Tm9sf5 is a member of the nonaspanin (TM9SF) protein family, characterized by a large non-cytoplasmic domain and nine putative transmembrane domains. The TM9SF family is highly conserved evolutionarily and may play a regulatory role in a specific and ancient cellular mechanism involved in innate immunity [1].

In zebrafish, the Tm9sf5 gene shows high sequence conservation with previously reported TM9SF members. It is maternally expressed and persists from embryogenesis to adulthood. Its expression is not regulated by pathogen-associated molecular patterns like LPS, CpG, or Poly I:C. An evolutionary conserved immunoreceptor tyrosine-based inhibition motif has been detected in its cytoplasmic domain between transmembrane domain 7 and 8, and a conserved TRAF2 binding domain can be predicted in its cytoplasmic region, which further supports its potential role in innate immunity-related mechanisms [1].

In summary, Tm9sf5, as part of the TM9SF family, likely has a significant role in innate immunity. The studies in zebrafish, a valuable research model, have provided insights into its expression pattern and conserved structural features related to immune-associated functions, which may help in understanding innate immunity-related disease mechanisms [1].

References:

1. Pruvot, Benoist, Laurens, Véronique, Salvadori, Françoise, Pichon, Laurent, Chluba, Johanna. 2010. Comparative analysis of nonaspanin protein sequences and expression studies in zebrafish. In Immunogenetics, 62, 681-99. doi:10.1007/s00251-010-0472-x. https://pubmed.ncbi.nlm.nih.gov/20820770/