Identity

HGNC
LOCATION
12q13.2
LOCUSID
ALIAS
AIDD,DCD-1,DSEP,HCAP,PIF

Abstract

Dermcidin (DCD) is a 110-amino acid protein, which is cleaved in several other peptides with different functions. The best-known function of this protein is as antimicrobial host defense, acting majorly in the skin, where many DCD derivatives were identified to be constitutively secreted, mainly by sweat glands. Additionally, Y-P30, one of such derivatives, has been described as a survival factor predominantly in stressed neural cells. This function has also been investigated in cancer cells, portraying DCD as an oncogene, as well a novel biomarker for this disease. Furthermore, PIF, another DCD derivative, may be an important inducer of non-fat weight loss, which has been related with cachexia. The present review assesses data on DCD and derivatives observing DNA, RNA, encoded proteins and their various functions, highlighting their relevance in cancer and other clinical conditions.

DNA/RNA

Description

The entire DCD gene is approximately 3.9 Kb; starts at 54644589 and ends at 54648493 bp; orientation: reverse strand.

Transcription

The DCD gene encodes 3 transcript variants (splice variants). There are two transcript variants deposited in the NCBI database (https://www.ncbi.nlm.nih.gov/gene) and one additional transcript variant reported in Ensembl (http://www.ensembl.org/). The transcript variant 1 is formed by 5 exons and 5 coding exons, resulting in a transcript length of 519 bps and a translation length of 110 amino acids (aa). The transcript variant 2 is the longest variant, with 6 exons and 6 coding exons (transcript length of 670 bps) and a translation length of 121 aa. The transcript variant 3 is formed by 6 exons and 3 coding exons (transcript length of 773 bps), which results in the shorter translation variant, with 77 aa.

Proteins

Description

The full-length dermcidin protein has 110 amino acids (aa) that consists of a 19-amino-acid signal peptide, a 43-amino-acid prodomain and a 48-amino-acid antimicrobial peptide domain (Schittek, 2012). This precursor is proteolytically processed into several derivatives. DCD-1 (47 aa), DCD-1L (48 aa), SSL-25 (25 aa) and SSL-23 (23 aa), the derivatives with the best described function, are secreted by eccrine sweat glands as antimicrobial peptides (Schittek et al., 2001; Steffen et al., 2006). The Y-P30 (30 aa) derivative has been described as a neuron survival-promoting peptide (Cunningham et al., 2000), while the PIF (20 aa) - Proteolysis-Inducing Factor, a proteolytic glycoprotein, is associated to a severe loss of skeletal muscles in cachectic cancer patients (Todorov et al., 1996; Lorite et al., 1997). The full primary structure of DCD is illustrated in Figure 1.
Atlas Image
Figure 1. Gene and protein structure of full-length dermcidin (variant 1) and derived peptides. (A) Dermcidin gene (DCD) is formed by 5 exons and 4 introns, which codifies a protein of 110 amino acids (aa). (B) Dermcidin protein comprises a signal peptide (19 aa), followed by a prodomain (43 aa) and an antimicrobial peptide domain (48 aa). (C) The full protein can be processed into another 17 peptides, among which 3 peptides derive from the prodomain (represented in orange) and 14 peptides result from the antimicrobial peptide domain (represented in green). Each peptide is listed by name, known function and aa length and sequence.

