MACF1

The protein encoded by this gene belongs to the plakin family of cytoskeletal linker proteins. This protein family forms bridges between different cytoskeletal elements through specialized modular domains. The encoded protein is one of the largest size proteins identified in human cytoskeletal proteins. It has functional actin and microtubule binding domains, and it appears to stabilize actin at sites where microtubules and microfilaments meet. It may function in microtubule dynamics to facilitate actin-microtubule interactions at the cell periphery and to couple the microtubule network to cellular junctions. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq]

microtubule-actin crosslinking factor 1

Isoform 2
F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854).
Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854).
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 (By similarity).
Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity).
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 (PubMed:27693509).
May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687).
Plays a key role in wound healing and epidermal cell migration (By similarity).
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 (By similarity).
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 (By similarity).

Golgi to plasma membrane protein transportManual Assertion Based On ExperimentIDA:UniProtKB
Intermediate filament cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of axon extensionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of Wnt signaling pathwayISS:UniProtKB
Regulation of cell migrationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of epithelial cell migrationISS:UniProtKB
Regulation of focal adhesion assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of microtubule-based processManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of neuron projection arborizationISS:UniProtKB
Wnt signaling pathwayIEA:UniProtKB-KW
Wound healingISS:UniProtKB

Isoform 2:
Cytoplasm, cytoskeleton
Cytoplasm
Golgi apparatus
Cell membrane
Cell projection, ruffle membrane
The phosphorylated form is found in the cytoplasm while the non-phosphorylated form associates with the microtubules (By similarity).
Localizes to the tips of microtubules (PubMed:27693509).
Associated with the minus-end of microtubules via interaction with CAMSAP3 (PubMed:27693509).
APC controls its localization to the cell membrane which is critical for its function in microtubule stabilization (PubMed:20937854).
Isoform 1:
Cytoplasm
Golgi apparatus
Localizes to the tips of microtubules.

Lissencephaly 9 with complex brainstem malformation (LIS9):
A form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS9 is an autosomal dominant form clinically characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements. Brain imaging shows malformation of the brainstem, in addition to pachygyria and lissencephaly.

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 (By similarity).