm . Nucleus . Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 (PubMed:15799969). Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex | |
Protein Description | 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.. | |
Protein Sequence | MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIRCSSVS | |
Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
---|---|---|---|---|---|
2 | Acetylation | ------MSSILPFTP ------CCCCCCCCH | 26.53 | 22814378 | |
2 | Phosphorylation | ------MSSILPFTP ------CCCCCCCCH | 26.53 | 29255136 | |
3 | Phosphorylation | -----MSSILPFTPP -----CCCCCCCCHH | 27.18 | 29255136 | |
8 | Phosphorylation | MSSILPFTPPIVKRL CCCCCCCCHHHHHHH | 26.64 | 29255136 | |
13 | Ubiquitination | PFTPPIVKRLLGWKK CCCHHHHHHHHCCCC | 37.74 | - | |
19 | Acetylation | VKRLLGWKKGEQNGQ HHHHHCCCCCCCCCC | 49.45 | 17074756 | |
20 | Acetylation | KRLLGWKKGEQNGQE HHHHCCCCCCCCCCH | 62.26 | 17074756 | |
29 | Acetylation | EQNGQEEKWCEKAVK CCCCCHHHHHHHHHH | 57.29 | 17478422 | |
33 | Acetylation | QEEKWCEKAVKSLVK CHHHHHHHHHHHHHH | 56.17 | 25953088 | |
33 | Ubiquitination | QEEKWCEKAVKSLVK CHHHHHHHHHHHHHH | 56.17 | PubMed | |
36 | Sumoylation | KWCEKAVKSLVKKLK HHHHHHHHHHHHHHH | 42.82 | - | |
36 | Acetylation | KWCEKAVKSLVKKLK HHHHHHHHHHHHHHH | 42.82 | 25953088 | |
36 | Sumoylation | KWCEKAVKSLVKKLK HHHHHHHHHHHHHHH | 42.82 | - | |
37 | Phosphorylation | WCEKAVKSLVKKLKK HHHHHHHHHHHHHHH | 31.62 | 24719451 | |
45 | Phosphorylation | LVKKLKKTGQLDELE HHHHHHHHCCHHHHH | 28.68 | 25599653 | |
53 | Ubiquitination | GQLDELEKAITTQNV CCHHHHHHHHHCCCC | 58.68 | PubMed | |
63 | Ubiquitination | TTQNVNTKCITIPRS HCCCCCCEEEEEECC | 20.59 | - | |
66 | Phosphorylation | NVNTKCITIPRSLDG CCCCEEEEEECCCCC | 34.11 | 24719451 | |
78 | Phosphorylation | LDGRLQVSHRKGLPH CCCCEEEECCCCCCE | 12.47 | 26670566 | |
81 | Ubiquitination | RLQVSHRKGLPHVIY CEEEECCCCCCEEEE | 60.42 | PubMed | |
88 | Phosphorylation | KGLPHVIYCRLWRWP CCCCEEEEEEECCCC | 3.14 | - | |
125 | Phosphorylation | DEVCVNPYHYQRVET CCEEECCCCCCCCCC | 14.14 | - | |
132 | Phosphorylation | YHYQRVETPVLPPVL CCCCCCCCCCCCCCC | 18.81 | 30266825 | |
179 | Phosphorylation | PQSNIPETPPPGYLS CCCCCCCCCCCCCCC | 35.42 | 19218245 | |
183 | Acetylation | IPETPPPGYLSEDGE CCCCCCCCCCCCCCC | 41.61 | 19608861 | |
204 | Phosphorylation | NHSMDAGSPNLSPNP CCCCCCCCCCCCCCC | 16.61 | 19218245 | |
208 | Phosphorylation | DAGSPNLSPNPMSPA CCCCCCCCCCCCCCC | 29.30 | 14512875 | |
213 | Phosphorylation | NLSPNPMSPAHNNLD CCCCCCCCCCCCCCC | 21.86 | 18032789 | |
264 | Phosphorylation | VDGFTDPSNSERFCL ECCCCCCCCCHHHHH | 56.66 | - | |
273 | Acetylation | SERFCLGLLSNVNRN CHHHHHHHHHCCCHH | 2.82 | 19608861 | |
275 | Phosphorylation | RFCLGLLSNVNRNAA HHHHHHHHCCCHHHH | 43.72 | 21712546 | |
286 | Phosphorylation | RNAAVELTRRHIGRG HHHHHHHHHHHCCCC | 16.49 | 29262532 | |
309 | Phosphorylation | EVFAECLSDSAIFVQ HHHHHHHCCCEEEEE | 40.97 | - | |
