8.A.76 The TMEM203 or PF14967 (TMEM203) Family
Members of the TMEM203 Family can be of about 130 - 140 aas in length and possess 4 TMSs in a possible 2 + 2 arrangement, or they can be of about twice this size (290 - 460 aas) with 7 ro 8 TMSs. They possess the Pfam conserved domain 185A.
Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane protein 203 (TMEM203) was identified in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator (Shambharkar et al. 2015). Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. The TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse embryonic fibroblasts derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes, and Tmem203 deficient spermatocytes exhibited significantly altered calcium handling. Thus, Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis, and provides a causal link between intracellular calcium regulation and spermiogenesis (Shambharkar et al. 2015).