The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
ECOD: An Evolutionary Classification of Protein Domains
Open accessAbstract
Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The ECOD homology level (“H level”) is a strict similarity criterion since it clusters domains even if they only have distant relationships.”
From Deep geometric representations for modeling effects of mutations on protein-protein binding affinity (2021) · cites this paper as [37]
In the citing paper
“we used the ECOD classifier [37] (file: “ecod.develop277.domains.txt”, version: “develop277”) to remove the similar complexes and ensure the training complexes share no ECOD homology domain with the benchmark datasets.”
From Deep geometric representations for modeling effects of mutations on protein-protein binding affinity (2021) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · cited 3×
“E) PSI-BLAST alignment of the Duf371 repeats detected with Mefer0473 sequence supports the duplication event, with sequence similarities indicated between N-terminal and C-terminal halves.”
MethodInfluentialCytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · cited 2×
“In Cytoscape [26] display of SCOP domains and high-scoring links between them, numerous links with HHsearch probability above 90% exist between SAM MTases and Rossmann domains.”
BackgroundMethodMUSCLE: multiple sequence alignment with high accuracy and high throughput
Edgar, R. C. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh340 · Cited by 44,662 · cited 1×
“75 domains were automatically mapped into the ECOD hierarchy using MUSCLE alignments [27].”
MethodBerman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
BLAST+: architecture and applications
Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., & Madden, T. L. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-421 · Cited by 22,074 · cited 5×
“Domains from the input chains could be classified by any combination of the three sequence-based methods (chain BLAST, domain BLAST, or domain HHsearch).”
MethodInfluentialThe Pfam Protein Families Database
Bateman, A. G. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.276 · Cited by 14,075
Murzin, A. G., Brenner, S. E., Hubbard, T., & Chothia, C. (1995) · Journal of Molecular Biology · doi:10.1016/s0022-2836(05)80134-2 · Cited by 6,435 · cited 1×
“Currently, the two leading structure classifications are SCOP (Structural Classification of Proteins) [4] and CATH (Class, Architecture, Topology, Homology) [5], both of which are widely used in analyzing protein sequence, structure, function, and evolution and in developing various bioinformatics tools.”
BackgroundProtein Structure Comparison by Alignment of Distance Matrices
Holm, L., & Sander, C. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1489 · Cited by 3,984 · cited 4×
“In order to extend distant evolutionary relationships beyond the SCOP superfamily level in ECOD, we apply state of the art homology-inference algorithms both developed in our group [19,20] as well as by others [21,22], manually analyze and verify the suggested homologous links, and incorporate findings from literature.”
MethodInfluentialThe HHpred interactive server for protein homology detection and structure prediction
Söding, J., Biegert, A., & Lupas, A. N. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki408 · Cited by 3,775
TM-align: a protein structure alignment algorithm based on the TM-score
Zhang, Y. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki524 · Cited by 3,774 · cited 1×
“similarity and TMalign to reflect structure similarity [21,40].”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 431
Schaeffer, R. D., Kinch, L. N., Kryshtafovych, A., & Grishin, N. V. (2021) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26225 · Cited by 11
“5 The division of a target into domains is a complex process that is aided by the evolutionary classification of protein domains (ECOD), which plays a pivotal role 6,7 in determining the complexity of templates available at the time of the CASP experiment.”
BackgroundSykes, J., Holland, B. R., & Charleston, M. (2022) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12905 · Cited by 10
“The lack of distinct boundaries in some regions of the ECOD database also lends support to a continuous view of protein space (Cheng et al., 2014).”
BackgroundInfluentialPatel, D. T., Stogios, P. J., Jaroszewski, L., Urbanus, M. L., Sedova, M., Semper, C., Le, C., Takkouche, A., Ichii, K., Innabi, J., et al. (2024) · Molecular Systems Biology · doi:10.1038/s44320-024-00076-z · Cited by 10
“In cases when structural similarities did not allow for clear assignment at the topology level, the assignment was done at the higher ECOD homology (H) level (19 domain types are assigned at this level).”
