TISIDB

Summary
Symbol	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
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	May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.

> Gene Ontology [ TOP ]
Biological Process	GO:0002011 morphogenesis of an epithelial sheet GO:0022617 extracellular matrix disassembly GO:0030198 extracellular matrix organization GO:0030574 collagen catabolic process GO:0032963 collagen metabolic process GO:0035313 wound healing, spreading of epidermal cells 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:0044319 wound healing, spreading of cells GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050679 positive regulation of epithelial cell proliferation GO:0060054 positive regulation of epithelial cell proliferation involved in wound healing GO:0090504 epiboly GO:0090505 epiboly involved in wound healing
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	-
Reactome	R-HSA-1442490: Collagen degradation R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1474244: Extracellular matrix organization

Summary
Symbol	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MMP12 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 MMP12 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21378275	Lung Adenocarcinoma	Inhibit immunity	Both in vitro and in vivo studies showed an immunosuppressive function on T-cell proliferation and function by CD11b(+)/Gr-1(+) immature cells from MMP12-overexpressing bitransgenic mice. MMP12 directly stimulated lineage-negative (Lin?) progenitor cells to differentiate into CD11b(+)/Gr-1(+) immature cells that showed immunosuppression on T-cell proliferation and function in vitro. Regulatory T cells (Tregs) were increased. In the lung, the concentration of IL-6 was increased, which aberrantly activated oncogenic Stat3 and increased expression of Stat3 downstream genes in epithelial tumor progenitor cells. Spontaneous emphysema and lung adenocarcinoma were sequentially developed after MMP12 overexpression. BM chimeras confirmed that the MMP12-induced myeloid cell autonomous defect led to abnormal myelopoiesis, immune suppression, and lung adenocarcinoma.

Summary
Symbol	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
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 MMP12 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	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
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 MMP12 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	-0.858	0.184
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.228	0.842
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.303	0.133
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.473	0.0436
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.812	0.252
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.041	0.609
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.547	0.596
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.851	0.597
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.494	0.754
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.564	0.104

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MMP12 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	3.7	5.5	-1.8	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	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	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MMP12. 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	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MMP12. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MMP12. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MMP12. 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	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MMP12 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MMP12 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MMP12
Name	matrix metallopeptidase 12
Aliases	HME; macrophage elastase; matrix metalloproteinase 12 (macrophage elastase); ME; MMP-12; matrix metallopepti ......
Chromosomal Location	11q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MMP12 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MMP12.

ID	Name	Drug Type	Targets	#Targets
DB00551	Acetohydroxamic Acid	Small Molecule	MMP12	1
DB00786	Marimastat	Small Molecule	MMP1, MMP10, MMP11, MMP12, MMP13, MMP14, MMP15, MMP16, MMP17, MMP1 ......	23
DB02118	CP-271485	Small Molecule	MMP12	1
DB03367	PF-00356231	Small Molecule	MMP12	1
DB03880	Batimastat	Small Molecule	ADAM28, ADAMTS5, MMP12, MMP16, MMP8	5
DB04405	2-[2-(1,3-Dioxo-1,3-Dihydro-2h-Isoindol-2-Yl)Ethyl]-4-(4'-Ethoxy-1,1'-Biphenyl-4-Yl)-4-Oxobutanoic Acid	Small Molecule	MMP12	1
DB05387	AE-941	Small Molecule	MMP12, MMP2, MMP9	3
DB07026	(1S,5S,7R)-N~7~-(BIPHENYL-4-YLMETHYL)-N~3~-HYDROXY-6,8-DIOXA-3-AZABICYCLO[3.2.1]OCTANE-3,7-DICARBOXAMIDE	Small Molecule	MMP12	1
DB07446	N-(biphenyl-4-ylsulfonyl)-D-leucine	Small Molecule	MMP12	1
DB07556	N-HYDROXY-2(R)-[[(4-METHOXYPHENYL)SULFONYL](3-PICOLYL)AMINO]-3-METHYLBUTANAMIDE HYDROCHLORIDE	Small Molecule	MMP1, MMP12	2
DB07683	N-(dibenzo[b,d]thiophen-3-ylsulfonyl)-L-valine	Small Molecule	MMP12	1
DB07920	N-oxo-2-[(4-phenylphenyl)sulfonylamino]ethanamide	Small Molecule	MMP12	1
DB07921	2-[(4-fluorophenyl)sulfonylamino]-N-oxo-ethanamide	Small Molecule	MMP12	1
DB07922	N-oxo-2-(phenylsulfonylamino)ethanamide	Small Molecule	MMP12	1
DB08271	N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID	Small Molecule	MMP10, MMP12, MMP20, MMP3	4
DB08599	N-[(4-methoxyphenyl)sulfonyl]-D-alanine	Small Molecule	MMP12	1

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