Timp3 TIMP metallopeptidase inhibitor 3 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Timp3provided by RGD
Official Full Name: TIMP metallopeptidase inhibitor 3provided by RGD
Primary source: RGD:3865
See related: EnsemblRapid:ENSRNOG00000004303 AllianceGenome:RGD:3865
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Timp-3
Summary: Predicted to enable metalloendopeptidase inhibitor activity and zinc ion binding activity. Involved in several processes, including cellular response to peptide; mesenchymal cell differentiation involved in bone development; and negative regulation of vascular associated smooth muscle cell proliferation. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix and extracellular space. Biomarker of sciatic neuropathy and type 2 diabetes mellitus. Human ortholog(s) of this gene implicated in Sorsby's fundus dystrophy; breast carcinoma; and urinary bladder cancer. Orthologous to human TIMP3 (TIMP metallopeptidase inhibitor 3). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Kidney (RPKM 1880.2), Lung (RPKM 1045.3) and 8 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q13

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (19408539..19459558, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (17520827..17571850, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (23543125..23594170, complement)

Chromosome 7 - NC_086025.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

lncTIMP3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-214/Smad4 axis to relieve postmenopausal osteoporosis.
Title: lncTIMP3 promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-214/Smad4 axis to relieve postmenopausal osteoporosis.
MiR-221-3p regulates the microvascular dysfunction in diabetic retinopathy by targeting TIMP3.
Title: MiR-221-3p regulates the microvascular dysfunction in diabetic retinopathy by targeting TIMP3.
Overexpression of HOXA-AS2 inhibits inflammation and apoptosis in podocytes via sponging miRNA-302b-3p to upregulate TIMP3.
Title: Overexpression of HOXA-AS2 inhibits inflammation and apoptosis in podocytes via sponging miRNA-302b-3p to upregulate TIMP3.
Overexpression of TIMP3 inhibits discogenic pain by suppressing angiogenesis and the expression of substance P in nucleus pulposus.
Title: Overexpression of TIMP3 inhibits discogenic pain by suppressing angiogenesis and the expression of substance P in nucleus pulposus.
miR-21-5p inhibits neuropathic pain development via directly targeting C-C motif ligand 1 and tissue inhibitor of metalloproteinase-3.
Title: miR-21-5p inhibits neuropathic pain development via directly targeting C-C motif ligand 1 and tissue inhibitor of metalloproteinase-3.
miR-142-3p could promote neuronal cell cycle and inhibit apoptosis at least partially through suppressing CDKN1B and TIMP3 after peripheral nerve injury.
Title: MiR-142-3p Enhances Cell Viability and Inhibits Apoptosis by Targeting CDKN1B and TIMP3 Following Sciatic Nerve Injury.
ERK1 instead of ERK2 can regulate TGF-beta/Smad signalling, which may be the mechanism through which ERK1 regulates TGF-beta1-induced TIMP-3 expression.
Title: Crosstalk between Smad2/3 and specific isoforms of ERK in TGF-β1-induced TIMP-3 expression in rat chondrocytes.
upregulated expressions of MMP1/3 and downregulated expressions of TIMP1/3 at the messenger RNA (mRNA) and protein levels also appeared to be relevant to low Se intake. In conclusion, Se-deficient diet could cause low Se concentration in the liver, alterations of hepatocyte ultrastructure
Title: Long-Term Selenium-Deficient Diet Induces Liver Damage by Altering Hepatocyte Ultrastructure and MMP1/3 and TIMP1/3 Expression in Growing Rats.
Taken together, our results suggest that the imbalance between aggrecanase and TIMP-3 may play an important role in the pathogenesis of IDD and therefore be a potential therapeutic target for treating IDD.
Title: The imbalance between TIMP3 and matrix-degrading enzymes plays an important role in intervertebral disc degeneration.
The immunohistochemistry demonstrated greater expression of MMP-2 than MMP-9 and MMP-14 in all masseter muscles and there were few differences in the staining of 4 TIMPs.
Title: Histological, histochemical, and protein changes after induced malocclusion by occlusion alteration of Wistar rats.

Submit: New GeneRIF Correction See all GeneRIFs (22)

General gene information

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Markers

RH135110 (e-PCR)
- UniSTS:218387

G45201 (e-PCR)
- UniSTS:106003

Timp3 (e-PCR), detects polymorphism
- UniSTS:265762

RH144261 (e-PCR)
- UniSTS:233506

RH94615 (e-PCR)
- UniSTS:119863

BI278238 (e-PCR)
- UniSTS:244303

RH129267 (e-PCR)
- UniSTS:212574

RH128273 (e-PCR)
- UniSTS:211581

Timp3 (e-PCR), detects polymorphism
- UniSTS:265631

Timp3 (e-PCR), detects polymorphism
- UniSTS:144628

Gene Ontology Provided by RGD

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	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to interleukin-6	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to peptide	IEP Inferred from Expression Pattern more info	PubMed
involved_in mesenchymal cell differentiation involved in bone development	IMP Inferred from Mutant Phenotype more info	PubMed
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	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of membrane protein ectodomain proteolysis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of metalloendopeptidase activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of metalloendopeptidase activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of vascular associated smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to amino acid	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to cytokine	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to estrogen	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to folic acid	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to hormone	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to muscle activity	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to nutrient levels	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to organic cyclic compound	IEP Inferred from Expression Pattern more info	PubMed
involved_in tissue regeneration	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in basement membrane	IEA Inferred from Electronic Annotation more info
located_in basement membrane	ISO Inferred from Sequence Orthology more info
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: metalloproteinase inhibitor 3

Names: tissue inhibitor of metalloproteinase 3 (Sorsby fundus dystrophy, pseudoinflammatory); 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.

mRNA and Protein(s)

NM_012886.3 → NP_037018.2 metalloproteinase inhibitor 3 precursor

See identical proteins and their annotated locations for NP_037018.2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000007

UniProtKB/Swiss-Prot

P48032

UniProtKB/TrEMBL

F7FFD0, Q4V8L0

Related

ENSRNOP00000005746.3, ENSRNOT00000005746.7

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 ...