InfluentialBiomolecular Interaction Prediction: The Era of AI
Wang, H., Meng, X., & Zhang, Y. (2025) · Advanced Science · doi:10.1002/advs.202509501 · Cited by 12
Improved 3-D Protein Structure Predictions using Deep ResNet Model
Geethu, S., & Vimina, E. R. (2021) · The Protein Journal · doi:10.1007/s10930-021-10016-7 · Cited by 10
Protein Secondary Structure Prediction Using Cascaded Feature Learning Model
Geethu, S., & Vimina, E. R. (2023) · Applied Soft Computing · doi:10.1016/j.asoc.2023.110242 · Cited by 10
The ancestral KH peptide at the root of a domain family with three different folds
Pereira, J., & Lupas, A. N. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty480 · Cited by 9
Lázaro, M., Melero, R., Huet, C., López-Alonso, J. P., Delgado, S., Dodu, A., Bruch, E. M., Abriata, L. A., Alzari, P. M., Valle, M., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02222-x · Cited by 11
“The C-terminal region consists of a single helical domain that showed no detectable structural similarity to previously characterized proteins in Dali (Holm, 2020), ECOD (Cheng et al., 2014), CATH (Dawson et al., 2017) and VAST (Madej et al., 2014) searches and, therefore, constitutes a possible new fold.”
How do I get the most out of my protein sequence using bioinformatics tools?
Pereira, J., & Alva, V. (2021) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798321007907 · Cited by 10
Topological and Structural Plasticity of the Single Ig Fold and the Double Ig Fold Present in CD19
Youkharibache, P. (2021) · Biomolecules · doi:10.3390/biom11091290 · Cited by 10
Kaminski, K., Ludwiczak, J., Jasiński, M., Bukala, A., Madaj, R., Szczepaniak, K., & Dunin-Horkawicz, S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.05.440912 · Cited by 10
Sequence-structure-function relationships in the microbial protein universePreprint
Leman, J. K., Szczerbiak, P., Renfrew, P. D., Gligorijević, V., Berenberg, D., Vatanen, T., Taylor, B. C., Chandler, C., Janssen, S., Pataki, A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.18.484903 · Cited by 10
To, P., Bhagwat, A. M., Tarbox, H. E., Ecer, A., Wendorff, H., Jamieson, Z., Trcek, T., & Fried, S. D. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.25.546465 · Cited by 8
Proteome-Wide Assessment of Protein Structural Perturbations under High Pressure
Moran, H. M., Manriquez‐Sandoval, E., Sharma, P. A., Fried, S. D., & Gillilan, R. E. (2024) · PRX Life · doi:10.1103/prxlife.2.033011 · Cited by 9
Koga, N., & Koga, R. (2024) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168791 · Cited by 9
Zhang, Y., Dong, M., Deng, J., Wu, J., Zhao, Q., Gao, X., & Xiong, D. (2024) · Communications Biology · doi:10.1038/s42003-024-07066-9 · Cited by 9
Protein sequence classification using natural language processing techniques
Perveen, H., & Weeds, J. (2025) · Discover Artificial Intelligence · doi:10.1007/s44163-025-00304-x · Cited by 9
“To prevent data leakage, we utilized Evolutionary Classification of Protein Domains (ECOD) [47, 48], a hierarchical classification system that organizes protein domains based on their evolutionary relationships.”
Advancing active compound discovery for novel drug targets: insights from AI-driven approaches
Wang, X.-Y., Chen, Y., Li, Y.-F., Wei, C., Liu, M.-Y., Yuan, C.-X., Zheng, Y.-Y., Qin, M.-H., Sheng, Y.-F., Tong, X., et al. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01591-x · Cited by 12
Dybas, J. M., & Fiser, A. (2016) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25169 · Cited by 9
“The current structure classification methods employ manual6,46 or semi-auto-matic7,45 approaches to identify the structural and evolutionary relationships that guide the classification of domains.”
