S100A7 (S100 calcium binding protein A7)

2010-04-01   Jill I Murray , Martin J Boulanger 

Department of Biochemistry, Microbiology, University of Victoria, Victoria, British Columbia V8W 3P6, Canada





S100A7 is located on chromosome 1q21 within the epidermal differentiation complex.
Atlas Image
The S100A7 genomic organization includes 3 exons and 2 introns with exons 2 and 3 containing the protein encoding sequence (Semprini et al., 1999). The EF-hand domains are highlighted (Burgisser et al., 1995).


The S100A7 gene has 3 exons and 2 introns with a genomic structure similar to other S100 family members. Exon 1 encodes the 5 untranslated region while exons 2 and 3 contain the protein coding sequence. Exon 2 encodes the start codon and the non-canonical N-terminal EF-hand while exon 3 encodes the carboxyl-terminal EF-hand.


The S100A7 gene encodes for a single constitutively spliced transcript. An EST has been reported in which an alternative promoter is used to produce an identical S100A7 mRNA (See Ensembl, UCSC genome browser).


Five copies of S100A7 in the human genome have been reported including the closely related paralog S100A15 (also known as S100A7A) (Kulski et al., 2003; Wolf et al., 2003). Two of the five reported copies of S100A7, S100A7d (S100A7P1) and S100A7e (S100A7P2), are proposed to be non-coding pseudogenes (Kulski et al., 2003; Marenholz et al., 2006).



S100A7 is a member of the S100 family of calcium-binding signaling proteins. S100A7 has both intracellular and extracellular functions.
Atlas Image
A. S100A7 primary sequence highlighting the calcium- and zinc-binding residues and the EF-hand domains.
B. The 3D structure of zinc- and calcium-bound S100A7 dimer (2psr).


S100A7 is a small 11.4 kDa protein containing a C-terminal canonical calcium-binding EF-hand motif and an N-terminal non-canonical EF-hand motif which is characteristic of the S100 protein family. S100A7 forms a homodimer with one Ca2+ ion bound by the canonical EF-hand motif in each monomer and two Zn2+ ions located at the dimer interface (Brodersen et al., 1999). S100A7 monomers and putative higher order multimers have been observed in both psoriatic and healthy epidermis (Ruse et al., 2001).


S100A7 is present at low levels in healthy skin, however it is highly upregulated in psoriatic epidermal keratinocytes (Madsen et al., 1991). E. Coli has been shown to induce S100A7 expression in keratinocytes (Gläser et al., 2005).
S100A7 expression is upregulated in several cancers including skin, breast, lung, head, neck, cervix, bladder and gastric cancer (for review see Emberley et al., 2004).
S100A7 expression is induced in MCF10 cells by stresses such as serum deprivation and cell confluency (Enerback et al., 2002).
S100A7 is repressed by BRCA1 in a c-myc dependent manner in HCC-BR116 cells (Kennedy et al., 2005). 17beta-estradiol treatment increased S100A7 expression in an estrogen receptor beta dependent manner in MCF-7 cells (Skliris et al., 2007). Epidermal Growth Factor induces S100A7 expression in MCF-7 and MDA-MB-468 cells (Paruchuri et al., 2008).
S100A7 expression is induced by proinflammatory cytokines in skin and breast cancer cells. S100A7 expression is enhanced in human keratinocytes by stimulation with the cytokine IL-22 in combination with IL-17 or IL-17F (Liang et al., 2006). Oncostatin-M was shown to induce S100A7 expression in human epidermal cell skin equivalents (Gazel et al., 2006). S100A7 expression is induced by the cytokines oncostatin-M and IL-6 in MCF-7, TD47 and MDA-MB-468 cell lines (West and Watson, 2010).


S100A7 is localized to the cytoplasm, nucleus, cell periphery and is also secreted from cells. In keratinocytes, S100A7 is observed in the cytoplasm when untreated and at the cell periphery upon stimulation with calcium (Ruse et al., 2003). S100A7 is expressed at low levels or is not detected in healthy breast cells. In breast cancer cells, however, S100A7 is observed in the nucleus and cytoplasm and is also secreted (Al-Haddad et al., 1999; Enerback et al., 2002).


