According to Entrez Gene, PEA15 maps to NC_000001.10 and spans a region of 10042 bases. PEA15 consists of four exons. Exon 1 and the beginning of exon 2 contain untranslated sequences. The end of exon 2, exon 3, and the beginning of exon 4 contain the coding sequence.

Two transcripts, with lengths of 2,5 and 1,7 kb, have been identified. They are identical except for the length of their 3 UTRs.

No pseudogene of PEA15 known.

PEA-15 is a 130-amino-acid protein with a predicted molecular mass of 15054 daltons and a calculated isoelectric point of 5.12.

Ovary, breast, brain, placenta, liver, eye, lung, heart, endothelial cells, pancreas, testis, uterus, adrenal gland, prostate gland, kidney, spleen, and astrocytes.

Cytoplasm. PEA-15 has a leucine-rich nuclear export sequence (NES), which is required for predominantly localizing in the cytoplasm (Formstecher et al., 2001).

PEA-15 is a ubiquitously expressed protein that exists in non-phosphorylated, mono-phosphorylated, and double-phosphorylated forms (Danziger et al., 1995). PEA-15 does not have an enzymatic domain but serves as a binding molecule in protein complexes. PEA-15 is an endogenous substrate that depends on two distinct serine sites: Ser104, which is phosphorylated by protein kinase C (PKC) (Kubes et al., 1998), and Ser116, which is phosphorylated by Ca2+/calmodulin kinase II (CaMKII) (Kubes et al., 1998) or by AKT (Trencia et al., 2003). At its NH2 terminus, PEA-15 has a PLD-interacting region, which enhances PLD 1 stability and activity (Zhang et al., 2000), and a death effector domain (DED), which enables interaction with DED-containing signaling proteins, including Fas-associated protein with death domain (FADD) and FADD-like IL-1β-converting enzyme (Peter et al., 1999). At its COOH terminus, PEA-15 has a microtubule-binding region, which regulates the stability of tubulins (Danziger et al., 1995).
ERK inhibition. PEA-15 can bind to ERK and sequester it in the cytoplasm. The resulting inhibition of ERKs translocalization into the nucleus blocks ERK-dependent transcriptional activity and cell proliferation (Formstecher et al., 2001).
Apoptosis and anti-apoptosis. PEA-15 interacts with different DED-containing proteins such as FADD and FLICE and inhibits Fas/TNFR1-induced apoptosis by preventing formation of the death-inducing signaling complex (DISC) (Condorelli et al., 1999; Song et al., 2006). On the other hand, under different cellular stresses, PEA-15 acts as a substrate of Omi/HtrA2, which is a proapoptotic mitochondrial serine protease; it results in reducing anti-apoptotic action of Omi/HtrA2 and triggering apoptotic programs (Trencia et al., 2004).
Metabolism. In skeletal muscle and adipose cells, PEA-15 binds to PLD1 and enhances PKC-α activity, thereby inducing resistance to insulin action in glucose uptake (Condorelli et al., 1998).
Invasion. A high expression level of PEA-15 is correlated with low invasive behavior of breast cancer (Glading et al., 2007). PEA-15s prevention of ERKs nuclear localization results in reduced invasion capability in breast cancer.
Tumorigenicity. In human breast cancers, low levels of PEA-15 expression correlated with high nuclear grade and with negative hormone receptor status. Overexpression of PEA-15 in breast cancer cells resulted in growth inhibition, reduction in DNA synthesis, and onset of caspase-8-dependent apoptosis (Bartholomeusz et al., 2010). In transgenic mice with overexpression of PEA-15, its expression level had a significant impact on skin tumor development upon chemically induced skin carcinogenesis (Formisano et al., 2005). In in vitro studies, PEA-15 enhanced Ras-MAPK/ERK signaling in the presence of constitutively active H-Ras and drove transformation of kidney epithelial cells (Sulzmaier et al., 2012; Ramos et al., 2000).

The mouse and human sequences are conserved. In both species, the 3 UTR of the 2,5-kb PEA15 cDNA contains the proto-oncogene MAT1 (Tsukamoto et al., 2000).

No known mutations have been reported.