Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and mouse

Miao, Benpeng; Xiao, Qingyu; Chen, Weiran; Li, Yixue; Wang, Zhen

doi:10.1186/s12864-018-4661-6

Cited by 11 publications

(16 citation statements)

References 52 publications

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“…Our result seems to contradict to the notion that the cellular function of phosphosites in an island depends on the number of phosphorylated residues rather than specific phosphorylated sites, whereas individual phosphosites operate as single-site switches and hence should be more conserved (Landry et al 2014). However, this argument implies that phosphorylation of most individual phosphosites is important for the organism's fitness, which may be not true (Landry et al 2014;Miao et al 2018) and hence our results do not contradict the model of evolution of functionally important phosphosites.…”

Section: Clustered Vs Individual Phosphositescontrasting

confidence: 60%

“…3a). In earlier studies, only mutations of serines or to serines had been considered, as the available data did not allow for statistically significant results for threonine and tyrosine (Kurmangaliyev et al 2011;Miao et al 2018). Here, we see that phosphorylated threonines from the HMR dataset tend to mutate to serines (Fig.…”

Section: Mutational Patterns Of Phosphorylated Amino Acidsmentioning

confidence: 66%

“…As protein phosphorylation in a vast majority of organisms has not been studied or has been studied rather poorly (Huang et al 2017), the evolutionary analyses of phosphosites typically rely on the assumption of absolute conservation of the phosphorylation label assigned to STY amino acids on a considered tree (Kurmangaliyev et al 2011;Miao et al 2018). Thus, if, for instance, a serine is phosphorylated in human, we, following this approach, would consider any mutation in the homologous position of the type S-to-X to be a mutation of a phosphorylated serine to amino acid X (Fig.…”

Section: Conserved Phosphositesmentioning

confidence: 99%

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Phospho-islands and the evolution of phosphorylated amino acids in mammals

Moldovan

Gelfand

2020

Preprint

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BackgroundProtein phosphorylation is the best studied post-translational modification strongly influencing protein function. Phosphorylated amino acids not only differ in physico-chemical properties from non-phosphorylated counterparts, but also exhibit different evolutionary patterns, tending to mutate to and originate from negatively charged amino acids. The distribution of phosphosites along protein sequences is non-uniform, as phosphosites tend to cluster, forming so-called phospho-islands.MethodsHere, we have developed an HMM-based procedure for the identification of phospho-islands and studied the properties of the obtained phosphorylation clusters. To check robustness of evolutionary analysis, we consider different models for the reconstructions of ancestral phosphorylation states.ResultsClustered phosphosites differ from individual phosphosites in several functional and evolutionary aspects including underrepresentation of phosphotyrosines, higher conservation, more frequent mutations to negatively charged amino acids. The spectrum of tissues, frequencies of specific phosphorylation contexts, and mutational patterns observed near clustered sites also are different.

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Section: Clustered Vs Individual Phosphositescontrasting

confidence: 60%

Section: Mutational Patterns Of Phosphorylated Amino Acidsmentioning

confidence: 66%

Section: Conserved Phosphositesmentioning

confidence: 99%

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Phospho-islands and the evolution of phosphorylated amino acids in mammals

Moldovan

Gelfand

2020

Preprint

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“…This is similar to the reported incidence of non-functional phosphorylation sites in mammalian and fungal proteomes and the loose substrate specificity of many protein kinases. In these studies evolutionarily conserved phosphorylation sites were more likely to be functional compared to poorly conserved sites 30 . These data all suggest that many post-translational modifications within the proteome may not actually have a function.…”

Section: Discussionmentioning

confidence: 93%

Juxta-membrane S-acylation of plant receptor-like kinases is likely fortuitous and does not necessarily impact upon function

Hurst

Wright

Turnbull

et al. 2019

Sci Rep

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S-acylation is a common post-translational modification of membrane protein cysteine residues with many regulatory roles. S-acylation adjacent to transmembrane domains has been described in the literature as affecting diverse protein properties including turnover, trafficking and microdomain partitioning. However, all of these data are derived from mammalian and yeast systems. Here we examine the role of S-acylation adjacent to the transmembrane domain of the plant pathogen perceiving receptor-like kinase FLS2. Surprisingly, S-acylation of FLS2 adjacent to the transmembrane domain is not required for either FLS2 trafficking or signalling function. Expanding this analysis to the wider plant receptor-like kinase family we find that S-acylation adjacent to receptor-like kinase domains is common, affecting ~25% of Arabidopsis receptor-like kinases, but poorly conserved between orthologues through evolution. This suggests that S-acylation of receptor-like kinases at this site is likely the result of chance mutation leading to cysteine occurrence. As transmembrane domains followed by cysteine residues are common motifs for S-acylation to occur, and many S-acyl transferases appear to have lax substrate specificity, we propose that many receptor-like kinases are fortuitously S-acylated once chance mutation has introduced a cysteine at this site. Interestingly some receptor-like kinases show conservation of S-acylation sites between orthologues suggesting that S-acylation has come to play a role and has been positively selected for during evolution. The most notable example of this is in the ERECTA-like family where S-acylation of ERECTA adjacent to the transmembrane domain occurs in all ERECTA orthologues but not in the parental ERECTA-like clade. This suggests that ERECTA S-acylation occurred when ERECTA emerged during the evolution of angiosperms and may have contributed to the neo-functionalisation of ERECTA from ERECTA-like proteins.

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“…The phosphorylation of serine and threonine is more likely to be non-functional in disordered areas. In a study of 2018, based on large-scale data of human and mouse phosphorylation sites, it was found that the sites in the senior group were more likely to function and participate in the signaling pathways than those in the young group, and serine phosphorylation may be related to the occurrence of neurodegenerative diseases [78]. Mutations of some specific genes lead to neurodegeneration through the loss of protein function [79][80][81], PTM can regulate the structure and function of proteins, and also regulate toxicity among several pathogenic proteins.…”

Section: Discussionmentioning

confidence: 99%

Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

Liu

Pan

Hua

et al. 2020

Preprint

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Aging is an inevitable course of life. Additionally, the risk of chronic diseases or cancer increases with age. The comprehensive identification of signs related to aging can be beneficial for the prevention and early diagnosis of geriatric diseases. The comparison of global modifications in the urine proteome is a means of multidimensional information mining. This approach is based on urine, in which changes from whole-body metabolism can accumulate. This study used the urine of healthy people at different ages (22 children, 10 young people, 6 senior people) as the research object and using high-resolution tandem mass spectrometry, label-free quantitation combined with non-limiting modification identification algorithms and random group test, compared the differences in protein chemical modifications among three groups. The results show that multi-sites oxidative modifications and amino acid substitutions are noticeable features that distinguish these three age groups of people. The proportion of multi-site oxidations in urine proteins of senior (29.76%) is significantly higher than the young group (13.71% and 12.97%), which affect the biological processes of various proteins. This study could provide a reference for studies of aging mechanisms and biomarkers of age-related disease.

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Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and mouse

Cited by 11 publications

References 52 publications

Phospho-islands and the evolution of phosphorylated amino acids in mammals

Phospho-islands and the evolution of phosphorylated amino acids in mammals

Juxta-membrane S-acylation of plant receptor-like kinases is likely fortuitous and does not necessarily impact upon function

Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

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