S100A7 has been shown to function as a chemotactic factor for neutrophils and CD4+ T cells (Jinquan et al., 1996). S100A7 binds RAGE (receptor for advanced glycation end products) in a zinc-dependent manner and is proposed to mediate chemotaxis in a RAGE-dependent manner (Wolf et al., 2008). S100A7 present in skin functions as a Zn-dependent antimicrobial towards E.Coli (Glaser et al., 2005). S100A7 has also been shown to play an antibacterial role in wound healing (Lee and Eckert, 2007). S100A7 is a substrate for transglutaminase (Ruse et al., 2001).
S100A7 interacts, co-purifies and colocalizes in the cytoplasm with epidermal-type fatty acid-binding protein (E-FABP), a protein which is also upregulated in psoriasis (Hagens et al., 1999; Ruse et al., 2003). S100A7 has been shown to interact with RanBPM by yeast two-hybrid and co-immunoprecipitation studies in breast cancer cells (Emberley et al., 2002). S100A7 has been shown to interact with the multifunctional signalling protein, Jab1, yeast two-hybrid and co-immunoprecipitation studies in breast cancer cells (Emberley et al., 2003). The Jab1-S100A7 interaction and downstream effects were disrupted by mutation of a Jab1-binding site (Emberley et al., 2003; West et al., 2009).


S100A7 is a member of the S100 family of vertebrate proteins. Among the S100 family, S100A7 is the most divergent (Burgisser et al., 1995) with the exception of a recently identified paralog S100A715 (or S100A7A), with which it shares 93% similarity (Wolf et al., 2003). A bovine ortholog to S100A7, Bosd3 (Virtanen, 2006) and equine ortholog (Leeb et al., 2005) have also been reported. The mouse S100A7, which has 40% similarity (Webb et al., 2005), has been assigned the designation mouse S100A15 (Wolf et al., 2006).



An allergy associated polymorphism of S100A7 (rs3014837) has been reported (Bryborn et al., 2008).

Implicated in

Entity name
Psoriasis and other skin diseases
S100A7 is associated with inflammation in several skin diseases (Algermissen et al., 1996). S100A7 was originally identified as a protein secreted from psoriatic skin (Madsen et al., 1991). S100A7 is also overexpressed in skin lesions of patients with lichen sclerosus (Gambichler et al., 2009), acne inversa (Schlapbach et al., 2009), and middle ear cholesteatoma (Kim et al., 2009).
Entity name
Non-melanoma skin cancer
S100A7 may play a role in the progression of skin cancer. S100A7 expression is not observed in healthy epidermis. When S100A7 levels were studied by immunohistochemistry in squamous cell carcinoma skin lesions, higher levels of expression were found in pre-invasive squamous cell carcinoma in situ compared to invasive squamous cell carcinoma (Alowami et al., 2003). In a separate study, S100A7 mRNA levels, determined by real-time PCR, were upregulated in pre-cancerous skin lesions and epithelial skin tumours including basal cell carcinoma and squamous cell carcinoma (Moubayed et al., 2007).
Entity name
S100A7 protein was observed at higher levels in the urine of melanoma patients compared to healthy controls (Brouard et al., 2002), although S100A7 was not detected in melanoma cells (Petersson et al., 2009).
Entity name
Ductal carcinoma in situ (DCIS) and breast cancer
S100A7 was first associated with primary breast cancer (Moog-Lutz et al., 1995). Later studies identified S100A7 as one of the most highly expressed genes in DCIS, a key stage before the transition to invasive breast cancer (Leygue et al., 1996; Enerback et al., 2002). When S100A7 is expressed in later stages of breast cancer it is associated with the agressive estrogen-negative tumors and poor prognosis (Al-Haddad et al., 1999; Emberley et al., 2004). In vivo mouse model studies have shown that S100A7 promotes tumorigenesis (Emberley et al., 2003; Krop et al., 2005). Several of the tumorigenic effects of S100A7, including upregulation of NF-kappaB, PI3K-Akt, and AP-1 as well as promotion of cell survival, are mediated by the interaction of S100A7 with Jab1 (Emberley et al., 2003; Emberley et al., 2005).
Entity name
Epithelial ovarian cancer
S1007 mRNA and protein levels are upregulated in epithelial ovarian carcinoma tissue compared to normal and benign ovary tissue (Gagnon et al., 2008). Autoantibodies to S100A7 were detected at higher levels in the plasma of early and late-stage ovarian cancer patients compared to healthy controls (Gagnon et al., 2008). S100A7 autoantibodies may be useful as a biomarker for epithelial ovarian cancer (for review see Piura and Piura, 2009).
Entity name
Lung squamous cell carcinoma
S100A7 is associated with non-small lung squamous cell carcinoma metastasis to the brain (Zhang et al., 2007). Proteomic studies identified S100A7 as a protein upregulated in a brain metastasis lung squamous cell carcinoma cell line and S100A7 overexpression was confirmed in brain metastasis tissues (Zhang et al., 2007).
Entity name
Bladder squamous cell carcinoma
S100A7 was detected in bladder squamous cell carcinoma tumors and also in the urine of patients with bladder squamous cell carcinoma (Celis et al., 1996; Ostergaard et al., 1997). As a result, S100A7 has been proposed to be a potential biomarker for bladder squamous cell carcinoma (Celis et al., 1996; Ostergaard et al., 1997; Ostergaard et al., 1999).
Entity name
Oral squamous cell carcinoma
S100A7 is associated with oral squamous cell carcinoma (Zhou et al., 2008; Kesting et al., 2009). RT-PCR and immunofluorescence studies showed that S100A7 mRNA and protein levels respectively are up-regulated in oral squamous cell carcinoma tissues compared to normal oral tissues (Kesting et al., 2009).
Entity name
Head-and-neck squamous cell carcinoma
S100A7 is a highly upregulated biomarker in head-and-neck squamous cell carcinomas (Ralhan et al., 2008).
Entity name
Gastric cancer
SAGE (serial analysis of gene expression) studies identified S100A7 as one of the top twenty genes upregulated in gastric cancer (El-Rifai et al., 2002). Further mining of publicly available SAGE, virtual Northern Blot, and microarray data confirmed the association of S100 proteins such as S100A7 with gastric cancer (Liu et al., 2008).
Entity name
Chronic rhinosinusitis
Chronic rhinosinusitis (CRS) is characterized by a persistant inflammation of the nasal mucosa. It has been proposed that the antibacterial function of S100A7 play a role in protecting against the environmental factors that contribute to chronic rinosinusitis (for review see Tieu et al., 2009). Reduced levels of S100A7 were detected in the nasal lavage fluid of patients with allergic rhinitis when compared to controls (Bryborn et al., 2005). A polymorphism (RS3014837) has been linked with allergic individuals in Sweden (Bryborn et al., 2008).
Entity name
Systemic sclerosis (SSc)
S100A7 is upregulated in the saliva of patients with systemic sclerosis when compared to healthy individuals and has been proposed as a potential biomarker for systemic sclerosis with pulmonary involvement (Giusti et al., 2007; Baldini et al., 2008).
Entity name
Alzheimers disease
A recent study has suggested that S100A7 is a potential biomarker for Alzheimers disease. Increased levels of S100A7 were detected in the cerebralspinal fluid and brain of patients with Alzheimers disease (Qin et al., 2009).