Expression

Dermcidin is constitutively expressed by the dark mucous cells of the secretory coil of eccrine sweat glands, unlike the other antimicrobial peptides that are induced by injury and inflammation (Schittek et al., 2001; Rieg et al., 2004; Rieg et al., 2006). In these glands, the DCD mRNA is translated into a 110-amino acid peptide that can be processed and secreted into sweat or cleaved by several proteases in this fluid (Schittek et al., 2001; Schittek, 2012; Rieg et al., 2004; Flad et al., 2002). There are 14 DCD-derived peptides that occur in sweat. The C-terminal region of the protein contains the majority of the peptides with antimicrobial activity: DCD-1, DCD-1L, SSL-23, SSL-25, SSL-45 and SSL-46 (Schittek et al., 2001; Steffen et al., 2006; Mühlhäuser et al., 2017). Furthermore, there is one peptide derived from the prodomain YDP-42 (Schittek, 2012). Even DCD-1 or DCD-1L can be processed in sweat into smaller peptides like LEK-24 and SSL-25 by enzymes such as cathepsin D, 1,10-phenanthroline-sensitive carboxypeptidase and endoproteases (Baechle et al., 2006).
Dermcidin is also expressed by sebaceous glands and neutrophils in immunity-related circumstances (Dahlhoff et al., 2016; Lominadze et al., 2005) and, moreover, has been shown to be overexpressed in the context of HIV infection of monocytoid cells (Pathak et al., 2009). Additionally, oxidatively stressed neural cell lines express dermcidin in the form of the signal peptide Y-P30, described firstly as DSEP, the diffusible survival/evasion peptide, which can, indeed, be detected in culture media (Cunningham et al., 2002).
The human term placental tissue may express DCD as two splice variants under a restricted spatiotemporal pattern, which may be related to the involvement of dermcidin in the molecular mechanisms of pregnancy. Placental dermcidin can be processed into DCD-1 and defend the fetus against invading microorganisms (Motoyama et al., 2007), or into Y-P30 to exert neuritogenic activity during fetus brain development (Mikhaylova et al., 2014).
In plasma, dermcidin may be found in different conditions: 1) in hepatocellular carcinoma patients (Qiu et al., 2018); 2) overexpressed in patients with arterial hypertension, as a player in modulation of NO levels and induction of platelet aggregation (Ghosh et al., 2011; Ghosh et al., 2012a); 3) in type I diabetes mellitus, inhibiting the synthesis of insulin in hepatocytes and pancreatic cells (Ghosh et al., 2011; Ghosh et al., 2012b). Dermcidin is also secreted by ischemic skeletal muscles, enhancing cardiomyocytes apoptosis under hypoxic conditions and infarct size after permanent coronary artery ligation (Esposito et al., 2015). Moreover, dermcidin is abundantly present in exhaled breath condensate of asthmatic and lung cancer patients, and it can be regarded as a biomarker in these diseases (Bloemen et al., 2001; Chang et al., 2010).
Also, dermcidin has revealed a relevant role in cancer; it offers a survival advantage in some tumors, as reported for breast cancers (Porter et al., 2003; Brauer et al., 2014); prostate cancer (Wang et al., 2003; Stewart et al., 2007); lung cancer, as a biomarker in exhaled breath condensate (Chang et al., 2010); hepatic cancer cells (Lowrie et al., 2006; Shen et al., 2011; Qiu et al., 2018; Lowrie et al., 2011); gastro-oesophageal cancer (Deans et al., 2006); pancreatic cancer cells (Stewart et al., 2008a); a myelogenous leukemia cell line (Stocki et al., 2011); and melanoma (Smith et al., 2005; Rieg et al., 2004; Trzoss et al., 2014). Additionally, tumor cells express PIF, which is resistant to proteolytic digestion by trypsin and the human cancer expression has been related to inhibition of muscle cell differentiation and a high weight loss (Majczak et al., 2007; Todorov et al., 1997; Wigmore et al., 2000; Jiang and Clemens, 2006; Wieland et al., 2007). In fact, PIF was discovered in 1996 in mice and later described as a potent catabolic factor that acts as a cachectic cancer factor (Tisdale et al., 2004; Schittek et al., 2012; Todorov et al., 1996). Although the role of murine PIF is well established, its biology remains speculative in humans (Stewart et al., 2008b).

