SH3D21 is a nuclear protein that is encoded by the SH3D21 gene. In humans, this gene is located on chromosome 1 p34.3.[5] The human mRNA transcript is 2527 base pairs and the final protein product is 756 amino acids.[6] While the exact function of this protein remains unknown, due to the presence of three SH3 domains, it has been implicated in protein-protein interactions.[7]
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]
^Kashkin K, A.G. Perevoschoikov (May–June 2000). "Deletion of the Alu-VpA/MycL1(1p34.3) locus is a negative prognostic sign in human colorectal cancer". Molecular Biology. 34 (3): 337–344. doi:10.1007/bf02759663. S2CID8301557.