Pubmed IDLast YearTitleAuthors
105959351999Psoriasin (S100A7) expression and invasive breast cancer.Al-Haddad S et al
88441191996Differential expression of CRABP II, psoriasin and cytokeratin 1 mRNA in human skin diseases.Algermissen B et al
126002742003Psoriasin (S100A7) expression is altered during skin tumorigenesis.Alowami S et al
186341492008Association of psoriasin (S100A7) with clinical manifestations of systemic sclerosis: is its presence in whole saliva a potential predictor of pulmonary involvement?Baldini C et al
85300091995Refined mapping of the psoriasin gene S100A7 to chromosome 1cen-q21.Børglum AD et al
100262471999Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states.Brodersen DE et al
124596532002Urinary excretion of epidermal-type fatty acid-binding protein and S100A7 protein in patients with cutaneous melanoma.Brouard MC et al
162361632005Psoriasin, one of several new proteins identified in nasal lavage fluid from allergic and non-allergic individuals using 2-dimensional gel electrophoresis and mass spectrometry.Bryborn M et al
183738642008Comprehensive evaluation of genetic variation in S100A7 suggests an association with the occurrence of allergic rhinitis.Bryborn M et al
85269201995Amino acid sequence analysis of human S100A7 (psoriasin) by tandem mass spectrometry.Bürgisser DM et al
86183451996Bladder squamous cell carcinomas express psoriasin and externalize it to the urine.Celis JE et al
124608932002Gastric cancers overexpress S100A calcium-binding proteins.El-Rifai W et al
159949442005The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer.Emberley ED et al
117823562002Psoriasin expression in mammary epithelial cells in vitro and in vivo.Enerbäck C et al
182455372008Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients.Gagnon A et al
195585562009Significant upregulation of antimicrobial peptides and proteins in lichen sclerosus.Gambichler T et al
169174972006A characteristic subset of psoriasis-associated genes is induced by oncostatin-M in reconstituted epidermis.Gazel A et al
177222262007Specific proteins identified in whole saliva from patients with diffuse systemic sclerosis.Giusti L et al
155680272005Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection.Gläser R et al
101912751999Calcium-binding protein S100A7 and epidermal-type fatty acid-binding protein are associated in the cytosol of human keratinocytes.Hagens G et al
87528301996Psoriasin: a novel chemotactic protein.Jinquan T et al
162880142005BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage-inducible gene.Kennedy RD et al
191473912009Psoriasin (S100A7) up-regulation in oral squamous cell carcinoma and its relation to clinicopathologic features.Kesting MR et al
197079012009Psoriasin (S100A7), an antimicrobial peptide, is increased in human middle ear cholesteatoma.Kim KH et al
163571392005A putative role for psoriasin in breast tumor progression.Krop I et al
126641602003Genomic and phylogenetic analysis of the S100A7 (Psoriasin) gene duplications within the region of the S100 gene cluster on human chromosome 1q21.Kulski JK et al
171599092007S100A7 (Psoriasin)--mechanism of antibacterial action in wounds.Lee KC et al
159064702005Assignment of the equine S100A7 gene (psoriasin 1) to chromosome 5p12-->p13 by fluorescence in situ hybridization and radiation hybrid mapping.Leeb T et al
88409711996Differential expression of psoriasin messenger RNA between in situ and invasive human breast carcinoma.Leygue E et al
169828112006Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides.Liang SC et al
187934472008In silico analysis and verification of S100 gene expression in gastric cancer.Liu J et al
19404421991Molecular cloning, occurrence, and expression of a novel partially secreted protein "psoriasin" that is highly up-regulated in psoriatic skin.Madsen P et al
169383602006An update of the S100 nomenclature.Marenholz I et al
75912201995Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22.Moog-Lutz C et al
171363472007Psoriasin (S100A7) is significantly up-regulated in human epithelial skin tumours.Moubayed N et al
93073011997Proteome profiling of bladder squamous cell carcinomas: identification of markers that define their degree of differentiation.Ostergaard M et al
183200592008S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation.Paruchuri V et al
195212632009Expression patterns of S100 proteins in melanocytes and melanocytic lesions.Petersson S et al
201457202009Autoantibodies to tumor-associated antigens in epithelial ovarian carcinoma.Piura B et al
191590132009S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10.Qin W et al
183397952008Discovery and verification of head-and-neck cancer biomarkers by differential protein expression analysis using iTRAQ labeling, multidimensional liquid chromatography, and tandem mass spectrometry.Ralhan R et al
128395732003S100A7 (psoriasin) interacts with epidermal fatty acid binding protein and localizes in focal adhesion-like structures in cultured keratinocytes.Ruse M et al
112589322001S100A7, S100A10, and S100A11 are transglutaminase substrates.Ruse M et al
192491262009Human beta-defensin-2 and psoriasin are overexpressed in lesions of acne inversa.Schlapbach C et al
101903231999Genomic structure, promoter characterisation and mutational analysis of the S100A7 gene: exclusion of a candidate for familial psoriasis susceptibility.Semprini S et al
170091052007Estrogen receptor-beta regulates psoriasin (S100A7) in human breast cancer.Skliris GP et al
195605772009Alterations in epithelial barrier function and host defense responses in chronic rhinosinusitis.Tieu DD et al
166125622006Psoriasin and its allergenic bovine homolog Bos d 3.Virtanen T et al
157179262005Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis.Webb M et al
198449562009Structural and functional characterization of a triple mutant form of S100A7 defective for Jab1 binding.West NR et al
201012262010S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer.West NR et al
186067052008Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.Wolf R et al
129230692003Molecular cloning and characterization of alternatively spliced mRNA isoforms from psoriatic skin encoding a novel member of the S100 family.Wolf R et al
165283632006The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation.Wolf R et al
174184462007Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain.Zhang H et al
182236932008Reciprocal negative regulation between S100A7/psoriasin and beta-catenin signaling plays an important role in tumor progression of squamous cell carcinoma of oral cavity.Zhou G et al

