Thbs4 thrombospondin 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Thbs4provided by MGI
Official Full Name: thrombospondin 4provided by MGI
Primary source: MGI:MGI:1101779
See related: Ensembl:ENSMUSG00000021702 AllianceGenome:MGI:1101779
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: TSP4
Summary: Predicted to enable several functions, including fibronectin binding activity; heparin binding activity; and laminin-1 binding activity. Involved in behavioral response to pain; regulation of tissue remodeling; and response to endoplasmic reticulum stress. Located in collagen-containing extracellular matrix; extracellular space; and sarcoplasmic reticulum. Is expressed in several structures, including brain; genitourinary system; gut; heart; and skeletal musculature. Orthologous to human THBS4 (thrombospondin 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in colon adult (RPKM 80.2), ovary adult (RPKM 47.3) and 2 other tissues See more
Orthologs: human all
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Genomic context

Location:: 13 C3; 13 47.75 cM

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	13	NC_000079.7 (92888094..92931326, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	13	NC_000079.6 (92751586..92794818, complement)

Chromosome 13 - NC_000079.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

Downregulation of Thbs4 caused by neurogenic niche changes promotes neuronal regeneration after traumatic brain injury.
Title: Downregulation of Thbs4 caused by neurogenic niche changes promotes neuronal regeneration after traumatic brain injury.
The P387 thrombospondin-4 variant promotes accumulation of macrophages in atherosclerotic lesions.
Title: The P387 thrombospondin-4 variant promotes accumulation of macrophages in atherosclerotic lesions.
Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages.
Title: Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages.
at least two proteins enriched in young blood, THBS4 and SPARCL1, directly act on neurons as synaptogenic factors
Title: Specific factors in blood from young but not old mice directly promote synapse formation and NMDA-receptor recruitment.
Like wild-type Thbs4, a secretion-defective mutant upregulates the adaptive ER stress response and expands the ER and intracellular vesicles in cardiomyocytes. However, only the secretion-defective Thbs4 mutant produces cardiomyopathy with sarcolemmal weakness and rupture that is associated with reduced adhesion-forming glycoproteins in the membrane.
Title: Defective Flux of Thrombospondin-4 through the Secretory Pathway Impairs Cardiomyocyte Membrane Stability and Causes Cardiomyopathy.
TSP-4 is an important protein in the development of cardiac hypertrophy and aortic dissections in Ang II-induced hypertension.
Title: Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension.
The findings demonstrate reciprocal regulation of the unfolded protein response, including ATF6alpha activation and endoplasmic reticulum expansion, and reduced contractile differentiation in bladder outlet obstruction occurring independently of thrombospondin-4, which however is a sensitive indicator of obstruction.
Title: Assessing the contribution of thrombospondin-4 induction and ATF6α activation to endoplasmic reticulum expansion and phenotypic modulation in bladder outlet obstruction.
Loss of the Thbs4 gene causes spontaneous dystrophic changes with aging and accelerates disease in 2 mouse models of muscular dystrophy, while overexpression of mouse Thbs4 is protective and mitigates dystrophic disease.
Title: Thrombospondin expression in myofibers stabilizes muscle membranes.
TSP-4 plays a role in angiotensin II induced hypertension, affecting cardiac hypertrophy, aortic aneurysm formation, as well as endothelial-dependent relaxation in resistance arteries.
Title: Thrombospondin-4 knockout in hypertension protects small-artery endothelial function but induces aortic aneurysms.
This study demonstrated THAT elevated TSP4 after peripheral nerve injury may contribute to hypersensitivity of peripheral sensory systems by decreasing HVA and increasing LVA in DRG neurons by targeting the alpha2delta1 calcium subunit.
Title: Thrombospondin-4 divergently regulates voltage-gated Ca2+ channel subtypes in sensory neurons after nerve injury.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Variation

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Alleles

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

Targeted (2)
Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (2)

General gene information

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Markers

UniSTS:496018 (e-PCR)
- UniSTS:496018

Thbs4 (e-PCR), detects polymorphism
- UniSTS:496018

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables collagen binding	ISO Inferred from Sequence Orthology more info
enables extracellular matrix structural constituent	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables fibronectin binding	ISO Inferred from Sequence Orthology more info
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables heparin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables integrin binding	ISO Inferred from Sequence Orthology more info
enables laminin-1 binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in behavioral response to pain	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in behavioral response to pain	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell-cell adhesion	ISO Inferred from Sequence Orthology more info
involved_in myoblast migration	ISO Inferred from Sequence Orthology more info
involved_in nervous system development	ISO Inferred from Sequence Orthology more info
involved_in neuron projection morphogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of cell division	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neutrophil chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of tissue remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to unfolded protein	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within tissue remodeling	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in basement membrane	ISO Inferred from Sequence Orthology more info
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in collagen-containing extracellular matrix	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in neuromuscular junction	ISO Inferred from Sequence Orthology more info
located_in sarcoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: thrombospondin-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_011582.3 → NP_035712.1 thrombospondin-4 precursor

See identical proteins and their annotated locations for NP_035712.1

Status: VALIDATED

Source sequence(s)

CT009509, CT025667

Consensus CDS

CCDS26684.1

UniProtKB/Swiss-Prot

Q9QYS3, Q9WUE0, Q9Z1T2

UniProtKB/TrEMBL

B2RTL6

Related

ENSMUSP00000022213.8, ENSMUST00000022213.8

Conserved Domains (7) summary

cd00054
Location:381 → 415

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00001
Location:616 → 653

TSP3; TSP3 repeat_long [structural motif]

sd00002
Location:498 → 533

TSP3; TSP3 repeat_long [structural motif]

pfam02412
Location:499 → 533

TSP_3; Thrombospondin type 3 repeat

pfam05735
Location:747 → 944

TSP_C; Thrombospondin C-terminal region

cd16080
Location:221 → 264

TSP-4cc; Coiled coil region of thrombospondin-4 (TSP-4)

cl22861
Location:26 → 194

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...