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279  structures 63  species 2  interactions 1006  sequences 21  architectures

Family: S_100 (PF01023)

Summary: S-100/ICaBP type calcium binding domain

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This is the Wikipedia entry entitled "S-100 protein". More...

S-100 protein Edit Wikipedia article

S-100/ICaBP type calcium binding domain
Protein S100B PDB 1b4c.png
Structure of the S100B protein. Based on PyMOL rendering of PDB 1b4c.
Symbol S_100
Pfam PF01023
InterPro IPR013787
SCOP 1cnp

The S-100 proteins (often styled without the hyphen, S100) are a family of low-molecular-weight proteins found in vertebrates and characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand type") conformation. There are at least 21 different S-100 proteins.[1] Their name is derived from the fact that these proteins are soluble in 100%, i.e. saturated ammonium sulfate at neutral pH. They are encoded by a family of genes whose symbols use the S100 prefix, for example, S100A1, S100A2, S100A3.


Most S100 proteins are homodimeric, consisting of two identical polypeptides, which are held together by non-covalent bonds. S100 proteins are structurally similar to calmodulin. On the other hand they differ from calmodulin on the other features. For instance, their expression pattern is cell-specific, i.e. they are expressed in particular cell types. Their expression depends on environmental factors. To contrast, calmodulin is a ubiquitous and universal intracellular Ca2+ receptor widely expressed in many cells.

Normal function

S100 is normally present in cells derived from the neural crest (Schwann cells, and melanocytes), chondrocytes, adipocytes, myoepithelial cells, macrophages, Langerhans cells, dendritic cells, and keratinocytes. It may be present in some breast epithelial cells.

S100 proteins have been implicated in a variety of intracellular and extracellular functions.[2] S100 proteins are involved in regulation of protein phosphorylation, transcription factors, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response. S100A7 (psoriasin) and S100A15 have been found to act as cytokines in inflammation, particularly in autoimmune skin conditions such as psoriasis.[3]


Several members of the S-100 protein family are useful as markers for certain tumors and epidermal differentiation. It can be found in melanomas,[4] 100% of schwannomas, 100% of neurofibromas (weaker than schwannomas), 50% of malignant peripheral nerve sheath tumors (may be weak and/or focal), paraganglioma stromal cells, histiocytoma and clear cell sarcomas. Further, S100 proteins are markers for inflammatory diseases and can mediate inflammation and act as antimicrobials.[5]

S100 proteins have been used in the lab as cell markers for anatomic pathology.

Human genes


See also


  1. ^ Marenholz I, Heizmann CW, Fritz G (October 2004). "S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature)". Biochem. Biophys. Res. Commun. 322 (4): 1111–22. doi:10.1016/j.bbrc.2004.07.096. PMID 15336958. 
  2. ^ Donato R (April 2003). "Intracellular and extracellular roles of S100 proteins". Microsc. Res. Tech. 60 (6): 540–51. doi:10.1002/jemt.10296. PMID 12645002. 
  3. ^ Wolf R, Howard OM, Dong HF, Voscopoulos C, Boeshans K, Winston J et al. (2008). "Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.". J Immunol 181 (2): 1499–506. doi:10.4049/jimmunol.181.2.1499. PMC 2435511. PMID 18606705. 
  4. ^ Nonaka D, Chiriboga L, Rubin BP (November 2008). "Differential expression of S100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors". J. Cutan. Pathol. 35 (11): 1014–9. doi:10.1111/j.1600-0560.2007.00953.x. PMID 18547346. 
  5. ^ Wolf R, Ruzicka T, Yuspa SH (July 2010). "Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function". Amino Acids 41 (4): 789–96. doi:10.1007/s00726-010-0666-4. PMID 20596736. 

Further reading

  • Wolf R, Voscopoulos CJ, FitzGerald PC, et al. (2006). "The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation". J. Invest. Dermatol. 126 (7): 1600–8. doi:10.1038/sj.jid.5700210. PMID 16528363. 
  • Ronald Wolf, O. M. Zack Howard, Hui-Fang Dong, Christopher Voscopoulos, Karen Boeshans, Jason Winston, Rao Divi, Michele Gunsior, Paul Goldsmith, Bijan Ahvazi, Triantafyllos Chavakis, Joost J. Oppenheim and Stuart H. Yuspa (2010). "Chemotactic Activity of S100A7 (Psoriasin) Is Mediated by the Receptor for Advanced Glycation End Products and Potentiates Inflammation with Highly Homologous but Functionally Distinct S100A15.". The Journal of Immunology 181 (2): 1499–1506. 
  • Ronald Wolf, Francesca Mascia, Alif Dharamsi, O. M. Zack Howard, Christophe Cataisson, Val Bliskovski, Jason Winston, Lionel Feigenbaum, Ulrike Lichti, Thomas Ruzicka Triantafyllos Chavakis, and Stuart H. Yuspa. (2010). "Gene from a Psoriasis Susceptibility Locus Primes the Skin for Inflammation.". Science Translational Medicine 2 (61): 61ra90. doi:10.1126/scitranslmed.3001108. PMID 21148126. 

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

S-100/ICaBP type calcium binding domain Provide feedback

The S-100 domain is a subfamily of the EF-hand calcium binding proteins.

Literature references

  1. Sastry M, Ketchem RR, Crescenzi O, Weber C, Lubienski MJ, Hidaka H, Chazin WJ; , Structure 1998;6:223-231.: The three-dimensional structure of Ca(2+)-bound calcyclin: implications for Ca(2+)-signal transduction by S100 proteins. PUBMED:9519412 EPMC:9519412

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013787

The calcium-binding domain found in S100 and CaBP-9k proteins is a subfamily of the EF-hand calcium-binding domain [PUBMED:15284904]. S100s are small dimeric acidic calcium and zinc-binding proteins abundant in the brain, with S100B playing an important role in modulating the proliferation and differentiation of neurons and glia cells [PUBMED:15006498]. S100 proteins have two different types of calcium-binding sites: a low affinity one with a special structure, and a 'normal' EF-hand type high-affinity site.

Calbindin-D9k (CaBP-9k) also belong to this family of proteins, but it does not form dimers. CaBP-9k is a cytosolic protein expressed in a variety of tissues. Although its precise function is unknown, it appears to be under the control of the steroid hormones oestrogen and progesterone in the female reproductive system [PUBMED:16288660]. In the intestine, CaBP-9k may be involved in calcium absorption by mediating intracellular diffusion [PUBMED:12520541].

This entry represents a subdomain of the calcium-binding domain found in S100, CaBP-9k, and related proteins.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan EF_hand (CL0220), which has the following description:

The EF hand is a calcium binding domain found in a wide variety of proteins [1].

The clan contains the following 16 members:

Caleosin Dockerin_1 EF-hand_1 EF-hand_10 EF-hand_2 EF-hand_3 EF-hand_4 EF-hand_5 EF-hand_6 EF-hand_7 EF-hand_8 EF-hand_9 EF-hand_like EFhand_Ca_insen S_100 SPARC_Ca_bdg


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_242 (release 3.0)
Previous IDs: S_100_domain;
Type: Domain
Author: Finn RD, Bateman A
Number in seed: 24
Number in full: 1006
Average length of the domain: 43.00 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 14.75 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.3 21.0
Noise cut-off 20.1 20.1
Model length: 44
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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There are 2 interactions for this family. More...

S_100 EF-hand_1


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the S_100 domain has been found. There are 279 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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