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SELENOP (selenoprotein P, plasma, 1)

Written2011-03Ewa 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)

Identity

Alias_namesSEPP1
selenoprotein P
Alias_symbol (synonym)SeP
SELP
SEPP
Other alias
HGNC (Hugo) SELENOP
LocusID (NCBI) 6414
Atlas_Id 46513
Location 5p12  [Link to chromosome band 5p12]
Location_base_pair Starts at 42799880 and ends at 42812076 bp from pter ( according to hg19-Feb_2009)  [Mapping SELENOP.png]
Local_order According to NCBI Map Viewer, SEPP1 gene is located between: LOC100420450, GHR, CCDC152 (in telomeric position) and LOC100420275, LOC402213 (in centromeric position).

DNA/RNA

Description The genomic DNA of SEPP1 spans about 12 kb. SEPP1 consists of 6 exons.
Transcription 3 alternative mRNAs exist encoding 2 different isoforms of selenoprotein P. Transcript variants 1 and 2 encode isoform 1 and transcript variant 3 encodes isoform 2.

Protein

Note SEPP1 belongs to selenoproteins, all of which contain selenium in the form of selenocysteine (SeC) and are being synthesized in the presence of UGA codon, specific stem loop structure in 3' UTR of mRNA called SECIS (Selenocysteine Insertion Sequence) and other specific factors. Selenoprotein P is a glycoprotein present mainly in plasma, where it accounts for 40 - 65% of total selenium in this blood compartment. Plasma SEPP1 concentration is regarded as a functional biomarker of human selenium status (Saito and Takahashi, 2002; Méplan et al., 2009; Xia et al., 2010).
Description Selenoprotein P consists of 381 amino acids and contains ten selenocysteines: nine are located in Sec-rich C-terminal domain (suggested as the region responsible for selenium delivery) and one is present in N-terminal domain (region with redox properties responsible for enzymatic activity of the protein). Two protein isoforms were identified in human plasma: 50 kDa and 60 kDa (Méplan et al., 2007; Méplan et al., 2009).
Expression SEPP1 is expressed mainly in the liver, from where it is exported to plasma and other tissues. Other organs expressing the protein include mainly brain, thyroid gland, prostate and mammary gland. Its expression has been found to be significantly reduced in cancer, including prostate, colon and lung (Gonzalez-Moreno et al., 2010).
SEPP1 expression is downregulated by different cytokines (Al-Taie et al., 2002). Also hepatic factors such as insulin and glucocorticoids may regulate SEPP1 expression (Speckmann et al., 2008).
Localisation Plasma.
Function It is supposed that SeP is responsible for the transport of selenium within body and delivering the microelement to the cells. In brain and testis (organs, in which selenium plays an important role), SEPP1 uptake is mediated by apolipoprotein E receptor-2 (apoER2). In kidneys, the uptake is regulated by another receptor, called megalin (Burk and Hill, 2009) (figure 1).
Additionally, SEPP1 is involved in the reduction of oxidative stress due to its redox properties (Saito et al., 2004).
 
  Figure 1. SEPP1 in selenium homeostasis and transport to the testis, brain and kidney. Whole - body selenium excretion is controlled by selenium excretion in the urine. SEPP1 and selenium excretory metabolites compete for metabolically available selenium in the liver, determining urinary selenium excretion. The lipoprotein receptor apoER2 binds SEPP1 and facilitates its uptake into the testis where selenium is incorporated into spermatozoa. ApoER2 also maintains brain selenium. SEPP1 is filtered by the kidney into the glomerular filtrate and binds to megalin in the brush border of proximal convoluted tubules. Those cells endocytose the SEPP1 bound to megalin and presumably use its selenium to synthesize plasma glutathione peroxidase (GPx3) (adapted from Burk and Hill, 2009, with the authors' permission).
Homology SEPP1 is conserved in chimpanzee, dog, cow, mouse, rat and zebrafish.

Mutations

Note No mutations in SEPP1 gene have been identified yet.
Genetic variations: several SNPs were identified.
Most often studied polymorphisms within SEPP1:
- Ala234Thr (rs 3877899) - associated with a G/A transition at position 24731 of mRNA, with the amino acid change from alanine to threonine in the codon 234. This polymorphism influences the SePP1 isoform pattern. Using Western blot analysis, it was shown that in the individuals possessing Ala/Ala genotype, 60 kDa protein was a dominating isoform, whereas in those with Ala/Thr genotype, the band for 50 kDa isoform was stronger (Thr/Thr genotype was not analyzed in this study). It was also observed, that within Ala/Ala and Ala/Thr individuals, males had less 60 kDa isoform as compared to females (Méplan et al., 2009).
- r25191g/a (rs 7579) - G/A transition at position 25191 within 3'-UTR. Similarly as rs 3877899 SNP, this SNP seems to influence the proportion of SEPP1 isoforms. Individuals with GG genotype had lower proportion of 60 kDa isoform as compared to those with GA or AA genotype (Méplan et al., 2009).
- (TC)5/(TC)3 repeats at promoter region. It was shown in in vitro study that TC3 allele reduced the promoter activity of reporter gene constructs in HepG2 cells (Al-Taie et al., 2002).

