SMAD2
entrez
4087
canonical
uniprot
Q15796
canonical
ensembl
ENSG00000175387
resolver
ensp
ENSP00000262160
resolver
ensp
ENSP00000349282
resolver
ensp
ENSP00000384449
resolver
ensp
ENSP00000465355
resolver
ensp
ENSP00000466254
resolver
ensp
ENSP00000467075
resolver
ensp
ENSP00000776816
resolver
enst
ENST00000591214
resolver
genesymbol
SMAD2
resolver
genesymbol_syn
MADH2
resolver
genesymbol_syn
MADR2
resolver
hgnc
HGNC:6768
resolver
uniprot
B7Z5N5
resolver
uniprot
Q53XR6
resolver
uniprot_entry
B7Z5N5_HUMAN
resolver
uniprot_entry
Q53XR6_HUMAN
resolver
uniprot_entry
SMAD2_HUMAN
resolver
amino_acid_sequence
MSSILPFTPPVVKRLLGWKKSAGGSGGAGGGEQNGQEEKWCEKAVKSLVKKLKKTGRLDELEKAITTQNCNTKCVTIPSTCSEIWGLSTPNTIDQWDTTGLYSFSEQTRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELKAIENCEYAFNLKKDEVCVNPYHYQRVETPVLPPVLVPRHTEILTELPPLDDYTHSIPENTNFPAGIEPQSNYIPETPPPGYISEDGETSDQQLNQSMDTGSPAELSPTTLSPVNHSLDLQPVTYSEPAFWCSIAYYELNQRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNVNRNATVEMTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSVRCSSMS
uniprot
proteins
disease_involvement
DISEASE: Congenital heart defects, multiple types, 8, with or without heterotaxy (CHTD8) [MIM:619657]: An autosomal dominant disorder characterized by congenital developmental abnormalities involving structures of the heart. Common CHTD8 features include double-outlet right ventricle, unbalanced complete atrioventricular canal, and valvular anomalies. Vascular anomalies include dextroposition of the great arteries, anomalous pulmonary venous return, and superior vena cava to left atrium defect. Patients may also exhibit laterality defects, including dextrocardia, atrial isomerism, dextrogastria, left-sided gallbladder, and intestinal malrotation. {ECO:0000269|PubMed:23665959, ECO:0000269|PubMed:26247899, ECO:0000269|PubMed:30157302}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Loeys-Dietz syndrome 6 (LDS6) [MIM:619656]: A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Most LDS6 patients have thoracic aortic aneurysm involving the ascending aorta and/or aortic root, but cerebral and iliac arteries can be affected, and abdominal aortic aneurysm has been observed. Arterial tortuosity involving cerebral vessels, the aorta, and/or iliac arteries has also been reported. LDS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:26247899, ECO:0000269|PubMed:28283438, ECO:0000269|PubMed:29967133, ECO:0000269|PubMed:30157302}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells (By similarity). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. May act as a tumor suppressor in colorectal carcinoma (PubMed:8752209). {ECO:0000250|UniProtKB:Q62432, ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:9892009}.
