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On the abundance of intrinsically disordered proteins in the human proteome and its relation to diseases: there is no enrichment [article]

Antonio Deiana, Andrea Giansanti
2014 arXiv   pre-print
There is a well-established line of research that intends to reveal the crucial role played by intrinsically disordered proteins (IDPs) in the development of human diseases.  ...  In this note we compare the frequency of disorder in human proteins, both disease-related and not. The frequency of disorder is comparable in the two sub-groups of proteins.  ...  Alfredo Colosimo for the stimulating atmosphere and the support during those years; the study of intrinsic disorder in proteins has been the main theme of Antonio Deiana's doctoral thesis.  ... 
arXiv:1410.4465v1 fatcat:qork3z75yngillxaiphimmheqy

Alterations in the brain interactome of the intrinsically disordered N-terminal domain of the cellular prion protein (PrPC) in Alzheimer's disease

Sarah Ulbrich, Petra Janning, Ralf Seidel, Jakob Matschke, Anika Gonsberg, Sebastian Jung, Markus Glatzel, Martin Engelhard, Konstanze F. Winklhofer, Jörg Tatzelt, Human Rezaei
2018 PLoS ONE  
prion protein (PrP C ) in Alzheimer's disease.  ...  In addition to newly identified proteins we found many previously described PrP interactors, indicating a crucial role of the intrinsically disordered part of PrP in mediating protein interactions.  ...  This concept was extended when it became evident that intrinsically disordered domains (IDDs) and proteins can participate in a broad range of defined physiological activities and play a major role in  ... 
doi:10.1371/journal.pone.0197659 pmid:29791485 pmcid:PMC5965872 fatcat:yfgxltnz3nfqlpuvbzu6x3u5qa

Variants of intrinsic disorder in the human proteome [article]

Antonio Deiana, Andrea Giansanti
2016 arXiv   pre-print
IDRPs probably do not play a specific role in the development of complex diseases, since their frequency is similar in disease-related proteins and in the entire human proteome.  ...  IDRPs and IDPs are differently present among human disease-related proteins.  ...  disorder in the development of many human diseases [16, 17] .  ... 
arXiv:1611.06072v1 fatcat:tpolhloejfakrpz7ey7yaeajre

Unfoldomics of human diseases: linking protein intrinsic disorder with diseases

Vladimir N Uversky, Christopher J Oldfield, Uros Midic, Hongbo Xie, Bin Xue, Slobodan Vucetic, Lilia M Iakoucheva, Zoran Obradovic, A Keith Dunker
2009 BMC Genomics  
Conclusion: Proteins associated with various human diseases are enriched in intrinsic disorder. These disease-associated IDPs and IDRs are real, abundant, diversified, vital, and dynamic.  ...  Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) lack stable tertiary and/or secondary structure yet fulfills key biological functions.  ...  Acknowledgements This work was supported in part by the grants R01 LM007688-01A1 (to  ... 
doi:10.1186/1471-2164-10-s1-s7 pmid:19594884 pmcid:PMC2709268 fatcat:is2rnkngnvaabm5tnuborfjaim

Novel Strategies for Drug Discovery Based on Intrinsically Disordered Proteins (IDPs)

Jihua Wang, Zanxia Cao, Liling Zhao, Shuqiang Li
2011 International Journal of Molecular Sciences  
At the same time, intrinsic disorder is very common in disease-associated proteins.  ...  It is reported that intrinsic disorder is common in diseasome, and proteins from different diseases possess different levels of intrinsic disorder.  ... 
doi:10.3390/ijms12053205 pmid:21686180 pmcid:PMC3116186 fatcat:3t2zfk4c35hyljcnakcrbb65ty

Intrinsically disordered proteins and structured proteins with intrinsically disordered regions have different functional roles in the cell

