The gene is about 4,468 bases encoded by two exons separated by a short intron.

5, upstream promoter drives expression of longer Brn-3a transcript encoding for Brn-3a(l) protein which includes exons 1 and 2. Regulatory sequences within the intron control expression of short Brn-3a transcript entirely from exon 2, which encodes Brn-3a(s) protein.

Protein product for Brn-3a(l) is 423 amino acids with estimated molecular weight of about 42.9 kDa whereas Brn-3a(s) protein is 339 amino acids; about 32 kDa.

Nervous System: Originally isolated from brain cDNA, Brn-3a is expressed in specific neurons of midbrain and hindbrain in CNS and in peripheral sensory neurons (trigeminal ganglia, dorsal root ganglia, spinal cord). It is first seen in neural crest cells that are destined to form sensory neurons and expression persists in mature neurones. Brn-3a is also expressed in retinal ganglion cells and vestibular somatosensory cells, where it cooperates with Brn-3b and Brn-3c respectively to determine cell fate.
Non-neuronal cell: Brn-3a is also expressed in T-cells, heart, testis, ovary, breast epithelium.
Cancers: implicated in neuroblastoma, Ewing sarcoma, cervical cancers, prostate cancers.

Nuclear

Brn-3a proteins act as transcription factors to regulate the expression of target genes, which can alter cell fate. In neuron, Brn-3a protects cells from apoptosis (by transactivating anti-apoptotic genes while repressing expression of pro-apoptotic proteins -see below). Brn-3a also enhances differentiation of neuronal cells in vitro and in-vivo by its ability to transactivate multiple neuronal target promoters. Brn-3a is required for the generation of proprioceptors in trigeminal ganglia.
The POU domain found at the C terminal end of Brn-3a proteins is a bipartite DNA binding domain that can recognize and bind with high affinity and specificity to specific DNA sequences present in the promoters of target genes. DNA consensus sites recognized by Brn-3a include a core A/T rich octamer sequence e.g. ATAATTAAT with the POU-homeodomain (POU-HD) facilitating high affinity binding, whilst the POU-specific (POU-s) domain enhances specificity.
The POU domain of Brn-3a protein also has transactivation function and since Brn-3a(l) and Brn-3a(s) are identical in this region, both proteins can regulate specific subsets of target genes that require POU domain transactivation function e.g. neurofilament, SNAP 25, synaptophysin, Hsp-27. However, some Brn-3a target genes require the N terminal transactivation domain that is found only in Brn-3a(l) protein and therefore these target genes can only be activated by Brn-3a(l) protein e.g. Bcl-2, Bcl-XL, alpha-internexin. Other target genes regulated by Brn-3a include TrkA, neuroD1 and neuroD4, Nav1.7 sodium channel, Doppel glycoprotein, iNOS, p53, NGFI-A, Hsp-27, tyrosine hydroxylase. Brn-3a also auto-regulate its own expression.
In addition to its direct effects on specific target genes, Brn-3a can also alter gene expression by its interaction with other cellular factors. For example, Brn-3a interacts physically with p53 protein, and modifies its effects on specific target genes that regulate cell fate. Thus Brn-3a cooperates with p53 to increase the expression of the cell cycle regulator, p21cip1/waf1 whilst antagonising p53 mediated expression of pro-apoptotic target genes, Bax and Noxa.
Brn-3a other interacting partner includes Rin1 (on target gene, Egr1), HIPK1 (alters TrkA expression), EWS- Fli1 fusion protein (represses Brn-3a mediated effects on survival / differentiation genes).
In addition to cellular target genes, Brn-3a also controls expression of viral genes such as those encoding the human papilloma virus (HPV) immediate early E6/E7 gene (required for HPV transformation of cervical cells) by binding to and transactivating the viral promoter. It is thought that the ability of Brn-3a to transactivate this promoter contributes to its effects in transformation of cervical cancer cells.

High homology with other POU4 family members in the POU domain (C terminal end of the protein), and in the POU4 box (region of homology within the N terminal transactivation domain, present only in Brn-3a(l)). Family members include mammalian POU4f2 (Brn-3b), POU4f3 (Brn-3c), drosophila I-POU and nematode, unc-86.