This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM). Expression of this gene is induced in response to mitogenic stimulation and this netrin domain-containing protein is localized to the ECM. Mutations in this gene have... See more...

Aliases for TIMP3 Gene

Aliases for TIMP3 Gene

  • TIMP Metallopeptidase Inhibitor 3 2 3 5
  • Tissue Inhibitor Of Metalloproteinases 3 3 4
  • Metalloproteinase Inhibitor 3 3 4
  • Protein MIG-5 3 4
  • TIMP-3 3 4
  • Tissue Inhibitor Of Metalloproteinase 3 (Sorsby Fundus Dystrophy, Pseudoinflammatory) 2
  • MIG-5 Protein 3
  • HSMRK222 3
  • K222TA2 3
  • TIMP3 5
  • K222 3
  • SFD 3

External Ids for TIMP3 Gene

Previous HGNC Symbols for TIMP3 Gene

  • SFD

Previous GeneCards Identifiers for TIMP3 Gene

  • GC22P029893
  • GC22P031521
  • GC22P033196
  • GC22P016154

Summaries for TIMP3 Gene

Entrez Gene Summary for TIMP3 Gene

  • This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix (ECM). Expression of this gene is induced in response to mitogenic stimulation and this netrin domain-containing protein is localized to the ECM. Mutations in this gene have been associated with the autosomal dominant disorder Sorsby's fundus dystrophy. [provided by RefSeq, Jul 2008]

GeneCards Summary for TIMP3 Gene

TIMP3 (TIMP Metallopeptidase Inhibitor 3) is a Protein Coding gene. Diseases associated with TIMP3 include Sorsby Fundus Dystrophy and Fundus Dystrophy. Among its related pathways are NF-KappaB Family Pathway and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include protease binding and metalloendopeptidase inhibitor activity. An important paralog of this gene is TIMP4.

UniProtKB/Swiss-Prot Summary for TIMP3 Gene

  • 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 Wiki entry for TIMP3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIMP3 Gene

Genomics for TIMP3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TIMP3 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 TIMP3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIMP3

Top Transcription factor binding sites by QIAGEN in the TIMP3 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • COUP
  • MyoD
  • Sp1

Genomic Locations for TIMP3 Gene

Genomic Locations for TIMP3 Gene
chr22:32,801,701-32,863,043
(GRCh38/hg38)
Size:
61,343 bases
Orientation:
Plus strand
chr22:33,196,802-33,259,030
(GRCh37/hg19)
Size:
62,229 bases
Orientation:
Plus strand

Genomic View for TIMP3 Gene

Genes around TIMP3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIMP3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIMP3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIMP3 Gene

Proteins for TIMP3 Gene

  • Protein details for TIMP3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35625-TIMP3_HUMAN
    Recommended name:
    Metalloproteinase inhibitor 3
    Protein Accession:
    P35625
    Secondary Accessions:
    • B2RBY9
    • Q5THV4
    • Q9UC74
    • Q9UGS2

    Protein attributes for TIMP3 Gene

    Size:
    211 amino acids
    Molecular mass:
    24145 Da
    Quaternary structure:
    • Interacts with EFEMP1.

    Three dimensional structures from OCA and Proteopedia for TIMP3 Gene

neXtProt entry for TIMP3 Gene

Post-translational modifications for TIMP3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TIMP3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TIMP3 Gene

Domains & Families for TIMP3 Gene

Gene Families for TIMP3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for TIMP3 Gene

InterPro:
Blocks:
  • Tissue inhibitor of metalloproteinase
ProtoNet:

Suggested Antigen Peptide Sequences for TIMP3 Gene

GenScript: Design optimal peptide antigens:
  • K222 protein (Q14867_HUMAN)
  • Tissue inhibitor of metalloproteinases 3 (TIMP3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P35625

UniProtKB/Swiss-Prot:

TIMP3_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 TIMP3: view

Function for TIMP3 Gene

Molecular function for TIMP3 Gene

UniProtKB/Swiss-Prot 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.
GENATLAS Biochemistry:
matrix metalloproteinase,tissue inhibitor 3,expressed in retinal pigment epithelium,placenta,localized in extracellular matrix (glycosylated or not form),embedded in intron V of SYN3,inactivated by methylation in uterus,breast,renal,colon,brain carcinomas

