MMP2 (matrix metallopeptidase 2)

Gene

• Entrez ID: 4313
• Gene name: Matrix metallopeptidase 2
• Gene symbol: MMP2
• Synonyms: CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1
• Chromosome: 16
• Chromosome location: 16q12.2
• Summary: This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs41459945	G>A,C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs121912953	G>A	Pathogenic	Coding sequence variant, missense variant
rs121912954	C>A,G	Pathogenic	Coding sequence variant, stop gained
rs121912955	G>A	Pathogenic	Coding sequence variant, missense variant
rs140172728	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Synonymous variant, coding sequence variant
rs148801200	C>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, synonymous variant
rs786205497	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs794727275	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs794727916	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1567378779	C>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005570	hsa-miR-29b-3p	Luciferase reporter assay, qRT-PCR, Western blot	20657750
MIRT005570	hsa-miR-29b-3p	Western blot	23254643
MIRT005570	hsa-miR-29b-3p	Western blot	24130681
MIRT005570	hsa-miR-29b-3p	Immunofluorescence, Immunohistochemistry, Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	24130168
MIRT005570	hsa-miR-29b-3p	Microarray	22942087
MIRT005570	hsa-miR-29b-3p	Western blot	24147037
MIRT005570	hsa-miR-29b-3p	Luciferase reporter assay, qRT-PCR	23354167
MIRT005570	hsa-miR-29b-3p	Luciferase reporter assay	22745231
MIRT005570	hsa-miR-29b-3p	Luciferase reporter assay, qRT-PCR, Western blot	26063204
MIRT005742	hsa-miR-451a	qRT-PCR, Western blot	20816946
MIRT005742	hsa-miR-451a	qRT-PCR, Western blot	27173190
MIRT018099	hsa-miR-335-5p	Microarray	18185580
MIRT019228	hsa-miR-338-3p	Western blot;qRT-PCR	21671467
MIRT030716	hsa-miR-21-5p	qRT-PCR	19435867
MIRT031370	hsa-miR-17-5p	Western blot	20209605
MIRT053245	hsa-miR-29c-3p	qRT-PCR, Western blot	23175151
MIRT053245	hsa-miR-29c-3p	Immunofluorescence, Immunohistochemistry, Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	24130168
MIRT053245	hsa-miR-29c-3p	Luciferase reporter assay, qRT-PCR, Western blot	23936390
MIRT053245	hsa-miR-29c-3p	Luciferase reporter assay	22745231
MIRT053336	hsa-miR-491-5p	Immunohistochemistry, Microarray, qRT-PCR, Western blot	23725476
MIRT053481	hsa-miR-9-5p	qRT-PCR	21931274
MIRT053580	hsa-miR-29a-3p	Immunofluorescence, Immunohistochemistry, Luciferase reporter assay, Northern blot, qRT-PCR, Western blot	24130168
MIRT053580	hsa-miR-29a-3p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	24210072
MIRT053580	hsa-miR-29a-3p	Luciferase reporter assay	22745231
MIRT053580	hsa-miR-29a-3p	Luciferase reporter assay	26700017
MIRT053787	hsa-miR-452-5p	Microarray, qRT-PCR	22952876
MIRT437388	hsa-miR-708-5p	Flow, qRT-PCR, Western blot	23754151
MIRT437572	hsa-miR-767-5p	Luciferase reporter assay	22745231
MIRT438153	hsa-miR-106b-5p	Luciferase reporter assay	24164962
MIRT438234	hsa-miR-221-3p	Western blot	24147037
MIRT440222	hsa-miR-544a	HITS-CLIP	24374217
MIRT724933	hsa-miR-1238-3p	HITS-CLIP	19536157
MIRT724934	hsa-miR-670-3p	HITS-CLIP	19536157
MIRT724935	hsa-miR-29b-2-5p	HITS-CLIP	19536157
MIRT724936	hsa-miR-6749-3p	HITS-CLIP	19536157
MIRT724937	hsa-miR-6792-3p	HITS-CLIP	19536157
MIRT724938	hsa-miR-4691-5p	HITS-CLIP	19536157
MIRT731061	hsa-miR-130b-3p	qRT-PCR, Luciferase reporter assay, Western blot	25154741
MIRT731453	hsa-miR-125b-5p	Luciferase reporter assay	27133077
MIRT732848	hsa-miR-520g-3p	In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	28292471
MIRT733143	hsa-miR-524-5p	qRT-PCR, Western blot	26998102
MIRT733418	hsa-miR-302a-5p	ELISA, Western blot	26191138
MIRT734261	hsa-miR-218-5p	qRT-PCR, Western blot	26133092
MIRT734404	hsa-miR-203a-5p	Western blot	26278219
MIRT734784	hsa-miR-143-3p	qRT-PCR, Western blot	26722463
MIRT734996	hsa-miR-519d-3p	Luciferase reporter assay	25803859

