TISIDB

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted, extracellular space, extracellular matrix
Domain	PF00045 Hemopexin PF00413 Matrixin PF01471 Putative peptidoglycan binding domain
Function	Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.

> Gene Ontology [ TOP ]
Biological Process	GO:0000302 response to reactive oxygen species GO:0006979 response to oxidative stress GO:0010035 response to inorganic substance GO:0010310 regulation of hydrogen peroxide metabolic process GO:0010727 negative regulation of hydrogen peroxide metabolic process GO:0022617 extracellular matrix disassembly GO:0030198 extracellular matrix organization GO:0030574 collagen catabolic process GO:0031334 positive regulation of protein complex assembly GO:0032459 regulation of protein oligomerization GO:0032461 positive regulation of protein oligomerization GO:0032963 collagen metabolic process GO:0034599 cellular response to oxidative stress GO:0034614 cellular response to reactive oxygen species GO:0036473 cell death in response to oxidative stress GO:0042743 hydrogen peroxide metabolic process GO:0043062 extracellular structure organization GO:0043254 regulation of protein complex assembly GO:0044089 positive regulation of cellular component biogenesis GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0051259 protein oligomerization GO:0071241 cellular response to inorganic substance GO:0071731 response to nitric oxide GO:0071732 cellular response to nitric oxide GO:0072593 reactive oxygen species metabolic process GO:1900407 regulation of cellular response to oxidative stress GO:1900409 positive regulation of cellular response to oxidative stress GO:1902170 cellular response to reactive nitrogen species GO:1902882 regulation of response to oxidative stress GO:1902884 positive regulation of response to oxidative stress GO:1903201 regulation of oxidative stress-induced cell death GO:1903209 positive regulation of oxidative stress-induced cell death GO:2000377 regulation of reactive oxygen species metabolic process GO:2000378 negative regulation of reactive oxygen species metabolic process
Molecular Function	GO:0004175 endopeptidase activity GO:0004222 metalloendopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0008236 serine-type peptidase activity GO:0008237 metallopeptidase activity GO:0017171 serine hydrolase activity
Cellular Component	GO:0005578 proteinaceous extracellular matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04668 TNF signaling pathway
Reactome	R-HSA-1592389: Activation of Matrix Metalloproteinases R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures R-HSA-1442490: Collagen degradation R-HSA-1474290: Collagen formation R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1474228: Degradation of the extracellular matrix R-HSA-2179392: EGFR Transactivation by Gastrin R-HSA-1474244: Extracellular matrix organization R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-168256: Immune System R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-449147: Signaling by Interleukins

> KEGG and Reactome Pathway

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KEGG

hsa04668 TNF signaling pathway

Reactome

R-HSA-1592389: Activation of Matrix Metalloproteinases
R-HSA-2022090: Assembly of collagen fibrils and other multimeric structures
R-HSA-1442490: Collagen degradation
R-HSA-1474290: Collagen formation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-2179392: EGFR Transactivation by Gastrin
R-HSA-1474244: Extracellular matrix organization
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-168256: Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-449147: Signaling by Interleukins

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MMP3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between MMP3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16891318	Glioblastoma	Promote immunity	Yet again, MP inhibition by the broad spectrum inhibitors GM 6001 or MMP inhibitor III selectively enhanced the expression of MICA and ULBP2 on the surface of LNT- 229 cells but not of other NKG2DL (Fig. 4A). For MICA, this effect was significantly more prominent on control than on TGF-b1/2 siRNA cells. Thus, escape from NKG2D-mediated immune surveillance of malignant gliomas in vivo may be promoted by the inhibition of MICA and ULBP2 expression via an autocrine TGF-beta loop and by MP-dependent shedding from the cell surface.

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of MMP3 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of MMP3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.765	0.353
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.939	0.145
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.103	0.927
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.248	0.713
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.41	0.347
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.221	0.511
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-1.36	0.182
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.182	0.404
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.241	0.432
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.121	0.366
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	3.309	0.0246
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.28	0.506

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MMP3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	5.5	-5.5	0.572
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	6.8	-6.8	0.304
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MMP3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MMP3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MMP3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MMP3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MMP3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MMP3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MMP3
Name	matrix metallopeptidase 3
Aliases	STMY1; STMY; matrix metalloproteinase 3 (stromelysin 1, progelatinase); stromelysin 1; CHDS6; MMP-3; SL-1; S ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MMP3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MMP3.

