SH3D21

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SH3D21 is a nuclear protein that is encoded by the SH3D21 gene. In humans, this gene is located on chromosome 1 p34.3.[1] The human mRNA transcript is 2527 base pairs and the final protein product is 756 amino acids.[2] 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.[3]

Gene

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SH3D21 is expressed in low levels in most tissue.[4] Microarray analysis has shown SH3D21 expression to be decreased in TP63 knockout mice.[5] SH3D21 has been shown to be expressed highly in the superior cervical ganglion, the dorsal root ganglia and the trigeminal ganglion.[4][6] Transcription of SH3D21 is known to be upregulated in the presence of testosterone.[7]

Protein

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SH3D21 contains three SH3 domains.[3][8][9] 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.[1] The human protein has two isoforms and no paralogs.[2] The second isoform is 645 amino acids long and is identical to the first isoform, except it is missing the first 111 amino acids.[10] Due to this, the second isoform is missing the first, and half of the second, N-terminal SH3 domain.[10] Secondary structure analysis of SH3D21 indicates a long alpha helical structure near the C-terminus.[11][12] 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.[13][14]

This image is a multiple sequence alignment of the three SH3 domains found in the human SH3D21 protein. Note the conserved Asp-Glu-Leu motif. This image was generated using publicly available sequence data and open source software.

Function

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The function of this gene is still unclear. However, research has linked SH3D21 expression changes to male infertility and Ataxia Telangiectasia.[15][16] Further studies have implicated the chromosomal region of 1p34.3 in Intracranial Aneurysm and as a negative prognosis sign in colorectal cancer.[17][18] These studies do not, however, directly mention SH3D21.

Homology

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Phylogenetic tree generated using open source, free software and publicly available sequence data.

SH3D21 is well-conserved in mammals. BLAST analysis found distant orthologs in Osteichthyes with a max identity of 28%.[19] Sequence identity was calculated using available sequence data and ALIGN software.[20]

Species Species common name NCBI Accession Number (Protein) Length (aa) Sequence identity
Homo sapiens Human NP_001156002 756aa 100%
Gorilla gorilla Gorilla XP_004025512 761 aa 97.1%
Pongo abelii Orangutan XP_002811093 755aa 94.9%
Macaca mulatta Macaques XP_001110607 755aa 91.4%
Papia anubir Olive Baboon XP_003891645/ 761aa 91.2%
Saimiri boliviensis Black Capped Squirrel Monkey XP_003308029 650aa 82.0%
Bos taurus Cattle NP_001156006 676aa 58.70%
Cavia porcellus Guinea pig XP_003471528 658aa 52.60%
Oreochromis niloticus Nile Talapia XP_003450596 505aa 28.1%

References

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