Localisation

Dermcidin is mainly found in the cytoplasm or extracellularly.
In the dark mucous cells of the secretory coil of eccrine sweat glands, dermcidin is detected in the Golgi complex and in the secretory granules, released in the cell surface and transported to epidermal surface by the sweat duct (Schittek et al., 2001; Rieg et al., 2006, Sakurada et al., 2010). There are differences in the levels of DCD-derived peptides in eccrine sweat of distinct anatomic sites; highest concentrations are found in palms, arms and forehead, where the density of eccrine sweat glands is higher and the body is more exposed to pathogens and minor trauma (Rieg et al., 2004).
Although less profusely, dermcidin is also found in basal tears, in cervicovaginal fluid and in breast milk, in which it also assumes a function associated to innate immunity (You et al., 2010; Shaw et al., 2007; Azkargorta et al., 2015; Chow et al., 2016). Furthermore, dermcidin-derived peptides can be found in lipid droplets secreted by the holocrine sebaceous glands and in the granules of neutrophils, suggesting that this protein has, likewise, an immunity related purpose in these cells (Dahlhoff et al., 2016; Lominadze et al., 2005).

Function

DCD-1, DCD-1L, SSL-25, SSL-23, SSL-45 and SSL-46 peptides have a broad and overlapping spectrum regarding antimicrobial activity against, for example, Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans (Schittek et al., 2001; Steffen et al., 2006; Mühlhäuser et al., 2017). Anionic DCD-1L monomers can bind bacterial membrane and fold into an amphiphilic alpha-helix, interacting parallelly to the surface. Further studies indicate the proteins can self-assemble into high-order oligomers and form ion channels, which can lead to bacterial cell death by abrogation of the transmembrane potential (Paulmann et al., 2012; Song et al., 2013). Such conformation is indeed favored by transmembrane potential as well as by the presence of Zn2+ due to neutralization of protein charge. On the other hand, SSL-29, LEK-44, LEK-45 and YDP-42 peptides showed no antimicrobial activity against the same bacterial species: S. aureus, E. faecalis, S. epidermidis, E. coli and P. aeruginosa (Rieg et al., 2005; Steffen et al., 2006).
DCD-1L has been studied as a stimulant for production of pro-inflammatory cytokines and chemokines by human keratinocytes cells controlled by G-protein and mitogen-activated protein kinase (MAPK) signaling pathways, thus contributing to the cutaneous immunity (Niyonsaba et al., 2009).
High blood levels of dermcidin variant 2 was found in patients following acute ischemic heart disease. There have been further investigations on rather such variant may inhibit synthesis and release of insulin by the pancreas, an effect that was then shown to be reversed by aspirin or insulin administration (Bank et al., 2014; Ghosh et al., 2014). As a consequence of insulin resistance, there may be increase in blood pressure and atherosclerosis through inhibition of NO production and promotion of prothrombotic effects (Ghosh et al., 2011). The same role for dermcidin was observed in ischemic and hemorrhagic stroke patients (Bank et al., 2015).
Dermcidin has been shown to interact with few proteins within the cell. In this context, phosphorylation at Tyr20 enabled dermcidin to interact with the SH2 domain of NCK1, which, through effector proteins like the PAK1 /ARHGEF6 (also called PIX) complex, stimulates Rho GTPases RAC1 and CDC42 and reorganizes actin cytoskeleton, ultimately promoting cell migration in a hepatocellular carcinoma cell line (SK-HEP1) (Shen et al., 2011). Furthermore, in a gastric cancer cell line (BGC-823), dermcidin protein was one of the proteins bound to a long non-coding RNA (STCAT3), while overexpression of both dermcidin and STCAT3 were related to poor prognosis for patients (Zhang et al., 2018). Considering small molecules - natural products, in this case - dermcidin has been shown to bind paclitaxel and seriniquinone, a marine bacterium derived compound. In the first setting, dermcidin precursor was recovered, along with HSP90AA1 and actinin, from a paclitaxel-biotin probe fed to drug-sensitive breast cancer cell line (MCF7), but not from their paclitaxel-resistant analogue, suggesting a role of dermcidin in the cell resistance profile to this compound and cross-resistance to other anticancer drugs (Zuo et al., 2010). Regarding the later natural product , dermcidin protein was revealed to be a direct target of a seriniquinone probe, which was found to be further bound to other proteins, such as GAPDH and Hsp70, in a colorectal carcinoma cell line (HCT 116) model (Trzoss et al., 2014).
Y-P30 was first seen overexpressed as a neuron survival-promoting peptide in response to oxidative stress (Cunningham et al., 1998), promoting survival of cortical neurons after cerebral lesions by retaining calreticulin in the cytosol and reducing calcium signaling to a degree in which it is protective, regardless of any immune cell inhibition (Cunningham et al., 2000). During hypoxia and hypoglycemia, Y-P30 expression is associated with reduced neural cell death in vitro (Schneeberg et al., 2009). This protein is also related to induction of neurite outgrowth in cortical neurons during early brain development, a role that is suggested by the effect of binding of Y-P30 to PTN (pleiotrophin) in the extracellular axonal membrane, thus increasing syndecan local concentrations and promoting neurite growth (Landgraf et al., 2008). Furthermore, this mechanism can be related to calcium/calmodulin-dependent serine kinase ( CASK) migration to the nucleus, where Y-P30 interacts differently with syndecan-2 ( SDC2) or -3 ( SDC3) in immature or mature neurons, contributing with migration and axonal outgrowth (Landgraf et al., 2014; Neumann et al., 2019).
PIF has been investigated as a catalytic protein, which can induce proteasome expression through NF-kB activation (Wyke and Tisdale, 2005). Consequently, this process results in decreased protein synthesis and severe degradation of skeletal muscle, thus correlating with the weight loss in cachectic cancer patients, an effect typically attributed to PIF (Todorov et al., 1996; Lorite et al., 1997; Todorov et al., 2007). PIF was also associated with the release of Ca2+ from intracellular stocks, suggesting PIF receptor (a zinc-sensing receptor) is coupled to a G-protein to cause calcium release from endoplasmic reticulum (Mirza and Tisdale, 2012). Reinforcing these data, direct and indirect inhibitors of NF-kB were able to attenuate the development of muscle loss (Wyke et al., 2004; Russell et al., 2007).

