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

    Gene ID: 7078, updated on 22-May-2013
    Official Symbol
    TIMP3provided by HGNC
    Official Full Name
    TIMP metallopeptidase inhibitor 3provided by HGNC
    Primary source
    HGNC:11822
    Locus tag
    RP1-309I22.1
    See related
    Ensembl:ENSG00000100234; HPRD:01785; MIM:188826; Vega:OTTHUMG00000030784
    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]
    Location :
    22q12.3
    Sequence :
    Chromosome: 22; NC_000022.10 (33196802..33259028)
    See TIMP3 in Epigenomics, MapViewer

    Chromosome 22 - NC_000022.10Genomic Context describing neighboring genes Neighboring gene BPI fold containing family C Neighboring gene F-box protein 7 Neighboring gene synapsin III Neighboring gene like-glycosyltransferase Neighboring gene microRNA 4764 Neighboring gene LARGE antisense RNA 1

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes. Yan D, et al. Gene, 2013 Mar 15. PMID 23313877.
    2. Differential regulation of extracellular tissue inhibitor of metalloproteinases-3 levels by cell membrane-bound and shed low density lipoprotein receptor-related protein 1. Scilabra SD, et al. J Biol Chem, 2013 Jan 4. PMID 23166318.
    3. Multivalent pseudopeptides targeting cell surface nucleoproteins inhibit cancer cell invasion through tissue inhibitor of metalloproteinases 3 (TIMP-3) release. Destouches D, et al. J Biol Chem, 2012 Dec 21. PMID 23109338.
    4. Prognostic significance of TIMP3 hypermethylation in post-treatment salivary rinse from head and neck squamous cell carcinoma patients. Rettori MM, et al. Carcinogenesis, 2013 Jan. PMID 23042095.
    5. Heterogeneous epigenetic regulation of TIMP3 in prostate cancer. Shinojima T, et al. Epigenetics, 2012 Nov. PMID 23023649.

    See all (178) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. We report 2 patients with novel mutations in Exon 1 of the N-terminal domain. Although the mutation occurs at a different location on the TIMP3 gene, the clinical features are similar to other reported patients with Sorsby fundus dystrophy.
      Title: A novel mutation at the N-terminal domain of the TIMP3 gene in Sorsby fundus dystrophy.
    2. TIMP3 mRNA expression is decreased in prostate tumors due to aberrant histone modification.
      Title: Heterogeneous epigenetic regulation of TIMP3 in prostate cancer.
    3. Downregulation of TIMP-3 is associated with osteoarthritis.
      Title: Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes.
    4. Loss of TIMP-3 may increase IL-6 production via the tumor necrosis factor alpha/nuclear factor kappaB axis, thereby promoting tumor malignancy.
      Title: Loss of TIMP-3 promotes tumor invasion via elevated IL-6 production and predicts poor survival and relapse in HPV-infected non-small cell lung cancer.
    5. Multivalent pseudopeptides targeting cell surface nucleoproteins inhibit cancer cell invasion through tissue inhibitor of metalloproteinases 3 (TIMP-3) release.
      Title: Multivalent pseudopeptides targeting cell surface nucleoproteins inhibit cancer cell invasion through tissue inhibitor of metalloproteinases 3 (TIMP-3) release.
    6. the detection of TIMP3 promoter hypermethylation in post-treatment salivary rinse as an independent prognostic maker for local recurrence-free survival in patients with HNSCC
      Title: Prognostic significance of TIMP3 hypermethylation in post-treatment salivary rinse from head and neck squamous cell carcinoma patients.
    7. analysis of difference in regulation of extracellular tissue inhibitor of metalloproteinases-3 levels by cell membrane-bound and shed low density lipoprotein receptor-related protein 1
      Title: Differential regulation of extracellular tissue inhibitor of metalloproteinases-3 levels by cell membrane-bound and shed low density lipoprotein receptor-related protein 1.
    8. study showed that ADAMTS-1, -4, -5 and TIMP3 were expressed at differential levels in hepatocellular carcinoma cell lines
      Title: Expression of ADAMTS-1, ADAMTS-4, ADAMTS-5 and TIMP3 by hepatocellular carcinoma cell lines.
    9. In papillary thyroid cancer, significant correlations between the methylation status of the TIMP3 gene and the V600E BRAF mutation were found.
      Title: Correlation between BRAF mutation and promoter methylation of TIMP3, RARβ2 and RASSF1A in thyroid cancer.
    10. No evidence was found to support an association between the rs9621532 variant and susceptibility to either nAMD or PCV in a Chinese Han population.
      Title: An rs9621532 variant near the TIMP3 gene is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Chinese Han population.
    Submit: New GeneRIF Correction See all (128)