333 | Acetylation | WHPATVCKIPPGCNL CCCCCEEECCCCCCE | 54.64 | 25953088 | |
334 | Acetylation | HPATVCKIPPGCNLK CCCCEEECCCCCCEE | 4.15 | 19608861 | |
375 | Phosphorylation | RMCTIRMSFVKGWGA HHHHHHHHHHCCCCC | 19.62 | 22393057 | |
378 | Malonylation | TIRMSFVKGWGAEYR HHHHHHHCCCCCCHH | 47.11 | 26320211 | |
378 | Acetylation | TIRMSFVKGWGAEYR HHHHHHHCCCCCCHH | 47.11 | 19608861 | |
388 | Phosphorylation | GAEYRRQTVTSTPCW CCCHHCEECCCCCEE | 24.76 | - | |
412 | Phosphorylation | QWLDKVLTQMGSPSI HHHHHHHHHCCCCCC | 21.35 | 29396449 | |
416 | Phosphorylation | KVLTQMGSPSIRCSS HHHHHCCCCCCCCCC | 15.33 | 25159151 | |
418 | Phosphorylation | LTQMGSPSIRCSSVS HHHCCCCCCCCCCCC | 25.10 | 21712546 | |
422 | Phosphorylation | GSPSIRCSSVS---- CCCCCCCCCCC---- | 24.75 | 25056879 | |
423 | Phosphorylation | SPSIRCSSVS----- CCCCCCCCCC----- | 29.97 | 9380693 | |
425 | Phosphorylation | SIRCSSVS------- CCCCCCCC------- | 36.13 | 9380693 |
Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
---|---|---|---|---|---|---|
8 | T | Phosphorylation | Kinase | CDK2 | P24941 | Uniprot |
8 | T | Phosphorylation | Kinase | CDK4 | P30285 | PSP |
8 | T | Phosphorylation | Kinase | CDK2 | P97377 | PSP |
8 | T | Phosphorylation | Kinase | CDK4 | P11802 | Uniprot |
179 | T | Phosphorylation | Kinase | CDK9 | P50750 | PSP |
179 | T | Phosphorylation | Kinase | CDK8 | P49336 | PSP |
179 | T | Phosphorylation | Kinase | CDK4 | P30285 | PSP |
179 | T | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
179 | T | Phosphorylation | Kinase | MAPK | - | Uniprot |
179 | T | Phosphorylation | Kinase | CDK4 | P11802 | Uniprot |
179 | T | Phosphorylation | Kinase | CDK2 | P97377 | PSP |
179 | T | Phosphorylation | Kinase | AKT1 | P31749 | PSP |
179 | T | Phosphorylation | Kinase | CDK2 | P24941 | Uniprot |
204 | S | Phosphorylation | Kinase | MAPK | - | Uniprot |
204 | S | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
204 | S | Phosphorylation | Kinase | MELK | Q61846 | PSP |
204 | S | Phosphorylation | Kinase | GSK3 | - | Uniprot |
204 | S | Phosphorylation | Kinase | CDK4 | P11802 | PSP |
208 | S | Phosphorylation | Kinase | MAPK | - | Uniprot |
208 | S | Phosphorylation | Kinase | CDK9 | P50750 | PSP |
208 | S | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
208 | S | Phosphorylation | Kinase | CDK4 | P11802 | PSP |
208 | S | Phosphorylation | Kinase | CDK8 | P49336 | PSP |
213 | S | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
213 | S | Phosphorylation | Kinase | CDK2 | P24941 | Uniprot |
213 | S | Phosphorylation | Kinase | CDK2 | P97377 | PSP |
213 | S | Phosphorylation | Kinase | CDK4 | P11802 | Uniprot |
213 | S | Phosphorylation | Kinase | CDK4 | P30285 | PSP |
213 | S | Phosphorylation | Kinase | CDK9 | P50750 | PSP |
213 | S | Phosphorylation | Kinase | CDK8 | P49336 | PSP |
