Editing CATH database (section)

==Hierarchical organization==
Experimentally determined protein three-dimensional structures are obtained from the [[Protein Data Bank]] and split into their consecutive [[polypeptide chains]], where applicable. Protein domains are identified within these chains using a mixture of automatic methods and manual curation.<ref>{{Cite web |title=CATH |url=http://cathdb.info/wiki/doku/?id=faq |access-date=2024-09-14 |website=cathdb.info |language=en}}</ref>

The domains are then classified within the CATH structural hierarchy: at the Class (C) level, domains are assigned according to their [[Protein secondary structure|secondary structure]] content, i.e. all [[Alpha helix|alpha]], all [[Beta sheet|beta]], a mixture of alpha and beta, or little secondary structure; at the Architecture (A) level, information on the secondary structure arrangement in three-dimensional space is used for assignment; at the Topology/fold (T) level, information on how the secondary structure elements are connected and arranged is used; assignments are made to the [[Protein superfamily|Homologous superfamily]] (H) level if there is good evidence that the domains are related by evolution<ref name="Orengo_1997" /> i.e. they are homologous.

{| class="wikitable"
|+The four main levels of the CATH hierarchy:
!#
!Level
!Description
|-
|1 || '''C'''lass || the overall secondary-structure content of the domain. (Equivalent to the [[Structural Classification of Proteins database|SCOP]] [[Protein fold class|Class]])
|-
|2 || '''A'''rchitecture || high structural similarity but no evidence of [[homology (biology)|homology]].
|-
|3 || '''T'''opology/fold || a large-scale grouping of topologies which share particular structural features (Equivalent to the 'fold' level in SCOP)
|-
|4 || '''H'''omologous superfamily || indicative of a demonstrable evolutionary relationship. (Equivalent to SCOP [[protein superfamily|superfamily]])
|}

Additional sequence data for domains with no experimentally determined structures are provided by CATH's sister resource, Gene3D, which are used to populate the homologous superfamilies. Protein sequences from UniProtKB and Ensembl are scanned against CATH HMMs to predict domain sequence boundaries and make homologous superfamily assignments.