Details of the Target

General Information of Target

Target ID LDTP02267
Target Name 72 kDa type IV collagenase (MMP2)
Gene Name MMP2
Gene ID 4313
Synonyms
CLG4A; 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]
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD
KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD
GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN
GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT
SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY
ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL
MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ
IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY
WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP
GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC
Target Type
Successful
Target Bioclass
Enzyme
Family
Peptidase M10A family
Subcellular location
Cytoplasm; Secreted, extracellular space, extracellular matrix
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.
TTD ID
T68251
Uniprot ID
P08253
DrugMap ID
TTDO3RC
Ensemble ID
ENST00000219070.9
HGNC ID
HGNC:7166
ChEMBL ID
CHEMBL333

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.I128L .
HT115 SNV: p.E641D .
IGROV1 SNV: p.M170V .
IPC298 SNV: p.G505R .
KMRC1 SNV: p.P506R .
MCC26 SNV: p.A278V; p.G318D DBIA    Probe Info 
NCIH1793 SNV: p.A29P .
NCIH716 SNV: p.N380H .
REH SNV: p.Y110C .
RKO SNV: p.M5I DBIA    Probe Info 
SISO SNV: p.R385H .
SW1271 SNV: p.E404G .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FBPP2
 Probe Info  		24.07  LDD0318  [1]
DBIA
 Probe Info  		C60(1.58)  LDD3332  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A-172 C60(1.50)  LDD2251  [2]
 LDCM0023  KB03 A-172 C60(2.22); C65(3.35)  LDD2668  [2]
 LDCM0024  KB05 MKN45 C60(1.58)  LDD3332  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Proprotein convertase subtilisin/kexin type 9 (PCSK9) Peptidase S8 family Q8NBP7
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Amyloid-beta precursor protein (APP) APP family P05067
Other
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Collagen alpha-1(V) chain (COL5A1) Fibrillar collagen family P20908
Metalloproteinase inhibitor 2 (TIMP2) Protease inhibitor I35 (TIMP) family P16035
Signal peptide, CUB and EGF-like domain-containing protein 3 (SCUBE3) . Q8IX30

The Drug(s) Related To This Target

Approved
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Captopril Small molecular drug DB01197
Prinomastat Small molecular drug D00MDP
Phase 3
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Epigallocatechin Gallate Small molecular drug D0U2BH
Marimastat Small molecular drug D05VZE
Phase 1
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Metastat Small molecular drug D0IJ7O
Neovastat . D0T4BL
Preclinical
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ro-26-2853 . D0C0ME
Investigative
Click To Hide/Show 34 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(+/-)5-(Biphenyl-4-yl)-3-hydroxypentanoic Acid Small molecular drug D0G3YZ
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic Acid Small molecular drug D0E5MB
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide Small molecular drug D05THD
3-(4-(2-phenylethynyl)Benzoyl)Pentanoic Acid Small molecular drug D0L4EO
3-(4-phenylethynylbenzoyl)Nonanoic Acid Small molecular drug D0A5MV
4-(4-(Dec-1-ynyl)Phenyl)-4-oxobutanoic Acid Small molecular drug D05JPV
5-(4-phenoxy-phenyl)-pyrimidine-2,4,6-trione Small molecular drug D07LTB
5-biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione Small molecular drug D0Y7NV
5-biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione Small molecular drug D0Q9LC
5-hexyl-5-phenyl-pyrimidine-2,4,6-trione Small molecular drug D0K4TI
Cis-2-aminocyclohexylcarbamoylphosphonic Acid Small molecular drug D0T1FR
Clinopodic Acid C Small molecular drug D0H9BL
Folate Gamma-hydroxamic Acid Small molecular drug D0P8EY
Folate Gamma-l-proline-hydroxamic Acid Small molecular drug D0ZB6O
Ik-862 Small molecular drug D0W2UK
Lithospermic Acid Small molecular drug D06ALC
Methotrexate Gamma-hydroxamic Acid Small molecular drug D0B0UI
Methotrexate Gamma-l-proline-hydroxamic Acid Small molecular drug D01HKU
Mmi270 Small molecular drug D0A4TC
N-hydroxy-2-(4-phenoxy-benzenesulfonyl)Benzamide Small molecular drug D0S9OL
N-hydroxy-3-(2-oxo-2h-chromen-3-yl)Propanamide Small molecular drug D00RNA
N-hydroxy-3-(6-methoxy-2-oxo-2h-chromen-3-yl) Small molecular drug D08ICI
Pd-169469 Small molecular drug D02EFQ
Pnu-107859 Small molecular drug D0F7BE
Ro-37-9790 Small molecular drug D0XL8K
Roche 28-2653 Small molecular drug D0U7CD
Sc-74020 Small molecular drug D08NSS
Sr-973 Small molecular drug D03AMR
Uk-356618 Small molecular drug D0NP8A
[2-(Biphenyl-4-sulfonyl)Phenyl]Acetic Acid Small molecular drug D07MJD
Ae-941 . DB05387
Endostatin . DB06423
Halofuginone . DB04866
Oleandrin . DB12843
Patented
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pmid29130358-compound-figure10(2a) Small molecular drug D05GAP
Pmid29130358-compound-figure11(3) Small molecular drug D0Y1LO
Pmid29130358-compound-figure13(4) Small molecular drug D0Q4QB
Pmid29130358-compound-figure16(9a) Small molecular drug D0LS4Y
Pmid29130358-compound-figure16(9b) Small molecular drug D0A9ZW
Pmid29130358-compound-figure16(9c) Small molecular drug D0S3PN
Pmid29130358-compound-figure18(14) Small molecular drug D0O8RQ
Pmid29130358-compound-figure18(14a) Small molecular drug D0X6GG
Pmid29130358-compound-lonimacranthoidevii Small molecular drug D0W7HO
Pmid29130358-compound-sb-3ct Small molecular drug D0DB0Z
Discontinued
Click To Hide/Show 10 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bb-1101 Small molecular drug D05VNG
Bb-3644 Small molecular drug D08WBF
Bms 275291 Small molecular drug D01EUF
Galarubicin Small molecular drug D05WTZ
Gm6001 Small molecular drug D0T9HG
L-696418 Small molecular drug D08CEE
Rs-130830 Small molecular drug D03BOZ
Sc-44463 Small molecular drug D0Y1XT
Tanomastat Small molecular drug D0Q1CD
Cdp-845 . D02GYD

References

1 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840