Phenotypes From GWAS Catalog for TIMP3 Gene

Gene Ontology (GO) - Molecular Function for TIMP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IBA 21873635
GO:0004857 enzyme inhibitor activity IEA --
GO:0005515 protein binding IPI 18344519
GO:0008191 metalloendopeptidase inhibitor activity TAS 18638486
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with TIMP3: view
genes like me logo Genes that share phenotypes with TIMP3: view

Human Phenotype Ontology for TIMP3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TIMP3 Gene

MGI Knock Outs for TIMP3:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMP3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TIMP3 Gene

Localization for TIMP3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIMP3 Gene

Secreted, extracellular space, extracellular matrix.

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 TIMP3 gene
Compartment Confidence
extracellular 5
nucleus 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TIMP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005604 basement membrane IEA --
GO:0005615 extracellular space IBA 21873635
GO:0005634 nucleus HDA 21630459
GO:0031012 extracellular matrix IBA 21873635
genes like me logo Genes that share ontologies with TIMP3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TIMP3 Gene

Pathways & Interactions for TIMP3 Gene

PathCards logo

SuperPathways for TIMP3 Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
2 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
3 ERK Signaling
.61
.61
.58
.51
.49
4 Nanog in Mammalian ESC Pluripotency
.62
.62
.59
.48
5 CREB Pathway
.68
.68
.63
.50
genes like me logo Genes that share pathways with TIMP3: view

Pathways by source for TIMP3 Gene

1 GeneGo (Thomson Reuters) pathway for TIMP3 Gene
  • Cell adhesion_ECM remodeling
55 Qiagen pathways for TIMP3 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 TIMP3 Gene

SIGNOR curated interactions for TIMP3 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for TIMP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002576 platelet degranulation TAS --
GO:0007601 visual perception IEA --
GO:0009725 response to hormone IBA 21873635
GO:0010033 response to organic substance IBA 21873635
GO:0010466 negative regulation of peptidase activity IEA --
genes like me logo Genes that share ontologies with TIMP3: view

Drugs & Compounds for TIMP3 Gene

(20) Drugs for TIMP3 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pimagedine Investigational Pharma Target 4

(23) Additional Compounds for TIMP3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TIMP3: view

Transcripts for TIMP3 Gene

mRNA/cDNA for TIMP3 Gene

1 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
1 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 TIMP3

Alternative Splicing Database (ASD) splice patterns (SP) for TIMP3 Gene

No ASD Table

Relevant External Links for TIMP3 Gene

GeneLoc Exon Structure for
TIMP3

Expression for TIMP3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIMP3 Gene

Protein differential expression in normal tissues from HIPED for TIMP3 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (19.0) and Breast (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TIMP3 Gene



Protein tissue co-expression partners for TIMP3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIMP3

SOURCE GeneReport for Unigene cluster for TIMP3 Gene:

Hs.644633

Evidence on tissue expression from TISSUES for TIMP3 Gene

  • Pancreas(4.7)
  • Kidney(4.7)
  • Nervous system(4.6)
  • Eye(4.4)
  • Lung(4.3)
  • Skin(4.3)
  • Bone(3.9)
  • Heart(3.7)
  • Muscle(3.5)
  • Spleen(3.3)
  • Intestine(3.2)
  • Liver(3.2)
  • Thyroid gland(3.1)
  • Lymph node(3)
  • Blood(2.9)
  • Adrenal gland(2.8)
  • Stomach(2.6)
  • Gall bladder(2.4)
  • Bone marrow(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TIMP3 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • head
General:
  • blood
  • blood vessel
  • peripheral nervous system
genes like me logo Genes that share expression patterns with TIMP3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for TIMP3 Gene

