Gene description for TIMP2
Gene name TIMP metallopeptidase inhibitor 2
Gene symbol TIMP2
Other names/aliases CSC-21K
DDC8
Species Homo sapiens
 Database cross references - TIMP2
ExoCarta ExoCarta_7077
Vesiclepedia VP_7077
Entrez Gene 7077
HGNC 11821
MIM 188825
UniProt P16035  
 TIMP2 identified in exosomes derived from the following tissue/cell type
Bone marrow mesenchymal stem cells 36408942    
Bone marrow mesenchymal stem cells 36408942    
Bone marrow mesenchymal stem cells 36408942    
Bone marrow mesenchymal stem cells 36408942    
Chondrocytes 35931686    
Chondrocytes 35931686    
Chondrocytes 35931686    
Chondrocytes 35931686    
Colorectal cancer cells 23161513    
Colorectal cancer cells 23161513    
Colorectal cancer cells 23161513    
Hepatocellular carcinoma cells 26054723    
Mesenchymal stem cells Unpublished / Not applicable
Mesenchymal stem cells 25669974    
Prostate cancer cells 25857301    
 Gene ontology annotations for TIMP2
Molecular Function
    integrin binding GO:0005178 IEA
    metal ion binding GO:0046872 IEA
    metalloendopeptidase inhibitor activity GO:0008191 IEA
    enzyme activator activity GO:0008047 IEA
    protease binding GO:0002020 IBA
    protein binding GO:0005515 IPI
Biological Process
    extracellular matrix organization GO:0030198 TAS
    response to drug GO:0042493 IEA
    negative regulation of metalloenzyme activity GO:0048553 IBA
    central nervous system development GO:0007417 IEA
    extracellular matrix disassembly GO:0022617 TAS
    cellular response to organic substance GO:0071310 IEA
    regulation of Rap protein signal transduction GO:0032487 IEA
    negative regulation of mitotic cell cycle GO:0045930 IEA
    positive regulation of adenylate cyclase activity GO:0045762 IEA
    negative regulation of cell proliferation GO:0008285 IEA
    negative regulation of endopeptidase activity GO:0010951 TAS
    positive regulation of MAPK cascade GO:0043410 IEA
    response to hormone GO:0009725 IBA
    positive regulation of neuron differentiation GO:0045666 IEA
    negative regulation of Ras protein signal transduction GO:0046580 IEA
    negative regulation of membrane protein ectodomain proteolysis GO:0051045 IBA
    response to cytokine GO:0034097 IBA
    aging GO:0007568 IEA
Subcellular Localization
    proteinaceous extracellular matrix GO:0005578 IBA
    growth cone GO:0030426 IEA
    cell surface GO:0009986 IEA
    extracellular region GO:0005576 TAS
    extracellular space GO:0005615 IBA
    neuronal cell body GO:0043025 IEA
    basement membrane GO:0005604 IEA
    extracellular exosome GO:0070062 IDA
 Experiment description of studies that identified TIMP2 in exosomes
1
Experiment ID 489
MISEV standards
✔
EM
EV Biophysical techniques
✔
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
EV Enriched markers
✔
Canx
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ.
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 6
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
2
Experiment ID 490
MISEV standards
✔
EM
EV Biophysical techniques
✔
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
EV Enriched markers
✔
Canx
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ.
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 7
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
3
Experiment ID 491
MISEV standards
✔
EM
EV Biophysical techniques
✔
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
EV Enriched markers
✔
Canx
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ.
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 8
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
4
Experiment ID 492
MISEV standards
✔
EM
EV Biophysical techniques
✔
Cd9|Cd81|Cd63|Gapdh|Sdcbp|Lamp1|Aqp1|Rab5a|Icam1|Cd82|Itga2b|Tsg101|Lamp2|Rab35|Flot1|Flot2|Cd151|Rab5b|Tfrc|Uchl1
EV Enriched markers
✔
Canx
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 36408942    
Organism Rattus norvegicus
Experiment description Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells
Authors Xu X, Yin F, Guo M, Gan G, Lin G, Wen C, Wang J, Song P, Wang J, Qi ZQ, Zhong CQ.
