FunctionInhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli.
Tissue specificityIsoform 4 is the most abundantly expressed isoform. It is ubiquitously expressed throughout most tissues, except the liver, colon, breast and uterine myometrium. Isoform 1 is expressed in the ovary and testis. Isoform 4 is expressed in several types of tumor cell lines, and at consistently high levels in leukemia and lymphoma cell lines. Isoform 1 is expressed in the prostate, breast and leukemia cell lines. Isoform 3 is the least abundant isoform in tumor cell lines (at protein level).
Sequence similaritiesContains 1 BAG domain. Contains 1 ubiquitin-like domain.
Post-translational modificationsUbiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation.
Cellular localizationCytoplasm. Nucleus. Isoform 2 localizes to the cytoplasm and shuttles into the nucleus in response to heat shock; Nucleus. Cytoplasm. Isoform 1 localizes predominantly to the nucleus and Cytoplasm. Nucleus. Isoform 4 localizes predominantly to the cytoplasm. The cellular background in which it is expressed can influence whether it resides primarily in the cytoplasm or is also found in the nucleus. In the presence of BCL2, localizes to intracellular membranes (what appears to be the nuclear envelope and perinuclear membranes) as well as punctate cytosolic structures suggestive of mitochondria.