MethodDockground Tool for Development and Benchmarking of Protein Docking Procedures
Kundrotas, P. J., Kotthoff, I., Choi, S. W., Copeland, M. M., & Vakser, I. A. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0708-4_17 · Cited by 8
Structural motifs in protein cores and at protein–protein interfaces are different
Hadarovich, A., Chakravarty, D., Tuzikov, A. V., Ben‐Tal, N., Kundrotas, P. J., & Vakser, I. A. (2020) · Protein Science · doi:10.1002/pro.3996 · Cited by 8
A Structurally-Validated Multiple Sequence Alignment of 497 Human Protein Kinase DomainsPreprint
Modi, V., & Dunbrack, R. L. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/776740 · Cited by 9
How to select the best model from AlphaFold2 structures?Preprint
Takei, Y., & Ishida, T. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.05.487218 · Cited by 11
“The domain number of each target was obtained from the ECOD database[48, 49] classification (version 2021-10-04).”
MethodPereira, J., & Lupas, A. N. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.895496 · Cited by 8
Fast protein structure searching using structure graph embeddings
Greener, J. G., & Jamali, K. (2024) · Bioinformatics Advances · doi:10.1093/bioadv/vbaf042 · Cited by 19
“A t-SNE embedding for the AlphaFold database TED domains compared to ECOD ( Cheng et al. 2014) and the AlphaFold 21 organisms set (Varadi et al. 2022, Bordin et al. 2023) shows the volume of new structural information available in the AlphaFold database.”
InfluentialClustering protein functional families at large scale with hierarchical approaches
Bordin, N., Scholes, H. M., Rauer, C., Roca‐Martínez, J., Sillitoe, I., & Orengo, C. A. (2024) · Protein Science · doi:10.1002/pro.5140 · Cited by 7
“…structural data with experimental and in silico approaches, various resources have classified proteins into homologous super-families containing members related by evolution, including CATH, SCOP2, SCOPe, and ECOD (Andreeva et al., 2014; Cheng et al., 2014; Fox et al., 2014; Sillitoe et al., 2021).”
BackgroundKandathil, S. M., Lau, A. M. C., Buchan, D. W. A., & Jones, D. T. (2025) · Bioinformatics · doi:10.1093/bioinformatics/btaf277 · Cited by 15
“…challenge, searches can be conducted at the domain level by initially decomposing a query protein into its constituent domains before comparing them against a library of annotated domains, such as those found in SCOP (Andreeva et al. 2020), CATH (Sillitoe et al. 2021), and ECOD (Cheng et al. 2014).”
InfluentialClustering the protein universe of life using DIAMOND DeepClust
Buchfink, B., Barbe, E., Ashkenazy, H., Reuter, K., Kennedy, J. A., & Drost, H. (2026) · Nature Methods · doi:10.1038/s41592-026-03030-z · Cited by 33
Conservation of knotted and slipknotted topology in transmembrane transporters
Zayats, V., Sikora, M., Perlinska, A. P., Stasiulewicz, A., Gren, B. A., & Sulkowska, J. I. (2023) · Biophysical Journal · doi:10.1016/j.bpj.2023.10.031 · Cited by 8
The UBR-box and its relationship to binuclear RING-like treble clef zinc fingers
Kaur, G., & Subramanian, S. (2015) · Biology Direct · doi:10.1186/s13062-015-0066-5 · Cited by 9
“However, we note the presence of permuted treble clefs in other structures such as the triquetra knot containing protein Rds3p (PDB identifier 2K0A_A; ECOD identifiers e2k0aA1, e2k0aA2, e2k0aA3) (Additional file 4: Figure S3).”
BackgroundA sequence family database built on ECOD structural domains
Liao, Y., Schaeffer, R. D., Pei, J., & Grishin, N. V. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty214 · Cited by 8
“Families in ECOD were primarily dependent on the Pfam data-base (Cheng et al. , 2014; Schaeffer et al. , 2017).”
BackgroundMethodInfluentialProtodomains: Symmetry-Related Supersecondary Structures in Proteins and Self-Complementarity
Youkharibache, P. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9161-7_10 · Cited by 7
“More recently ECOD has been added [19].”
