Alternative titles; symbols
HGNC Approved Gene Symbol: TMEM119
Cytogenetic location: 12q23.3 Genomic coordinates (GRCh38): 12:108,589,851-108,598,084 (from NCBI)
TMEM119 is a plasma membrane protein associated with osteoblast differentiation (Kanamoto et al., 2009). TMEM119 is also a marker for microglia, the tissue-resident macrophages of brain and spinal cord (Bennett et al., 2016).
Using microarray screening, Kanamoto et al. (2009) identified mouse Tmem119, which they called Obif, as a gene involved in differentiation of osteoblasts. They cloned human OBIF by RT-PCR of fetal brain RNA. The deduced human and mouse proteins contain 283 and 280 amino acids, respectively, and both have a signal sequence, a transmembrane domain, and a glutamic acid-rich region. OBIF has several potential O-glycosylation sites between the signal sequence and transmembrane domain, suggesting that it is a type Ia membrane protein. Orthologs of OBIF are present in chicken, zebrafish, and Xenopus. Immunostaining showed that FLAG-tagged mouse or human OBIF localized to the plasma membrane of mouse preosteoblastic MC3T3-E1 cells. During mouse embryonic development, Obif was initially observed in limb bud and was highly expressed in osteoblasts later in development. Obif expression decreased during early postnatal stages.
Gross (2020) mapped the TMEM119 gene to chromosome 12q23.3 based on an alignment of the TMEM119 sequence (GenBank BC096825) with the genomic sequence (GRCh38).
Kanamoto et al. (2009) showed that Obif expression was upregulated during osteoblastic differentiation in mouse cell lines. Exogenous expression of mouse or human OBIF stimulated osteoblastic differentiation of preosteoblastic MC3T3-E1 cells, whereas Obif knockdown inhibited osteoblastic differentiation. The extracellular domain of Obif exhibited functions similar to those of full-length Obif in induction of MC3T3-E1 differentiation.
By a comparative analysis, Satoh et al. (2016) identified TMEM119 as a human microglia marker. Using brains of humans with various neurologic diseases, they demonstrated that TMEM119 could distinguish resident microglia from blood-derived macrophages.
Independently, Bennett et al. (2016) demonstrated that TMEM119 could distinguish microglia from infiltrating macrophages after inflammation and injury in mouse and human central nervous system.
Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., Weissman, I. L., Chang, E. F., Li, G., Grant, G. A., Hayden Gephart, M. G., Barres, B. A. New tools for studying microglia in the mouse and human CNS. Proc. Nat. Acad. Sci. 113: E1738-E1746, 2016. [PubMed: 26884166] [Full Text: https://doi.org/10.1073/pnas.1525528113]
Gross, M. B. Personal Communication. Baltimore, Md. 8/17/2020.
Kanamoto, T., Mizuhashi, K., Terada, K., Minami, T., Yoshikawa, H., Furukawa, T. Isolation and characterization of a novel plasma membrane protein, osteoblast induction factor (obif), associated with osteoblast differentiation. BMC Dev. Biol. 9: 70, 2009. Note: Electronic Article. [PubMed: 20025746] [Full Text: https://doi.org/10.1186/1471-213X-9-70]
Satoh, J., Kino, Y., Asahina, N., Takitani, M., Miyoshi, J., Ishida, T., Saito, Y. TMEM119 marks a subset of microglia in the human brain. Neuropathology 36: 39-49, 2016. [PubMed: 26250788] [Full Text: https://doi.org/10.1111/neup.12235]