Homology

The DCD gene is highly homologous among different non-human primate species, as shown in Table 1, which compares DCD isoform 1 among species.
Table 1. Comparative identity of human DCD with other species.
% Identity for: Homo sapiens CDCSymbolProteinDNA
vs. P. paniscus DCD 100 100
vs. P. abelii DCD 96.9 98.2
vs. N. leucogenys DCD 93.8 98.4
vs. H. moloch DCD 92.8 91.7
vs. T. francoisi DCD 91.7 95.3
vs. R. roxellana DCD 91.7 94.2
vs. C. angolensis palliatus DCD 91.7 94
vs. C. jacchus DCD 91 96
vs. P. tephrosceles DCD 90.7 92.7
vs. M. mulatta DCD 89.7 95.2
vs. T. gelada DCD 89.7 91.1
vs. M. leucophaeus DCD 89.7 95.9
vs. M. nemestrina DCD 89.7 89.9
vs. C. sabaeus DCD 84.8 93.7
vs. A. nancymaae DCD 82.3 96.8
vs. S. boliviensis boliviensis DCD 80.4 95.0
vs. S. apella DCD 77.3 94.3
vs. C. capucinus imitator DCD 76.5 95.2

(Source: http://www.ncbi.nlm.nih.gov/homologene)

Mutations

Somatic

From 37420 unique samples reported in COSMIC (Catalogue of Somatic Mutations in Cancer; http://cancer.sanger.ac.uk/cancergenome/projects/cosmic), a total of 145 unique samples presented DCD mutations, of which 67 different mutations are distributed among 47 missense substitutions, 16 synonymous substitutions, 2 frameshift insertion and 2 frameshift deletions. Somatic mutation frequency of 0.3% is similar to that reported in cBioPortal (http://www.cbioportal.org). From 10967 samples, 31 mutations are classified as 25 missense substitutions and 6 truncated mutations.