Transcription factors

Transcription factor	Regulation	Reference
ATF2	Activation	17079470;17258390
ATF3	Repression	11792711;15102941
CEBPE	Unknown	19853299
CREB1	Unknown	10506168
ETS2	Unknown	19939245;22108824
ETV4	Unknown	10506168;15317818
ETV5	Unknown	22968857
EZH2	Activation	21629038
HDAC3	Repression	17079677
HIF1A	Activation	17335808
HIF1A	Repression	17332917;18570733
HOXB7	Activation	21183939
HTATIP2	Repression	19349353
JUN	Activation	15777790
KLF4	Activation	22407433
MSC	Activation	18279606
MZF1	Repression	22846578
NFKB1	Activation	17498959;19303700;20352621
NR4A1	Activation	22551568
PAX6	Unknown	17047041
RELA	Activation	17498959;19303700;20352621
RUNX2	Activation	22641097
SP1	Activation	21469139
SP1	Unknown	10506168;15317818;19853299;21045016
SP3	Unknown	15317818
SRF	Activation	12654640
SSX2	Unknown	15781633
STAT3	Activation	17533737;19284568;20069389
STAT3	Repression	17533737
STAT3	Unknown	16540670
TFAP2A	Unknown	10506168;10589685;19853299;19939245;20145123
TFAP2C	Unknown	19853299
TP53	Activation	10029407;11792711;9343394
TP53	Unknown	19853299;19939245
TWIST1	Activation	20646316
TWIST2	Activation	20646316
YBX1	Unknown	10589685

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEA
GO:0001666	Process	Response to hypoxia	IBA	21873635
GO:0001955	Process	Blood vessel maturation	IEA
GO:0001957	Process	Intramembranous ossification	IEA
GO:0004175	Function	Endopeptidase activity	IDA	23845380
GO:0004222	Function	Metalloendopeptidase activity	IBA	21873635
GO:0004222	Function	Metalloendopeptidase activity	TAS
GO:0004252	Function	Serine-type endopeptidase activity	EXP	17428795
GO:0004252	Function	Serine-type endopeptidase activity	TAS
GO:0005515	Function	Protein binding	IPI	12032297, 20979576, 21441952, 25613181, 25897080, 28106549, 28514442, 32296183, 32814053
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	20551380
GO:0005615	Component	Extracellular space	IDA	18492766, 24236012, 24784232
GO:0005634	Component	Nucleus	IEA
GO:0005739	Component	Mitochondrion	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0006508	Process	Proteolysis	IDA	15863497
GO:0007566	Process	Embryo implantation	IEA
GO:0008237	Function	Metallopeptidase activity	IDA	24236012
GO:0008270	Function	Zinc ion binding	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0022617	Process	Extracellular matrix disassembly	TAS	24970228
GO:0030017	Component	Sarcomere	IEA
GO:0030198	Process	Extracellular matrix organization	IBA	21873635
GO:0030574	Process	Collagen catabolic process	IBA	21873635
GO:0030574	Process	Collagen catabolic process	TAS
GO:0034614	Process	Cellular response to reactive oxygen species	IEA
GO:0035987	Process	Endodermal cell differentiation	IEP	23154389
GO:0044267	Process	Cellular protein metabolic process	TAS
GO:0048013	Process	Ephrin receptor signaling pathway	TAS
GO:0048771	Process	Tissue remodeling	IBA	21873635
GO:0060325	Process	Face morphogenesis	IEA
GO:0060346	Process	Bone trabecula formation	IEA
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	23979707
GO:0062023	Component	Collagen-containing extracellular matrix	HDA	28327460
GO:0071230	Process	Cellular response to amino acid stimulus	IEA
GO:0071492	Process	Cellular response to UV-A	IDA	31380578
GO:1904645	Process	Response to amyloid-beta	ISS
GO:1904707	Process	Positive regulation of vascular associated smooth muscle cell proliferation	IMP	18667463

Other IDs

• MIM: 120360
• HGNC: 7166
• e!Ensembl: ENSG00000087245

Protein

• UniProt ID: P08253
• Protein name: 72 kDa type IV collagenase (EC 3.4.24.24) (72 kDa gelatinase) (Gelatinase A) (Matrix metalloproteinase-2) (MMP-2) (TBE-1) [Cleaved into: PEX]
• Protein function: Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.; PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.; [Isoform 2]: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
• PDB: 1CK7, 1CXW, 1EAK, 1GEN, 1GXD, 1HOV, 1J7M, 1KS0, 1QIB, 1RTG, 3AYU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01471	PG_binding_1	43 → 97	Putative peptidoglycan binding domain	Domain
  PF00413	Peptidase_M10	118 → 446	Matrixin	Domain
  PF00040	fn2	233 → 274	Fibronectin type II domain	Domain
  PF00040	fn2	291 → 332	Fibronectin type II domain	Domain
  PF00040	fn2	349 → 390	Fibronectin type II domain	Domain
  PF00045	Hemopexin	475 → 518	Hemopexin	Repeat
  PF00045	Hemopexin	520 → 563	Hemopexin	Repeat
  PF00045	Hemopexin	568 → 615	Hemopexin	Repeat
  PF00045	Hemopexin	617 → 660	Hemopexin	Repeat

• Sequence:

  MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
  PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
  KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
  GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
  GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
  SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
  ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
  MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
  IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
  WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
  GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
  

• Sequence length: 660