S-100 (IPR034325)

Short name: S-100_dom

Overlapping homologous superfamilies

Domain relationships


This entry represents the S-100 domain. Proteins containing this domain are belonging to the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins [PMID: 16683912, PMID: 10191501, PMID: 12507480]. Many S100 proteins have been found to bind transition metals, such as Zn2+ and Cu2+ [PMID: 27764152].

The most unusual characteristic of certain S100 proteins is their occurrence in extracellular space, where they act in a cytokine-like manner through RAGE, the receptor for advanced glycation products. Structural data suggest that many S100 members exist within cells as homo- or heterodimers and even oligomers; oligomerization contributes to their functional diversification. Upon binding calcium, most S100 proteins change conformation to a more open structure exposing a hydrophobic cleft. This hydrophobic surface represents the interaction site of S100 proteins with their target proteins. There is experimental evidence showing that many S100 proteins have multiple binding partners with diverse mode of interaction with different targets [PMID: 11833360].

In addition to S100 proteins, this group includes the 'fused' gene family, a group of calcium binding S100-related proteins. The 'fused' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin [PMID: 15854042], hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These 'fused' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signaling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, 'fused' gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins [PMID: 27764152].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0046914 transition metal ion binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.