Implicated in

Entity name
Breast cancer
Note
DCD is overexpressed in approximately 10% of breast carcinomas; in some cases, it is associated with a focal copy number gain of its locus at 12q13.2, or with advanced clinical staging and poor prognosis. In animal models, dermcidin was found in high concentrations in serum of early breast cancer rats, whereas women displayed increased levels of dermcidin just prior to diagnosis. Moreover, such high dermcidin levels were related to disease progression and more aggressive types of this neoplasm (Brauer et al., 2014). Besides its function in cell growth and survival, overexpression of dermcidin results in a reduction of serum dependency by the tumor (Porter et al., 2003). Furthermore, cell survival and growth-promoting functions of dermcidin were described as a consequence of modulation of ERBB receptor by dermcidin (Bancovik et al., 2015). Dermcidin also coordinates the expression of genes involved in oxidative stress as well as amino acid and glucose metabolism, while it may be likewise associated to drug resistance in breast cancer cells (Moreira et al., 2008).
Dermcidin was found among intracellular proteins bound to paclitaxel in a naïve breast cancer cell line (MCF7), however it was not analogously recovered in the paclitaxel resistant counterpart, suggesting involvement of dermcidin in the drug-resistance phenotype (Zuo et al., 2010).
Entity name
Cervical cancer
Note
Studies with human uterine cervical cancer (Yumoto) transplanted mice revealed the expression of PIF in tumor, serum and urine of cachexia-induced murine models. Furthermore, PIF expression and cachexia development were reversed by administration of a fluorinated pyrimidine (5-deoxy-5-fluorouridine) (Hussey et al., 2000).
Entity name
Colon cancer
Note
Studies with murine colon adenocarcinoma cell line (MAC 16) transplanted mice demonstrated expression of PIF in tumor, serum and urine in cachexia-induced animals, while this peptide was absent in non-cachexic models. PIF expression and cachexia development were also completely reversed by administration of a fluorinated pyrimidine (5-deoxy-5-fluorouridine) (Hussey et al., 2000).
Entity name
Gastro-oesophageal cancer
Note
DCD mRNA expression was analyzed in primary tissues of gastric cancers (n=20) and 25% of the samples had detectable levels of mRNA; in turn, 14% of oesophageal cancers samples (n=28) displayed detectable DCD mRNA expression (Stewart et al., 2008).
Patients with PIF expression from gastric cancer tissues also presented detectable PIF in urine samples and higher percentages of weight loss (Cabal-Manzano et al., 2001). PIF expression in gastro-oesophageal tumors were found to be elevated in 59% of the cancer samples analyzed and in 67% of adjacent benign tissues. Although this study revealed a high correlation between PIF expression and cancer, upregulation of PIF did not show correlation with cachexia or prognosis (Deans et al., 2006).
Prognosis
STCAT3, a long non-coding RNA (lncRNA), is highly expressed in gastric cancer tissues and is has been associated with specific cancer features, such as proliferation, migration and invasion. Furthermore, upregulation of this lncRNA is related to poor prognosis. Dermcidin protein was shown to bind STCAT3 in a gastric cancer cell line (BGC-823); as expression of both markers are positively correlated, dermcidin overexpression was also identified in cancer tissues and associated to poor prognosis in patients (Zhang et al., 2018).
Entity name
Liver cancer
Note
Dermcidin, when compared with non-tumoral hepatic tissues, is overexpressed in hepatocellular carcinoma, mainly in SK-HEP1 cell line, a high invasive endothelial cell line. The role of dermcidin in metastasis was described using such cell line: this protein is phosphorylated at Tyr20 allowing its interaction with the SH2 domain of Nck1, which, in turn, binds to proline-rich sequences of several effector proteins. One example of these proteins is the PAK1/ARHGEF6 complex that stimulates Rho GTPases RAC1 and CDC42 and regulates cell adhesion, migration and gene transcription, mainly by reorganizing actin cytoskeleton (Shen et al., 2011).
Additionally, dermcidin has, likewise, been associated to cell survival in this cancer type (Lowrie et al., 2006), while Y-P30/PIF-core was accounted for cell proliferation in HuH7 hepatic cancer cell lines through different pathways (Lowrie et al., 2011). Dermcidin has been studied as a hepatocellular cancer biomarker, as it is significantly increased in patients enduring this disease (Qiu et al., 2018).
Entity name
Lung cancer
Note