Orthologs for TIMP3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TIMP3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TIMP3 30 31
  • 99.37 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TIMP3 31
  • 94 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia TIMP3 30 31
  • 93.84 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TIMP3 30 31
  • 93.68 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TIMP3 31
  • 92 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Timp3 30
  • 89.89 (n)
Mouse
(Mus musculus)
Mammalia Timp3 30 17 31
  • 89.73 (n)
OneToOne
Chicken
(Gallus gallus)
Aves -- 31
  • 82 (a)
OneToMany
TIMP3 30 31
  • 77.73 (n)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia TIMP3 31
  • 83 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia timp3 30
  • 79.23 (n)
Species where no ortholog for TIMP3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Rainbow Trout (Oncorhynchus mykiss)
  • 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)
  • Zebrafish (Danio rerio)

Evolution for TIMP3 Gene

ENSEMBL:
Gene Tree for TIMP3 (if available)
TreeFam:
Gene Tree for TIMP3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIMP3: view image

Paralogs for TIMP3 Gene

Paralogs for TIMP3 Gene

(3) SIMAP similar genes for TIMP3 Gene using alignment to 1 proteins:

  • TIMP3_HUMAN
genes like me logo Genes that share paralogs with TIMP3: view

Variants for TIMP3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIMP3 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
735600 Likely Benign: not provided 32,858,030(+) T/C SYNONYMOUS_VARIANT,INTRON_VARIANT
740469 Likely Benign: not provided 32,802,130(+) C/T INTRON_VARIANT
837921 Uncertain Significance: not provided 32,802,014(+) C/T MISSENSE_VARIANT,INTRON_VARIANT
843268 Pathogenic: Retinal dystrophy; not provided 32,802,114(+) C/G MISSENSE_VARIANT,INTRON_VARIANT
847790 Uncertain Significance: not provided 32,859,298(+) G/A MISSENSE_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for TIMP3 Gene

Structural Variations from Database of Genomic Variants (DGV) for TIMP3 Gene

Variant ID Type Subtype PubMed ID
esv1085289 CNV insertion 17803354
nsv1059368 CNV loss 25217958
nsv191249 CNV insertion 16902084
nsv3599 CNV deletion 18451855
nsv955482 CNV deletion 24416366

Variation tolerance for TIMP3 Gene

Residual Variation Intolerance Score: 36.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.45; 9.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIMP3 Gene

Human Gene Mutation Database (HGMD)
TIMP3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIMP3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TIMP3 Gene

Disorders for TIMP3 Gene

MalaCards: The human disease database

(47) MalaCards diseases for TIMP3 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
sorsby fundus dystrophy
  • sfd
fundus dystrophy
  • retinal dystrophy
inherited retinal disorder
  • retinal dystrophy
juvenile pilocytic astrocytoma
  • pilocytic astrocytoma
choroidal dystrophy, central areolar, 1
  • cacd1
- elite association - COSMIC cancer census association via MalaCards
Search TIMP3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TIMP3_HUMAN
  • Sorsby fundus dystrophy (SFD) [MIM:136900]: Rare autosomal dominant macular disorder with an age of onset in the fourth decade. It is characterized by loss of central vision from subretinal neovascularization and atrophy of the ocular tissues. Generally, macular disciform degeneration develops in the patients eye within 6 months to 6 years. {ECO:0000269 PubMed:7550309, ECO:0000269 PubMed:7894485, ECO:0000269 PubMed:8634721, ECO:0000269 PubMed:8728699, ECO:0000269 PubMed:8981947}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TIMP3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TIMP3: view

No data available for Genatlas for TIMP3 Gene

Publications for TIMP3 Gene

  1. Cloning of the cDNA encoding human tissue inhibitor of metalloproteinases-3 (TIMP-3) and mapping of the TIMP3 gene to chromosome 22. (PMID: 8188246) Apte SS … Olsen BR (Genomics 1994) 2 3 4 23
  2. 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
  3. Structural determinants of the ADAM inhibition by TIMP-3: crystal structure of the TACE-N-TIMP-3 complex. (PMID: 18638486) Wisniewska M … Bode W (Journal of molecular biology 2008) 3 4 23
  4. Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression. (PMID: 17033924) Lei H … Försti A (Breast cancer research and treatment 2007) 3 23 41
  5. Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms. (PMID: 15944607) Ogata T … Kuivaniemi H (Journal of vascular surgery 2005) 3 23 41

Products for TIMP3 Gene

Sources for TIMP3 Gene