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

    Gene ID: 7078, updated on 28-Oct-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
    mouse all
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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 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
    		Compare labs

    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)

    Genotypes

    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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