Dermcidin was identified in the peptidome of exhaled breath condensate (EBC) from lung cancer patients. In this context, dermcidin expression was confirmed in two out of six squamous cell carcinoma and in three out of six adenocarcinoma tissues assessed (Chang et al., 2010). The expression was also present in lung cancer cell lines (H520, squamous cell carcinoma; and PC13, adenocarcinoma), which underwent growth reduction upon DCD knockdown (Chang et al., 2010). Similarly, another study found higher levels of dermcidin in EBCs of lung cancer patients and have suggested this protein as a novel biomarker for diagnosis (López-Sánchez et al., 2017; Núñez-Naveira et al., 2019).
Analogously, PIF displayed elevated expression levels in non-small-cell lung cancer (NSCLC) tissues, which was higher in patients supporting greater weight losses. Although there was no correlation between PIF and tumor clinical staging, a significant correlation between weight loss and survival in the PIF-positive patients was identified (Wang et al., 2010).
Entity name
Melanoma
Note
DCD mRNA expression was detected following pro-inflammatory stimuli (exposure to 12-O-tetradeca-noyl-phorbol-13-acetate, TNF (tumor necrosis factor-alpha), lipopolysaccharide or H2O2) in SK-MEL-28 and MeWo melanoma cell lines (Rieg et al., 2004).
Production of PIF was also identified in human melanoma cell line G361. Within this study, the protein was further purified and administered to mice, and those who received treatment experienced weight loss specifically by non-fat mass (Todorov et al., 1999). Moreover, expression of PIF by the melanoma cell line Mel impaired muscle cell differentiation; a feature that could be then counteracted by treatment with a caspase-8-like inhibitory protein (Jiang and Clemens, 2006).
Prognosis
Serum levels of dermcidin have displayed prognostic potential in melanoma patients, once early staged patients (stages I and II) who developed metastasis showed lower concentration of the protein, thus presenting this as an important biomarker to predict such event. In turn, dermcidin was elevated in III-IV staged patients, which displayed poor survival rates (Ortega-Martínez et al., 2016). A new cohort of patients then confirmed this observation, further enabling the establishment of an algorithm to predict the risk of tumor metastasis where dermcidin levels is actually one of the variables (Mancuso et al., 2020).
Entity name
Pancreatic cancer
Note
Tissue samples of pancreatic cancer demonstrated that 3 of the 5 tumors subjected to analysis displayed moderate to high DCD mRNA expression. The pancreatic cell line MIA-Pa-Ca-2 also revealed increased levels of DCD mRNA (Stewart et al., 2008).
First evidences of the part taken by PIF in pancreatic cancer revealed the protein was only present in urine samples of cancer patients with high proportions of weight loss per month, while it was absent in patients with low to normal weight loss rates (Todorov et al., 1996). Furthermore, PIF was detected in 80% of urine samples from patients with pancreatic cancer (n=55), which also revealed to be the same group that supported a high rate of weight loss (Wigmore et al., 2000). Nevertheless, the occurrence of PIF in urine does not appear to correlate with malignancy of the pancreatic tumor (Teich et al., 2005). Interestingly, cachectic pancreatic cancer patients consuming a nutritional fish oil-enriched supplement decreased their urinary excretion of PIF and actually presented weight gain, suggesting important metabolic modulations between cancer and cachexia (Barber et al., 2001).
Entity name
Prostate cancer
Note
Insulin resistance has been described as a risk factor for cardiovascular diseases in patients with prostate cancer, where high expression levels of dermcidin isoform-2 were related with a low production or function impairment of insulin through NO inhibition, further contributing to cardiovascular disease in these patients (Ray et al., 2019).
DCD demonstrated to be proliferative and survival factors for DCD-transfected PC-3M prostate cell line under oxidative stress or hypoxia conditions, besides PIF portion was attributed to these effects (Stewart et al., 2007). Same authors did not detect DCD mRNA expression in primary prostate cancer tissues (Stewart et al., 2008).
Human cachexia-associated protein (HCAP), a homolog to the PIF protein, is expressed in prostate cancer: cell lines, primary tumors, metastases and present in the urine of cachectic patients, but not in healthy prostate (Wang et al., 2003). Additionally, PIF expression was detected in a prostate cancer cell line (PC-3) causing inhibition of muscle cell differentiation, what could be reversed by cellular caspase-8-like inhibitory protein treatment in vitro (Jiang and Clemens, 2006).
Entity name
Retinoblastoma
Note
Y-P30 is expressed after the induction of oxidative stress with H2O2 in human retinoblastoma Y79 cell line, acting as a survival-promoting peptide (Cunningham et al., 1998).

