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S100A7 (S100 calcium binding protein A7)

Written2010-04Jill I Murray, Martin J Boulanger
Department of Biochemistry, Microbiology, University of Victoria, Victoria, British Columbia V8W 3P6, Canada

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPSOR1
S100 calcium-binding protein A7 (psoriasin 1)
S100 calcium binding protein A7 (psoriasin 1)
Alias_symbol (synonym)S100A7c
Other alias
HGNC (Hugo) S100A7
LocusID (NCBI) 6278
Atlas_Id 42194
Location 1q21.3  [Link to chromosome band 1q21]
Location_base_pair Starts at 153457744 and ends at 153460661 bp from pter ( according to hg19-Feb_2009)  [Mapping S100A7.png]
Local_order S100A7 is located on chromosome 1cen-q21 between D1Z5 and MUC1 (Borglum et al., 1995).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note S100A7 is also known as psoriasin, psoriasin 1, S100 calcium binding protein A7, S100-A7, S100A7c, and PSOR1.
S100A7, a member of the S100 family, was first identified as a protein upregulated in psoriasis (Madsen et al., 1991).

DNA/RNA

Note S100A7 is located on chromosome 1q21 within the epidermal differentiation complex.
 
  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).
Description 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.
Transcription 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).
Pseudogene 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).

Protein

Note S100A7 is a member of the S100 family of calcium-binding signaling proteins. S100A7 has both intracellular and extracellular functions.
 
  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).
Description 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).
Expression 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).
Localisation 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).
Function 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).
Homology 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).

Mutations

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

Implicated in

Note
  
Entity Psoriasis and other skin diseases
Note 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 Non-melanoma skin cancer
Note 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 Melanoma
Note 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 Ductal carcinoma in situ (DCIS) and breast cancer
Note 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 Epithelial ovarian cancer
Note 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 Lung squamous cell carcinoma
Note 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 Bladder squamous cell carcinoma
Note 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 Oral squamous cell carcinoma
Note 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 Head-and-neck squamous cell carcinoma
Note S100A7 is a highly upregulated biomarker in head-and-neck squamous cell carcinomas (Ralhan et al., 2008).
  
  
Entity Gastric cancer
Note 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 Chronic rhinosinusitis
Note 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 Systemic sclerosis (SSc)
Note 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 Alzheimer's disease
Note A recent study has suggested that S100A7 is a potential biomarker for Alzheimer's disease. Increased levels of S100A7 were detected in the cerebralspinal fluid and brain of patients with Alzheimer's disease (Qin et al., 2009).
  

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S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer.
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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.
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Molecular cloning and characterization of alternatively spliced mRNA isoforms from psoriatic skin encoding a novel member of the S100 family.
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The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation.
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Identification and validation of S100A7 associated with lung squamous cell carcinoma metastasis to brain.
Zhang H, Wang Y, Chen Y, Sun S, Li N, Lv D, Liu C, Huang L, He D, Xiao X.
Lung Cancer. 2007 Jul;57(1):37-45. Epub 2007 Apr 5.
PMID 17418446
 
Reciprocal 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, Xie TX, Zhao M, Jasser SA, Younes MN, Sano D, Lin J, Kupferman ME, Santillan AA, Patel V, Gutkind JS, Ei-Naggar AK, Emberley ED, Watson PH, Matsuzawa SI, Reed JC, Myers JN.
Oncogene. 2008 Jun 5;27(25):3527-38. Epub 2008 Jan 28.
PMID 18223693
 

Citation

This paper should be referenced as such :
Murray, JI ; Boulanger, MJ
S100A7 (S100 calcium binding protein A7)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):59-64.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/S100A7ID42194ch1q21.html


