Thrombospondin-4 (THBS4)
The protein contains 961 amino acids for an estimated molecular weight of 105869 Da.
Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of vascular inflammation and adaptive responses of the heart to pressure overload and in myocardial function and remodeling. Binds to structural extracellular matrix (ECM) proteins and modulates the ECM in response to tissue damage, contributing to cardioprotective and adaptive ECM remodeling. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors and protects myocardium from pressure overload. May contribute to spinal presynaptic hypersensitivity and neuropathic pain states after peripheral nerve injury. May play a role in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury in a NOTCH1-dependent manner (By similarity). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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No binding partner found
Biological Process
Behavioral response to pain
Endothelial cell-cell adhesion
Myoblast migration
Negative regulation of angiogenesis
Positive regulation of cell division
Positive regulation of endothelial cell proliferation
Positive regulation of neutrophil chemotaxis
Positive regulation of peptidyl-tyrosine phosphorylation
Regulation of tissue remodeling
Response to endoplasmic reticulum stress
Response to unfolded protein
Tissue remodeling
The reference OMIM entry for this protein is 600715
Thrombospondin iv; thbs4
DESCRIPTION
The thrombospondins are a family of extracellular calcium binding proteins involved in cell proliferation, adhesion, and migration.CLONING
Thrombospondin 4 (THBS4) was originally identified from a Xenopus stage 45 cDNA library. Lawler et al. (1995) isolated a cDNA for the human THBS4 gene (which they called TSP4) from a heart expression library. Overall, the 961-amino acid predicted protein is 73% identical to the X. laevis sequence; however, the C-terminal 220 residues are over 92% identical. The TSP4 mRNA is approximately 3.4 kb. In contrast to thrombospondin-4 of Xenopus laevis, the human protein contains an RGD (arg-gly-asp) cell-binding sequence in the third type 3 repeat. Transfection of mouse NIH 3T3 fibroblasts or C2C12 myoblasts with a full-length human thrombospondin-4 cDNA resulted in the expression of a polypeptide with a reduced molecular weight of 140,000. In the absence of reducing agent, the expressed protein had an apparent molecular weight of 550,000. Lawler et al. (1995) purified recombinant thrombospondin-4 from the culture supernatant. Electron microscopy indicated that it is composed of 5 subunits with globular domains at each end. Thus, they concluded that thrombospondin-4 is a pentameric protein that binds to heparin and calcium.GENE FUNCTION
Benner et al. (2013) demonstrated in mice that subventricular zone (SVZ)-generated astrocytes express high levels of the secreted homopentameric glycoprotein Thbs4, in contrast to cortical astrocytes, which express low levels of Thbs4. Benner et al. (2013) found that localized photothrombotic/ischemic cortical injury initiates a marked increase in Thbs4(hi) astrocyte production from the postnatal SVZ niche. Tamoxifen-inducible nestin-creER(tm)4 lineage tracing demonstrated that it is these SVZ-generated Thbs4(hi) astrocytes, and not doublecortin (300121)-positive neuroblasts (also generated within the SVZ), that home in on the injured cortex. This robust postinjury astrogenic response required SVZ Notch (190198) activation modulated by Thbs4 via direct Notch1 receptor binding and endocytosis to activate downstream signals, including increased Nfia (600727) transcription factor expression important for glia production. Consequently, Thbs4 homozygous knockout mice showed severe defects in cortical injury-induced SVZ astrogenesis, instead producing cells expressing doublecortin migrating from SVZ to the injury sites. These alterations in cellular responses resulted in abnormal glial scar formation after injury, and significantly increased microvascular hemorrhage into the brain parenchyma of Thbs4-null mice. Taken together, Benner et al. (2013) concluded that their findings have important implications for postinjury applications of endogenous and transplanted NSCs in the therapeutic setting, as well as disease states where Thbs family members have important roles.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the THBS4 gene to chromosome 5 (TMAP SHGC-12514).MOLECULAR GENETICS
McCarthy et al. (2004) analyzed 210 polymorphisms in 111 candidate genes in 352 white subjects with familial premature coronary heart disease and 418 white controls, and found the strongest association with an ala387-to-pro (A387P) variant in THBS4 (p = 0.002). Eumycetoma is a tumorous fungal infection, typically of the hands or feet, characterized by the infiltration of large numbers of neutrophils. It is caused b ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600715 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).