TIMP2 Gene (Protein Coding)

TIMP Metallopeptidase Inhibitor 2

GC17M078852
GIFtS:
44
This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppres... See more...

Aliases for TIMP2 Gene

Aliases for TIMP2 Gene

  • TIMP Metallopeptidase Inhibitor 2 2 3 5
  • CSC-21K 2 3 4
  • Tissue Inhibitor Of Metalloproteinases 2 3 4
  • Metalloproteinase Inhibitor 2 3 4
  • Tissue Inhibitor Of Metalloproteinase 2 2
  • Testicular Secretory Protein Li 57 3
  • TIMP-2 4
  • TIMP2 5
  • DDC8 3

External Ids for TIMP2 Gene

Previous GeneCards Identifiers for TIMP2 Gene

  • GC17M076623
  • GC17M080115
  • GC17M077310
  • GC17M077446
  • GC17M074363
  • GC17M076850
  • GC17M072271

Summaries for TIMP2 Gene

Entrez Gene Summary for TIMP2 Gene

  • This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

GeneCards Summary for TIMP2 Gene

TIMP2 (TIMP Metallopeptidase Inhibitor 2) is a Protein Coding gene. Diseases associated with TIMP2 include Conjunctivochalasis and Sorsby Fundus Dystrophy. Among its related pathways are Degradation of the extracellular matrix and NF-KappaB Family Pathway. Gene Ontology (GO) annotations related to this gene include integrin binding and enzyme activator activity. An important paralog of this gene is TIMP4.

UniProtKB/Swiss-Prot Summary for TIMP2 Gene

  • Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.

Gene Wiki entry for TIMP2 Gene

Additional gene information for TIMP2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIMP2 Gene

Genomics for TIMP2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for TIMP2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TIMP2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIMP2

Top Transcription factor binding sites by QIAGEN in the TIMP2 gene promoter:
  • AP-1
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA
  • ATF
  • p53
  • Sp1

Genomic Locations for TIMP2 Gene

Genomic Locations for TIMP2 Gene
chr17:78,852,977-78,925,387
(GRCh38/hg38)
Size:
72,411 bases
Orientation:
Minus strand
chr17:76,849,059-76,921,472
(GRCh37/hg19)
Size:
72,414 bases
Orientation:
Minus strand

Genomic View for TIMP2 Gene

Genes around TIMP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIMP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIMP2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for TIMP2 Gene

Proteins for TIMP2 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for TIMP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P16035-TIMP2_HUMAN
    Recommended name:
    Metalloproteinase inhibitor 2
    Protein Accession:
    P16035
    Secondary Accessions:
    • Q16121
    • Q93006
    • Q9UDF7

    Protein attributes for TIMP2 Gene

    Size:
    220 amino acids
    Molecular mass:
    24399 Da
    Quaternary structure:
    • Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity.

    Three dimensional structures from OCA and Proteopedia for TIMP2 Gene

neXtProt entry for TIMP2 Gene

Protein Expression for TIMP2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for TIMP2 Gene

  • The activity of TIMP2 is dependent on the presence of disulfide bonds.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TIMP2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for TIMP2

No data available for DME Specific Peptides for TIMP2 Gene

Domains & Families for TIMP2 Gene

Gene Families for TIMP2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for TIMP2 Gene

InterPro:
Blocks:
  • Tissue inhibitor of metalloproteinase
ProtoNet:

Suggested Antigen Peptide Sequences for TIMP2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ57920, highly similar to Metalloproteinase inhibitor 2 (B4DFW2_HUMAN)
  • Tissue inhibitor of metalloproteinases 2 (TIMP2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P16035

UniProtKB/Swiss-Prot:

TIMP2_HUMAN :
  • Belongs to the protease inhibitor I35 (TIMP) family.
Family:
  • Belongs to the protease inhibitor I35 (TIMP) family.
genes like me logo Genes that share domains with TIMP2: view

Function for TIMP2 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for TIMP2 Gene

UniProtKB/Swiss-Prot Function:
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.
UniProtKB/Swiss-Prot Induction:
Down-regulated by TGFB1.
GENATLAS Biochemistry:
matrix metalloproteinase,tissue inhibitor 2,with two alternatively spliced forms may be associated with SYN4,involved in the invasive phenotype of acute myelogenous leukemia