ID	Name	Drug Type	Targets	#Targets
DB00786	Marimastat	Small Molecule	MMP1, MMP10, MMP11, MMP12, MMP13, MMP14, MMP15, MMP16, MMP17, MMP1 ......	23
DB01877	N-Hydroxy 1n(4-Methoxyphenyl)Sulfonyl-4-(Z,E-N-Methoxyimino)Pyrrolidine-2r-Carboxamide	Small Molecule	MMP3	1
DB01996	3-Methylpyridine	Small Molecule	MMP13, MMP3	2
DB02090	A Disubstituted Succinyl Caprolactam Hydroxymate Mmp3inhibitor	Small Molecule	MMP3	1
DB02350	N-Hydroxy-4-[(4-Methoxylphenyl)Sulfonyl]-2,2-Dimethyl-Hexahydro-1,4-Thiazepine-3(S)-Carboxamide	Small Molecule	MMP3	1
DB02367	(1n)-4-N-Butoxyphenylsulfonyl-(2r)-N-Hydroxycarboxamido-(4s)-Methanesulfonylamino-Pyrrolidine	Small Molecule	MMP3	1
DB02449	3-(1h-Indol-3-Yl)-2-[4-(4-Phenyl-Piperidin-1-Yl)-Benzenesulfonylamino]-Propionic Acid	Small Molecule	MMP3	1
DB02697	Hydroxyaminovaline	Small Molecule	MMP13, MMP3	2
DB03033	1-Methyloxy-4-Sulfone-Benzene	Small Molecule	MMP13, MMP3	2
DB03368	5-Methyl-5-(4-Phenoxy-Phenyl)-Pyrimidine-2,4,6-Trione	Small Molecule	MMP3	1
DB04140	1-Benzyl-3-(4-Methoxy-Benzenesulfonyl)-6-Oxo-Hexahydro-Pyrimidine-4-Carboxylic Acid Hydroxyamide	Small Molecule	MMP3	1
DB04232	N-Hydroxy-1-(4-Methoxyphenyl)Sulfonyl-4-Benzyloxycarbonyl-Piperazine-2-Carboxamide	Small Molecule	MMP3	1
DB04416	R-2-{[4'-Methoxy-(1,1'-Biphenyl)-4-Yl]-Sulfonyl}-Amino-6-Methoxy-Hex-4-Ynoic Acid	Small Molecule	MMP3	1
DB07390	2-[3-(5-MERCAPTO-[1,3,4]THIADIAZOL-2-YL)-UREIDO]-N-METHYL-3-PHENYL-PROPIONAMIDE	Small Molecule	MMP3	1
DB07986	[4-(4-PHENYL-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-ACETIC ACID	Small Molecule	MMP3	1
DB07987	[2-(5-MERCAPTO-[1,3,4]THIADIAZOL-2-YLCARBAMOYL)-1-PHENYL-ETHYL]-CARBAMIC ACID BENZYL ESTER	Small Molecule	MMP3	1
DB07988	2-[3-(5-MERCAPTO-[1,3,4]THIADIAZOL-2YL)-UREIDO]-N-METHYL-3-PENTAFLUOROPHENYL-PROPIONAMIDE	Small Molecule	MMP3	1
DB08029	N~2~-(biphenyl-4-ylsulfonyl)-N-hydroxy-N~2~-(2-hydroxyethyl)glycinamide	Small Molecule	MMP3	1
DB08030	3-[(4'-cyanobiphenyl-4-yl)oxy]-N-hydroxypropanamide	Small Molecule	MMP3	1
DB08271	N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID	Small Molecule	MMP10, MMP12, MMP20, MMP3	4
DB08507	N-[[2-METHYL-4-HYDROXYCARBAMOYL]BUT-4-YL-N]-BENZYL-P-[PHENYL]-P-[METHYL]PHOSPHINAMID	Small Molecule	MMP3	1
DB08643	2-(2-{2-[(BIPHENYL-4-YLMETHYL)-AMINO]-3-MERCAPTO-PENTANOYLAMINO}-ACETYLAMINO)-3-METHYL-BUTYRIC ACID METHYL ESTER	Small Molecule	MMP3	1

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