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    P35625 P78536 ADAM17    HPRD  PubMed  
    P35625 Q12805 EFEMP1    HPRD  PubMed  
    P35625 P35968 KDR    HPRD  PubMed  
    P35625 P45452 MMP13    HPRD  PubMed  
    P35625 P50281 MMP14    HPRD  PubMed  
    P35625 P08253 MMP2    HPRD  PubMed  
    P35625 P08254 MMP3    HPRD  PubMed  
    P35625 P14780 MMP9    HPRD  PubMed  
    BioGRID:112934 BioGRID:112731 ADAM17    BioGRID  PubMed Reconstituted Complex 
    BioGRID:112934 BioGRID:110457 MMP2    BioGRID  PubMed Reconstituted Complex 
    • Angiogenesis, organism-specific biosystem (from WikiPathways)
      Angiogenesis, organism-specific biosystemThis pathway is a concise and simplified version of the basic proteins involved in angiogenesis. The proces is regulated by hyopoxia, which results in the transcription of eg. VEGF1, FGF2, PDGFbeta, ...
    • Endochondral Ossification, organism-specific biosystem (from WikiPathways)
      Endochondral Ossification, organism-specific biosystem
      Endochondral Ossification
    • Matrix Metalloproteinases, organism-specific biosystem (from WikiPathways)
      Matrix Metalloproteinases, organism-specific biosystemMatrix metalloproteinases (MMPs) are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzi...
    • Oncostatin M Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Oncostatin M Signaling Pathway, organism-specific biosystemOncostatin M (OSM) is a member of the multifunctional cytokine interleukin 6 (IL6) - type cytokine family. It is mainly produced in cell types such as activated T lymphocytes, macrophages, monocytes,...
    • Proteoglycans in cancer, organism-specific biosystem (from KEGG)
      Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
    • Proteoglycans in cancer, conserved biosystem (from KEGG)
      Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...

    Markers

    Genotypes

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    metalloendopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    cellular response to organic substance IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of membrane protein ectodomain proteolysis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    visual perception IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    basement membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    colocalizes_with extracellular matrix IDA
    Inferred from Direct Assay
    more info
    		  
    Preferred Names
    metalloproteinase inhibitor 3
    Names
    metalloproteinase inhibitor 3
    TIMP-3
    MIG-5 protein
    protein MIG-5
    tissue inhibitor of metalloproteinases 3

    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_009117.1 RefSeqGene

      Range
      5001..67227
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000362.4 → NP_000353.1  metalloproteinase inhibitor 3 precursor

      Status: REVIEWED

      Source sequence(s)
      AF035289, AL023282, BC014277, Z98256
      Consensus CDS
      CCDS13911.1
      UniProtKB/Swiss-Prot
      P35625
      Related
      ENSP00000266085, OTTHUMP00000028880, ENST00000266085, OTTHUMT00000075672
      Conserved Domains (1) summary
      cd03585
      Location:24 – 200
      Blast Score: 772
      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: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000022.10 Reference GRCh37.p10 Primary Assembly

      Range
      33196802..33259028
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000154.1 Alternate HuRef

      Range
      16154700..16216984
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018933.1 Alternate CHM1_1.0

      Range
      17118505..17180728
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01055381.1 (226974..289258) None
    genomic AF001361.1 AAB68799.1
    genomic AL023282.1 (4370..8983) None
    genomic AMYH01012730.1 (40723..102946) None
    genomic CH471095.1 EAW60038.1
    genomic S79779.1 None
    genomic U33110.1 AAC50393.1
    genomic U33114.1 AAC50393.1
    genomic U38955.1 AAB17602.1
    genomic Z30183.1 CAA82918.1
    genomic Z73979.1 (101..40926) None
    genomic Z98256.1 (105..16891) None
    mRNA AF035289.1 None
    mRNA AK098517.1 None
    mRNA AK298126.1 BAG60406.1
    mRNA AK314871.1 BAG37386.1
    mRNA BC013086.1 None
    mRNA BC014277.2 AAH14277.1
    mRNA BT006848.1 AAP35494.1
    mRNA CR456593.1 CAG30479.1
    mRNA D45917.1 BAA08348.1
    mRNA L15078.1 AAA21815.1
    mRNA S78453.1 AAB34532.1
    mRNA U02571.1 AAA17672.1
    mRNA U14394.1 AAB60373.1
    mRNA U67195.1 AAB07547.1
    mRNA X76227.1 CAA53813.1
    mRNA X80791.1 None
    other-genetic CU013193.1 CAK54624.1
    other-genetic CU013481.1 CAK54923.1
    other-genetic DQ892581.2 ABM83507.1
    other-genetic DQ895798.2 ABM86724.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P35625.2 GenPept UniProtKB/Swiss-Prot:P35625

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
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        Citations in PubMed identified from shared sequence and PMC links.
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        Link to Protein RefSeqs
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        Related UniSTS records

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