Domain-based and family-specific sequence identity thresholds increase the levels of reliable protein function transfer

Journal of Molecular Biology
Sarah AddouChristine Orengo

Abstract

Divergence in function of homologous proteins is based on both sequence and structural changes. Overall enzyme function has been reported to diverge earlier (50% sequence identity) than overall structure (35%). We herein study the functional conservation of enzymes and non-enzyme sequences using the protein domain families in CATH-Gene3D. Despite the rapid increase in sequence data since the last comprehensive study by Tian and Skolnick, our findings suggest that generic thresholds of 40% and 60% aligned sequence identity are still sufficient to safely inherit third-level and full Enzyme Commission numbers, respectively. This increases to 50% and 70% on the domain level, unless the multi-domain architecture matches. Assignments from the Kyoto Encyclopedia of Genes and Genomes and the Munich Information Center for Protein Sequences Functional Catalogue seem to be less conserved with sequence, probably due to a more pathway-centric view: 80% domain sequence identity is required for safe function transfer. Comparing domains (more pairwise relationships) and the use of family-specific thresholds (varying evolutionary speeds) yields the highest coverage rates when transferring functions to model proteomes. An average twofold increas...Continue Reading

References

Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Apr 16, 1998·Nature Genetics·P Bork, E V Koonin
Apr 28, 1999·Trends in Genetics : TIG·S E Brenner
Dec 11, 1999·Nucleic Acids Research·A Bairoch
Aug 16, 2000·Proteins·D Devos, A Valencia
Apr 5, 2001·Journal of Molecular Biology·A E ToddJ M Thornton
Jul 27, 2001·Bioinformatics·G ApicS A Teichmann
Jun 8, 2002·Journal of Molecular Biology·Burkhard Rost
Dec 20, 2002·Bioinformatics·Walter R GilksChristos A Ouzounis
Oct 22, 2003·Journal of Molecular Biology·Weidong Tian, Jeffrey Skolnick
Mar 8, 2005·Mathematical Biosciences·Walter R GilksChristos A Ouzounis
Dec 31, 2005·Nucleic Acids Research·Corin YeatsChristine A Orengo
Aug 10, 2007·BMC Bioinformatics·Vineet SangarArthur M Lesk
Oct 18, 2007·Nucleic Acids Research·Peter D KarpJohn Ingraham

❮ Previous
Next ❯

Citations

Jan 1, 2010·Cellular and Molecular Life Sciences : CMLS·Ursula Hinz, UNKNOWN UniProt Consortium
Jul 15, 2011·Applied Microbiology and Biotechnology·Boris A KolvenbachPhilippe F X Corvini
Jan 29, 2013·Nature Methods·Predrag RadivojacIddo Friedberg
Jun 30, 2011·Briefings in Bioinformatics·Kimmen SjölanderGrant M Shoffner
Mar 27, 2013·BMC Bioinformatics·Robert Rentzsch, Christine A Orengo
Jun 23, 2011·PLoS Computational Biology·Nathan L NehrtMatthew W Hahn
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shivas R AminOlivier Lichtarge
Mar 19, 2013·Biochimica Et Biophysica Acta·Benoit H DessaillyChristine A Orengo
Oct 6, 2015·Methods : a Companion to Methods in Enzymology·Sayoni Das, Christine A Orengo
Mar 3, 2009·Trends in Biotechnology·Robert Rentzsch, Christine A Orengo
Jun 15, 2011·Proteins·Wyatt T Clark, Predrag Radivojac
Jul 28, 2015·Frontiers in Zoology·Andrey RozenbergJ Robert Manak
Apr 19, 2015·BMC Bioinformatics·Tianmin WangTakuji Yamada
Dec 29, 2009·Journal of Molecular Biology·Serkan ErdinOlivier Lichtarge
Jan 8, 2015·Frontiers in Genetics·Luis Sanchez-Pulido, Chris P Ponting
Jun 23, 2016·PLoS Computational Biology·David LeeChristine Orengo
Apr 6, 2018·PLoS Computational Biology·Jacquelyn S Fetrow, Patricia C Babbitt
Dec 7, 2017·Bioinformatics·Nelson Gil, Andras Fiser
Jun 27, 2018·Plant Signaling & Behavior·M HüdigV G Maurino
Dec 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Diana Kopcsayová, Eva Vranová
Oct 22, 2010·Autophagy·Michael DuszenkoPaul A M Michels
Jan 9, 2020·Nature Communications·Chang LiuShuang-Jiang Liu
Nov 6, 2014·Acta Crystallographica. Section D, Biological Crystallography·Marcin J MiziantyLukasz Kurgan
Aug 9, 2019·Current Medicinal Chemistry·Chen Wang, Lukasz Kurgan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.