Timp4 TIMP metallopeptidase inhibitor 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Timp4provided by RGD
Official Full Name: TIMP metallopeptidase inhibitor 4provided by RGD
Primary source: RGD:69077
See related: EnsemblRapid:ENSRNOG00000007955 AllianceGenome:RGD:69077
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Timp-4
Summary: Predicted to enable metalloendopeptidase inhibitor activity and zinc ion binding activity. Involved in several processes, including ovulation cycle; response to lipopolysaccharide; and response to peptide hormone. Located in extracellular space and sarcomere. Biomarker of abdominal aortic aneurysm; congestive heart failure; and renal hypertension. Human ortholog(s) of this gene implicated in nephroblastoma. Orthologous to human TIMP4 (TIMP metallopeptidase inhibitor 4). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Brain (RPKM 134.0), Heart (RPKM 106.0) and 7 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 4q42

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	4	NC_086022.1 (149978667..149985350, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	4	NC_051339.1 (148306021..148312558, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	4	NC_005103.4 (147156948..147163467, complement)

Chromosome 4 - NC_086022.1 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
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?

Defect of TIMP4 Is Associated with High Myopia and Participates in Rat Ocular Development in a Dose-Dependent Manner.
Title: Defect of TIMP4 Is Associated with High Myopia and Participates in Rat Ocular Development in a Dose-Dependent Manner.
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.
OPG regulated the proliferation of chondrocytes via MEK/ERK signaling, and directly affected chondrocytes by influencing the expression profile of ADAMTS-5 and TIMP-4.
Title: Osteoprotegerin promotes the proliferation of chondrocytes and affects the expression of ADAMTS-5 and TIMP-4 through MEK/ERK signaling.
These findings provide evidence of a novel causal role of TIMP-4 and TIMP-3 in the direct inhibitory effect of hypoxia on cardiomyocyte proliferation in the developing heart
Title: Hypoxia inhibits cardiomyocyte proliferation in fetal rat hearts via upregulating TIMP-4.
important role of MMP-2, MMP-9, and TIMP-4 in hypertensive remodeling of the cortex and medulla in the SHR rat
Title: Mechanism of matrix accumulation and glomerulosclerosis in spontaneously hypertensive rats.
ovarian mRNA and protein levels were examined in adult cycling rats
Title: Localization and expression of tissue inhibitor of metalloproteinase-4 in the immature gonadotropin-stimulated and adult rat ovary.

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General gene information

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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
acts_upstream_of_or_within Notch signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of membrane protein ectodomain proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in ovulation cycle	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 cytokine	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 lipopolysaccharide	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to peptide hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed

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	IDA Inferred from Direct Assay more info	PubMed
located_in sarcomere	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: metalloproteinase inhibitor 4

Names: tissue inhibitor of metalloproteinase 4; 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_001109393.1 → NP_001102863.1 metalloproteinase inhibitor 4 precursor

See identical proteins and their annotated locations for NP_001102863.1

Status: PROVISIONAL

Source sequence(s)

CH473964

UniProtKB/Swiss-Prot

P81556

UniProtKB/TrEMBL

A6IKY2

Related

ENSRNOP00000010748.4, ENSRNOT00000010748.5

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 ...

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086022.1 Reference GRCr8

Range

149978667..149985350 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039108336.2 → XP_038964264.1 metalloproteinase inhibitor 4 isoform X1

UniProtKB/TrEMBL

A0A8L2Q5Q1

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 ...
XM_063286672.1 → XP_063142742.1 metalloproteinase inhibitor 4 isoform X2