Protein folds as synapomorphies of the tree of life
Romei, M., Sapriel, G., Imbert, P., Jamay, T., Chomilier, J., Lecointre, G., & Carpentier, M. (2022) · Evolution · doi:10.1111/evo.14550 · Cited by 8
TopEnzyme: a framework and database for structural coverage of the functional enzyme space
van der Weg, K. J., & Gohlke, H. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad116 · Cited by 7
“2021) (CATH Protein Structure Classification Database), and ECOD (Cheng et al. 2014) (Evolutionary Classification of Protein Domains).”
BackgroundTADOSS: computational estimation of tandem domain swap stability
Lafita, A., Tian, P., Best, R. B., & Bateman, A. G. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty974 · Cited by 8
Youkharibache, P., Tran, A., & Abrol, R. (2020) · Journal of Molecular Evolution · doi:10.1007/s00239-020-09934-4 · Cited by 8
“1997) have been used for a long time, and more recently ECOD (Cheng et al. 2014; Schaeffer et al. 2017).”
MethodAn adaptor for feedback regulation of heme biosynthesis by the mitochondrial protease CLPXPPreprint
Cottle, T., Joh, L., Posner, C., DeCosta, A., & Kardon, J. R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.05.602318 · Cited by 8
DrugDomain : The evolutionary context of drugs and small molecules bound to domains
Medvedev, K. E., Schaeffer, R. D., & Grishin, N. V. (2024) · Protein Science · doi:10.1002/pro.5116 · Cited by 6
“Our team has developed and maintains the Evolutionary Classification Of protein Domains (ECOD), which primarily groups domains based on homology rather than topology (Cheng et al., 2014; Schaeffer et al., 2019).”
MethodFunctional Ambidexterity of an Ancient Nucleic Acid‐Binding Domain
Weil‐Ktorza, O., Naveh‐Tassa, S., Fridmann‐Sirkis, Y., Despotović, D., Cherukuri, K. P., Corlett, T., Levy, Y., Metanis, N., & Longo, L. M. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202505188 · Cited by 12
DIONYSUS: a database of protein–carbohydrate interfaces
Gheeraert, A., Bailly, T., Ren, Y., Hamraoui, A., Te, J., Meersche, Y. V., Cretin, G., Lin, R. L. F., Gelly, J., Pérez, S., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae890 · Cited by 8
Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases
Demkiv, A. O., Toledo‐Patiño, S., Medina‐Carmona, E., Berg, A., Pinto, G., Parracino, A., Sánchez‐Ruiz, J. M., Hengge, A. C., Laurino, P., Longo, L. M., et al. (2025) · Molecular Biology and Evolution · doi:10.1093/molbev/msaf055 · Cited by 7
“To better understand the conformational dynamics and evolutionary history of the Walker A motif, we analyzed the hexapeptide SGAGKT, which was previously hypothesized to form nests upon interaction with phosphate (Watson and Milner-White 2002; Bianchi et al. 2012; Milner-White 2019), by HREX-MD…”
Simpler Protein Domain Identification Using Spectral Clustering
Cazals, F., Herrmann, J., & Sarti, E. (2025) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26808 · Cited by 7
Searching ECOD for Homologous Domains by Sequence and Structure
Schaeffer, R. D., Liao, Y., & Grishin, N. V. (2018) · Current Protocols in Bioinformatics · doi:10.1002/cpbi.45 · Cited by 7
“ECOD (Evolutionary Classification Of protein Domains) is a database of evolutionary domains (Cheng et al., 2014).”
BackgroundMethodXu, E.-R., Lafita, A., Bateman, A. G., & Hyvönen, M. (2020) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319016747 · Cited by 7
“In order to highlight the structural coverage of the families in the network, domain sequences in the ECOD database v.248 (23 August 2019; Cheng et al., 2014) matching any of the TSP1 Pfam family models were included using the same procedure as described here.”
