SH3D21

SH3D21 is expressed in low levels in most tissue.^[8] Microarray analysis has shown SH3D21 expression to be decreased in TP63 knockout mice.^[9] SH3D21 has been shown to be expressed highly in the superior cervical ganglion, the dorsal root ganglia and the trigeminal ganglion.^[8][10] Transcription of SH3D21 is known to be upregulated in the presence of testosterone.^[11]

SH3D21 contains three SH3 domains.^[7][12][13] These domains are located near the N-terminus of the protein. In humans, these SH3 domains have a common amino acid sequence Asp-Glu-Leu. This sequence motif is also conserved in other species. SH3D21 has been found to interact with Adenylate Kinase 2, Artemin, and Importin 13.^[5] The human protein has two isoforms and no paralogs.^[6] The second isoform is 645 amino acids long and is identical to the first isoform, except it is missing the first 111 amino acids.^[14] Due to this, the second isoform is missing the first, and half of the second, N-terminal SH3 domain.^[14] Secondary structure analysis of SH3D21 indicates a long alpha helical structure near the C-terminus.^[15][16] The purpose of this structure is unknown. SH3D21 is predicted to have many phosphorylation sites and multiple sumoylation sites throughout the entirety of the protein.^[17][18]

The function of this gene is still unclear. However, research has linked SH3D21 expression changes to male infertility and Ataxia Telangiectasia.^[19][20] Further studies have implicated the chromosomal region of 1p34.3 in Intracranial Aneurysm and as a negative prognosis sign in colorectal cancer.^[21][22] These studies do not, however, directly mention SH3D21.

SH3D21 is well-conserved in mammals. BLAST analysis found distant orthologs in Osteichthyes with a max identity of 28%.^[23] Sequence identity was calculated using available sequence data and ALIGN software.^[24]