TBRG4

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

Structure
TGF-β shares structural characteristics of the FASTKD family, including an amino 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). The mitochondrial targeting domain directs TGF-β to be imported into the mitochondria. Though the functions of the C-terminal domains are unknown, RAP possibly binds RNA during trans-splicing. TGF-β also contains multiple putative leucine zipper domains.

Function
As a member of the FASTKD family, TGF-β localizes to the mitochondria to modulate their energy balance, especially under conditions of stress. Though ubiquitously expressed in all tissues, TGF-β appears more abundantly in skeletal muscle, heart muscle, and other tissues enriched in mitochondria. TGF-β also localizes to the is_associated_with::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.

Clinical significance
The involvement of TGF-β in hematopoiesis links it to is_associated_with::multiple myeloma (MM), which stems from malignant proliferation of plasma cells in the bone marrow.