Macf1
Developmental stage
Isoform 2 is highly expressed in neuronal tissues and the foregut of 8.5 dpc embryos and the head fold and primitive streak of 7.5 dpc embryos (at protein level). Isoform 1: Expressed throughout the development of the embryo.
Domain
The C-terminal tail is required for phosphorylation by GSK3B and for microtubule-binding.
Function
Isoform 2
F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:16815997, PubMed:18854161, PubMed:21295697). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (By similarity). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (PubMed:16815997). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (PubMed:18854161). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration (By similarity). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (By similarity). Plays a key role in wound healing and epidermal cell migration (PubMed:21295697). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (PubMed:21295697). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (PubMed:26526844).
Post-translational modifications
Phosphorylated on serine residues in the C-terminal tail by GSK3B. Phosphorylation inhibits microtubule-binding and this plays a critical role in bulge stem cell migration and skin wound repair. Wnt-signaling can repress phosphorylation.
Sequence Similarities
Belongs to the plakin or cytolinker family.
Tissue Specificity
Enriched in the hair follicle stem cells (at protein level). Isoform 1 and isoform 2 are ubiquitous expressed, with higher levels seen in lung, heart, thymus, spleen and brain.
Cellular localization
- Isoform 2
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Golgi apparatus
- Cell membrane
- Cell projection
- Ruffle membrane
- APC controls its localization to the cell membrane which is critical for its function in microtubule stabilization. Localizes to the tips of microtubules. Associated with the minus-end of microtubules via interaction with CAMSAP3. The phosphorylated form is found in the cytoplasm while the non-phosphorylated form associates with the microtubules.
- Isoform 1
- Cytoplasm
- Golgi apparatus
Alternative names
Acf7, Aclp7, Kiaa0754, Macf, Macf1, Actin cross-linking family 7