MFHAS1
Function
Probable GTP-binding protein (PubMed:24286120). Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways (PubMed:26599367, PubMed:28471450, PubMed:28609714). Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP-1 subunit JUN which is required for proper activation of the transcription factor (PubMed:28609714). Both inhibits and activates the TLR2-dependent signaling pathway (PubMed:26599367). Positively regulates the TLR2 signaling pathway to activate specifically the downstream p38 and JNK MAP kinases and promote the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). It may also play a role in the regulation of inflammation induced by high glucose through the PKB/AKT signaling pathway (PubMed:29168081). Also involved in erythrocyte differentiation through activation of the ERK1/ERK2 signaling pathway (PubMed:23327923).
Involvement in disease
A chromosomal aberration involving MFHAS1 may be a cause of B-cell lymphoma. Translocation t(8;14)(p23.1;q21) with a cryptic exon named '14q21 element'. The resulting fusion protein named 'chimeric MASL1' is tumorigenic in nude mice.
Post-translational modifications
Ubiquitinated. Ubiquitination by PJA2 does not lead MFHAS1 to proteasomal degradation but positively regulates its function in polarization of macrophages.
Tissue Specificity
Ubiquitously expressed. Overexpressed in malignant fibrous histiocytomas (PubMed:9973190). Expressed in red blood cells (at protein level) (PubMed:23327923).
Cellular localization
- Cytoplasm
Alternative names
MASL1, MFHAS1, Malignant fibrous histiocytoma-amplified sequence 1, Malignant fibrous histiocytoma-amplified sequence with leucine-rich tandem repeats 1