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184039142008The dermcidin gene in cancer: role in cachexia, carcinogenesis and tumour cell survival.Stewart GD et al
159697572005The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour.Teich N et al
86022221996Characterization of a cancer cachectic factor.Todorov P et al
180564702007Identification and characterization of a membrane receptor for proteolysis-inducing factor on skeletal muscle.Todorov PT et al
252713222014Seriniquinone, a selective anticancer agent, induces cell death by autophagocytosis, targeting the cancer-protective protein dermcidin.Trzoss L et al
208374612010Expression and clinicopathologic significance of proteolysis-inducing factor in non-small-cell lung cancer: an immunohistochemical analysis.Wang Q et al
126720422003Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia.Wang Z et al
177855482007Is there a human homologue to the murine proteolysis-inducing factor?Wieland BM et al
106069112000Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor.Wigmore SJ et al
154778672004Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-kappaB activation.Wyke SM et al
157142072005NF-kappaB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle.Wyke SM et al
205064192010Post-translation modification of proteins in tears.You J et al
118075452002Antimicrobial peptides of multicellular organisms.Zasloff M et al
238416262013Dermcidin: what is its antibiotic potential?Zeth K et al
291641032017The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions.Zeth K et al
302265442018Dermcidin as a novel binding protein of lncRNA STCAT3 and its effect on prognosis in gastric cancer.Zhang J et al
274661232016Human commensals producing a novel antibiotic impair pathogen colonization.Zipperer A et al
209260152010Establishment of a paclitaxel resistant human breast cancer cell strain (MCF-7/Taxol) and intracellular paclitaxel binding protein analysis.Zuo KQ et al

Other Information

Locus ID:

NCBI: 117159
MIM: 606634
HGNC: 14669
Ensembl: ENSG00000161634

Variants:

dbSNP: 117159
ClinVar: 117159
TCGA: ENSG00000161634
COSMIC: DCD

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000161634ENST00000293371P81605
ENSG00000161634ENST00000456047P81605
ENSG00000161634ENST00000546807P81605

Expression (GTEx)

0
500
1000
1500
2000

Pathways

PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Antimicrobial peptidesREACTOMER-HSA-6803157

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
190203232008Genotype score in addition to common risk factors for prediction of type 2 diabetes.304
116948822001Dermcidin: a novel human antibiotic peptide secreted by sweat glands.126
208898532011Genetic risk reclassification for type 2 diabetes by age below or above 50 years using 40 type 2 diabetes risk single nucleotide polymorphisms.65
198338882010Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function.54
197208442009Use of multiple metabolic and genetic markers to improve the prediction of type 2 diabetes: the EPIC-Potsdam Study.41
159443072005Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo.40
234266252013Crystal structure and functional mechanism of a human antimicrobial membrane channel.31
163546542006Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L.27
205717542010Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population.26
222628612012Structure-activity analysis of the dermcidin-derived peptide DCD-1L, an anionic antimicrobial peptide present in human sweat.25

Citation

Amanda Soares Hirata ; Rodrigo dos Anjos Miguel ; Paula Christine Jimenez ; Letícia Veras Costa-Lotufo

DCD (dermcidin)

Atlas Genet Cytogenet Oncol Haematol. 2020-07-01

Online version: http://atlasgeneticsoncology.org/gene/46314/dcd-(dermcidin)