SOHLH2 (spermatogenesis and oogenesis specific basic helix-loop-helix 2)

Note	Molecular weight: NP_060296.2 ~46.9 kDa, 425aa; NP_001269076.1 ~25.1 kDa, 225 aa
	Figure 1 - Schematic representation of the human SOHLH2 protein SOHLH2 is a 425aa protein with one basic helix-loop-helix DNA-binding motif (bHLH, 197-257aa)
Description	SOHLH2 is a ~46.9 kDa protein (initially described as a 51kDa (Ballow et al., 2006)), composed of 425 amino acids, with an isoelectric point of 7.1377. SOHLH2 has a basic helix-loop-helix DNA-binding (bHLH) motif of 60aa (197-257aa) thus it has being described as a transcription factor (figure 1). The amino-terminal portion of bHLH corresponds to the basic domain, enabling the binding of the protein to its consensus sequence at the DNA, known as E-Box. The HLH portion is at the carboxy-terminal portion of bHLH and is a structure covering two α -helices connected by a loop which is responsible for the interactions with other protein subunits to form homo- and heterodimeric complexes (Jones, 2004; Gyoja, 2017).
Expression	SOHLH2 protein expression is observed in the nuclei of oocytes, and weak staining is present in the cytoplasm of theca cells and granular cells in the ovary. The SOHLH2 transcripts expression are detectable specifically in the oocytes of small follicles of female embryonic gonad. In adult ovaries, SOHLH2 protein is present in primordial follicles and absent in growing oocytes (Ballow et al., 2006). In testis, SOHLH2 is found mainly in spermatogonia and Sertoli cells in seminiferous tubule and Leydig cells outside of seminiferous tubules (Ballow et al., 2006; Zhang et al., 2015). Although SOHLH2 has been initially described in testis and oocytes, it is widely expressed in normal adult human tissues. The expression of SOHLH2 is also observed in the cytoplasm of the three kinds of muscle tissues: skeletal, cardiac and smooth. SOHLH2 protein expression was also found in other tissues derived from embryonic mesoderm such as kidney and uterine tube (Zhang et al., 2015). In neurons, Sohlh2 were detected mainly in the nuclei, while it was not detectable by IHC in neuroglial cells. The expression of SOHLH2 gene was also detected in some other tissues derived from embryonic ectoderm including iris, ciliary body, and retina (Zhang et al., 2015).
Localisation	SOHLH2 is an intracellular protein present predominantly in the nucleus but also in the cytoplasm of specific cell types (Zhang et al., 2015; Shin et al., 2017). Its translocation from the cytoplasm is associated with expression of SOHLH1 (Shin et al., 2017).
Function	Tissue-specific basic helix-loop-helix (bHLH) transcription factors play critical roles in cell differentiation SOHLH2 is described as a transcription regulator of both male and female germline differentiation. SOHLH2, together with SOHLH1, regulates oocyte growth and differentiation (Shin et al., 2017). SOHLH proteins modulate the expression of genes involved in spermatogonial stem cells maintenance (SSC), such as RET, GFRA1, NANOS2, and POU5F1. Also, it regulates the expression of genes essential for spermatogonial differentiation such as KIT, and SOX3 (Suzuki et al., 2012). According to Toyoda et al. SOHLH2 forms a ternary complex with SOHLH1, and SP1 and cooperatively regulates the transcription of SOHLH1 gene (Toyoda et al., 2014).
	Figure 2 - Schematic representation of the mechanism of action of SOHLH2. SOHLH2 negatively regulates cell proliferation trough upregulation of APC expression and inhibition of Wnt/βcatenin signaling and suppresses migration and invasion by down-regulation of IL-8. SOHLH2 - spermatogenesis and oogenesis specific basic helix-loop-helix 2; APC - adenomatosis polyposis coli/APC regulator of WNT signaling pathway; IL-8 - Interleukin 8 (Zhang et al., 2016; Ji et al, 2016)
Homology	Although SOHLH2 was identified as a homologue of SOHLH1, their limited homology is confined to the bHLH domains (~50%) (Suzuki et al., 2012). The bHLH protein domain of SOHLH2 is the most conserved region among different species (Ballow et al., 2006). The described identity among mouse SOHLH2 protein with the rat and human orthologue is 84% and 50%, respectively (Ballow et al., 2006).

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