Thbs4 thrombospondin 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Thbs4provided by RGD
Official Full Name: thrombospondin 4provided by RGD
Primary source: RGD:62046
See related: EnsemblRapid:ENSRNOG00000012471 AllianceGenome:RGD:62046
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
Summary: Enables several functions, including fibronectin binding activity; identical protein binding activity; and laminin-1 binding activity. Involved in behavioral response to pain and neuron projection morphogenesis. Located in neuromuscular junction. Orthologous to human THBS4 (thrombospondin 4). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Muscle (RPKM 402.7), Heart (RPKM 44.2) and 1 other tissue See more
Orthologs: human mouse all
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Genomic context

Location:: 2q12

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	2	NC_086020.1 (25718219..25760345, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	2	NC_051337.1 (23983158..24025289, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	2	NC_005101.4 (22343727..22385855, complement)

Chromosome 2 - NC_086020.1 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?

The role and mechanism of thrombospondin-4 in pulmonary arterial hypertension associated with congenital heart disease.
Title: The role and mechanism of thrombospondin-4 in pulmonary arterial hypertension associated with congenital heart disease.
Histone methyltransferase MLL4 protects against pressure overload-induced heart failure via a THBS4-mediated protection in ER stress.
Title: Histone methyltransferase MLL4 protects against pressure overload-induced heart failure via a THBS4-mediated protection in ER stress.
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.
Results show that TSP4 regulates Ca2+ homeostasis in primary sensory neurons by affecting Ca2+ influx and buffering, including SERCA and PMCA, via PKC signaling after binding to Cavalpha2delta1. Elevated TSP4 expression may be a key factor that disrupts Ca2+ homeostasis after neuronal injury, and may serve as a valuable target for treatment of neuropathic pain.
Title: Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons.
This study advances the understanding of the timing and role of afferent activity in TSP4 expression after injury, which is critical for the therapeutic targeting of TSP4 to treat persistent pain conditions.
Title: Spinal Astrocytic Thrombospondin-4 Induced by Excitatory Neuronal Signaling Mediates Pain After Facet Capsule Injury.
TSP4 promoted neuronal differentiation of NG2 cells by inhibiting ERK/MAPK signaling.
Title: Thrombospondin-4 Promotes Neuronal Differentiation of NG2 Cells via the ERK/MAPK Pathway.
these data identify the critical intracellular functional domains of thrombospondin-4, which was formerly thought to have only extracellular functions
Title: Dissection of Thrombospondin-4 Domains Involved in Intracellular Adaptive Endoplasmic Reticulum Stress-Responsive Signaling.
following peripheral nerve injury TSP4 protein expression is elevated in the cytoplasm of axotomized sensory neurons and in the surrounding interstitial space.
Title: Painful nerve injury upregulates thrombospondin-4 expression in dorsal root ganglia.
thrombospondin-4 protein levels are up-regulated in dorsal spinal cord of spinal cord injury rats with nociceptive hyperreflexia
Title: Thrombospondin-4 contributes to spinal cord injury-induced changes in nociception.
Expression of mRNA for thrombospondins (TSP-1, TSP-2, TSP-4) was greater than 5-fold higher in vena cava versus thoracic aorta.
Title: Differential expression of pancreatitis-associated protein and thrombospondins in arterial versus venous tissues.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH131881 (e-PCR)
- UniSTS:215164

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

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

THBS4 (e-PCR)
- UniSTS:504996

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables collagen binding	IDA Inferred from Direct Assay more info	PubMed
enables fibronectin binding	IDA Inferred from Direct Assay more info	PubMed
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables heparin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables integrin binding	IEA Inferred from Electronic Annotation more info
enables integrin binding	ISO Inferred from Sequence Orthology more info
enables laminin-1 binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in behavioral response to pain	IEA Inferred from Electronic Annotation more info
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
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell-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	IEA Inferred from Electronic Annotation more info
involved_in myoblast migration	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in nervous system development	IDA Inferred from Direct Assay more info	PubMed
involved_in neuron projection morphogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell division	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	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	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neutrophil chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of tissue remodeling	IEA Inferred from Electronic Annotation more info
involved_in regulation of tissue remodeling	ISO Inferred from Sequence Orthology more info
involved_in regulation of tissue remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to endoplasmic reticulum stress	IEA Inferred from Electronic Annotation more info
involved_in response to endoplasmic reticulum stress	ISO Inferred from Sequence Orthology more info
involved_in response to endoplasmic reticulum stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to unfolded protein	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in tissue remodeling	IEA Inferred from Electronic Annotation more info

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 collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in collagen-containing extracellular matrix	ISO Inferred from Sequence Orthology more info
located_in collagen-containing extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info
located_in extracellular space	ISS Inferred from Sequence or Structural Similarity more info
located_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
located_in sarcoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in sarcoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info

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_017133.1 → NP_058829.1 thrombospondin-4 precursor

Status: VALIDATED

Source sequence(s)

JAXUCZ010000002

UniProtKB/TrEMBL

A0A0G2K7L8, F1LMS5

Related

ENSRNOP00000074259.1, ENSRNOT00000083531.3

Conserved Domains (7) summary

cd00054
Location:379 → 413

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:591 → 613

TSP3; TSP3 repeat_short [structural motif]

sd00002
Location:496 → 531

TSP3; TSP3 repeat_long [structural motif]

pfam02412
Location:497 → 531

TSP_3; Thrombospondin type 3 repeat

pfam05735
Location:745 → 942

TSP_C; Thrombospondin C-terminal region

cd16080
Location:219 → 262

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

cl22861
Location:24 → 192

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 ...