Antonio Deiana, Sergio Forcelloni, Alessandro Porrello, Andrea Giansanti, Eugene A. Permyakov
2019 PLoS ONE  
We show here that IDPs and IDPRs have non-overlapping functional spectra, play different roles in human diseases, and deserve to be treated as distinct categories of proteins.  ...  Taking into account both criteria we separate the human proteome, taken as a case study, into three variants of proteins: i) ordered proteins (ORDPs), ii) structured proteins with intrinsically disordered  ...  Importantly, many proteins with disordered regions have been associated with human diseases [9,31,32], and a D 2 concept (disorder in disorders) emerged [33] .  ... 
doi:10.1371/journal.pone.0217889 pmid:31425549 pmcid:PMC6699704 fatcat:ect4zee2rvgb7kktxhzvoyxh3e

Protein disorder in the human diseasome: unfoldomics of human genetic diseases

Uros Midic, Christopher J Oldfield, A Keith Dunker, Zoran Obradovic, Vladimir N Uversky
2009 BMC Genomics  
Our analyses revealed that (i) Intrinsic disorder is common in proteins associated with many human genetic diseases; (ii) Different disease classes vary in the IDP contents of their associated proteins  ...  However, the abundance of intrinsically disordered proteins involved in human genetic diseases and the functional repertoire of these proteins have never been before.  ...  Acknowledgements This work was supported in part by the grants R01 LM007688-01A1 (to A.K.D and V.N.U.) and GM071714-01A2 (to A.K.D and V.N.U.) from the National Institutes of Health and the Program of  ... 
doi:10.1186/1471-2164-10-s1-s12 pmid:19594871 pmcid:PMC2709255 fatcat:yrpkx5woybgsdcxylvliv7apja

Intrinsic Protein Disorder as a Drug Target in Oncology: Designing Drugs Targeting Plasticity

Andreas G. Tzakos
2012 Biochemistry & Pharmacology Open Access  
Editorial Open Access Cancer is gradually becoming the leading disease-related cause of death of the human population.  ...  The "one-gene-one-disease" theory sculpted the drug design concept to treat diseases by targeting individual chemoreceptors with a "magic-bullet" therapy [4].  ...  Interestingly, proteins associated with various human diseases are enriched in intrinsic disorder, and the disease-related unfoldome has been mapped to cover a significant part of the human proteome [  ... 
doi:10.4172/2167-0501.1000e107 fatcat:o2do42qm4neinmbigtdejsmqgq

Insights into the Evolutionary Features of Human Neurodegenerative Diseases

Arup Panda, Tina Begum, Tapash Chandra Ghosh, Christian Schönbach
2012 PLoS ONE  
Comparative analyses between human disease and non-disease genes are of great interest in understanding human disease gene evolution.  ...  To elucidate the conserved nature of NDD genes, we incorporated the evolutionary attributes like gene expression level, number of regulatory miRNAs, protein connectivity, intrinsic disorder content and  ...  Acknowledgments We are thankful to two anonymous referees for their helpful suggestions in improving our manuscript. We acknowledge S. Chakraborty and S. Podder for their valuable comments and help.  ... 
doi:10.1371/journal.pone.0048336 pmid:23118989 pmcid:PMC3484049 fatcat:nu7444qrxjd2ldba2gii6zcjyy

Targeting intrinsically disordered proteins in neurodegenerative and protein dysfunction diseases: another illustration of the D2concept

Vladimir N Uversky
2010 Espert Review of Proteomics  
Their functions complement the functional repertoire of ordered proteins, with intrinsically disordered proteins (IDPs) often being involved in regulation, signaling and control.  ...  IDPs are highly abundant in various human diseases, including neurodegeneration and other protein dysfunction maladies and, therefore, represent attractive novel drug targets.  ...  Acknowledgments This review would not be possible without many colleagues who, over the years, contributed to the introduction and development of the intrinsically disordered protein field.  ... 
doi:10.1586/epr.10.36 pmid:20653509 pmcid:PMC3371274 fatcat:tvvjedxhrvbdbaszjonmqjwxcy

