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SELENOF (15 kDa selenoprotein)

Written2010-10Ewa Jablonska, Jolanta Gromadzinska, Edyta Reszka, Wojciech Wasowicz
Nofer Institute of Occupational Medicine, St Teresy 8, 91-348 Lodz, Poland

(Note : for Links provided by Atlas : click)


HGNC Alias symb16-Sep
HGNC Alias nameselenoprotein F (15kDa)
LocusID (NCBI) 9403
Atlas_Id 42260
Location 1p22.3  [Link to chromosome band 1p22]
Location_base_pair Starts at 86862445 and ends at 86914365 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping SELENOF.png]
Local_order According to NCBI Map Viewer, SEP15 gene is located between: SH3GLB1 (SH3-domain GRB2-like endophilin B1), RPL17P5 (ribosomal protein L17 pseudogene 5) (in telomeric position), HS2ST1 (heparan sulfate 2-O-sulfotransferase 1) and potential gene LOC339524 (in centromeric position).
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 SEP15 is one of the 25 genes encoding human selenoproteins. The product of this gene, 15 kDa selenoprotein contains selenocysteine (Sec), which is encoded (like in the case of all selenoproteins) by the UGA codon, normally serving as stop/termination codon. Due to specific mechanism involving selenocysteine insertion sequence (SECIS), a secondary DNA structure common for all selenoproteins, UGA codon is being recognized as Sec codon.


Note Genetic locus of SEP15, 1p31 is commonly mutated or deleted in human cancer.
  Figure 1. Structural organization of the human SEP15 cDNA sequence with the relative positions of ATG initiation and the TGA Sec codons, the TAA termination signal, the detected polymorphisms (C811T in the SECIS-like structure and G1125A in the SECIS element), alternative 3'-end sequences (position 1244 or 1519 within the cDNA) of exon 5. Short vertical lines correspond to exon-exon junctions and number under junction sites correspond to the last nucleotides in the preceding exons (adapted with minimal modification from Kumaraswamy et al., 2000).
Description The genomic DNA of SEP15 spans about 52 kb. The gene consists of 5 exons, with the Sec codon being placed in exon 3 (codon 93). Specific stem loop structure called SECIS element is present within 3'-untranslated region of mRNA. Second stem loop structure close to SECIS element was identified, but it is not active (does not take part in the translation process). Structure of 15-kDa selenoprotein cDNA sequence is presented in figure 1.
Single nucleotide polymorphism (SNP) within SEP15 SECIS element was identified, which is associated with G/A transition at position 1125 (rs5859). SEP15 1125G/A polymorphism was shown in in vitro studies to influence the efficiency of Sec codon (UGA) readthrough during translation process.
Other investigated SNPs within SEP15 gene: rs5845, rs479341, rs56104, rs527281, rs1407131.
Transcription Two alternative transcripts of SEP15 exist. Transcript variant 1 is longer and consists of 5 exons. Transcript variant 2 lacks an exon in the 3' coding region. Compared to isoform 1, the isoform 2 has a shorter and distinct C-terminus.
Pseudogene According to Entrez Gene, no SEP15 pseudogene was identified.


Note 15 kDa selenoprotein was described for the first time in 1995 by Kacklosch et al., who found the protein in rat prostate. In 1998 the protein was identified in humans, by Gladyshev et al..
SEP15 possesses enzymatic activity of oxidoreductase and catalyzes disulfide bonds formation. The protein contains one atom of selenium which is present in the form of selenocysteine. Selenium is involved in human cancer development, playing dual role in this process - from protection to promotion. It is supposed that role of selenium in cancer may be partially associated with selenoproteins, including SEP15.
Description 162 amino acids, with size of 17790 Da. Possesses redox activity due to Cys-X-Sec motif (similar to Cys-X-X-Cys motif present in thioredoxin).
Expression Highly expressed in prostate, liver, brain, kidneys and testis. The protein expression was shown to be increased in colon cancer and decreased in liver cancer and prostate cancer.
Localisation Endoplasmic reticulum lumen.
Function Studies in vitro suggest that SEP15 is involved in the process of posttranslational protein folding. It forms a 1:1 complex with the UDP-glucose: glycoprotein glucosyltransferase (UGGT), an enzyme that is responsible for quality control in the endoplasmic reticulum by oxidative folding and structural maturation of N-glycosylated proteins. It is supposed that SEP15 serves as a disulfide isomerase of glycoproteins targeted by UGGT. Due to redox activity it may also function as an antioxidant.
Homology SEP15 is a distant sequence homolog of other human selenoprotein, SelM. Intraspecies homologs of SEP15 are highly conserved and were identified in dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C. elegans, A. thaliana and rice.