MethodPereira, J., & Lupas, A. N. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa1085 · Cited by 7
Analyzing the symmetrical arrangement of structural repeats in proteins with CE-SymmPreprint
Bliven, S. E., Lafita, A., Rose, P. W., Capitani, G., Prlić, A., & Bourne, P. E. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/297960 · Cited by 7
PconsC4: fast, free, easy, and accurate contact predictionsPreprint
Michel, M., Hurtado, D. M., & Elofsson, A. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/383133 · Cited by 7
“Furthermore, chains from the same ECOD (Cheng et al., 2014) H-group as any protein in the benchmark dataset or dating from after 2016-05-01 was removed to avoid potential overlap with the test datasets.”
Methodlocalpdb—a Python package to manage protein structures and their annotations
Ludwiczak, J., Winski, A., & Dunin-Horkawicz, S. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac121 · Cited by 7
Kandathil, S. M., Lau, A. M. C., Buchan, D. W. A., & Jones, D. T. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.25.586696 · Cited by 7
Tarbox, H. E., Branch, A., & Fried, S. D. (2025) · Science Advances · doi:10.1126/sciadv.adt3778 · Cited by 8
“Domains for each protein were assigned using DomainMapper ( 93 ), which uses domain definitions from Evolutionary Classifications of Domains (ECOD) ( 94 ).”
Kerk, D., Valdés‐Tresanco, M. E., Toth, R., Noskov, S. Y., Ng, K. K.-S., & Moorhead, G. B. G. (2021) · BBA Advances · doi:10.1016/j.bbadva.2021.100005 · Cited by 6
Ribonuclease T2 represents a distinct circularly permutated version of the BECR RNases
Li, H., Schneider, T., Tan, Y., & Zhang, D. (2022) · Protein Science · doi:10.1002/pro.4531 · Cited by 5
Computational analysis of regulatory regions in human protein kinases
Pei, J., & Cong, Q. (2023) · Protein Science · doi:10.1002/pro.4764 · Cited by 5
“The domain architecture of a protein plays a critical role in determining its biological function, regulating its activity, and facilitating interactions with other molecules (Cheng et al., 2014; Orengo et al., 1997).”
Recent Advances in Protein Folding Pathway Prediction through Computational Methods
Zhao, K., Liang, F., Xia, Y., Hou, M., & Zhang, G. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673265249231004193520 · Cited by 5
Insights into virulence: structure classification of the Vibrio parahaemolyticus RIMD mobilome
Kinch, L. N., Schaeffer, R. D., Zhang, J., Cong, Q., Orth, K., & Grishin, N. V. (2023) · mSystems · doi:10.1128/msystems.00796-23 · Cited by 6
“The Evolutionary Classification of Domains (ECOD) database provides such a resource, which has been used in combination with an automated Domain Parser for AlphaFold Models (DPAM) to classify the human proteome (33, 43, 44).”
MethodImplications of divergence of methionine adenosyltransferase in archaea
Chouhan, B. S., Gade, M., Martinez, D., Toledo‐Patiño, S., & Laurino, P. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13312 · Cited by 7
Bayesian nonparametrics in protein remote homology search
Margelevičius, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw213 · Cited by 6
The evolutionary history of topological variations in the CPA/AT transporters
Sudha, G., Bassot, C., Lamb, J., Shu, N., Huang, Y. H., & Elofsson, A. (2021) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1009278 · Cited by 5
Youkharibache, P. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/153528 · Cited by 6
Geometric description of self-interaction potential in symmetric protein complexes
Empereur‐mot, C., Garcia‐Seisdedos, H., Elad, N., Dey, S., & Levy, E. D. (2019) · Scientific Data · doi:10.1038/s41597-019-0058-x · Cited by 6
Weidmann, L., Dijkstra, T. M. H., Kohlbacher, O., & Lupas, A. N. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/706119 · Cited by 6
Protein surface chemistry encodes an adaptive tolerance to desiccation
Romero-Pérez, P. S., Moran, H. M., Cordone, D. P., Horani, A., Truong, A., Manriquez-Sandoval, E., Ramirez, J. F., Martinez, A., Gollub, E., Hunter, K., et al. (2025) · Cell Systems · doi:10.1016/j.cels.2025.101407 · Cited by 9
Improving diffusion-based protein backbone generation with global-geometry-aware latent encoding
(2025) · doi:10.1038/s42256-025-01059-x · Cited by 7
“The other two datasets, SCOPe and ECOD, were used solely during the inference stage, and we restricted the included structures to single-chain proteins with a maximum of 256 residues.”
