Structural Classification of Proteins database

The broadest groups on SCOP version 1.75 are the protein fold classes. These classes group structures with similar secondary structure composition, but different overall tertiary structures and evolutionarily origins. This is the top level "root" of the SCOP hierarchical classification.

1. All alpha proteins [46456] (284): Domains consisting of α-helices
2. All beta proteins [48724] (174): Domains consisting of β-sheets
3. Alpha and beta proteins (a/b) [51349] (147): Mainly parallel beta sheets (beta-alpha-beta units)
4. Alpha and beta proteins (a+b) [53931] (376): Mainly antiparallel beta sheets (segregated alpha and beta regions)
5. Multi-domain proteins (alpha and beta) [56572] (66): Folds consisting of two or more domains belonging to different classes
6. membrane and cell surface proteins and peptides [56835] (58): Does not include proteins in the immune system
7. Small proteins [56992] (90): Usually dominated by metal ligand, cofactor, and/or disulfide bridges
8. coiled-coil proteins [57942] (7): Not a true class
9. Low resolution protein structures [58117] (26): Peptides and fragments. Not a true class
10. Peptides [58231] (121): peptides and fragments. Not a true class.
11. Designed proteins [58788] (44): Experimental structures of proteins with essentially non-natural sequences. Not a true class

The number in brackets, called a "sunid", is a SCOP unique integer identifier for each node in the SCOP hierarchy. The number in parentheses indicates how many elements are in each category. For example, there are 284 folds in the "All alpha proteins" class. Each member of the hierarchy is a link to the next level of the hierarchy.

Each class contains a number of distinct folds. This classification level indicates similar tertiary structure, but not necessarily evolutionary relatedness. For example, the "All-α proteins" class contains >280 distinct folds, including: Globin-like (core: 6 helices; folded leaf, partly opened), long alpha-hairpin (2 helices; antiparallel hairpin, left-handed twist) and Type I dockerin domains (tandem repeat of two calcium-binding loop-helix motifs, distinct from the EF-hand).

Domains within a fold are further classified into superfamilies. This is a largest grouping of proteins for which structural similarity is sufficient to indicate evolutionary relatedness and therefore share a common ancestor. However, this ancestor is presumed to be distant, because the different members of a superfamily have low sequence identities. For example, the two superfamilies of the "Globin-like" fold are: the Globin superfamily and alpha-helical ferredoxin superfamily (contains two Fe4-S4 clusters).

Protein families are more closely related than superfamilies. Domains are placed in the same family if that have either:

1. >30% sequence identity
2. some sequence identity (e.g., 15%) and perform the same function

The similarity in sequence and structure is evidence that these proteins have a closer evolutionary relationship than do proteins in the same superfamily. Sequence tools, such as BLAST, are used to assist in placing domains into superfamilies and families. For example, the four families in the "globin-like" superfamily of the "globin-like" fold are truncated hemoglobin (lack the first helix), nerve tissue mini-hemoglobin (lack the first helix but otherwise is more similar to conventional globins than the truncated ones), globins (Heme-binding protein), and phycocyanin-like phycobilisome proteins (oligomers of two different types of globin-like subunits containing two extra helices at the N-terminus binds a bilin chromophore). Families in SCOP are each assigned a concise classification string, sccs, where the letter identifies the class to which the domain belongs; the following integers identify the fold, superfamily, and family, respectively (e.g., a.1.1.2 for the "Globin" family).[10]

A "TaxId" is the taxonomy ID number and links to the NCBI taxonomy browser, which provides more information about the species to which the protein belongs. Clicking on a species or isoform brings up a list of domains. For example, the "Hemoglobin, alpha-chain from Human (Homo sapiens)" protein has >190 solved protein structures, such as 2dn3 (complexed with cmo), and 2dn1 (complexed with hem, mbn, oxy). Clicking on the PDB numbers is supposed to display the structure of the molecule, but the links are currently broken (links work in pre-SCOP).

By 2009, the original SCOP database manually classified 38,000 PDB entries into a strictly hierarchical structure. With the accelerating pace of protein structure publications, the limited automation of classification could not keep up, leading to a non-comprehensive dataset. The Structural Classification of Proteins extended (SCOPe) database was released in 2012 with far greater automation of the same hierarchical system and is full backwards compatible with SCOP version 1.75. In 2014, manual curation was reintroduced into SCOPe to maintain accurate structure assignment. As of February 2015, SCOPe 2.05 classified 71,000 of the 110,000 total PDB entries.[11]

SCOP2 prototype was a beta version of Structural classification of proteins and classification system that aimed to more the evolutionary complexity inherent in protein structure evolution.[12] It is therefore not a simple hierarchy, but a directed acyclic graph network connecting protein superfamilies representing structural and evolutionary relationships such as circular permutations, domain fusion and domain decay. Consequently, domains are not separated by strict fixed boundaries, but rather are defined by their relationships to the most similar other structures. The prototype was used for the development of the SCOP version 2 database.[7] The SCOP version 2, release January 2020, contains 5134 families and 2485 superfamilies compared to 3902 families and 1962 superfamilies in SCOP 1.75. The classification levels organise more than 41 000 non-redundant domains that represent more than 504 000 protein structures.

The Evolutionary Classification of Protein Domains (ECOD) database released in 2014 is a similar to SCOPe expansion of SCOP version 1.75. Unlike the compatible SCOPe, it renames the class-fold-superfamily-family hierarchy into an architecture-X-homology-topology-family (A-XHTF) grouping, with the last level mostly defined by Pfam and supplemented by HHsearch clustering for uncategorized sequences.[13] ECOD has the best PDB coverage of all three successors: it covers every PDB structure, and is updated biweekly.[14] The direct mapping to Pfam has proven useful to Pfam curators who use the homology-level category to supplement their "clan" grouping.[15]