Timp2 TIMP metallopeptidase inhibitor 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Timp2provided by RGD
Official Full Name: TIMP metallopeptidase inhibitor 2provided by RGD
Primary source: RGD:61312
See related: Ensembl:ENSRNOG00000033143 AllianceGenome:RGD:61312
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
Summary: Enables integrin binding activity and metalloendopeptidase inhibitor activity. Involved in several processes, including positive regulation of adenylate cyclase activity; positive regulation of neuron differentiation; and regulation of intracellular signal transduction. Located in several cellular components, including cell surface; growth cone; and neuronal cell body. Used to study portal hypertension. Biomarker of cardiomyopathy; congestive heart failure; and intracranial aneurysm. Human ortholog(s) of this gene implicated in Moyamoya disease. Orthologous to human TIMP2 (TIMP metallopeptidase inhibitor 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Lung (RPKM 702.5), Heart (RPKM 595.0) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 10q32.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	10	NC_086028.1 (104041604..104089214, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	10	NC_051345.1 (103541199..103590611, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	10	NC_005109.4 (107338465..107386072, complement)

Chromosome 10 - NC_086028.1 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?

Trabecular Bone Parameters, TIMP-2, MMP-8, MMP-13, VEGF Expression and Immunolocalization in Bone and Cartilage in Newborn Offspring Prenatally Exposed to Fumonisins.
Title: Trabecular Bone Parameters, TIMP-2, MMP-8, MMP-13, VEGF Expression and Immunolocalization in Bone and Cartilage in Newborn Offspring Prenatally Exposed to Fumonisins.
Long noncoding RNA MEG3 silencing protects against hypoxia-induced pheochromocytoma-12 cell injury through inhibition of TIMP2 promoter methylation.
Title: Long noncoding RNA MEG3 silencing protects against hypoxia-induced pheochromocytoma-12 cell injury through inhibition of TIMP2 promoter methylation.
High TIMP2 expression is associated with myocardial fibrosis in cardiac hypertrophy.
Title: Copper-induced reduction in myocardial fibrosis is associated with increased matrix metalloproteins in a rat model of cardiac hypertrophy.
Exogenous TIMP-2 interfered with local MMP-2 expression, delaying peak expression of MMP-2 and slowing the scarring of filtering blebs during wound healing of subconjunctival tissue.
Title: Exogenous Tissue Inhibitor of Metalloproteinase-2 Affects Matrix Metalloproteinase-2 Expression in Conjunctival Filtering Blebs and Bleb Scarring in Rats.
Dynamics of distribution of capillaries with MMP2 and TIMP2 expressed in rat brain during development of experimental hypertension has been reported.
Title: Dynamics of Distribution of Capillaries with Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Rat Brain during Development of Experimental Hypertension.
During the processes of conjunctival filtering bleb and scar formation in rats, the changes in MMP-2 and TIMP-2 levels in the filtering area, together with a corresponding proliferation of fibroblasts and the accumulation of collagen fibres, resulted in scarring of filtering blebs.
Title: Correlation between Tissue Characterization and Dynamic Expression of Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Conjunctival Filtering Bleb of Rats.
These findings suggested that artesunate attenuates alveolitis and pulmonary fibrosis by regulating expression of collagen-IV, TIMP-1 and 2, as well as MMP-2 and -9, to reduce ECM accumulation.
Title: Artesunate modulates expression of matrix metalloproteinases and their inhibitors as well as collagen-IV to attenuate pulmonary fibrosis in rats.
Data suggest that amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.
Title: Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats.
decreased in diabetic skin
Title: The skin remodeling in type 1 diabetes and insulin resistance animal models.
Lung tissue from burn animals showed increased matrix metalloproteinase activity, decreased levels of TIMP-2, and no difference in levels of active MMP-9 in burn vs. control groups.
Title: Tissue inhibitor of metalloproteinase-2 inhibits burn-induced derangements and hyperpermeability in microvascular endothelial cells.