InfluentialTen rules for a structural bioinformatic analysis
Wankowicz, S. A. M. (2025) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1013094 · Cited by 5
“Family and domain classifications, including Pfam, SCOP, ECOD, and CATH [14,31,35,107,108], are accessible via SIFTS [35].”
Reused Protein Segments Linked to Functional Dynamics
Kutlu, Y., Axel, G., Kolodny, R., Ben‐Tal, N., & Haliloǧlu, T. (2024) · Molecular Biology and Evolution · doi:10.1093/molbev/msae184 · Cited by 5
“…H-group 109.35) e4adyA2 from 26S proteasome subunit Rpn2 (PDB ID: 4ADY) (sequence identity of 27% and 26% to e2of3A1 and e1b3uA1, respectively) (Cheng et al. 2014). supplementary table S5, Supplementary Material online lists the themes detected in the three protein domains and their sequence…”
BackgroundInfluentialJagadeesh, J., & Vembar, S. S. (2024) · Scientific Reports · doi:10.1038/s41598-024-79937-4 · Cited by 5
β‐Strand ‐mediated interactions of protein domains
Bhat, A., Kinch, L. N., & Grishin, N. V. (2020) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25970 · Cited by 5
“Structure topology classifications such as CATH, 15 SCOP, 16 and ECOD 17 provide a solid basis for such evaluation by establishing the functional and evolutionary relationships of existing protein structures.”
BackgroundMethodMedvedev, K. E., Schaeffer, R. D., Chen, K. S.-M., & Grishin, N. V. (2023) · Scientific Reports · doi:10.1038/s41598-023-39273-5 · Cited by 5
Pellequer, J. (2024) · Journal of Molecular Recognition · doi:10.1002/jmr.3102 · Cited by 6
“Manual and automated computational approaches have been developed to detect domains in protein structures [137– 139] and evolutionary-based domain identification has also been developed in Ecod [140].”
Three-dimensional Structure Databases of Biological Macromolecules
Waman, V., Orengo, C. A., Kleywegt, G. J., & Lesk, A. M. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-2095-3_3 · Cited by 6
Impact of structure space continuity on protein fold classification
Xu, J., & Zhang, J. (2016) · Scientific Reports · doi:10.1038/srep23263 · Cited by 5
“Many hierarchical classifications of domain structures have been developed 2–6 .”
BackgroundExtending the Small Molecule Similarity Principle to All Levels of BiologyPreprint
Duran‐Frigola, M., Pauls, E., Guitart-Pla, O., Bertoni, M., Orozco-Ruiz, M., Alcalde, V., Diaz, V. M., Berenguer, A., Amat, D., Juan-Blanco, T., et al. (2019) · SSRN Electronic Journal · doi:10.2139/ssrn.3380254 · Cited by 6
Coenzyme-Protein Interactions since Early LifePreprint
Sánchez-Rocha, A. C., Makarov, M., Pravda, L., Novotný, M., & Hlouchová, K. (2024) · eLife · doi:10.7554/elife.94174.1 · Cited by 5
On use of tertiary structure characters in hidden Markov models for protein fold predictionPreprint
Malik, A. J., Puente-Lelièvre, C., Matzke, N. J., & Ascher, D. B. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.08.588419 · Cited by 6
“Three popular hierarchical databases, namely SCOP [11], CATH [12] and ECOD [13] leverage structural robustness and gather structures based on shared structural and functional similarity into hierarchical groups, where gathered proteins share similar folds.”
Co-translational assembly promotes functional diversification of paralogous proteinsPreprint
Mallik, S., Cisneros, A. F., Landry, C. R., & Levy, E. D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.22.634331 · Cited by 5
Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History
Matsumoto, R., Matsuura, T., & Longo, L. M. (2024) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26780 · Cited by 4
“An HMM profile corresponding to the PPK2 protein family was obtained from the Evolutionary Classification of Protein Domains (ECOD) database [26, 27] version 279 (profile name PPK2, F-group 2004.1.1.140).”
