S100A7 is located on chromosome 1q21 within the epidermal differentiation complex.

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.

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).