Редактирование: ANK2

Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) [ANKB]

==Publications==

{{medline-entry
|title=SerThr-PhosphoProteome of Brain from Aged [[PINK1]]-KO A53T-[[SNCA]] Mice Reveals pT1928-[[MAP1B]] and pS3781-[[ANK2]] Deficits, as Hub between Autophagy and Synapse Changes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31277379
|abstract=Hereditary Parkinson's disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein ([[SNCA]]) as stressor or the autosomal recessive deficiency of [[PINK1]] Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of [[PINK1]]-knockout with overexpression of [[SNCA]]  in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As an exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in [[MAP1B]], a microtubule-associated protein, and a similar reduction of phosphoSer3781 in [[ANK2]], an interactor of microtubules. [[MAP1B]] depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension, and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was also detected for other microtubule and microfilament factors, namely [[MAP2]] , [[MARK1]] , [[MAP1A]] , [[KIF1A]] , 4.1N , 4.1G , and [[ADD2]] . While the [[MAP1B]] heavy chain supports regeneration and growth cones, its light chain assists [[DAPK1]]-mediated autophagy. Interestingly, relevant phosphorylation decreases of [[DAPK2]] , [[VPS13D]] , and [[VPS13C]]  in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM [[C2]] domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of [[ANK2]]/[[MAP1B]] expression on [[PINK1]] levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that [[MAP1B]]/[[ANK2]] phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in [i]Drosophila melanogaster[/i] that the [[MAP1B]] ortholog futsch in the presynapse is a primary target of the PARK8 protein [[LRRK2]], and on a report that [[MAP1B]] is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, [i][[ANK2]][/i] gene locus variants are associated with the risk of PD, [[ANK2]] interacts with [[PINK1]]/Parkin-target proteins such as MIRO1 or [[ATP1A2]], and [[ANK2]]-derived peptides are potent inhibitors of autophagy.
|mesh-terms=* Aging
* Amino Acid Sequence
* Animals
* Ankyrins
* Autophagy
* Brain
* Mice, Knockout
* Mice, Mutant Strains
* Microtubule-Associated Proteins
* Microtubules
* Phosphoproteins
* Phosphorylation
* Phosphoserine
* Phosphothreonine
* Protein Domains
* Protein Kinases
* Proteome
* Synapses
* alpha-Synuclein
|keywords=* PINK1
* Parkinson’s disease
* alpha-synuclein
* autophagy
* brain phosphorylome
* microtubular cytoskeleton
* synaptic signaling
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651490
}}
{{medline-entry
|title=Ankyrin-B syndrome: enhanced cardiac function balanced by risk of cardiac death and premature senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17940615
|abstract=Here we report the unexpected finding that specific human [[ANK2]] variants represent a new example of balanced human variants. The prevalence of certain [[ANK2]] (encodes ankyrin-B) variants range from 2 percent of European individuals to 8 percent in individuals from West Africa. Ankyrin-B variants associated with severe human arrhythmia phenotypes (eg E1425G, V1516D, R1788W) were rare in the general population. Variants associated with less severe clinical and in vitro phenotypes were unexpectedly common. Studies with the ankyrin-B( /-) mouse reveal both benefits of enhanced cardiac contractility, as well as costs in earlier senescence and reduced lifespan. Together these findings suggest a constellation of traits that we term "ankyrin-B syndrome", which may contribute to both aging-related disorders and enhanced cardiac function.
|mesh-terms=* Aging
* Animals
* Ankyrins
* Cellular Senescence
* Death
* Echocardiography
* Heart Diseases
* Humans
* Mice
* Mice, Inbred C57BL
* Myocardial Contraction
* Phenotype
* Risk
* Syndrome

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013943
}}