TISIDB

Summary
Symbol	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
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 Secreted
Domain	PF00045 Hemopexin PF00413 Matrixin PF01471 Putative peptidoglycan binding domain
Function	Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.

> Gene Ontology [ TOP ]
Biological Process	GO:0001501 skeletal system development GO:0001503 ossification GO:0001958 endochondral ossification GO:0003416 endochondral bone growth GO:0003417 growth plate cartilage development GO:0022617 extracellular matrix disassembly GO:0030198 extracellular matrix organization GO:0030282 bone mineralization GO:0030574 collagen catabolic process GO:0031214 biomineral tissue development GO:0032963 collagen metabolic process GO:0035265 organ growth GO:0036075 replacement ossification GO:0043062 extracellular structure organization GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0048705 skeletal system morphogenesis GO:0051216 cartilage development GO:0060348 bone development GO:0060349 bone morphogenesis GO:0060350 endochondral bone morphogenesis GO:0060351 cartilage development involved in endochondral bone morphogenesis GO:0061448 connective tissue development GO:0098868 bone growth
Molecular Function	GO:0004175 endopeptidase activity GO:0004222 metalloendopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0005518 collagen binding 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	-
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-1474228: Degradation of the extracellular matrix R-HSA-1474244: Extracellular matrix organization

Summary
Symbol	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MMP13 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 MMP13 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	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
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 MMP13 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	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
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 MMP13 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	-2.073	0.0328
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-3.63	0.0155
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.966	0.517
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.293	0.0756
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.576	0.255
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.931	0.596
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-2.04	0.0717
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.957	0.224
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-2.052	0.234
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.663	0.323
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	-0.663	0.472
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-1.206	0.00893

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MMP13 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	4.1	-4.1	0.561
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	5.1	-5.1	0.549
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	5.9	8.4	0.613
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	15.4	9.1	6.3	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	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
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	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
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 MMP13. 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	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
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 MMP13. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MMP13. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
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 MMP13. 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	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MMP13 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MMP13 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MMP13
Name	matrix metallopeptidase 13
Aliases	CLG3; collagenase 3; matrix metalloproteinase 13 (collagenase 3); MANDP1; MMP-13; matrix metallopeptidase 13 ......
Chromosomal Location	11q22.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MMP13 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MMP13.

ID	Name	Drug Type	Targets	#Targets
DB00786	Marimastat	Small Molecule	MMP1, MMP10, MMP11, MMP12, MMP13, MMP14, MMP15, MMP16, MMP17, MMP1 ......	23
DB01996	3-Methylpyridine	Small Molecule	MMP13, MMP3	2
DB02049	2-{4-[4-(4-Chloro-Phenoxy)-Benzenesulfonyl]-Tetrahydro-Pyran-4-Yl}-N-Hydroxy-Acetamide	Small Molecule	MMP13	1
DB02071	WAY-151693	Small Molecule	MMP13	1
DB02697	Hydroxyaminovaline	Small Molecule	MMP13, MMP3	2
DB03033	1-Methyloxy-4-Sulfone-Benzene	Small Molecule	MMP13, MMP3	2
DB04759	PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-(3-METHYL-BENZYLAMIDE)	Small Molecule	MMP13	1
DB04760	PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-(4-FLUORO-3-METHYL-BENZYLAMIDE)	Small Molecule	MMP13	1
DB04761	PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-[(PYRIDIN-3-YLMETHYL)-AMIDE]	Small Molecule	MMP13	1
DB07013	TERT-BUTYL 4-({[4-(BUT-2-YN-1-YLAMINO)PHENYL]SULFONYL}METHYL)-4-[(HYDROXYAMINO)CARBONYL]PIPERIDINE-1-CARBOXYLATE	Small Molecule	MMP13	1
DB07827	4-{[1-METHYL-2,4-DIOXO-6-(3-PHENYLPROP-1-YN-1-YL)-1,4-DIHYDROQUINAZOLIN-3(2H)-YL]METHYL}BENZOIC ACID	Small Molecule	MMP13	1
DB08388	5-(2-ETHOXYETHYL)-5-[4-(4-FLUOROPHENOXY)PHENOXY]PYRIMIDINE-2,4,6(1H,3H,5H)-TRIONE	Small Molecule	MMP13	1
DB08490	CTS-1027	Small Molecule	MMP13	1
DB08561	BENZYL 6-BENZYL-5,7-DIOXO-6,7-DIHYDRO-5H-[1,3]THIAZOLO[3,2-C]PYRIMIDINE-2-CARBOXYLATE	Small Molecule	MMP13	1

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