418 | S | Phosphorylation | Kinase | CK1G2 | P78368 | PSP |
418 | S | Phosphorylation | Kinase | CK1 | - | Uniprot |
422 | S | Phosphorylation | Kinase | TGFBR1 | P36897 | Uniprot |
423 | S | Phosphorylation | Kinase | TGFBR1 | P36897 | Uniprot |
425 | S | Phosphorylation | Kinase | TGFBR1 | P36897 | Uniprot |
- | K | Ubiquitination | E3 ubiquitin ligase | WWP2 | O00308 | PMID:21258410 |
- | K | Ubiquitination | E3 ubiquitin ligase | NEDD4L | Q96PU5 | PMID:19917253 |
- | K | Ubiquitination | E3 ubiquitin ligase | STUB1 | Q9UNE7 | PMID:15781469 |
- | K | Ubiquitination | E3 ubiquitin ligase | BTRC | Q9Y297 | PMID:11359933 |
- | K | Ubiquitination | E3 ubiquitin ligase | PJA1 | Q8NG27 | PMID:22199232 |
- | K | Ubiquitination | E3 ubiquitin ligase | RNF111 | Q6ZNA4 | PMID:18950738 |
- | K | Ubiquitination | E3 ubiquitin ligase | SMURF2 | Q9HAU4 | PMID:15108358 |
* Distance = the distance between SAP position and PTM sites.
Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of SMAD3_HUMAN !! |
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Acetylation | |
Reference | PubMed |
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-378, AND MASS SPECTROMETRY. | |
"Smad3 is acetylated by p300/CBP to regulate its transactivationactivity."; Inoue Y., Itoh Y., Abe K., Okamoto T., Daitoku H., Fukamizu A.,Onozaki K., Hayashi H.; Oncogene 26:500-508(2007). Cited for: ACETYLATION AT LYS-378, FUNCTION, AND MUTAGENESIS OF LYS-333; LYS-341;LYS-378; LYS-409 AND 422-SER--SER-425. | |
Phosphorylation | |
Reference | PubMed |
"Transforming growth factor-{beta}-inducible phosphorylation ofSmad3."; Wang G., Matsuura I., He D., Liu F.; J. Biol. Chem. 284:9663-9673(2009). Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION,FUNCTION, AND MUTAGENESIS OF THR-179; SER-204 AND SER-208. | |
"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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND MASSSPECTROMETRY. | |
"Ligand-dependent ubiquitination of Smad3 is regulated by caseinkinase 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). Cited for: INTERACTION WITH CSNK1G2, UBIQUITINATION, PHOSPHORYLATION AT SER-418BY CSNK1G2/CK1, AND MUTAGENESIS OF SER-418. | |
"Identification and characterization of ERK MAP kinase phosphorylationsites in Smad3."; Matsuura I., Wang G., He D., Liu F.; Biochemistry 44:12546-12553(2005). Cited for: PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION,FUNCTION, AND MUTAGENESIS OF THR-179; SER-204 AND SER-208. | |
"Cyclin-dependent kinases regulate the antiproliferative function ofSmads."; Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.; Nature 430:226-231(2004). Cited for: PHOSPHORYLATION AT THR-8; THR-179; SER-204; SER-208 AND SER-213,FUNCTION, AND MUTAGENESIS OF THR-8; THR-179; SER-204; SER-208 ANDSER-213. | |
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8, AND MASSSPECTROMETRY. |