Abstract
The alternative pathway regulator Factor H-like protein 1 (FHL-1) is composed of the first 7 N-terminal complement control protein domains of Factor H (FH) and protects host surfaces from uncontrolled complement attack. Although FHL-1 shares the N-terminal regulatory domains with FH, it was thought to be a weaker regulator. Recently, the regulatory activity of FHL-1 was shown to be comparable to FH. Nonetheless, the question remained whether FHL-1 is an indispensable, unique regulator. The discovery that FHL-1 is the predominant regulator on Bruch’s membrane, a critical site for the onset and progression of age-related-macular degeneration (AMD), showed that FHL-1 is essential for complement regulation. A common single nucleotide polymorphism in FH/FHL-1 that predisposes for AMD underlines the important role of FHL-1 in this context. Reports that some cancer tissues specifically upregulate FHL-1 expression, thereby evading immune surveillance, suggests a pronounced regulatory activity of the splice variant. Several microorganisms specifically recruit FHL-1 to evade complement attack. From a phylogenetic point of view, FHL-1 appears much later than other complement regulators, which could imply a specific role that is possibly not systemic but rather tissue specific. This review focuses on the current knowledge of FHL-1 and its physiological and pathophysiological roles.
Highlights
The complement system is an essential part of the innate immune system protecting against infections and helping in maintaining tissue homeostasis
The perception of Factor H-like protein 1 (FHL-1) has changed because several studies showed that the splice variant is a unique molecule with many shared and some unique properties compared to Factor H (FH)
An in-silico gene analysis revealed that similar gene structures to FH that allow for alternative splicing of a truncated FH version are not found prior to the order of old-world monkeys [14]
Summary
Its Alternative Splice Variant FHL-1 Share a Gene but Not All Functions. The alternative pathway regulator Factor H-like protein 1 (FHL-1) is composed of the first 7 N-terminal complement control protein domains of Factor H (FH) and protects host surfaces from uncontrolled complement attack. FHL-1 shares the N-terminal regulatory domains with FH, it was thought to be a weaker regulator. The regulatory activity of FHL-1 was shown to be comparable to FH. Reports that some cancer tissues upregulate FHL-1 expression, thereby evading immune surveillance, suggests a pronounced regulatory activity of the splice variant. Several microorganisms recruit FHL-1 to evade complement attack. From a phylogenetic point of view, FHL-1 appears much later than other complement regulators, which could imply a specific role that is possibly not systemic but rather tissue specific.
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