Timp4 tissue inhibitor of metalloproteinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Timp4provided by MGI
Official Full Name: tissue inhibitor of metalloproteinase 4provided by MGI
Primary source: MGI:MGI:109125
See related: Ensembl:ENSMUSG00000030317 AllianceGenome:MGI:109125
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Timp-4
Summary: Predicted to enable metalloendopeptidase inhibitor activity and protease binding activity. Acts upstream of or within Notch signaling pathway. Predicted to be located in sarcomere. Predicted to be active in extracellular matrix and extracellular space. Is expressed in several structures, including brain ventricular layer; heart; ovary; skin; and ventral grey horn. Human ortholog(s) of this gene implicated in nephroblastoma. Orthologous to human TIMP4 (TIMP metallopeptidase inhibitor 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in genital fat pad adult (RPKM 71.5), subcutaneous fat pad adult (RPKM 64.7) and 8 other tissues See more
Orthologs: human all
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Genomic context

Location:: 6 E3; 6 53.29 cM

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	6	NC_000072.7 (115221405..115229166, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	6	NC_000072.6 (115244444..115252205, complement)

Chromosome 6 - NC_000072.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tissue inhibitor of metalloproteinase-4 deletion in mice impacts maternal cardiac function during pregnancy and postpartum.
Title: Tissue inhibitor of metalloproteinase-4 deletion in mice impacts maternal cardiac function during pregnancy and postpartum.
Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels.
Title: Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels.
The CRN2 increased the secretion of TIMP4 as well as the catalytic activity of MMP14.
Title: CRN2 binds to TIMP4 and MMP14 and promotes perivascular invasion of glioblastoma cells.
High TIMP4 expression is associated with obesity, fatty liver and dyslipidemia.
Title: Absence of Tissue Inhibitor of Metalloproteinase-4 (TIMP4) ameliorates high fat diet-induced obesity in mice due to defective lipid absorption.
there are 7 CpG islands in the TIMP4 promoter which get methylated during the progression of heart failure which leads to its epigenetic silencing.
Title: Epigenetic silencing of TIMP4 in heart failure.
High fat diet-induced obesity downregulates adipocyte MMP3 expression to trigger adipogenesis, and adipocyte TIMP4 may modulate this process to regulate hyperplastic vs. hypertrophic adipose tissue expansion, fat distribution, and metabolic health in a sex- and depot-dependent manner.
Title: High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent adipose expansion in C57BL/6J mice.
Our findings highlight a protective mechanism induced by PPARgamma in deoxycorticosterone acetate-salt treatment, establishing a novel mechanistic link between PPARgamma and TIMP-4.
Title: Protective Role for Tissue Inhibitor of Metalloproteinase-4, a Novel Peroxisome Proliferator-Activated Receptor-γ Target Gene, in Smooth Muscle in Deoxycorticosterone Acetate-Salt Hypertension.
TIMP4 augments contractility and induces differentiation of embryonic stem cells into cardiac phenotype.
Title: Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy.
TIMP-4 might act as a negative regulator of adipogenesis through NFkB cascade modulation.
Title: Tissue inhibitor of metalloproteases-4 (TIMP-4) modulates adipocyte differentiation in vitro.
Replenishment of myocardial TIMP4 could serve as an effective therapy in post-I/R recovery for patients with reduced TIMP4.
Title: Myocardial recovery from ischemia-reperfusion is compromised in the absence of tissue inhibitor of metalloproteinase 4.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (2) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables enzyme inhibitor activity	IEA Inferred from Electronic Annotation more info
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 peptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protease binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of membrane protein ectodomain proteolysis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of peptidase activity	IEA Inferred from Electronic Annotation 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

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

General protein information

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Preferred Names: metalloproteinase inhibitor 4

Names: tissue inhibitor of metalloproteinases 4

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_001356406.1 → NP_001343335.1 metalloproteinase inhibitor 4 isoform 2

Status: VALIDATED

Source sequence(s)

AC153907

UniProtKB/TrEMBL

A0A0N4SUR1

Conserved Domains (1) summary

cl02512
Location:30 → 176

NTR_like; NTR_like domain; a beta barrel with an oligosaccharide/oligonucleotide-binding fold found in netrins, complement proteins, tissue inhibitors of metalloproteases (TIMP), and procollagen C-proteinase enhancers (PCOLCE), amongst others. In netrins, the ...
NM_080639.4 → NP_542370.3 metalloproteinase inhibitor 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_542370.3

Status: VALIDATED

Source sequence(s)

AC153907

Consensus CDS

CCDS20438.1

UniProtKB/Swiss-Prot

Q924B7, Q9JHB3

UniProtKB/TrEMBL

Q3USH7, Q8C577, Q8CAG3

Related

ENSMUSP00000032462.7, ENSMUST00000032462.9

Conserved Domains (1) summary

cd03585
Location:30 → 211

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 ...