InfluentialConformation-aware structure prediction of antigen-recognizing immune proteins
Dreyer, F. A., Ludwiczak, J., Martinkus, K., Abanades, B., Alberstein, R. G., Kessel, P., Rao, P., Lee, J. H., Bonneau, R., Watkins, A. M., et al. (2025) · mAbs · doi:10.1080/19420862.2025.2602217 · Cited by 8
“Uncertainties are modeled through a pLDDT head, which predicts a projection of local confidence into 50 bins.”
Mahmoudi, I., Quignot, C., Martins, C., & Andreani, J. (2024) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1012650 · Cited by 4
Chaperone dependency during biogenesis does not correlate with chaperone dependency during refolding
Yadav, D., Demiralp, I. I., Fakler, M. J., & Fried, S. D. (2025) · Molecular Systems Biology · doi:10.1038/s44320-025-00166-6 · Cited by 4
“Perhaps the most striking difference is seen when we consider the fold types of the constituent domains, which we identify using the ECOD system (Cheng et al, 2014).”
Evolutionary analysis of a novel zinc ribbon in the N-terminal region of threonine synthase
Kaur, G., & Subramanian, S. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1363937 · Cited by 4
“75) and ECOD (release 25 January, 2017) databases do not classify this region.(9,10) Class I TS from A.”
BackgroundComparative Analysis of TM and Cytoplasmic β-barrel Conformations Using Joint Descriptor
Thangappan, J., Wu, S., & Lee, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-32136-4 · Cited by 4
A Thermodynamic Atlas of Proteomes Reveals Energetic Innovation across the Tree of Life
Chin, A. F., Wrabl, J. O., & Hilser, V. J. (2022) · Molecular Biology and Evolution · doi:10.1093/molbev/msac010 · Cited by 4
“Primary sequence and experimental secondary structure data for 572,263 proteins, 96,019,709 residues, were retrieved from the Protein Data Bank (Berman et al. 2000) (rcsb.org) and the develop275 release of the ECOD database (Cheng et al. 2014) (prodata.swmed.edu/ecod).”
Methods for discovering catalytic activities for pseudokinases
Black, M. H., Gradowski, M., Pawłowski, K., & Tagliabracci, V. S. (2022) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2022.03.047 · Cited by 4
A structural database of chain–chain and domain–domain interfaces of proteins
Sen, N., & Madhusudhan, M. S. (2022) · Protein Science · doi:10.1002/pro.4406 · Cited by 4
“The domain definitions/boundaries of individual proteins have been characterized in SCOP/SCOPe [29,30], CATH [31–33], Pfam [34] and Ecod [35] which can be utilized to identify interfaces between different protein domains.”
The PCI domains are “winged” HEAT domains
Paul, E. E., & Marintchev, A. (2022) · PLOS ONE · doi:10.1371/journal.pone.0268664 · Cited by 4
“edu/ecod/) [10, 11] groups the HEAT and PCI domains in the ARM-repeat H-group, along with multiple other helical repeat domain proteins.”
BackgroundMurata, H., Toko, K., & Chikenji, G. (2024) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012282 · Cited by 5
Armstrong, D. R., Berrisford, J. M., Conroy, M. J., Clark, A. R., Gupta, D. S., & Mukhopadhyay, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809633-8.20280-x · Cited by 4
A Proteome-Wide Map of Chaperone-Assisted Protein Refolding in the CytosolPreprint
To, P., Xia, Y., Devlin, T., Fleming, K. G., & Fried, S. D. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.20.469408 · Cited by 4
Coenzyme-protein interactions since early life
Sánchez-Rocha, A. C., Makarov, M., Pravda, L., Novotný, M., & Hlouchová, K. (2024) · eLife · doi:10.1101/2023.10.28.563965 · Cited by 4
“To explore the fold diversity of domains containing the coenzyme binding sites, we assigned their ECOD X-groups (Cheng et al., 2014) at a residue level (Supplementary Table 3).”