Phenotypes From GWAS Catalog for TIMP2 Gene

Gene Ontology (GO) - Molecular Function for TIMP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 9573338
GO:0004857 enzyme inhibitor activity IEA --
GO:0005178 integrin binding IEA --
GO:0005515 protein binding IEA,IPI 12032297
GO:0008191 metalloendopeptidase inhibitor activity IEA,IBA 21873635
genes like me logo Genes that share ontologies with TIMP2: view
genes like me logo Genes that share phenotypes with TIMP2: view

Animal Models for TIMP2 Gene

MGI Knock Outs for TIMP2:

Animal Model Products

  • Taconic Biosciences Mouse Models for TIMP2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMP2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TIMP2 Gene

Localization for TIMP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIMP2 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TIMP2 gene
Compartment Confidence
extracellular 5
plasma membrane 3
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TIMP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA,TAS --
GO:0005615 extracellular space IEA,IBA 21873635
GO:0009986 cell surface IEA --
GO:0030426 growth cone IEA --
GO:0031012 extracellular matrix IBA 21873635
genes like me logo Genes that share ontologies with TIMP2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TIMP2 Gene

Pathways & Interactions for TIMP2 Gene

PathCards logo

SuperPathways for TIMP2 Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
PPAR Pathway
.66
Rac1 Pathway
.65
Glioma Invasiveness
.64
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Rap1 Pathway
.57
Nuclear Receptor Activation by Vitamin-A
.57
2 GPCR Pathway
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
3 ERK Signaling
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
4 Nanog in Mammalian ESC Pluripotency
GSK3 Signaling
.62
Nanog in Mammalian ESC Pluripotency
.62
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
5 CREB Pathway
CREB Pathway
.68
IP3 Pathway
.68
Activation of PKC through GPCR
.63
Intracellular Calcium Signaling
.50
genes like me logo Genes that share pathways with TIMP2: view

Pathways by source for TIMP2 Gene

2 GeneGo (Thomson Reuters) pathways for TIMP2 Gene
  • Cell adhesion_Cell-matrix glycoconjugates
  • Cell adhesion_ECM remodeling
55 Qiagen pathways for TIMP2 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR
1 Cell Signaling Technology pathway for TIMP2 Gene

SIGNOR curated interactions for TIMP2 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for TIMP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007417 central nervous system development IEA --
GO:0007568 aging IEA --
GO:0008285 negative regulation of cell proliferation IEA --
GO:0009725 response to hormone IBA 21873635
GO:0010033 response to organic substance IBA 21873635
genes like me logo Genes that share ontologies with TIMP2: view

Drugs & Compounds for TIMP2 Gene

Products:

  1. Drug

(49) Drugs for TIMP2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(39) Additional Compounds for TIMP2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TIMP2: view

Transcripts for TIMP2 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for TIMP2 Gene

1 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMP2

Alternative Splicing Database (ASD) splice patterns (SP) for TIMP2 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b · 7c · 7d
SP1: - - - - -
SP2: -
SP3:
SP4: -
SP5: - - -

Relevant External Links for TIMP2 Gene

GeneLoc Exon Structure for
TIMP2

Expression for TIMP2 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIMP2 Gene

mRNA expression in normal human tissues for TIMP2 Gene
mRNA expression by BioGPS for TIMP2 GenemRNA expression by GTEx for TIMP2 Gene

mRNA differential expression in normal tissues according to GTEx for TIMP2 Gene

This gene is overexpressed in Artery - Aorta (x4.1).

Protein differential expression in normal tissues from HIPED for TIMP2 Gene

This gene is overexpressed in Amniocyte (39.0) and Serum (14.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TIMP2 Gene



Protein tissue co-expression partners for TIMP2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIMP2

SOURCE GeneReport for Unigene cluster for TIMP2 Gene:

