1. Home
  2. Targets
  3. Collagenase 3

Tchem Collagenase 3

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.

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

 Comments

Property Summary

NCBI Gene PubMed Count 259
Grant Count 375
R01 Count 282
Funding $27,823,983.36
PubMed Score 1132.95
PubTator Score 649.81

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Relevance (21)

Disease Z-score Confidence
Osteoarthritis 96 7.242 3.6
Degenerative disc disease 28 4.884 2.4
Rheumatoid Arthritis 1,160 4.523 2.3
Cancer 2,346 4.379 2.2
periodontitis 269 3.776 1.9
Synovitis 38 3.359 1.7
Vascular disease 281 3.252 1.6
Breast cancer 3,094
Craniofacial Abnormalities 147
Liver Cirrhosis, Experimental 108
Metaphyseal anadysplasia 2
Metaphyseal chondrodysplasia Spahr type 1
Prostatic Neoplasms 471
Spondyloepimetaphyseal Dysplasia, Missou... 1 
colon cancer 1,475
cutaneous lupus erythematosus 1,056
head and neck cancer 270
head and neck cancer and chronic obstruc... 237 
invasive ductal carcinoma 2,950
lung adenocarcinoma 2,713
non-small cell lung cancer 2,798

Expression

  Differential Expression (9)

Disease log2 FC p
cutaneous lupus erythematosus 1.700 0.046
periodontitis 1.100 0.000
non-small cell lung cancer 1.825 0.000
colon cancer 1.100 0.041
lung adenocarcinoma 1.700 0.000
invasive ductal carcinoma 1.222 0.033
Breast cancer 1.500 0.000
head and neck cancer 1.300 0.021
head and neck cancer and chronic obstruc... 1.300 0.012

Synonym

Accession P45452 A8K846 B2RCZ3 Q6NWN6
Symbols CLG3
MDST
MANDP1
MMP-13

Gene

MMP13

 Grant Application (375)

See all...

PDB

1EUB   1FLS   1FM1   1PEX   1UC1   1XUC   1XUD   1XUR   1YOU   1ZTQ   2D1N   2E2D   2OW9   2OZR   2PJT   2YIG   3ELM   3I7G   3I7I   3KEC   3KEJ   3KEK   3KRY   3LJZ   3O2X   3TVC   3WV1   3WV2   3WV3   3ZXH   456C   4A7B   4FU4   4FVL   4G0D   4JP4   4JPA   4L19   5BOT   5BOY   5BPA   830C  

 GO Function (5)

 GO Component (3)

 GO Process (8)

 Compartment GO Term (24)

See all...

 OMIM Term (3)

 MGI Term (6)

Pathway (25)

See all...

 UniProt Keyword (22)

See all...

Ligand (2,029)

Structure of CHEMBL250503

CHEMBL250503
pIC50 6.00

Structure of CHEMBL1940299

CHEMBL1940299
pIC50 6.00

Structure of CHEMBL319055

CHEMBL319055
pIC50 6.00

Structure of CHEMBL584559

CHEMBL584559
pIC50 6.01

Structure of CHEMBL311768

CHEMBL311768
pIC50 6.01

Structure of CHEMBL250710

CHEMBL250710
pIC50 6.02

Structure of CHEMBL70207

CHEMBL70207
pIC50 6.02

Structure of CHEMBL185279

CHEMBL185279
pKi 6.02

Structure of CHEMBL19179

CHEMBL19179
pIC50 6.02

Structure of CHEMBL496423

CHEMBL496423
pIC50 6.03

Structure of CHEMBL579067

CHEMBL579067
pIC50 6.03

Structure of CHEMBL1784339

CHEMBL1784339
pIC50 6.03

Structure of CHEMBL3358155

CHEMBL3358155
pIC50 6.03

Structure of CHEMBL3675599

CHEMBL3675599
pKi 6.03

Structure of CHEMBL181022

CHEMBL181022
pKi 6.03

Structure of CHEMBL276275

CHEMBL276275
pIC50 6.04

Structure of CHEMBL329043

CHEMBL329043
pKi 6.04

Structure of CHEMBL473326

CHEMBL473326
pIC50 6.04

Structure of CHEMBL3350685

CHEMBL3350685
pIC50 6.05

Structure of CHEMBL3675545

CHEMBL3675545
pKi 6.05

MLP Assay (6)

AID Type Active / Inconclusive / Inactive Description
570 screening 46 / 0 / 64879 Primary biochemical high-throughput screening assay for inhibitors of Matrix Metalloproteinase 13 (MMP13) activity
734 screening 8 / 0 / 5141 Assay to identify inhibitors among the possible fluorescent artifacts from the primary HTS inhibition assay of Matrix Metalloproteinase 13 (MMP13) activity
735 confirmatory 15 / 0 / 27 Dose-response biochemical assay for inhibitors of Matrix Metalloproteinase 13 (MMP13) activity
769 confirmatory 4 / 0 / 4 Dose response biochemical assay for autofluorescent inhibitors of Matrix Metalloproteinase 13 (MMP13) activity
1931 summary 2 / 0 / 0 Summary of probe development efforts to identify inhibitors of Matrix Metalloproteinase-13 (MMP-13)
2067 screening 9 / 0 / 0 Late stage results from the probe development efforts to identify inhibitors of Matrix Metalloproteinase-13 (MMP-13).