External links

Nomenclature
HGNC (Hugo)S100A7   10497
Cards
AtlasS100A7ID42194ch1q21
Entrez_Gene (NCBI)S100A7  6278  S100 calcium binding protein A7
AliasesPSOR1; S100A7c
GeneCards (Weizmann)S100A7
Ensembl hg19 (Hinxton)ENSG00000143556 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000143556 [Gene_View]  chr1:153457744-153460661 [Contig_View]  S100A7 [Vega]
ICGC DataPortalENSG00000143556
TCGA cBioPortalS100A7
AceView (NCBI)S100A7
Genatlas (Paris)S100A7
WikiGenes6278
SOURCE (Princeton)S100A7
Genetics Home Reference (NIH)S100A7
Genomic and cartography
GoldenPath hg38 (UCSC)S100A7  -     chr1:153457744-153460661 -  1q21.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)S100A7  -     1q21.3   [Description]    (hg19-Feb_2009)
EnsemblS100A7 - 1q21.3 [CytoView hg19]  S100A7 - 1q21.3 [CytoView hg38]
Mapping of homologs : NCBIS100A7 [Mapview hg19]  S100A7 [Mapview hg38]
OMIM600353   
Gene and transcription
Genbank (Entrez)AW238300 BC034687 BF090388 BX476368 CR542164
RefSeq transcript (Entrez)NM_002963
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)S100A7
Cluster EST : UnigeneHs.112408 [ NCBI ]
CGAP (NCI)Hs.112408
Alternative Splicing GalleryENSG00000143556
Gene ExpressionS100A7 [ NCBI-GEO ]   S100A7 [ EBI - ARRAY_EXPRESS ]   S100A7 [ SEEK ]   S100A7 [ MEM ]
Gene Expression Viewer (FireBrowse)S100A7 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6278
GTEX Portal (Tissue expression)S100A7
Human Protein AtlasENSG00000143556-S100A7 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP31151   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP31151  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP31151
Splice isoforms : SwissVarP31151
PhosPhoSitePlusP31151
Domaine pattern : Prosite (Expaxy)EF_HAND_1 (PS00018)    EF_HAND_2 (PS50222)    S100_CABP (PS00303)   
Domains : Interpro (EBI)EF-hand-dom_pair    EF_Hand_1_Ca_BS    EF_hand_dom    S-100_dom    S100/CaBP-9k_CS    S100_Ca-bd_sub    S100A7   
Domain families : Pfam (Sanger)S_100 (PF01023)   
Domain families : Pfam (NCBI)pfam01023   
Domain families : Smart (EMBL)S_100 (SM01394)  
Conserved Domain (NCBI)S100A7
DMDM Disease mutations6278
Blocks (Seattle)S100A7
PDB (SRS)1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
PDB (PDBSum)1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
PDB (IMB)1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
PDB (RSDB)1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
Structural Biology KnowledgeBase1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
SCOP (Structural Classification of Proteins)1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
CATH (Classification of proteins structures)1PSR    2PSR    2WND    2WOR    2WOS    3PSR    4AQJ   
SuperfamilyP31151
Human Protein Atlas [tissue]ENSG00000143556-S100A7 [tissue]
Peptide AtlasP31151
HPRD02645
IPIIPI00219806   
Protein Interaction databases
DIP (DOE-UCLA)P31151
IntAct (EBI)P31151
FunCoupENSG00000143556
BioGRIDS100A7
STRING (EMBL)S100A7
ZODIACS100A7
Ontologies - Pathways
QuickGOP31151
Ontology : AmiGOresponse to reactive oxygen species  angiogenesis  calcium ion binding  protein binding  extracellular region  extracellular region  nucleus  cytoplasm  cytoplasm  endoplasmic reticulum  cytosol  focal adhesion  zinc ion binding  zinc ion binding  epidermis development  positive regulation of T cell chemotaxis  antimicrobial humoral response  keratinocyte differentiation  response to lipopolysaccharide  azurophil granule lumen  neutrophil degranulation  innate immune response  RAGE receptor binding  defense response to Gram-negative bacterium  sequestering of metal ion  antimicrobial humoral immune response mediated by antimicrobial peptide  extracellular exosome  positive regulation of ERK1 and ERK2 cascade  positive regulation of granulocyte chemotaxis  positive regulation of monocyte chemotaxis  
Ontology : EGO-EBIresponse to reactive oxygen species  angiogenesis  calcium ion binding  protein binding  extracellular region  extracellular region  nucleus  cytoplasm  cytoplasm  endoplasmic reticulum  cytosol  focal adhesion  zinc ion binding  zinc ion binding  epidermis development  positive regulation of T cell chemotaxis  antimicrobial humoral response  keratinocyte differentiation  response to lipopolysaccharide  azurophil granule lumen  neutrophil degranulation  innate immune response  RAGE receptor binding  defense response to Gram-negative bacterium  sequestering of metal ion  antimicrobial humoral immune response mediated by antimicrobial peptide  extracellular exosome  positive regulation of ERK1 and ERK2 cascade  positive regulation of granulocyte chemotaxis  positive regulation of monocyte chemotaxis  
REACTOMEP31151 [protein]
REACTOME PathwaysR-HSA-6799990 [pathway]   
NDEx NetworkS100A7
Atlas of Cancer Signalling NetworkS100A7
Wikipedia pathwaysS100A7
Orthology - Evolution
OrthoDB6278
GeneTree (enSembl)ENSG00000143556
Phylogenetic Trees/Animal Genes : TreeFamS100A7
HOVERGENP31151
HOGENOMP31151
Homologs : HomoloGeneS100A7
Homology/Alignments : Family Browser (UCSC)S100A7
Gene fusions - Rearrangements
Tumor Fusion PortalS100A7
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerS100A7 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)S100A7
dbVarS100A7
ClinVarS100A7
1000_GenomesS100A7 
Exome Variant ServerS100A7
ExAC (Exome Aggregation Consortium)ENSG00000143556
GNOMAD BrowserENSG00000143556
Genetic variants : HAPMAP6278
Genomic Variants (DGV)S100A7 [DGVbeta]
DECIPHERS100A7 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisS100A7 
Mutations
ICGC Data PortalS100A7 
TCGA Data PortalS100A7 
Broad Tumor PortalS100A7
OASIS PortalS100A7 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICS100A7  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDS100A7
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch S100A7
DgiDB (Drug Gene Interaction Database)S100A7
DoCM (Curated mutations)S100A7 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)S100A7 (select a term)
intoGenS100A7
NCG5 (London)S100A7
Cancer3DS100A7(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600353   
Orphanet
DisGeNETS100A7
MedgenS100A7
Genetic Testing Registry S100A7
NextProtP31151 [Medical]
TSGene6278
GENETestsS100A7
Target ValidationS100A7
Huge Navigator S100A7 [HugePedia]
snp3D : Map Gene to Disease6278
BioCentury BCIQS100A7
ClinGenS100A7
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6278
Chemical/Pharm GKB GenePA34909
Clinical trialS100A7
Miscellaneous
canSAR (ICR)S100A7 (select the gene name)
Probes
Litterature
PubMed127 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineS100A7
EVEXS100A7
GoPubMedS100A7
iHOPS100A7
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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