MFHAS1

Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH.

Full Name

MALIGNANT FIBROUS HISTIOCYTOMA AMPLIFIED SEQUENCE 1

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).

Biological Process

Erythrocyte differentiation Source: UniProtKB
Inflammatory response Source: UniProtKB
Innate immune response Source: UniProtKB
Negative regulation of inflammatory response Source: UniProtKB
Negative regulation of protein dephosphorylation Source: UniProtKB
Negative regulation of protein localization to nucleus Source: UniProtKB
Negative regulation of toll-like receptor 2 signaling pathway Source: UniProtKB
Negative regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of JNK cascade Source: UniProtKB
Positive regulation of p38MAPK cascade Source: UniProtKB
Positive regulation of protein kinase B signaling Source: UniProtKB
Positive regulation of toll-like receptor 2 signaling pathway Source: UniProtKB
Regulation of macrophage activation Source: UniProtKB

Cellular Location

Cytoplasm

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.

PTM

Ubiquitinated. Ubiquitination by PJA2 does not lead MFHAS1 to proteasomal degradation but positively regulates its function in polarization of macrophages.