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TIMP3 TIMP metallopeptidase inhibitor 3 [ Homo sapiens (human) ]

Gene ID: 7078, updated on 27-Nov-2024

Summary

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Official Symbol
TIMP3provided by HGNC
Official Full Name
TIMP metallopeptidase inhibitor 3provided by HGNC
Primary source
HGNC:HGNC:11822
See related
Ensembl:ENSG00000100234 MIM:188826; AllianceGenome:HGNC:11822
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SFD; K222; K222TA2; HSMRK222
Summary
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]
Expression
Broad expression in placenta (RPKM 485.4), fat (RPKM 420.5) and 18 other tissues See more
Orthologs
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Genomic context

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See TIMP3 in Genome Data Viewer
Location:
22q12.3
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (32801705..32863041)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (33266136..33327517)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (33197691..33259028)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373002 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:33056914-33058113 Neighboring gene synapsin III Neighboring gene RNA, 5S ribosomal pseudogene 497 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33148296-33149080 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:33153563-33153744 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:33159884-33160394 Neighboring gene uncharacterized LOC124905104 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33216313-33216812 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:33271816-33272028 Neighboring gene Sharpr-MPRA regulatory region 12398 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:33283107-33283317 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:33347343-33347844 Neighboring gene Sharpr-MPRA regulatory region 592 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:33382939-33383840 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:33448207-33448890 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr22:33450113-33450805 Neighboring gene ETFRF1 pseudogene 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr22:33506225-33507424 Neighboring gene long intergenic non-protein coding RNA 1640 Neighboring gene LARGE xylosyl- and glucuronyltransferase 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Expression of Sorsby's fundus dystrophy mutations in human retinal pigment epithelial cells reduces matrix metalloproteinase inhibition and may promote angiogenesis. Qi JH, et al. J Biol Chem, 2002 Apr 19. PMID 11821400
  2. Polymorphisms and Plasma Levels of Tissue Inhibitor of Metalloproteinase-3: Impact on Genetic Susceptibility and Clinical Outcome of Oral Cancer. Su CW, et al. Medicine (Baltimore), 2015 Nov. PMID 26579821, Free PMC Article
  3. A rare penetrant TIMP3 mutation confers relatively late onset choroidal neovascularisation which can mimic age-related macular degeneration. Warwick A, et al. Eye (Lond), 2016 Mar. PMID 26493035, Free PMC Article
  4. A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby's fundus dystrophy. Langton KP, et al. J Biol Chem, 2000 Sep 1. PMID 10854443
  5. Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and Treatment Outcomes. Gliem M, et al. Invest Ophthalmol Vis Sci, 2015 Apr. PMID 25766588

See all (366) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. miR-21 Exerts Anti-proliferative and Pro-apoptotic Effects in LPS-induced WI-38 Cells via Directly Targeting TIMP3.
    Title: miR-21 Exerts Anti-proliferative and Pro-apoptotic Effects in LPS-induced WI-38 Cells via Directly Targeting TIMP3.
  2. Msi1 promotes breast cancer metastasis by regulating invadopodia-mediated extracellular matrix degradation via the Timp3-Mmp9 pathway.
    Title: Msi1 promotes breast cancer metastasis by regulating invadopodia-mediated extracellular matrix degradation via the Timp3-Mmp9 pathway.
  3. Associations between genetically predicted TIMP-3 levels and risk of venous thromboembolism: A two sample Mendelian randomization study.
    Title: Associations between genetically predicted TIMP-3 levels and risk of venous thromboembolism: A two sample Mendelian randomization study.
  4. Demethylation of TIMP2 and TIMP3 Inhibits Cell Proliferation, Migration, and Invasion in Pituitary Adenomas.
    Title: Demethylation of TIMP2 and TIMP3 Inhibits Cell Proliferation, Migration, and Invasion in Pituitary Adenomas.
  5. Abnormal stress promotes intervertebral disc degeneration through WTAP/YTHDF2-dependent TIMP3 m6A modification.
    Title: Abnormal stress promotes intervertebral disc degeneration through WTAP/YTHDF2-dependent TIMP3 m6A modification.
  6. Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech Families with Sorsby Fundus Dystrophy Associated with Novel p.(Tyr152Cys) Mutation.
    Title: Disease-Causing TIMP3 Variants and Deep Phenotyping of Two Czech Families with Sorsby Fundus Dystrophy Associated with Novel p.(Tyr152Cys) Mutation.
  7. Review: Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy.
    Title: Review: Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy.
  8. TIMP3/Wnt axis regulates gliosis of Muller glia.
    Title: TIMP3/Wnt axis regulates gliosis of Müller glia.
  9. Loss of TIMP3, but not TIMP4, exacerbates thoracic and abdominal aortic aneurysm.
    Title: Loss of TIMP3, but not TIMP4, exacerbates thoracic and abdominal aortic aneurysm.
  10. Targeting of HBP1/TIMP3 axis as a novel strategy against breast cancer.
    Title: Targeting of HBP1/TIMP3 axis as a novel strategy against breast cancer.
Submit: New GeneRIF Correction See all GeneRIFs (293)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Sorsby fundus dystrophy
MedGen: C1850938 OMIM: 136900 GeneReviews: Not available
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EBI GWAS Catalog

Description
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
EBI GWAS Catalog
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
EBI GWAS Catalog
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC).
EBI GWAS Catalog
Seven new loci associated with age-related macular degeneration.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables metalloendopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metalloendopeptidase inhibitor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in negative regulation of membrane protein ectodomain proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of membrane protein ectodomain proteolysis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of metalloendopeptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to cytokine IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in response to hormone IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in visual perception IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in basement membrane IEA
Inferred from Electronic Annotation
more info
  
colocalizes_with collagen-containing extracellular matrix HDA PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
is_active_in extracellular matrix IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus HDA PubMed 
located_in platelet dense granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
metalloproteinase inhibitor 3
Names
MIG-5 protein
TIMP-3
protein MIG-5
tissue inhibitor of metalloproteinases 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009117.2 RefSeqGene

    Range
    5001..66337
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000362.5 → NP_000353.1  metalloproteinase inhibitor 3 precursor

    See identical proteins and their annotated locations for NP_000353.1

    Status: REVIEWED

    Source sequence(s)
    AF035289, AL023282, BC014277, Z98256
    Consensus CDS
    CCDS13911.1
    UniProtKB/Swiss-Prot
    B2RBY9, P35625, Q5THV4, Q9UC74, Q9UGS2
    Related
    ENSP00000266085.5, ENST00000266085.7
    Conserved Domains (1) summary
    cd03585
    Location:24 → 200
    NTR_TIMP; NTR domain, TIMP subfamily; TIMPs, or tissue inibitors of metalloproteases, are essential regulators of extracellular matrix turnover and remodeling. They form complexes with matrix metalloproteases (MMPs) and inactivate them irreversibly by ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    32801705..32863041
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    33266136..33327517
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P35625.2 GenPept UniProtKB/Swiss-Prot:P35625

Gene LinkOut

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