Submit: New GeneRIF Correction See all GeneRIFs (40)

General gene information

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Markers

Timp2 (e-PCR), detects polymorphism
- UniSTS:265761

Timp2 (e-PCR), detects polymorphism
- UniSTS:259384

Ddc8 (e-PCR), detects polymorphism
- UniSTS:532065

Timp2 (e-PCR), detects polymorphism
- UniSTS:532066

Timp2 (e-PCR), detects polymorphism
- UniSTS:532067

Timp2 (e-PCR), detects polymorphism
- UniSTS:532068

Timp2 (e-PCR), detects polymorphism
- UniSTS:532069

Timp2 (e-PCR), detects polymorphism
- UniSTS:532070

Timp2 (e-PCR), detects polymorphism
- UniSTS:144626

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables enzyme activator activity	ISO Inferred from Sequence Orthology more info
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables integrin binding	ISO Inferred from Sequence Orthology 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 metalloendopeptidase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metalloendopeptidase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables molecular function inhibitor activity	ISO Inferred from Sequence Orthology more info
enables peptidase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables protease binding	IBA Inferred from Biological aspect of Ancestor more info
enables protease binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within cellular response to organic substance	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
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
involved_in negative regulation of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neuron differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in regulation of Rap protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of neuron differentiation	ISO Inferred from Sequence Orthology more info
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 xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in spermatogenesis	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in basement membrane	ISO Inferred from Sequence Orthology more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	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
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: metalloproteinase inhibitor 2

Names: TIMP-2; tissue inhibitor of metalloproteinase 2; tissue inhibitor of metalloproteinases 2

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_021989.3 → NP_068824.1 metalloproteinase inhibitor 2 precursor

See identical proteins and their annotated locations for NP_068824.1

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000010

UniProtKB/Swiss-Prot

P30121, Q546J4

UniProtKB/TrEMBL

A6HL48

Related

ENSRNOP00000004290.4, ENSRNOT00000004290.5

Conserved Domains (1) summary

cd03585
Location:27 → 209

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_086028.1 Reference GRCr8

Range

104041604..104089214 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039085773.2 → XP_038941701.1 metalloproteinase inhibitor 2 isoform X5

Conserved Domains (1) summary

cd03585
Location:2 → 166

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 ...
XM_063268839.1 → XP_063124909.1 metalloproteinase inhibitor 2 isoform X5
XM_063268841.1 → XP_063124911.1 metalloproteinase inhibitor 2 isoform X5
XM_063268840.1 → XP_063124910.1 metalloproteinase inhibitor 2 isoform X5
XM_063268838.1 → XP_063124908.1 metalloproteinase inhibitor 2 isoform X4

UniProtKB/TrEMBL

A0A8I6A3D8
XM_063268830.1 → XP_063124900.1 metalloproteinase inhibitor 2 isoform X1

UniProtKB/TrEMBL

A0A0G2JSV1
XM_063268837.1 → XP_063124907.1 metalloproteinase inhibitor 2 isoform X3

UniProtKB/TrEMBL

A0A8I6GM76, A6HL49, Q6AY32
XM_063268834.1 → XP_063124904.1 metalloproteinase inhibitor 2 isoform X3

UniProtKB/TrEMBL

A0A8I6GM76, A6HL49, Q6AY32
XM_063268833.1 → XP_063124903.1 metalloproteinase inhibitor 2 isoform X3

UniProtKB/TrEMBL

A0A8I6GM76, A6HL49, Q6AY32
XM_063268832.1 → XP_063124902.1 metalloproteinase inhibitor 2 isoform X3

UniProtKB/TrEMBL

A0A8I6GM76, A6HL49, Q6AY32
XM_063268835.1 → XP_063124905.1 metalloproteinase inhibitor 2 isoform X3

UniProtKB/TrEMBL

A0A8I6GM76, A6HL49, Q6AY32
XM_063268836.1 → XP_063124906.1 metalloproteinase inhibitor 2 isoform X3

UniProtKB/TrEMBL

A0A8I6GM76, A6HL49, Q6AY32
XM_063268831.1 → XP_063124901.1 metalloproteinase inhibitor 2 isoform X2

UniProtKB/TrEMBL

A0A8I6A7M6