Browse TIMP3

Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
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
 
Subcellular Location Secreted, extracellular space, extracellular matrix.
Domain PF00965 Tissue inhibitor of metalloproteinase
Function

Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15.

> Gene Ontology
 
Biological Process GO:0001933 negative regulation of protein phosphorylation
GO:0002576 platelet degranulation
GO:0006509 membrane protein ectodomain proteolysis
GO:0006887 exocytosis
GO:0007601 visual perception
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0009894 regulation of catabolic process
GO:0009895 negative regulation of catabolic process
GO:0010466 negative regulation of peptidase activity
GO:0010951 negative regulation of endopeptidase activity
GO:0031329 regulation of cellular catabolic process
GO:0031330 negative regulation of cellular catabolic process
GO:0033619 membrane protein proteolysis
GO:0036462 TRAIL-activated apoptotic signaling pathway
GO:0042176 regulation of protein catabolic process
GO:0042177 negative regulation of protein catabolic process
GO:0042326 negative regulation of phosphorylation
GO:0043409 negative regulation of MAPK cascade
GO:0045055 regulated exocytosis
GO:0045861 negative regulation of proteolysis
GO:0050953 sensory perception of light stimulus
GO:0051043 regulation of membrane protein ectodomain proteolysis
GO:0051045 negative regulation of membrane protein ectodomain proteolysis
GO:0051346 negative regulation of hydrolase activity
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070373 negative regulation of ERK1 and ERK2 cascade
GO:0097191 extrinsic apoptotic signaling pathway
GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902043 positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1902532 negative regulation of intracellular signal transduction
GO:1903121 regulation of TRAIL-activated apoptotic signaling pathway
GO:1903984 positive regulation of TRAIL-activated apoptotic signaling pathway
GO:1904683 regulation of metalloendopeptidase activity
GO:1904684 negative regulation of metalloendopeptidase activity
GO:1905048 regulation of metallopeptidase activity
GO:1905049 negative regulation of metallopeptidase activity
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001236 regulation of extrinsic apoptotic signaling pathway
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
Molecular Function GO:0002020 protease binding
GO:0004857 enzyme inhibitor activity
GO:0004866 endopeptidase inhibitor activity
GO:0008191 metalloendopeptidase inhibitor activity
GO:0030414 peptidase inhibitor activity
GO:0061134 peptidase regulator activity
GO:0061135 endopeptidase regulator activity
Cellular Component GO:0005578 proteinaceous extracellular matrix
GO:0005604 basement membrane
GO:0030141 secretory granule
GO:0031089 platelet dense granule lumen
GO:0031983 vesicle lumen
GO:0034774 secretory granule lumen
GO:0042827 platelet dense granule
GO:0044420 extracellular matrix component
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0099503 secretory vesicle
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-109582: Hemostasis
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TIMP3 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
 

There is no record.

Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
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
  Statistical results of TIMP3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
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
 
Points in the above scatter plot represent the expression difference of TIMP3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-1.3390.0053
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.5260.62
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-1.2030.598
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.360.445
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3780.879
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.340.912
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1540.798
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.2780.909
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0550.984
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1390.623
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 282.8940.352
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.310.0782
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TIMP3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TIMP3. 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
 
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TIMP3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TIMP3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TIMP3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TIMP3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TIMP3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTIMP3
NameTIMP metallopeptidase inhibitor 3
Aliases tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); HSMRK222; K222; K222T ......
Chromosomal Location22q12.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TIMP3 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TIMP3.
ID Name Drug Type Targets #Targets
DB05383PimagedineSmall MoleculeAKR1B1, NOS2, TIMP33