The Amazing World of IDPs in Human Diseases

Simona Maria Monti, Giuseppina De Simone, Emma Langella
2021 Biomolecules  
It has been clearly established that some proteins or protein regions are devoid of any stable secondary and/or tertiary structure under physiological conditions, but still possess fundamental biological  ...  In conclusion, in this Special Issue, examples of recent progress in the IDPs/IDRs have been reported with the aim to contribute to advancing the field of the intrinsic disorder issue in human disease  ...  The interaction between the intrinsically disordered NUPR1 and the human importinα3 (Impα3) was investigated in depth by Neira et al.  ... 
doi:10.3390/biom11020333 pmid:33672116 fatcat:yjmxcumkivay7n4dapcejz4s4u

Intrinsically disordered proteins and structured proteins with intrinsically disordered regions have different functional roles in the cell [article]

Andrea Giansanti, Antonio Deiana, Sergio Forcelloni, Alessandro Porrello
2019 bioRxiv   pre-print
We show here that IDPs and IDPRs have non-overlapping functional spectra, play different roles in human diseases, and deserve to be treated as distinct categories of proteins.  ...  Taking into account both criteria we separate the human proteome, taken as a case study, into three variants of proteins: i) ordered proteins (ORDPs), ii) structured proteins with intrinsically disordered  ...  roles of three broad 300 variants of intrinsic protein disorder: i) ordered proteins (ORDPs), ii) structured proteins with 301 intrinsically disordered protein regions (IDPRs), and iii) intrinsically  ... 
doi:10.1101/646901 fatcat:etgomz3gj5cabc2qdwof2spbim

Unfoldomics of Human Genetic Diseases

U. Midic, C.J. Oldfield, A.K. Dunker, Z. Obradovic, V.N. Uversky
2009 Biophysical Journal  
These hydrophobic contacts may account for more than 15-and 10-fold increase in affinity and potency, respectively.  ...  The replacements are mostly located at the periphery of the antigen binding-site but are potentially in contact with the antigen, thus encircling the center of the epitope recognized by these antibodies  ...  Our analyses revealed that (i) Intrinsic disorder is common in proteins associated with many human genetic diseases; (ii) Different disease classes vary in the IDP contents of their associated proteins  ... 
doi:10.1016/j.bpj.2008.12.1594 fatcat:ea5p5p7gwzgipngnqrfjn7cae4

Protein Intrinsic Disorder and Evolvability of MERS-CoV

Vladimir N. Uversky, Elrashdy M. Redwan, Abdullah A. Aljadawi
2021 Biomolecules  
Middle East Respiratory Syndrome (MERS) is a viral respiratory disease caused by one of the human coronaviruses, MERS-CoV [...]  ...  Figure 2 represents another angle in the relation between the intrinsic disorder of viral proteins and the evolvability of MERS-CoV within humans.  ...  Table 1 . 1 Changes in the intrinsic disorder status of 11 proteins from various MERS-CoV isolates.  ... 
doi:10.3390/biom11040608 pmid:33923962 fatcat:dhteomsm7rclne5wkqfbgbzsc4

Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases

Kundlik Gadhave, Prateek Kumar, Shivani K. Kapuganti, Vladimir N. Uversky, Rajanish Giri
2020 Biomolecules  
Our report represents the presence of significant intrinsic disorder and disorder-based binding regions in several UPS proteins, such as extraproteasomal polyubiquitin receptors (UBQLN1 and UBQLN2), proteasome-associated  ...  Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs).  ...  Here, we looked at the intrinsic disorder predisposition of 15 UPS proteins (Table 2) , which play a crucial role in this pathway and human diseases (see Table 1 ).  ... 
doi:10.3390/biom10050796 pmid:32455657 pmcid:PMC7278180 fatcat:6jb7nevnknb5jg35oygwjuof2u
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