Gene RIF (242)

PMID Text
26934732 Hyaluronic acid exhibits a pronounced suppressive effect on MMP-13 expression in osteoarthritis.
26474296 IL-1Ra is associated with MMP-13 expression and has a novel function in such regulation without interference of the IL-1 signaling cascade.
26447617 Report modified platelet deposition on matrix metalloproteinase 13 digested collagen I
26395178 Data show that the expression of transforming growth factor beta 1 (TGFB1) was correlated with the expression of SMA- and MAD-related protein 3 (SMAD3) and matrix metalloproteinase-13 (MMP13) in osteoarthritis (OA)-affected cartilage.
26378022 GP73 enhances MMP-13 expression through cAMP responsive element binding protein (CREB)-mediated transcription activation. Levels of GP73 and MMP-13 are increased and positively correlated in human HCC tissues. Augmented MMP-13 potentiates HCC cell metastasis.
26369384 SENP2 inhibits MMP13 expression in BC cells through de-SUMOylation of TBL1/TBLR1, which inhibits nuclear translocation of beta-catenin.
26362844 siRNA inhibited the effect of MMP13-containing exosomes on tumor cells metastasis as well as angiogenesis
26308852 RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13
26305549 Data show that blocking the interleukin-8 (IL-8)/androgen receptor (AR)/matrix metalloproteinases (MMPs) signals partially reversed the infiltrating B cells capacity to increase the bladder cancer (BCa) cell invasion.
26305372 together, these data demonstrate that SERPINE2 might prevent cartilage catabolism by inhibiting the expression of MMP-13, one of the most relevant collagenases, involved in cartilage breakdown in OA.
More...

AA Sequence 

MHPGVLAAFLFLSWTHCRALPLPSGGDEDDLSEEDLQFAERYLRSYYHPTNLAGILKENAASSMTERLRE      1 - 70
MQSFFGLEVTGKLDDNTLDVMKKPRCGVPDVGEYNVFPRTLKWSKMNLTYRIVNYTPDMTHSEVEKAFKK     71 - 140
AFKVWSDVTPLNFTRLHDGIADIMISFGIKEHGDFYPFDGPSGLLAHAFPPGPNYGGDAHFDDDETWTSS    141 - 210
SKGYNLFLVAAHEFGHSLGLDHSKDPGALMFPIYTYTGKSHFMLPDDDVQGIQSLYGPGDEDPNPKHPKT    211 - 280
PDKCDPSLSLDAITSLRGETMIFKDRFFWRLHPQQVDAELFLTKSFWPELPNRIDAAYEHPSHDLIFIFR    281 - 350
GRKFWALNGYDILEGYPKKISELGLPKEVKKISAAVHFEDTGKTLLFSGNQVWRYDDTNHIMDKDYPRLI    351 - 420
EEDFPGIGDKVDAVYEKNGYIYFFNGPIQFEYSIWSNRIVRVMPANSILWC                       421 - 471
//

Text Mined References (273)

PMID Year Title
26934732 2016 Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1? and Mechanical Load.
26474296 2015 Interleukin-1 Receptor Antagonist Has a Novel Function in the Regulation of Matrix Metalloproteinase-13 Expression.
26447617 2015 Modified platelet deposition on matrix metalloproteinase 13 digested collagen I.
26395178 2015 Overexpression of MMP13 in human osteoarthritic cartilage is associated with the SMAD-independent TGF-? signalling pathway.
26378022 2015 Golgi protein 73 activation of MMP-13 promotes hepatocellular carcinoma cell invasion.
26369384 2015 SENP2 regulates MMP13 expression in a bladder cancer cell line through SUMOylation of TBL1/TBLR1.
26362844 2015 Matrix metalloproteinase 13-containing exosomes promote nasopharyngeal carcinoma metastasis.
26308852 2015 RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.
26305549 2015 Tumor microenvironment B cells increase bladder cancer metastasis via modulation of the IL-8/androgen receptor (AR)/MMPs signals.
26305372 2015 SERPINE2 Inhibits IL-1?-Induced MMP-13 Expression in Human Chondrocytes: Involvement of ERK/NF-?B/AP-1 Pathways.
More...