S-100/ICaBP type calcium binding domain |
Structure of the S100B protein. Based on PyMOL rendering of PDB 1b4c.
|
Identifiers |
Symbol |
S_100 |
Pfam |
PF01023 |
InterPro |
IPR013787 |
PROSITE |
PDOC00275 |
SCOP |
1cnp |
SUPERFAMILY |
1cnp |
Available protein structures: |
Pfam |
structures |
PDB |
RCSB PDB; PDBe; PDBj |
PDBsum |
structure summary |
|
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.
Contents
- 1 Structure
- 2 Normal function
- 3 Pathology
- 4 Human genes
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Structure
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
S-100 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]
Pathology
S100 immunostain marking the sustentacular cells in a paraganglioma.
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
- S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A7 (psoriasin), S100A8, S100A9, S100A10, S100A11, S100A12, S100A13, S100A14(S100A14), S100A15 Koebnerisin, (S100A15), S100A16
- S100B
- S100P
- S100Z(S100Z)
CRNN; FLG; FLG2; HRNR; RPTN; S100G; TCHH; THHL1;
See also
- List of histologic stains that aid in diagnosis of cutaneous conditions
References
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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, Christopher Voscopoulos, Jason Winston, Alif Dharamsi, Paul Goldsmith Michele Gunsior, Barbara K. Vonderhaar, Melanie Olson, Peter H. Watson, and Stuart H. Yuspa. (2008). "Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer.". J. Cancer Lett. 277 (1): 101–107. doi:10.1016/j.canlet.2008.11.032. PMC 2680177. PMID 19136201.
- 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
- S100 Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
Cell signaling: calcium signaling / calcium metabolism
|
|
Cell membrane |
Ion pumps
|
- SERCA
- Sodium-calcium exchanger
|
|
Cell membrane calcium channels
|
- VDCC
- TRP
- NMDA receptor
- AMPA receptor
- 5-HT3 receptor
- P2X purinoreceptor
|
|
Adhesion molecules
|
|
|
Other
|
|
|
|
Intracellular signaling
& calc. regulation |
Second messengers
|
|
|
Store gates
(ligand-gated calcium channel)
|
|
|
Molecular switches, and kinases
|
- Troponin C
- Calmodulin
- CaM kinases
- PKC
- NCS
|
|
Chelators and calcium sensors
|
- Calbindin
- S100
- pervalbumin
- Calretinin
- Calsequestrin
- Sarcalumenin
- Phospholamban
- Synaptotagmins
|
|
Proteases
|
|
|
Cytoskeleton remodeling proteins
|
|
|
Chaperones
|
|
|
Other
|
|
|
|
Calcium-binding
protein domains |
|
|
Extracellular ligands |
- Parathyroid hormone
- Calcitonin
|
|
Calcium-binding proteins |
Intracellular calcium-sensing proteins
|
- Calmodulin
- Calnexin
- Calreticulin
- Gelsolin
- neuronal
- Hippocalcin
- Neurocalcin
- Recoverin
|
|
Membrane protein
|
- Vitamin D-dependent calcium-binding protein/Calbindin
- Calexcitin
- Calsequestrin
- Osteocalcin
- Osteonectin
- S-100
- Synaptotagmin
|
|
Cytoskeleton
|
|
|
Extracellular matrix
|
|
|
|
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
|
|
Protein: nerve tissue protein
|
|
Synuclein |
- Alpha-synuclein
- Beta-synuclein
- Gamma-synuclein
|
|
Other |
- Agrin
- Chimerin
- Granin
- FMR1
- Gap-43 protein
- GLUT3
- Myelin
- Brain natriuretic peptide
- Nerve growth factor
- SCG5
- Neurogranin
- Neuronal calcium sensor
- Neuropeptide
- Olfactory marker protein
- S-100 protein
- Synapsin
- Synaptophysin
- Tubulin
- GPM6A
|
|
Index of the central nervous system
|
|
Description |
- Anatomy
- meninges
- cortex
- association fibers
- commissural fibers
- lateral ventricles
- basal ganglia
- diencephalon
- mesencephalon
- fourth ventricle
- pons
- cerebellum
- medulla
- spinal cord
- Physiology
- Development
|
|
Disease |
- Meningitis
- Demylinating diseases
- Seizures and epilepsy
- Headache
- Stroke
- Sleep
- Congenital
- Injury
- Neoplasms and cancer
- Other
- Symptoms and signs
- head and neck
- eponymous
- lesions
|
|
Treatment |
- Procedures
- Drugs
- general anesthetics
- analgesics
- addiction
- epilepsy
- cholinergics
- migraine
- parkinson
- vertigo
- other
|
Index of the peripheral nervous system
|
|
Description |
- Anatomy
- Nerves
- cranial
- trigeminal
- cervical
- brachial
- lumbosacral plexus
- somatosensory
- spinal
- autonomic
- Physiology
- reflexes
- proteins
- neurotransmitters
- transporters
- Development
|
|
Disease |
- Autonomic
- Congenital
- Injury
- Neoplasms and cancer
- Other
- Symptoms and signs
|
|
Treatment |
- Procedures
- Local anesthetics
|
|
|
Tumor markers
|
|
Blood |
|
|
Endocrine |
Thyroid cancer
|
- Thyroglobulin
- Medullary thyroid cancer (Calcitonin
- Carcinoembryonic antigen)
|
|
Pheochromocytoma
|
- Normetanephrine
- Enolase 2
|
|
Neuroendocrine tumors
|
- Synaptophysin
- Chromogranin A
|
|
Neuroblastoma
|
|
|
|
Nervous system |
Brain tumor
|
|
|
Astrocytoma
|
- Glial fibrillary acidic protein
|
|
NC/Melanoma
|
- S-100 protein
- Melanoma inhibitory activity
|
|
|
Cardiovascular/
respiratory |
Lung cancer
|
- Carcinoembryonic antigen
- Enolase 2
- Autocrine motility factor
|
|
Hemangiosarcoma (endothelium)
|
|
|
|
Digestive |
Colorectal cancer
|
- CA19-9
- Carcinoembryonic antigen
|
|
Pancreatic cancer
|
- CA19-9
- Carcinoembryonic antigen
- CA 242
- Tumor-associated glycoprotein 72
|
|
Hepatocellular carcinoma
|
|
|
|
Reproductive/
urinary/
breast |
Ovarian tumor
|
- Surface epithelial-stromal tumor
- EC
- EST
- Choriocarcinoma
- Dysgerminoma
- Sertoli-Leydig cell tumour
- GCT
|
|
Testicular cancer
|
- βhCG
- Alpha-fetoprotein/AFP-L3
- CD30
|
|
Prostate cancer
|
- Prostate specific antigen
- Prostatic acid phosphatase
- Glutamate carboxypeptidase II
- erbB-3 receptor
- Early prostate cancer antigen-2
- SPINK1
- GOLPH2
- PCA3
- TMPRSS2
|
|
Germ cell tumor
|
|
|
Bladder cancer
|
|
|
Breast cancer
|
- CA 15-3
- erbB-2 receptor
- erbB-3 receptor
- Cathepsin D
|
|
|
General histology |
Sarcoma
|
|
|
Carcinoma (epithelium)
|
|
|
|
Musculoskeletal |
|
|
|
|
Description |
- Tumor suppressing and oncogenes
- Tumor markers
|
|
Disease |
- Neoplasms and cancer
- Symptoms and signs
- Paraneoplastic
|
|
Treatment |
- Drugs
- intracellular chemotherapeutics
- extracellular chemotherapeutics
- adjuvant detoxification
|
|
|