• The CATH database is a hierarchical domain
classification of protein structures in the
Protein Data Bank.
• There are 4 major levels in this hierarchy:
1. Class - C – Level
2. Architecture – A – Level
3. Topology – T – Level
4. Homologous Superfamily – H - Level
CATH Database – Level 1
• Determined according to the secondary structure composition and
packing within the structure. Three major classes are recognized:
3. Alpha – Beta
4. A fourth class is also identified which contains protein domains
which have low secondary structure content.
CATH Database – Level 2
• describes the overall shape of the
domain structure as determined by the
orientations of the secondary structure
but ignores the connectivity between the
• It is currently assigned manually using a
simple description of the secondary
CATH Database – Level 3
Topology (Fold Family): T-Level
• Structures are grouped into fold groups at
this level depending on both the overall
shape and the connectivity of the
• This is done using the structures
CATH Database – Level 4
Homologous (Superfamily): H-Level
• This level groups together protein domains which are thought to share a
common ancestor and can therefore be described as homologous.
• Similarities are identified either by high sequence identity or structure
comparison using SSAP.
• Structures are clustered into the same homologous superfamily if they
satisfy one of the following criteria:
1. Sequence identity >=35%, overlap >=60% of larger structure equivalent to
2. SSAP score >=80.0, sequence identity >= 20%, 60% of larger structure
equivalent to smaller.
3. SSAP score >= 70.0, 60% of larger structure equivalent to smaller, and
domains which have related functions, which is informed by the literature and
Pfam protein family database.
4. Significant similarity from HMM-sequence searches and HMM-HMM
comparisons using SAM.
CATH Hierarchy Search Example
• Class: Alpha, Beta, Alpha
• Architecture: Roll, Alpha-
Beta Barrel, Box
• Topology: Proliferating
Cell Nuclear Antigen
CATH Example Results