MCF2 Gene: Function, Mutations, and Associated Diseases

MCF2 (MCF.2 Cell Line Derived Transforming Sequence) encodes a Rho guanine nucleotide exchange factor (GEF) that activates Rho GTPases, such as RhoA, Rac1, and Cdc42, by catalyzing the exchange of GDP for GTP. The protein contains a Dbl homology (DH) domain and a pleckstrin homology (PH) domain, which are characteristic of Rho GEFs. MCF2 was originally identified as an oncogene from the MCF-7 breast cancer cell line and is involved in cytoskeletal reorganization, cell migration, and proliferation. Mutations and altered expression of MCF2 have been implicated in various cancers and neurodevelopmental disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Rho GTPase cycle (R-HSA-194840)

• Signaling by Rho GTPases (R-HSA-194315)

• RhoA signaling pathway (WP198)

The MCF2 protein (UniProt P10911) is a 925-amino acid Rho guanine nucleotide exchange factor containing an N-terminal Dbl homology (DH) domain and a pleckstrin homology (PH) domain. It catalyzes the exchange of GDP for GTP on Rho family GTPases, particularly RhoA, Rac1, and Cdc42. The protein is localized in the cytoplasm and at the plasma membrane, where it regulates cytoskeletal dynamics, cell adhesion, and migration. MCF2 is expressed in brain, testis, and various cancer cell lines, and its overexpression or mutation contributes to oncogenic transformation.