uniprot
proteins
mass_dalton
52306
uniprot
proteins
mutagenesis
MUTAGEN 19; /note="K->R: Loss of acetylation."; /evidence="ECO:0000269|PubMed:17074756"; MUTAGEN 20; /note="K->R: No effect on acetylation."; /evidence="ECO:0000269|PubMed:17074756"; MUTAGEN 221..225; /note="Missing: Loss of binding to SMURF2."; /evidence="ECO:0000269|PubMed:11389444"; MUTAGEN 368; /note="W->A: Loss of interaction with PMEPA1."; /evidence="ECO:0000269|PubMed:20129061"; MUTAGEN 381; /note="N->S: Loss of binding to SARA."; /evidence="ECO:0000269|PubMed:10615055"; MUTAGEN 398; /note="V->R: Increased binding to PPM1A."; /evidence="ECO:0000269|PubMed:16751101"; MUTAGEN 464; /note="S->A: Loss of phosphorylation by TGFBR1; when associated with A-465 and A-467."; /evidence="ECO:0000269|PubMed:8980228"; MUTAGEN 465..467; /note="SMS->AMA: Binds RANBP3."; /evidence="ECO:0000269|PubMed:19289081"; MUTAGEN 465..467; /note="SMS->DMD: Greatly reduced RANBP2 binding."; /evidence="ECO:0000269|PubMed:19289081"; MUTAGEN 465; /note="S->A: No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-467."; /evidence="ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:8980228"; MUTAGEN 465; /note="S->D: No change in binding to PPM1A."; /evidence="ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:8980228"; MUTAGEN 467; /note="S->A: No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-465."; /evidence="ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:8980228"; MUTAGEN 467; /note="S->D: No change in binding to PPM1A."; /evidence="ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:8980228
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. TGF-beta-induced Ser-465/467 phosphorylation declines progressively in a KMT5A-dependent manner. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1. {ECO:0000269|PubMed:11879191, ECO:0000269|PubMed:12193595, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:39143229, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9136927, ECO:0000269|PubMed:9346908}.; PTM: In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Monoubiquitinated, leading to prevent DNA-binding (By similarity). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD2 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD2 and regulating its turnover (By similarity). {ECO:0000250|UniProtKB:Q62432, ECO:0000269|PubMed:21947082}.; PTM: Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo. Acetylation in the nucleus by EP300 is enhanced by TGF-beta. {ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17074756, ECO:0000269|Ref.7}.
uniprot
proteins
protein_family
Dwarfin/SMAD family
uniprot
proteins
pubmed
10615055
uniprot
proteins
pubmed
10647776
uniprot
proteins
pubmed
10708948
uniprot
proteins
pubmed
10708949
uniprot
proteins
pubmed
10835638
uniprot
proteins
pubmed
11278756
uniprot
proteins
pubmed
11387212
uniprot
proteins
pubmed
11389444
uniprot
proteins
pubmed
11879191
uniprot
proteins
pubmed
12193595
uniprot
proteins
pubmed
15350224
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15601644
uniprot
proteins
pubmed
15647271
uniprot
proteins
pubmed
16200078
uniprot
proteins
pubmed
16751101
uniprot
proteins
pubmed
16751102
uniprot
proteins
pubmed
16862174
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17074756
uniprot
proteins
pubmed
17099224
uniprot
proteins
pubmed
17292623
uniprot
proteins
pubmed
17327236
uniprot
proteins
pubmed
18568018
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19049980
uniprot
proteins
pubmed
19289081
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20061380
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20129061
uniprot
proteins
pubmed
21145499
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21599657
uniprot
proteins
pubmed
21947082
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22781750
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23478445
uniprot
proteins
pubmed
23665959
uniprot
proteins
pubmed
24324267
uniprot
proteins
pubmed
24627487
uniprot
proteins
pubmed
25105025
uniprot
proteins
pubmed
26247899
uniprot
proteins
pubmed
28283438
uniprot
proteins
pubmed
29967133
uniprot
proteins
pubmed
30157302
uniprot
proteins
pubmed
39143229
uniprot
proteins
pubmed
8673135
uniprot
proteins
pubmed
8752209
uniprot
proteins
pubmed
8774881
uniprot
proteins
pubmed
8980228
uniprot
proteins
pubmed
9136927
uniprot
proteins
pubmed
9346908
uniprot
proteins
pubmed
9389648
uniprot
proteins
pubmed
9503010
uniprot
proteins
pubmed
9670020
uniprot
proteins
pubmed
9702198
uniprot
proteins
pubmed
9759503
uniprot
proteins
pubmed
9865696
uniprot
proteins
pubmed
9873005
uniprot
proteins
pubmed
9892009
uniprot
proteins
sequence_length
467
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:39143229, ECO:0000269|PubMed:9865696}. Nucleus {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:21599657, ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:9865696}. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 or with IPO7 (PubMed:21145499, PubMed:9865696). On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (PubMed:16751101, PubMed:19289081). Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm at the blastocyst and epiblast stages (By similarity). {ECO:0000250|UniProtKB:Q62432, ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:9865696}.
uniprot
proteins