Urayama, S., Fukudome, A., Mutz, P., Matsushita, Y., Takaki, Y., Nishimura, Y., Medvedeva, S., Krupovìč, M., Koonin, E. V., & Nunoura, T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.03.673927 · Cited by 4
Otwinowska, A., Koszucki, J., Panicker, V. R., Leconte, J., Olejniczak, S., Holt, K. E., Feil, E. J., Rocha, E. P. C., Smug, B., Maciejewska, B., et al. (2026) · PLOS Biology · doi:10.1371/journal.pbio.3003716 · Cited by 5
“We also mapped the locations of the major ECODs (Evolutionary Classification of Protein Domains) [51] detected in those proteins onto the 3D structures (see Fig 3B).”
Zhang, L., Zhou, X., Liang, L., & Lin, J. (2025) · ACS Omega · doi:10.1021/acsomega.5c08777 · Cited by 4
An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease
Cottle, T., Joh, L., Posner, C., DeCosta, A., Campagna, D. R., Fleming, M. D., Ducamp, S., & Kardon, J. R. (2026) · Science · doi:10.1126/science.ads5397 · Cited by 10
Unsupervised Domain Classification of AlphaFold2-Predicted Protein Structures
Barone, F., Laio, A., Punta, M., Cozzini, S., Ansuini, A., & Cazzaniga, A. (2025) · PRX Life · doi:10.1103/prxlife.3.023009 · Cited by 3
Kaur, G., & Subramanian, S. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty041 · Cited by 3
Sakuma, K., & Minami, S. (2021) · BMC Bioinformatics · doi:10.1186/s12859-021-04380-5 · Cited by 4
“We composed a subset of the ECOD database (version 238) whose sequence redundancy was reduced by 40% sequence identity [43].”
MethodMay, J. F., & Gonske, S. J. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151570 · Cited by 3
Structural basis for cooperative ssDNA binding by bacteriophage protein filament P12
Träger, L., Degen, M., Pereira, J., Durairaj, J., Teixeira, R. D., Hiller, S., & Huguenin‐Dezot, N. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf132 · Cited by 3
“To evaluate whether the P12 fold belongs to any already classified protein fold, our crystallographic model of P12 was first used as query for structural searches against the ECOD [ 29 ], CATH [ 30 ], and PDB [ 26 ] databases.”
Zhang, Y., Deng, J., Dong, M., Wu, J., Zhao, Q., Gao, X., & Xiong, D. (2025) · Neural Networks · doi:10.1016/j.neunet.2025.107476 · Cited by 3
PEGASUS : Prediction of MD ‐derived protein flexibility from sequence
Meersche, Y. V., Duval, G., Cretin, G., Gheeraert, A., Gelly, J., & Galochkina, T. V. (2025) · Protein Science · doi:10.1002/pro.70221 · Cited by 5
Metadata
- Authors
- Cheng, H., Schaeffer, R. D., Liao, Y., Kinch, L. N., Pei, J., Shi, S., Kim, B.-H., & Grishin, N. V.
- Affiliations
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Grishin, Nick V.
- Venue
- PLoS Computational Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-12-04
- Volume
- 10
- Issue
- 12
- Pages
- e1003926
- ISSN
- 1553-734X (ISSN-L)
- 1553-7358
- PMC
- PMC4256011
- OpenAlex
- W1965827393
- Cited by
- 426
- References
- 61
- Citations by year
- 2026: 34 · 2025: 48 · 2024: 62 · 2023: 46 · 2022: 46 · 2021: 46 · 2020: 31 · 2019: 24 · 2018: 40 · 2017: 20 · 2016: 14 · 2015: 14
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Computational Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- Welch Foundation (I-505)
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM094575, GM-094575)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- protein domain evolution, protein structure classification, homology, distant homologs, protein structure evolution, sequence families, PDB structures, protein domains, online databases
- MeSH terms
- Models, Molecular, Proteins, Protein Structure, Tertiary, Evolution, Molecular, Computational Biology, Databases, Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
