Details of Host Protein

KEGG: hsa05220 Pathway Download ×

KEGG: hsa05225 Pathway Download ×

KEGG: hsa05226 Pathway Download ×

KEGG: hsa05415 Pathway Download ×

KEGG: hsa04933 Pathway Download ×

KEGG: hsa05321 Pathway Download ×

KEGG: hsa04659 Pathway Download ×

KEGG: hsa05161 Pathway Download ×

KEGG: hsa05166 Pathway Download ×

KEGG: hsa04068 Pathway Download ×

KEGG: hsa04110 Pathway Download ×

Host Protein General Information (ID: PT0653)
Protein Name	Mothers against decapentaplegic homolog 3 (SMAD3)	Gene Name	SMAD3
Host Species	Homo sapiens	Uniprot Entry Name	SMAD3_HUMAN
Protein Families	Dwarfin/SMAD family
Subcellular Location	Cytoplasm Nucleus
External Link
	NCBI Gene ID	4088
	Uniprot ID	P84022
	Ensembl ID	ENSG00000166949
	HGNC ID	HGNC:6769
Function in Host	Receptor-regulated SMAD (R-SMAD) that is an intracellularsignal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Bindsthe TRE element in the promoter region of many genes that are regulatedby TGF-beta and, on formation of the SMAD3/SMAD4 complex, activatestranscription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has aninhibitory effect on wound healing probably by modulating both growthand migration of primary keratinocytes and by altering the TGF-mediatedchemotaxis of monocytes. This effect on wound healing appears to behormone-sensitive. Regulator of chondrogenesis and osteogenesis andinhibits early healing of bone fractures. Positively regulates PDPK1kinase activity by stimulating its dissociation from the 14-3-3 proteinYWHAQ which acts as a negative regulator. [1-11] Click to Show/Hide
Related KEGG Pathway
	Chronic myeloid leukemia	hsa05220		Pathway Map
	Hepatocellular carcinoma	hsa05225		Pathway Map
	Gastric cancer	hsa05226		Pathway Map
	Diabetic cardiomyopathy	hsa05415		Pathway Map
	AGE-RAGE signaling pathway in diabetic complications	hsa04933		Pathway Map
	Inflammatory bowel disease	hsa05321		Pathway Map
	Th17 cell differentiation	hsa04659		Pathway Map
	Hepatitis B	hsa05161		Pathway Map
	Human T-cell leukemia virus 1 infection	hsa05166		Pathway Map
	FoxO signaling pathway	hsa04068		Pathway Map
	Cell cycle	hsa04110		Pathway Map
3D Structure	PDB ID: 1MHD FASTA Download 2D PNG Download PDB File Download

Function of This Protein During Virus Infection
Virus Name	SARS-COV-2	Protein Function	Pro-viral	[12]
Infected Tissue	Kidney	Infection Time	NA
Infected Cell	Vero e6 cells (African green monkey kidny cell)	Cellosaurus ID	CVCL_YZ66
Method Description	To detect the role of host protein SMAD3 in viral infection, SMAD3 protein knockout Vero e6 cells were infected with SARS-COV-2 for several , and the effects on infection was detected through qRT-PCR.
Results	It is reported that Knockout of SMAD3 leads to the reduced SARS-CoV-2 RNA levels compared with control group.

Full List of Virus RNA Interacting with This Protien
*RNA Region: ORF10 (hCoV-19/Not Specified Virus Strain )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[13]
Strains Name	hCoV-19/Not Specified Virus Strain
RNA Binding Region	ORF10
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	Calu-3 cells (Human Lung Cancer Cell) (CVCL_0609 )
Cell Originated Tissue	Liver
Interaction Score	P-value < 0.05
Method Description	RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)

Differential Gene Expression During SARS-COV-2 Infection

GEO Accession: GSE152641

Sample Type: Blood

Samples Details: Healthy Control: 24; COVID-19: 62

Platform: GPL24676 Illumina NovaSeq 6000

PNG Download

GEO Accession: GSE162835

Sample Type: Nasopharyngeal Swabs

Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3

Platform: GPL24676 Illumina NovaSeq 6000

PNG Download

GEO Accession: GSE175779

Sample Type: Human Bronchial Epithelial Cells

Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)

Platform: GPL18573 Illumina NextSeq 500

PNG Download

Protein Phosphorylation after Virus Infection
S418 [14] PNG Download
T8 [14] PNG Download

Protein Sequence Information
MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIRCSSVS Click to Show/Hide

References
1	Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of TGF-beta signaling. Dev Cell. 2009 Mar;16(3):345-57.
2	Transforming growth factor-{beta}-inducible phosphorylation of Smad3. J Biol Chem. 2009 Apr 10;284(15):9663-73.
3	Smad3 is acetylated by p300/CBP to regulate its transactivation activity. Oncogene. 2007 Jan 25;26(4):500-8.
4	3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins. J Biol Chem. 2007 Apr 20;282(16):12272-89.
5	PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006 Jun 2;125(5):915-28.
6	Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry. 2005 Sep 20;44(37):12546-53.
7	The Smad3 linker region contains a transcriptional activation domain. Biochem J. 2005 Feb 15;386(Pt 1):29-34.
8	Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004 Jul 8;430(6996):226-31.
9	Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity. J Biol Chem. 2000 Dec 8;275(49):38802-12.
10	Roles of pathway-specific and inhibitory Smads in activin receptor signaling. Mol Endocrinol. 1999 Jan;13(1):15-23.
11	Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature. 1998 Aug 27;394(6696):909-13.
12	Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell. 2021 Jan 7;184(1):76-91.e13.
13	Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
14	Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.

Details of Host Protein

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