Hs.633514

Evidence on tissue expression from TISSUES for TIMP2 Gene

  • Skin(4.9)
  • Nervous system(4.8)
  • Lung(4.4)
  • Heart(4.3)
  • Eye(4.2)
  • Pancreas(4.2)
  • Muscle(3.6)
  • Blood(3.4)
  • Kidney(3.4)
  • Bone(3.3)
  • Intestine(3.2)
  • Liver(3.2)
  • Lymph node(3.1)
  • Spleen(3.1)
  • Gall bladder(2.8)
  • Adrenal gland(2.8)
  • Stomach(2.7)
  • Bone marrow(2.7)
  • Thyroid gland(2.6)
  • Urine(2.3)
genes like me logo Genes that share expression patterns with TIMP2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TIMP2 Gene

Orthologs for TIMP2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TIMP2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia TIMP2 30 31
  • 99.24 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia TIMP2 30 31
  • 92.27 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Timp2 30 17 31
  • 91.97 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Timp2 30
  • 91.97 (n)
Cow
(Bos Taurus)
 Mammalia TIMP2 30 31
  • 91.67 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia TIMP2 31
  • 79 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves TIMP2 30 31
  • 79.63 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia TIMP2 31
  • 85 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia timp2 30
  • 77.16 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.26350 30
Zebrafish
(Danio rerio)
 Actinopterygii timp2a 30 31
  • 75.8 (n)
 OneToMany
timp2b 31
  • 50 (a)
 OneToMany
timp2 30
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.4143 30
Species where no ortholog for TIMP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TIMP2 Gene

ENSEMBL:
Gene Tree for TIMP2 (if available)
TreeFam:
Gene Tree for TIMP2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIMP2: view image

Paralogs for TIMP2 Gene

Paralogs for TIMP2 Gene

(4) SIMAP similar genes for TIMP2 Gene using alignment to 3 proteins:

  • TIMP2_HUMAN
  • B4DFW2_HUMAN
  • K7EIX4_HUMAN
genes like me logo Genes that share paralogs with TIMP2: view

Variants for TIMP2 Gene

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  1. SNP Genotyping and Copy Number Assay

Additional dbSNP identifiers (rs#s) for TIMP2 Gene

Structural Variations from Database of Genomic Variants (DGV) for TIMP2 Gene

Variant ID Type Subtype PubMed ID
esv2031325 CNV deletion 18987734
esv2667094 CNV deletion 23128226
esv3554834 CNV deletion 23714750
nsv1057193 CNV gain 25217958
nsv1066843 CNV gain 25217958
nsv1070850 CNV deletion 25765185
nsv1112717 CNV deletion 24896259
nsv1118771 CNV deletion 24896259
nsv1134680 CNV deletion 24896259
nsv457917 CNV gain 19166990
nsv576101 CNV gain 21841781
nsv952376 CNV deletion 24416366
nsv952377 CNV deletion 24416366

Variation tolerance for TIMP2 Gene

Residual Variation Intolerance Score: 56.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.43; 9.51% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIMP2 Gene

Human Gene Mutation Database (HGMD)
TIMP2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIMP2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIMP2 Gene

Disorders for TIMP2 Gene

MalaCards: The human disease database

(65) MalaCards diseases for TIMP2 Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TIMP2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TIMP2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Database
(TGDB)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TIMP2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIMP2 Gene

Publications for TIMP2 Gene

  1. Gene polymorphisms related to angiogenesis, inflammation and thrombosis that influence risk for oral cancer. (PMID: 18674955) Vairaktaris E … Patsouris E (Oral oncology 2009) 3 23 41
  2. Host single nucleotide polymorphisms of MMP-9 -1562/TIMP-1 372 have gender differences in the risk of gastric intestinal metaplasia after Helicobacter pylori infection. (PMID: 19889076) Hung KH … Sheu BS (Helicobacter 2009) 3 23 41
  3. TIMP-2 gene polymorphism is associated with intracerebral hemorrhage. (PMID: 19844095) Reuter B … Fatar M (Cerebrovascular diseases (Basel, Switzerland) 2009) 3 23 41
  4. Polymorphisms in tissue inhibitors of metalloproteinases-2 and -3 and breast cancer susceptibility and survival. (PMID: 19431211) Peterson NB … Zheng W (International journal of cancer 2009) 3 23 41
  5. Association of TIMP-4 gene polymorphism with the risk of osteoarthritis in the Korean population. (PMID: 18301898) Lee HJ … Kim S (Rheumatology international 2008) 3 23 41

ExternalLinks

View latest publications for TIMP2 gene in Mastermind

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