FAM162A

Human growth and transformation-dependent protein (HGTD-P), also called E2-induced gene 5 protein (E2IG5), is a protein that in humans is encoded by the FAM162A gene on chromosome 3. This protein promotes cell death in response to hypoxia via interactions with hypoxia-inducible factor-1α (HIF-1α). As a result, it has been associated with cerebral ischemia, myocardial infarction, and various cancers.

Structure
HGTD-P contains two transmembrane domains that are required for its localization to the mitochondria and induction of cell death.

Function
HGTD-P localizes to the mitochondria, where it participates in regulation of apoptosis. This localization is aided by the chaperone Hsp90, which is required to stabilize the protein during the transit. HGTD-P primarily acts in response to hypoxia by interacting with HIF-1α, which then triggers apoptotic cascades that result in the release of cytochrome C, induction of mitochondrial permeability transition, and activation of caspase-9 and 3. In neuronal cells, it additionally stimulates mitochondrial release of AIFM1, which then translocates to the nucleus to effect apoptosis.

Clinical significance
Due to its involvement in hypoxia, HGTD-P has been implicated in cerebral ischemia and myocardial infarction, as well as numerous cancers, including cervical cancer and gastric cancer. In the case of cervical cancer, HGTD-P is expressed in the early developmental stages and, thus, may prove useful as a diagnostic marker to control the spread of the cancer. Despite its proapoptotic function, HGTD-P has been observed to coordinate with HIF-1α to promote cell growth and proliferation under hypoxic conditions in cervical cancer.

Interactions
HGTD-P has been shown to interact with Hsp90.