Journal name Proteomics
Publication year 2023
Sample Bone marrow mesenchymal stem cells
Sample name BMSC - Passage 9
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
5
Experiment ID 494
MISEV standards
✔
EM
EV Biophysical techniques
✔
CD9|CD81|CD151|CD63|CD82|FLOT1|FLOT2|GAPDH|LAMP1|LAMP2|SDCBP|TFRC|TSG101
EV Enriched markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35931686    
Organism Homo sapiens
Experiment description Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors Varela-Eirín M, Carpintero-Fernández P, Guitián-Caamaño A, Varela-Vázquez A, García-Yuste A, Sánchez-Temprano A, Bravo-López SB, Yañez-Cabanas J, Fonseca E, Largo R, Mobasheri A, Caeiro JR, Mayán MD.
Journal name Cell Death Dis
Publication year 2022
Sample Chondrocytes
Sample name Osteoarthritic cartilage
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
6
Experiment ID 496
MISEV standards
✘ EV Biophysical techniques
✔
CD9|CD151|CD63|CD81|CD82|FLOT1|FLOT2|GAPDH|LAMP1|LAMP2|SDCBP|TFRC|TSG101
EV Enriched markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35931686    
Organism Homo sapiens
Experiment description Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors Varela-Eirín M, Carpintero-Fernández P, Guitián-Caamaño A, Varela-Vázquez A, García-Yuste A, Sánchez-Temprano A, Bravo-López SB, Yañez-Cabanas J, Fonseca E, Largo R, Mobasheri A, Caeiro JR, Mayán MD.
Journal name Cell Death Dis
Publication year 2022
Sample Chondrocytes
Sample name Healthy cartilage
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
7
Experiment ID 497
MISEV standards
✘ EV Biophysical techniques
✔
CD9|CD151|CD63|CD81|CD82|FLOT1|FLOT2|GAPDH|LAMP1|LAMP2|RAB5A|SDCBP|TFRC|TSG101|UCHL1
EV Enriched markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35931686    
Organism Homo sapiens
Experiment description Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors Varela-Eirín M, Carpintero-Fernández P, Guitián-Caamaño A, Varela-Vázquez A, García-Yuste A, Sánchez-Temprano A, Bravo-López SB, Yañez-Cabanas J, Fonseca E, Largo R, Mobasheri A, Caeiro JR, Mayán MD.
Journal name Cell Death Dis
Publication year 2022
Sample Chondrocytes
Sample name T/C-28a2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
8
Experiment ID 498
MISEV standards
✔
EM
EV Biophysical techniques
✔
CD9|CD151|CD63|CD81|CD82|FLOT1|FLOT2|GAPDH|LAMP1|LAMP2|RAB5A|SDCBP|TFRC|TSG101|UCHL1
EV Enriched markers
✘ EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule Protein
Identification method Mass spectrometry
PubMed ID 35931686    
Organism Homo sapiens
Experiment description Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells contributing to osteoarthritis progression
Authors Varela-Eirín M, Carpintero-Fernández P, Guitián-Caamaño A, Varela-Vázquez A, García-Yuste A, Sánchez-Temprano A, Bravo-López SB, Yañez-Cabanas J, Fonseca E, Largo R, Mobasheri A, Caeiro JR, Mayán MD.
Journal name Cell Death Dis
Publication year 2022
Sample Chondrocytes
Sample name T/C-28a2
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectometry
9
Experiment ID 207
MISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|HSP70|FLOT1
EV Enriched markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name DKO-1
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
10
Experiment ID 208
MISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|HSP70|FLOT1
EV Enriched markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name Dks-8
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
11
Experiment ID 209
MISEV standards
✘ EV Biophysical techniques
✔
TSG101|HSP70|FLOT1
EV Enriched markers
✔
VDAC
EV Negative markers
✔
NTA
EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 23161513    
Organism Homo sapiens
Experiment description Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.
Authors Demory Beckler M, Higginbotham JN, Franklin JL, Ham AJ, Halvey PJ, Imasuen IE, Whitwell C, Li M, Liebler DC, Coffey RJ.
