FREM1 (FRAS1-related extracellular matrix protein 1) is an extracellular matrix protein that forms a ternary complex in the basement membrane with FRAS1 and FREM2 during epidermal development []. FREM1 also appears to act as a dermal mediator of basement membrane adhesion independently of the FRAS1 []. Mutations in the FREM1 gene cause two rare syndromes - bifid nose with or without anorectal and renal anomalies syndrome (BNAR; OMIM #608980) and Manitoba oculotrichoanal syndrome (MOTA; OMIM #248450) - whose phenotypic characteristics overlap those seen in individuals with Fraser syndrome [].
The calx-beta motif is present as a tandem repeat in the cytoplasmic domains of Calx Na-Ca exchangers, which are used to expel calcium from cells. This motif overlaps domains used for calcium binding and regulation. The calx-beta motif is also present in the cytoplasmic tail of mammalian integrin-beta4, which mediates the bi-directional transfer of signals across the plasma membrane, as well as in some cyanobacterial proteins. This motif is also found in Fras1/Frem family of extracellular proteins (extracellular matrix organizing protein FRAS1 and FRAS1-related extracellular matrix proteins FRAM1, 2 and 3) required for proper organogenesis during embryonic development and whose mutations lead to Fraser Syndrome, a rare congenital disorder characterised by multisystem malformation usually comprising abnormal brain formation, cryptophthalmos, syndactyly and renal defects []. This motif contains a series of β-strands and turns that form a self-contained β-sheet [, ].
The calx-beta motif is present as a tandem repeat in the cytoplasmic domains of Calx Na-Ca exchangers, which are used to expel calcium from cells. This motif overlaps domains used for calcium binding and regulation. The calx-beta motif is also present in the cytoplasmic tail of mammalian integrin-beta4, which mediates the bi-directional transfer of signals across the plasma membrane, as well as in some cyanobacterial proteins. This motif is also found in Fras1/Frem family of extracellular proteins (extracellular matrix organizing protein FRAS1 and FRAS1-related extracellular matrix proteins FRAM1, 2 and 3) required for proper organogenesis during embryonic development and whose mutations lead to Fraser Syndrome, a rare congenital disorder characterised by multisystem malformation usually comprising abnormal brain formation, cryptophthalmos, syndactyly and renal defects []. This motif contains a series of β-strands and turns that form a self-contained β-sheet [, ].