Note No mutations in SEP15 gene have been identified yet.

Implicated in

Entity Breast cancer
Disease Hu et al. (2001) found statistically significant difference in SEP15 allelic distribution for rs5859 between breast cancer individuals (DNA obtained from tumours, n=60) and cancer-free individuals (DNA obtained from lymphocytes, n=490) among African Americans.
Studies conducted by Nasr et al. (2003) also suggest possible role of SEP15 in breast cancer development among African American women. The authors used four highly polymorphic microsatellite markers on the chromosome 1 region that includes SEP15 gene, to assess the difference in heterozygosity index at studied loci between DNA obtained from breast cancer tumours (n=61) and DNA obtained from lymphocytes of cancer-free individuals (n=50). Significant reduction of heterozygosity was found for locus that was most tightly linked to SEP15 gene.
Entity Head and neck cancer
Disease Hu et al. (2001) found statistically significant difference in SEP15 allelic distribution for rs5859 between head and neck cancer individuals (DNA obtained from tumours, n=33) and cancer-free individuals (DNA obtained from lymphocytes, n=490) among African Americans.
Entity Mesothelioma
Disease Apostolou et al. (2004) reported that SEP15 gene expression was downregulated in malignant mesothelioma (MM) cell lines (14 out of 23 cell lines examined) and mesothelioma tumours (3 out of 5 tissue specimens examined). The authors examined also the effect of selenium in MM cell lines on the growth inhibition and apoptosis. They observed that suppression of SEP15 expression by siRNA affected the response of cells to selenium, making them more resistant to the microelement. The growth inhibition and apoptosis effects followed by selenium treatment were also less pronounced in cells with variant alleles of SEP15 (SEP15 1125A, rs5859) as compared to cells with wild type allele (SEP15 1125G).
Entity Lung cancer
Disease In the case control study (238 cases, 340 controls), Jablonska et al. (2008) observed a modifying effect of SEP15 polymorphism (rs5859) on lung cancer risk associated with selenium status. The high risk of lung cancer in the studied group was associated with low as well as with high plasma selenium concentration. After stratifying the data according to SEP15 genotype, it was found that among individuals with high selenium status, the risk of lung cancer was increased among those possessing at least one wild type allele, whereas in those with both variant alleles, the risk was decreased (figure 2).
No expression change for SEP15 was observed between malignant and non-malignant lung tissue (study of 33 non-small cell lung cancer patients, conducted by Gresner et al., 2009).
Figure 2. Joint effect of plasma selenium concentration and SEP15 1125G/A polymorphism for lung cancer development. OR - Odds Ratio for lung cancer risk. SEP15 genotypes: 1125GG (black line), 1125GA (yellow line), 1125AA (red line). Test for trends in SEP15 genotypes: p=0.038 for GG, p=0.035 for GA, p=0.030 for AA. Test for trend differences: AA vs. GG: p=0.049, AA vs. GA: p=0.025 (results of this study were published in Jablonska et al., 2008).
Entity Bladder cancer
Disease Reszka et al. (2009) indicated that SEP15 was down expressed in the blood leucocytes of bladder cancer patients (33 males) as compared to healthy controls (47 males). SEP15 expression was positively correlated with tumour grade.
Entity Prostate cancer
Disease Penney et al. (2010) conducted nested case control study among 1286 cases and 1267 controls to assess the relationship between five SEP15 polymorphisms (rs5859, rs479341, rs561104, rs527281, rs1407131), selenium status and prostate cancer risk and survival. Authors did not found any association between SEP15 polymorphisms and prostate cancer risk. However they observed that three variants (rs479341, rs1407131 and rs561104) were significantly associated with prostate cancer mortality and and one of the SNPs (rs561104) was shown to modify prostate cancer survival in association with selenium status.
Entity Colon/colorectal cancer
Disease Studies conducted in mice by Irons et al. (2010), showed that down regulation of SEP15 inhibited colon cancer development induced by injection of mouse CT26 colon cancer cells. Authors suggest that targeted down regulation of SEP15 in colon cancer cells may protect them from tumorigenesis.
Meplan et al. (2010) conducted case control study including 832 cases and 705 controls, in which they assessed the association between colorectal cancer and several SNPs within genes encoding selenoproteins and also other proteins. They found significant two-loci interaction between SEP15 (rs5859) and other selenoprotein (Sepp1) associated with colon cancer risk.
In a similar study, involving 827 cases and 733 controls, Sutherland et al. (2010) found two SNPs within SEP15 (rs5845 and rs5859) to be associated with colorectal cancer risk.


Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype.
Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR.
Oncogene. 2004 Jun 24;23(29):5032-40.
PMID 15107826
The link between selenium and chemoprevention: a case for selenoproteins.
Diwadkar-Navsariwala V, Diamond AM.
J Nutr. 2004 Nov;134(11):2899-902. (REVIEW)
PMID 15514248
NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family.
Ferguson AD, Labunskyy VM, Fomenko DE, Arac D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J.
J Biol Chem. 2006 Feb 10;281(6):3536-43. Epub 2005 Nov 30.
PMID 16319061
Genomics perspective on disulfide bond formation.
Fomenko DE, Gladyshev VN.
Antioxid Redox Signal. 2003 Aug;5(4):397-402. (REVIEW)
PMID 13678527
A new human selenium-containing protein. Purification, characterization, and cDNA sequence.
Gladyshev VN, Jeang KT, Wootton JC, Hatfield DL.
J Biol Chem. 1998 Apr 10;273(15):8910-5.
PMID 9535873
Expression of selenoprotein-coding genes SEPP1, SEP15 and hGPX1 in non-small cell lung cancer.
Gresner P, Gromadzinska J, Jablonska E, Kaczmarski J, Wasowicz W.
Lung Cancer. 2009 Jul;65(1):34-40. Epub 2008 Dec 6.
PMID 19058871
Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene.
Hu YJ, Korotkov KV, Mehta R, Hatfield DL, Rotimi CN, Luke A, Prewitt TE, Cooper RS, Stock W, Vokes EE, Dolan ME, Gladyshev VN, Diamond AM.
Cancer Res. 2001 Mar 1;61(5):2307-10.
PMID 11280803
Deficiency in the 15-kDa selenoprotein inhibits tumorigenicity and metastasis of colon cancer cells.
Irons R, Tsuji PA, Carlson BA, Ouyang P, Yoo MH, Xu XM, Hatfield DL, Gladyshev VN, Davis CD.
Cancer Prev Res (Phila). 2010 May;3(5):630-9. Epub 2010 Apr 13.
PMID 20388823
Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism.
Jablonska E, Gromadzinska J, Sobala W, Reszka E, Wasowicz W.
Eur J Nutr. 2008 Feb;47(1):47-54. Epub 2008 Jan 31.
PMID 18239845
A new selenoprotein found in the glandular epithelial cells of the rat prostate.
Kalcklosch M, Kyriakopoulos A, Hammel C, Behne D.
Biochem Biophys Res Commun. 1995 Dec 5;217(1):162-70.
PMID 8526906
Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology.
Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VN.
J Biol Chem. 2000 Nov 10;275(45):35540-7.
PMID 10945981
Sep15, a thioredoxin-like selenoprotein, is involved in the unfolded protein response and differentially regulated by adaptive and acute ER stresses.
Labunskyy VM, Yoo MH, Hatfield DL, Gladyshev VN.
Biochemistry. 2009 Sep 8;48(35):8458-65.
PMID 19650649
Genetic variants in selenoprotein genes increase risk of colorectal cancer.
Meplan C, Hughes DJ, Pardini B, Naccarati A, Soucek P, Vodickova L, Hlavata I, Vrana D, Vodicka P, Hesketh JE.
Carcinogenesis. 2010 Jun;31(6):1074-9. Epub 2010 Apr 8.
PMID 20378690
Allelic loss at the Sep15 locus in breast cancer.
Nasr MA, Hu YJ, Diamond AM
Cancer Ther. 2003;(1):293-298.
A large prospective study of SEP15 genetic variation, interaction with plasma selenium levels, and prostate cancer risk and survival.
Penney KL, Schumacher FR, Li H, Kraft P, Morris JS, Kurth T, Mucci LA, Hunter DJ, Kantoff PW, Stampfer MJ, Ma J.
Cancer Prev Res (Phila). 2010 May;3(5):604-10. Epub 2010 Apr 27.
PMID 20424130
Level of selenoprotein transcripts in peripheral leukocytes of patients with bladder cancer and healthy individuals.
Reszka E, Gromadzinska J, Jablonska E, Wasowicz W, Jablonowski Z, Sosnowski M.
Clin Chem Lab Med. 2009;47(9):1125-32.
PMID 19728855
Polymorphisms in the selenoprotein S and 15-kDa selenoprotein genes are associated with altered susceptibility to colorectal cancer.
Sutherland A, Kim DH, Relton C, Ahn YO, Hesketh J.
Genes Nutr. 2010; (5):215-23.