Journal name Mol Cell Proteomics
Publication year 2012
Sample Colorectal cancer cells
Sample name DLD-1
Isolation/purification methods Differential centrifugation
Filtration
Flotation density -
Molecules identified in the study Protein
Methods used in the study Mass spectrometry
12
Experiment ID 235
MISEV standards
✔
EM
EV Biophysical techniques
✔
TSG101|Alix|HSC70|GAPDH
EV Enriched markers
✔
HSP90B1
EV Negative markers
✔
qNano
EV Particle analysis
Identified molecule mRNA
Identification method RNA Sequencing
PubMed ID 26054723    
Organism Homo sapiens
Experiment description Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs
Authors He M, Qin H, Poon TC, Sze SC, Ding X, Co NN, Ngai SM, Chan TF, Wong N
Journal name Carcinogenesis
Publication year 2015
Sample Hepatocellular carcinoma cells
Sample name HKCI-8
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Sucrose density gradient
Flotation density 1.13-1.19 g/mL
Molecules identified in the study Protein
RNA
Methods used in the study Western blotting
Mass spectrometry
RT-PCR
RNA Sequencing
13
Experiment ID 126
MISEV standards
✘ EV Biophysical techniques
✔
GAPDH
EV Enriched markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Antibody array
PubMed ID Unpublished / Not applicable
Organism Homo sapiens
Experiment description Mesenchymal Stem Cell Exosomes: The Future MSC-based Therapy?
Authors Ruenn Chai Lai, Ronne Wee Yeh Yeo, Soon Sim Tan, Bin Zhang, Yijun Yin, Newman Siu Kwan Sze, Andre Choo, and Sai Kiang Lim
Journal name Mesenchymal Stem Cell Therapy
Publication year 2011
Sample Mesenchymal stem cells
Sample name huES9.E1
Isolation/purification methods HPLC
Flotation density -
Molecules identified in the study Protein
Methods used in the study Western blotting
Antobody array
Mass spectrometry
14
Experiment ID 261
MISEV standards
✔
EM
EV Biophysical techniques
✔
CD63|CD81|LAMP2|CD9
EV Enriched markers
✘ EV Negative markers
✔
Y
EV Particle analysis
Identified molecule protein
Identification method Western blotting
PubMed ID 25669974    
Organism Homo sapiens
Experiment description Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins,and metabolites
Authors Krishna C. Vallabhaneni1, Patrice Penfornis, Santosh Dhule, Francois Guillonneau, Kristen V. Adams, Yin Yuan Mo, Rui Xu, Yiming Liu, Kounosuke Watabe, Mohan C. Vemuri and Radhika Pochampally
Journal name Oncotarget
Publication year 2014
Sample Mesenchymal stem cells
Sample name hMSCs
Isolation/purification methods Differential centrifugation
Filtration
Ultracentrifugation
Flotation density -
Molecules identified in the study Protein
miRNA
Lipids
Metabolites
Methods used in the study Western blotting
Mass spectrometry
RT-PCR
Sequencing
15
Experiment ID 250
MISEV standards
✔
EM
EV Biophysical techniques
✔
GAPDH|TSG101|CD63|CD81
EV Enriched markers
✘ EV Negative markers
✘ EV Particle analysis
Identified molecule protein
Identification method Mass spectrometry
PubMed ID 25857301    
Organism Homo sapiens
Experiment description Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles.
Authors Minciacchi VR, You S, Spinelli C, Morley S, Zandian M, Aspuria PJ, Cavallini L, Ciardiello C, Reis Sobreiro M, Morello M, Kharmate G, Jang SC, Kim DK, Hosseini-Beheshti E, Tomlinson Guns E, Gleave M, Gho YS, Mathivanan S, Yang W, Freeman MR, Di Vizio D
Journal name Oncotarget
Publication year 2015
Sample Prostate cancer cells
Sample name DU145 - expressing DIAPH3 hRNA
Isolation/purification methods Differential centrifugation
Ultracentrifugation
OptiPrep density gradient
Flotation density 1.10 g/mL
Molecules identified in the study Protein
Methods used in the study Western blotting
Mass spectrometry
 Protein-protein interactions for TIMP2
  Protein Interactor ExoCarta ID Identification method PubMed Species
1 SNCG 6623
Affinity Capture-MS Homo sapiens
2 MMP8  
Invitro Homo sapiens
3 MMP2 4313
Invitro Homo sapiens
Invitro Homo sapiens
Two-hybrid Homo sapiens
Two-hybrid Homo sapiens
Co-crystal Structure Homo sapiens
Reconstituted Complex Homo sapiens
Two-hybrid Homo sapiens
4 MMP14 4323
Affinity Capture-Western Homo sapiens
Reconstituted Complex Homo sapiens
5 PSMA7 5688
Affinity Capture-MS Homo sapiens
View the network image/svg+xml
 Pathways in which TIMP2 is involved
PathwayEvidenceSource
Activation of Matrix Metalloproteinases TAS Reactome





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