SH3D21

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
Identifiers
Aliases	SH3D21, C1orf113, SH3 domain containing 21
External IDs	MGI: 1914188 HomoloGene: 12057 GeneCards: SH3D21
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p34.3 Start 36,306,368 bp[1] End 36,329,340 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.2 Start 126,150,602 bp[2] End 126,163,491 bp[2]
Orthologs
Species	Human	Mouse
Entrez	79729	66938
Ensembl	ENSG00000214193	ENSMUSG00000073758
UniProt	A4FU49	Q7TSG5
RefSeq (mRNA)	NM_001162530 NM_024676	NM_001162533 NM_025856
RefSeq (protein)	NP_001156002 NP_078952	NP_001156005 NP_080132
Location (UCSC)	Chr 1: 36.31 – 36.33 Mb	Chr 4: 126.15 – 126.16 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Gene

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]

Protein

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 sumolyation sites throughout the entirety of the protein.[17][18]

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

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.

Homology

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%.[23] Sequence identity was calculated using available sequence data and ALIGN software.[24]

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

1. GRCh38: Ensembl release 89: ENSG00000214193 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000073758 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "SH3D21". Genecards. Retrieved 3 May 2013.
6. "SH3D21". Gene. NCBI. Retrieved 8 May 2013.
7. "Conserved Domain Analysis of SH3D21". NCBI Conserved Domain Search. Retrieved 2 May 2013.
8. "BioGPS Expression Profile". Retrieved 2 May 2013.
9. "Transcription factor p63 null mutation effect on skin (MG-U74B)". Retrieved 1 March 2013.
10. "GEO Expression Profile". GEO Database. Retrieved 2 May 2013.
11. "Chemical Interaction Report". Retrieved 1 March 2013.
12. Pawson T, Schlessingert J (July 1993). "SH2 and SH3 domains". Current Biology. 3 (7): 434–42. doi:10.1016/0960-9822(93)90350-W. PMID 15335710.
13. Mayer BJ (April 2001). "SH3 domains: complexity in moderation". Journal of Cell Science. 114 (Pt 7): 1253–63. PMID 11256992.
14. "SH3 domain-containing protein 21 isoform 2". NCBI. Retrieved 9 May 2013.
15. "Phyre 2 Secondary Structure Analysis". Retrieved 14 May 2013.
16. "PELE Analysis". Retrieved 14 May 2013.
17. "SUMOplot Analysis". Retrieved 14 May 2013.
18. "NetPhos 2.0 Analysis". Retrieved 14 May 2013.
19. Mallott J, Kwan A, Church J, Gonzalez-Espinosa D, Lorey F, Tang LF, Sunderam U, Rana S, Srinivasan R, Brenner SE, Puck J (April 2013). "Newborn screening for SCID identifies patients with ataxia telangiectasia". Journal of Clinical Immunology. 33 (3): 540–9. doi:10.1007/s10875-012-9846-1. PMC 3591536. PMID 23264026.
20. Stouffs K, Vandermaelen D, Massart A, Menten B, Vergult S, Tournaye H, Lissens W (March 2012). "Array comparative genomic hybridization in male infertility". Human Reproduction. 27 (3): 921–9. doi:10.1093/humrep/der440. PMID 22238114.
21. Nahed BV, Seker A, Guclu B, Ozturk AK, Finberg K, Hawkins AA, DiLuna ML, State M, Lifton RP, Gunel M (January 2005). "Mapping a Mendelian form of intracranial aneurysm to 1p34.3-p36.13". American Journal of Human Genetics. 76 (1): 172–9. doi:10.1086/426953. PMC 1196421. PMID 15540160.
22. 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.
23. "BLAST". NCBI. Retrieved 3 May 2013.
24. "Sequence Alignment". ALIGN. Archived from the original on 11 August 2003. Retrieved 8 May 2013.