FMNL1 full-length cDNA (Favaro et al., 2003) was obtained from the EST IL5-MT0208-210201-356-f01 (GenBank Accession No. BI028593), generated from the Human Cancer Genome Project (Dias Neto et al., 2000). The entire FMNL1 gene is located in chromosome 17 (17q21) and has a size of approximately 25.8 Kb (start: 45221444 and end: 45247320 bp; orientation: Plus strand) and contains 17 exons. The FMNL1 cDNA contains 3973 bp and is located in chromosome 17 (17q21).

Formin proteins are characterized by a unique and highly conserved C-terminal formin homology (FH) 2 domain, responsible for its interaction with actin (Wallar and Alberts, 2003; Higgs, 2005). Diaphanous-related formins (DRF) are characterized by regulatory domains at the N-terminus, including the GTPase binding domain (GBD), Diaphanous inhibitory domain (DID), and dimerization domain (DD), and a single C-terminal Diaphanous autoregulatory domain (DAD) (Figure 1). DRFs are regulated by an autoinhibitory interaction of DAD with DID (Li and Higgs, 2003). This autoinhibition is relieved through binding of an activated RhoGTPase to the GBD, resulting in activation of formin to polymerize actin filaments (Kuhn and Geyer, 2014)(Figure 2).

In normal tissues, FMNL1 expression is restricted to peripheral blood mononuclear and homing tissues such as thymus, spleen, lymph nodes and bone marrow (Favaro et al., 2003; Schuster et al., 2007). In bone marrow, FMNL1 expression was restricted to myeloid cells and in lymph nodes, mature lymphocytes stain strongly for FMNL1 (Gardberg et al., 2014).
FMNL1 is highly expressed in a variety of hematopoietic malignancies, including cells from patients with lymphoid and myeloid leukemias and non-Hodgkins lymphomas, as well as malignant lymphoid and myeloid cell lines and in renal carcinoma cell lines (Favaro et al., 2003; Favaro et al., 2006; Schuster et al., 2007). Recently, Gardberg et al reported that FMNL1 to be also expressed in smooth muscle cells and myoepithelial cells (Gardberg et al., 2014).

Immunohistochemical analyses have shown that FMNL1 staining is cytoplasmatic (Gardberg et al., 2014).

Many functions have been attributed to FMNL1, such as cell adhesion, cytokinesis, cell polarization and migration in mitosis (Yayoshi-Yamamoto et al., 2000; Seth et al., 2006; Esue et al., 2008; Mersich et al., 2010). The silencing of FMNL1 reduces cell proliferation as well as migration of human leukemia cells and tumor growth (Favaro et al., 2013). FMNL1 is needed for cytotoxicity, polarization and maintenance of the Golgi complex in T-cells (Gomez et al., 2007; Colon-Franco et al., 2011). FMNL1 is involved in podosome dynamics in macrophage cell lines (Mersich et al., 2010) and a new splice variant of FMNL1, FMNL1γ, has been reported to induce polarized membrane nonapoptotic blebbing (Han et al., 2009). During mouse oocyte meiotic maturation, FMNL1 has shown to affect both actin dynamics and spindle formation, through a RHOA -FMNL1- GOLGA2 (GM130) pathway, leading to oocyte polar body extrusion (Wang et al., 2015; Yin and Sun, 2015)

FMNL1 shares homology with that of the other members of the formin protein family. FMNL1 also has a high homology among different species (Table 1).

Table 1. Comparative identity of human FMNL1 with other species

% Identity for:Homo sapiens FMNL1	Symbol	Protein	DNA
vs. P. troglodytes	FMNL1	99.0	99.0
vs. M. mulatta	FMNL1	98.0	96.0
vs. C. jacchus	FMNL1	95.0	95.0
vs. N. galili	Fmnl1	94.0	88.0
vs. B. taurus	FMNL1	93.0	86.0
vs. M. musculus	Fmnl1	93.0	85.0
vs. M. putorius	FMNL1	91.0	88.0
vs. C. lupus	FMNL1	91.0	87.0
vs. R. norvegicus	Fmnl1	89.0	84.0
vs. G. gallus	FMNL1	72.0	86.0
vs. I. punctalus	fmnl1	69.0	82.0

(Source: http://www.ncbi.nlm.nih.gov/homologene)

Recurrent mutations in the FMNL1 gene are rare, and 123 substitution missense, 4 substitution nonsense, 57 substitution synonymous, 5 insertion inframe, 1 insertion frameshift, 9 deletions inframe and 3 deletion frameshift mutations are reported in COSMIC (Catalogue of somatic mutations in cancer; http://cancer.sanger.ac.uk/cancergenome/projects/cosmic).