first tandem Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif) repeat of protein Spire homologs 1 and 2
This family contains the first tandem Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) domain in human Spire family proteins Spire-1 (also called Spir1) and Spire-2 (Spir2) and related proteins. Spire is an actin nucleator essential for establishing an actin mesh during oogenesis. It was first identified as a Drosophila maternal effect gene essential to establishment of both the anterior/posterior and dorsal/ventral body axes in developing oocytes and embryos. It has been found to sever filaments and sequester monomers in addition to nucleating new filaments; it remains associated with the slow-growing pointed end of the new filament. Spire is involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport. It is required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis. Spire contains four tandem WH2 domains. The mammalian genome encodes two Spire proteins, namely Spire-1 and Spire-2. This model contains WH2 domain 1 of human Spire-1 and Spire-2 . Major expression of both spire genes have been detected during embryogenesis in the developing nervous system). In addition, spire1 expression is found in the fetal liver, while spire2 expression is seen in early stages of intestinal development. In adult tissues, the spire2 gene shows a rather broad expression pattern, which includes the epithelial cells of the digestive tract, testical spermatocytes, and neuronal cells of the nervous system. In contrast, spire1 is mainly expressed in neuronal cells of the nervous system. Minor expression levels were detected in testis and spleen. Spire also acts in the nucleus where, together with Spire-1 and Spire-2, it promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage. High levels of spire1 expression are restricted to the nervous system, oocytes, and testis. Since function of Spire-1 and Spire-2 in oocyte maturation is redundant, spire1 mutant mice are fertile, overall brain anatomy is not altered, and visual and motor functions remain normal; however, detailed behavioral studies of the spire1 mutant mice unveiled a very specific and highly significant phenotype in terms of fear learning in male mice.
Jiyao W et al.(2023). "The conserved domain database in 2023.",