Structural and functional annotation of human FAM26F: A multifaceted protein having a critical role in the immune system

Malik, Uzma; Javed, Aneela; Ali, Amjad; Asghar, Kashif

doi:10.1016/j.gene.2016.10.029

Cited by 19 publications

(25 citation statements)

References 57 publications

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“…While little is known about the role of RGS10 in AML, in a meta-analysis of over 2700 AML patients across 25 published datasets RGS10 was identified in the top 25 most common differentially regulated genes—along with well-established AML associated genes such as HOXA9, MEIS1 and RUNX1T1 47 . FAM26F is a cation channel that regulates immune response by trafficking substances into or between cells 48 . It has recently been proposed as an early diagnostic marker as its increased expression is indicative of IFN-γ mediated immune responses 49 .…”

Section: Discussionmentioning

confidence: 99%

Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias

et al. 2018

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Acute myeloid leukaemia (AML) affects children and adults of all ages. AML remains one of the major causes of death in children with cancer and for children with AML relapse is the most common cause of death. Here, by modelling AML in vivo we demonstrate that AML is discriminated by the age of the cell of origin. Young cells give rise to myeloid, lymphoid or mixed phenotype acute leukaemia, whereas adult cells give rise exclusively to AML, with a shorter latency. Unlike adult, young AML cells do not remodel the bone marrow stroma. Transcriptional analysis distinguishes young AML by the upregulation of immune pathways. Analysis of human paediatric AML samples recapitulates a paediatric immune cell interaction gene signature, highlighting two genes, RGS10 and FAM26F as prognostically significant. This work advances our understanding of paediatric AML biology, and provides murine models that offer the potential for developing paediatric specific therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias

et al. 2018

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“… 38 In MPR, a serine (Ser) residue in the cytoplasmic tail having the tendency to get phosphorylated by casein kinase II (CK-II), is responsible for Golgi localization of the protein and is also closely linked with release from the TGN. 40 , 42 − 44 Consistently, FAM26F also contains a Ser residue in its cytoplasmic tail at the position 311 which is predicted to be phosphorylated by CKII 2 and which might also aid in the transport activities of FAM26F. Hence, in view of these results, FAM26F is affirmed to be localized in the Golgi apparatus, owing to its possession of TMD and the Ser-containing sequence, just like some of the other Golgi-retained proteins possessing both of these signals.…”

Section: Discussionmentioning

confidence: 92%

“… 28 FAM26F comes in the latter category. This is evident from the fact that FAM26F does not contain any “leader sequence” (signal peptide) attached to it and also does not undergo N-glycosylation, 2 omitting its chance to be targeted to other organelles or to the extracellular space. The Golgi resident proteins may in turn either be integral membrane proteins (embedded within the membrane) or peripheral membrane proteins present on the Golgi’s cytoplasmic face.…”

Section: Discussionmentioning

confidence: 99%

“…The Golgi resident proteins may in turn either be integral membrane proteins (embedded within the membrane) or peripheral membrane proteins present on the Golgi’s cytoplasmic face. FAM26F contains 3–5 transmembrane helices, 2 which readily makes it an integral membrane protein.…”

Section: Discussionmentioning

confidence: 99%

“…It comprises of 3–5 transmembrane helices as well as an immunoglobin-like fold, emphasizing its significance as an immune molecule. 2 So far, there are only three studies that provide a brief overview of the FAM26F’s function. In 2010, FAM26F was recognized as a toll-like receptor (TLR) signal-derived membrane molecule by Ebihara et al The molecule was found to modulate mDC–NK contact-mediated NK activation.…”

Section: Introductionmentioning

confidence: 99%

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Unveiling the Physical and Functional Niches of FAM26F by Analyzing Its Subcellular Localization and Novel Interacting Partners

et al. 2020

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The knowledge of a protein’s subcellular localization and interacting partners are crucial for elucidating its cellular function and associated regulatory networks. Although FAM26F (family with sequence similarity 26, member F) has been recognized as a vital player in various infections, stimulation studies, cancer, and immune pathogenesis, the precise location and function of FAM26F are not well understood. The current study is the first to focus on functional characterization of FAM26F by analyzing its subcellular localization and identifying its novel interacting partners using advanced proteome approaches. The immunofluorescence and confocal microscopy results revealed FAM26F to be largely localized within the Golgi apparatus of the cell. However, its minor presence in endoplasmic reticulum (ER) pointed toward the probable retrograde transfer of FAM26F from Golgi to ER during adverse conditions. Moreover, co-immunoprecipitation and MS/MS results demonstrated a total of 85 proteins, 44 of which significantly copurified with FAM26F. Interestingly, out of these 44 MS/MS identified proteins, almost 52% were involved in innate immunity, 38.6% in neutrophil degranulation, and remaining 10% were either involved in phosphorylation, degradation, or regulation of apoptosis. Further characterization through Ingenuity Pathway Analysis showed that majority of these proteins was involved in maintaining calcium homeostasis of cell. Consequently, the validation of selected proteins uncovered the key interaction of FAM26F with Thioredoxin, which essentially paved the way for depicting its mechanism of action under stress or disease conditions. It is proposed that activation and inhibition of the cellular immune response is essentially dependent on whether FAM26F or Thioredoxin considerably interact with CD30R.

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Novel insights in the genetics of steroid-sensitive nephrotic syndrome in childhood

et al. 2020

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Steroid sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood and there is growing evidence that genetics play a role in the susceptibility for the disease. Familial clustering has been observed and led to several studies on familiar SSNS trying to identify a monogenic cause of the disease. Until now, however, none of these have provided convincing evidence for Mendelian inheritance. This and the phenotypic variability within SSNS suggest a complex inheritance pattern, where multiple variants, interactions between those and the environment play a role in disease development. Genome wide association studies (GWAS) have been used to investigate this complex disease. We herein highlight new insights in the genetics of the disease provided by GWAS and how these fit into our understanding of the pathogenesis of SSNS.

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Structural and functional annotation of human FAM26F: A multifaceted protein having a critical role in the immune system

Cited by 19 publications

References 57 publications

Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias

Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias

Unveiling the Physical and Functional Niches of FAM26F by Analyzing Its Subcellular Localization and Novel Interacting Partners

Novel insights in the genetics of steroid-sensitive nephrotic syndrome in childhood

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