Other Information

Locus ID:

NCBI: 6278
MIM: 600353
HGNC: 10497
Ensembl: ENSG00000143556


dbSNP: 6278
ClinVar: 6278
TCGA: ENSG00000143556


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Antimicrobial peptidesREACTOMER-HSA-6803157
Metal sequestration by antimicrobial proteinsREACTOMER-HSA-6799990
Neutrophil degranulationREACTOMER-HSA-6798695
IL-17 signaling pathwayKEGGko04657
IL-17 signaling pathwayKEGGhsa04657

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
186067052008Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.56
221589452012S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways.51
202263012010Evidence for diminished levels of epithelial psoriasin and calprotectin in chronic rhinosinusitis.46
187540382009The antimicrobial protein psoriasin (S100A7) is upregulated in atopic dermatitis and after experimental skin barrier disruption.39
185887532008Epithelial genes in chronic rhinosinusitis with and without nasal polyps.34
171599092007S100A7 (Psoriasin)--mechanism of antibacterial action in wounds.31
255723312015RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment.31
163571392005A putative role for psoriasin in breast tumor progression.29
201012262010S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer.29
206286242010Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".29


Jill I Murray ; Martin J Boulanger

S100A7 (S100 calcium binding protein A7)

Atlas Genet Cytogenet Oncol Haematol. 2010-04-01

Online version: http://atlasgeneticsoncology.org/gene/42194/s100a7id42194ch1q21