This paper should be referenced as such :
Jablonska, E ; Gromadzinska, J ; Reszka, E ; Wasowicz, W
SEP15 (15 kDa selenoprotein)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):516-519.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)SELENOF   17705
Entrez_Gene (NCBI)SELENOF    selenoprotein F
GeneCards (Weizmann)SELENOF
Ensembl hg19 (Hinxton)ENSG00000183291 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000183291 [Gene_View]  ENSG00000183291 [Sequence]  chr1:86862445-86914365 [Contig_View]  SELENOF [Vega]
ICGC DataPortalENSG00000183291
Genatlas (Paris)SELENOF
Genetics Home Reference (NIH)SELENOF
Genomic and cartography
GoldenPath hg38 (UCSC)SELENOF  -     chr1:86862445-86914365 -  1p22.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SELENOF  -     1p22.3   [Description]    (hg19-Feb_2009)
GoldenPathSELENOF - 1p22.3 [CytoView hg19]  SELENOF - 1p22.3 [CytoView hg38]
Genome Data Viewer NCBISELENOF [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF051894 AF288991 AK225252 AK225640 AL833575
RefSeq transcript (Entrez)NM_004261 NM_203341
Consensus coding sequences : CCDS (NCBI)SELENOF
Gene Expression Viewer (FireBrowse)SELENOF [ Firebrowse - Broad ]
GenevisibleExpression of SELENOF in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9403
GTEX Portal (Tissue expression)SELENOF
Human Protein AtlasENSG00000183291-SELENOF [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60613   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60613  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60613
Domains : Interpro (EBI)Sep15/SelM_sf    Sep15_SelM    Sep15_SelM_dom    Thioredoxin-like_sf   
Domain families : Pfam (Sanger)Sep15_SelM (PF08806)   
Domain families : Pfam (NCBI)pfam08806   
Conserved Domain (NCBI)SELENOF
AlphaFold pdb e-kbO60613   
Human Protein Atlas [tissue]ENSG00000183291-SELENOF [tissue]
Protein Interaction databases
IntAct (EBI)O60613
Ontologies - Pathways
Ontology : AmiGOprotein binding  endoplasmic reticulum lumen  endoplasmic reticulum lumen  oxidoreductase activity  'de novo' posttranslational protein folding  
Ontology : EGO-EBIprotein binding  endoplasmic reticulum lumen  endoplasmic reticulum lumen  oxidoreductase activity  'de novo' posttranslational protein folding  
Atlas of Cancer Signalling NetworkSELENOF
Wikipedia pathwaysSELENOF
Orthology - Evolution
GeneTree (enSembl)ENSG00000183291
Phylogenetic Trees/Animal Genes : TreeFamSELENOF
Homologs : HomoloGeneSELENOF
Homology/Alignments : Family Browser (UCSC)SELENOF
Gene fusions - Rearrangements
Fusion : QuiverSELENOF
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSELENOF [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SELENOF
Exome Variant ServerSELENOF
GNOMAD BrowserENSG00000183291
Varsome BrowserSELENOF
Genomic Variants (DGV)SELENOF [DGVbeta]
DECIPHERSELENOF [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSELENOF 
Broad Tumor PortalSELENOF
OASIS PortalSELENOF [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSELENOF  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSELENOF
Mutations and Diseases : HGMDSELENOF
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)SELENOF
DoCM (Curated mutations)SELENOF
CIViC (Clinical Interpretations of Variants in Cancer)SELENOF
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry SELENOF
NextProtO60613 [Medical]
Target ValidationSELENOF
Huge Navigator SELENOF [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDSELENOF
Pharm GKB GenePA166181629
Clinical trialSELENOF
DataMed IndexSELENOF
PubMed48 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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