TBRG4

Transforming growth factor beta regulator 4 (TBRG4), also known as cell cycle progression restoration protein 2 (CPR2) and FAST kinase domain-containing protein 4 (FASTKD4), is a protein that in humans is encoded by the TBRG4 gene on chromosome 7.^[5][6][7] This protein is part of the FASTKD family, which is known for regulating the energy balance of mitochondria under stress and cell cycle progression.^[8][9] TBRG4 is involved in cell proliferation in hematopoiesis and multiple myeloma.^[10][11]

TBRG4
Identifiers
Aliases	TBRG4, CPR2, FASTKD4, transforming growth factor beta regulator 4
External IDs	OMIM: 611325; MGI: 1100868; HomoloGene: 31259; GeneCards: TBRG4; OMA:TBRG4 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p13 Start 45,100,100 bp[1] End 45,112,047 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A1 Start 6,565,598 bp[2] End 6,576,067 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon apex of heart granulocyte gastrocnemius muscle rectum muscle of thigh skin of leg right ovary body of stomach minor salivary glands Top expressed in epiblast primitive streak yolk sac tail of embryo internal carotid artery granulocyte muscle of thigh hair follicle endothelial cell of lymphatic vessel condyle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein kinase activity protein binding RNA binding Cellular component mitochondrion mitochondrial matrix Biological process cellular respiration protein phosphorylation positive regulation of cell population proliferation mRNA metabolic process regulation of mitochondrial mRNA stability mitochondrial mRNA processing Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9238 21379 Ensembl ENSG00000136270 ENSMUSG00000000384 UniProt Q969Z0 Q91YM4 RefSeq (mRNA) NM_199122 NM_001261834 NM_004749 NM_030900 NM_001130457 NM_134011 NM_001362713 NM_001362714 NM_001362715 NM_001362716 RefSeq (protein) NP_001248763 NP_004740 NP_112162 NP_954573 NP_001123929 NP_598772 NP_001349642 NP_001349643 NP_001349644 NP_001349645 Location (UCSC) Chr 7: 45.1 – 45.11 Mb Chr 11: 6.57 – 6.58 Mb PubMed search [3] [4]
Wikidata
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Structure

TBRG4 shares structural characteristics of the FASTKD family, including an N-terminal mitochondrial targeting domain and three C-terminal domains: two FAST kinase-like domains (FAST_1 and FAST_2) and a RNA-binding domain (RAP).^[8][9] The mitochondrial targeting domain directs TBRG4 to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing.^[8] TBRG4 also contains multiple putative leucine zipper domains.^[6]

Function

As a member of the FASTKD family, TBRG4 localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, TBRG4 appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria.^[8] TBRG4 also localizes to the bone marrow (BM), where it functions in hematopoiesis by inducing IL-6 and VEGF secretion, which then stimulate cell proliferation and angiogenesis. However, it inhibits immunoglobulin secretions by normal B cells.^[10]

Clinical significance

The involvement of TBRG4 in hematopoiesis links it to multiple myeloma (MM), which stems from malignant proliferation of plasma cells in the bone marrow.^[10] High expression of TBRG4 has been linked to enhanced cell proliferation and poorer outcome; thus, downregulation of its expression may contribute to reducing tumor growth by arresting cell cycle progression.^[11]