Implicated in

Note
  
Entity Cancer
Note Persson-Moschos et al. (2000) conducted a nested case control study, in which 12500 middle aged men were enrolled and the follow up time was between 1974-1988. Within the studied cohort, SEPP1 plasma concentration was significantly lower in the individuals who were diagnosed with cancer during the follow up (and whose plasma samples were available for analysis, n=302) as compared to control subjects (n=604). The authors of this study suggested that plasma SEPP1 level is associated with higher risk of cancer of respiratory and digestive tract.
  
  
Entity Colon cancer
Note Decreased expression of SePP1 mRNA was observed in colorectal cancer tissue as compared with normal colon mucosa (Al-Taie et al., 2004).
The study of 196 cases and 239 controls revealed no association between polymorphism at SEPP1 promoter region (TC)5/(TC)3 repeats and colon cancer risk. However, authors of the study observed genomic instability of Poly-(T)-single nucleotide repeat motif present in the SEPP1 promoter sequence in the colon cancer tissues as compared to normal colon mucosa from the same patients. This instability was observed in 10 out of 51 cases possessing two (TC)5 alleles (no instability was observed in 5 cases with (TC)5/(TC)3 genotype; (TC)3/(TC)3 homozygotes were not present in the studied group) (Al-Taie et al., 2002).
Other study, involving 772 cases and 777 controls, revealed that four SNPs within SEPP1 gene were significantly associated with risk of colorectal adenoma. The SNPs were: SEPP1 -4166G, rs12055266, rs3797310, rs2972994 (Peters et al., 2008).
In the study by Méplan et al. (2009), in which plasma samples from 20 colon cancer patients and 21 healthy individuals were analyzed, significantly lower proportion of 60 kDa isoform was observed in cases with SEPP1 GG genotype of rs 3877899 as compared to controls with the same genotype. Similar (statistically significant) difference between cases and controls was also indicated within individuals possessing GA genotype of rs7579.
  
  
Entity Prostate cancer
Note Expression of SEPP1 mRNA was down regulated in human prostate tumours as well as prostate carcinoma cell lines (Calvo et al., 2002).
Further investigation revealed that down-regulation of SEPP1 in prostate cancer cells leads to an increased production of reactive oxygen species (Gonzalez-Moreno et al., 2010).
In the study conducted on 90 males with prostate cancer and 100 control men, it was observed that protein's concentration measured in serum was lower in cases as compared to controls (Meyer et al., 2009).
The interaction between polymorphic variants of SePP1 and SOD2 genes in prostate cancer risk was found by Cooper et al. (2008). According to the results based on CAPS study (Prostate CAncer in Sweden), males being homozygous for SEPP1 Ala234 allele (rs 3877899) and who possessed at least one SOD2 Ala16 allele (rs 4880), were at significantly higher risk of prostate cancer.
In a study of 248 prostate cancer cases and 492 controls, borderline significant association between prostate cancer risk and SEPP1 polymorphism (rs 7579) was found (Steinbrecher et al., 2010).
  

Bibliography

Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis.
Al-Taie OH, Uceyler N, Eubner U, Jakob F, Mork H, Scheurlen M, Brigelius-Flohe R, Schottker K, Abel J, Thalheimer A, Katzenberger T, Illert B, Melcher R, Kohrle J.
Nutr Cancer. 2004;48(1):6-14.
PMID 15203372
 
Selenoprotein P-expression, functions, and roles in mammals.
Burk RF, Hill KE.
Biochim Biophys Acta. 2009 Nov;1790(11):1441-7. Epub 2009 Apr 1. (REVIEW)
PMID 19345254
 
Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors.
Calvo A, Xiao N, Kang J, Best CJ, Leiva I, Emmert-Buck MR, Jorcyk C, Green JE.
Cancer Res. 2002 Sep 15;62(18):5325-35.
PMID 12235003
 
Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk.
Cooper ML, Adami HO, Gronberg H, Wiklund F, Green FR, Rayman MP.
Cancer Res. 2008 Dec 15;68(24):10171-7.
PMID 19074884
 
Selenoprotein-P is down-regulated in prostate cancer, which results in lack of protection against oxidative damage.
Gonzalez-Moreno O, Boque N, Redrado M, Milagro F, Campion J, Endermann T, Takahashi K, Saito Y, Catena R, Schomburg L, Calvo A.
Prostate. 2010 Nov 17. [Epub ahead of print]
PMID 21086459
 
Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial.
Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, Broadley MR, Motley AK, Fairweather-Tait SJ.
Am J Clin Nutr. 2010 Apr;91(4):923-31. Epub 2010 Feb 24.
PMID 20181815
 
Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study).
Meplan C, Crosley LK, Nicol F, Beckett GJ, Howie AF, Hill KE, Horgan G, Mathers JC, Arthur JR, Hesketh JE.
FASEB J. 2007 Oct;21(12):3063-74. Epub 2007 May 29.
PMID 17536041
 
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
 
Relative abundance of selenoprotein P isoforms in human plasma depends on genotype, se intake, and cancer status.
Meplan C, Nicol F, Burtle BT, Crosley LK, Arthur JR, Mathers JC, Hesketh JE.
Antioxid Redox Signal. 2009 Nov;11(11):2631-40.
PMID 19453253
 
Reduced serum selenoprotein P concentrations in German prostate cancer patients.
Meyer HA, Hollenbach B, Stephan C, Endermann T, Morgenthaler NG, Cammann H, Kohrle J, Jung K, Schomburg L.
Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2386-90. Epub 2009 Aug 18.
PMID 19690186
 
Selenoprotein P in plasma in relation to cancer morbidity in middle-aged Swedish men.
Persson-Moschos ME, Stavenow L, Akesson B, Lindgarde F.
Nutr Cancer. 2000;36(1):19-26.
PMID 10798212
 
Variation in the selenoenzyme genes and risk of advanced distal colorectal adenoma.
Peters U, Chatterjee N, Hayes RB, Schoen RE, Wang Y, Chanock SJ, Foster CB.
Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1144-54.
PMID 18483336
 
Domain structure of bi-functional selenoprotein P.
Saito Y, Sato N, Hirashima M, Takebe G, Nagasawa S, Takahashi K.
Biochem J. 2004 Aug 1;381(Pt 3):841-6.
PMID 15117283
 
Characterization of selenoprotein P as a selenium supply protein.
Saito Y, Takahashi K.
Eur J Biochem. 2002 Nov;269(22):5746-51.
PMID 12423375
 
Selenoprotein P expression is controlled through interaction of the coactivator PGC-1alpha with FoxO1a and hepatocyte nuclear factor 4alpha transcription factors.
Speckmann B, Walter PL, Alili L, Reinehr R, Sies H, Klotz LO, Steinbrenner H.
Hepatology. 2008 Dec;48(6):1998-2006.
PMID 18972406
 
Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men.
Steinbrecher A, Meplan C, Hesketh J, Schomburg L, Endermann T, Jansen E, Akesson B, Rohrmann S, Linseisen J.
Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2958-68. Epub 2010 Sep 17.
PMID 20852007
 
Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects.
Xia Y, Hill KE, Li P, Xu J, Zhou D, Motley AK, Wang L, Byrne DW, Burk RF.
Am J Clin Nutr. 2010 Sep;92(3):525-31. Epub 2010 Jun 23.
PMID 20573787
 

Citation

This paper should be referenced as such :
Jablonska, E ; Gromadzinska, J ; Reszka, E ; Wasowicz, W
SEPP1 (selenoprotein P, plasma, 1)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(10):887-889.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SEPP1ID46513ch5p12.html


External links

Nomenclature
HGNC (Hugo)SELENOP   10751
Cards
AtlasSEPP1ID46513ch5p12
Entrez_Gene (NCBI)SELENOP  6414  selenoprotein P
AliasesSELP; SEPP; SEPP1; SeP
GeneCards (Weizmann)SELENOP
Ensembl hg19 (Hinxton)ENSG00000250722 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000250722 [Gene_View]  chr5:42799880-42812076 [Contig_View]  SELENOP [Vega]
ICGC DataPortalENSG00000250722
TCGA cBioPortalSELENOP
AceView (NCBI)SELENOP
Genatlas (Paris)SELENOP
WikiGenes6414
SOURCE (Princeton)SELENOP
Genetics Home Reference (NIH)SELENOP
Genomic and cartography
GoldenPath hg38 (UCSC)SELENOP  -     chr5:42799880-42812076 -  5p12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SELENOP  -     5p12   [Description]    (hg19-Feb_2009)
EnsemblSELENOP - 5p12 [CytoView hg19]  SELENOP - 5p12 [CytoView hg38]
Mapping of homologs : NCBISELENOP [Mapview hg19]  SELENOP [Mapview hg38]
OMIM601484   
Gene and transcription
Genbank (Entrez)AK094640 AK096125 AK225801 AK311392 AL599162
RefSeq transcript (Entrez)NM_001085486 NM_001093726 NM_005410
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SELENOP
Cluster EST : UnigeneHs.745017 [ NCBI ]
CGAP (NCI)Hs.745017
Alternative Splicing GalleryENSG00000250722
Gene ExpressionSELENOP [ NCBI-GEO ]   SELENOP [ EBI - ARRAY_EXPRESS ]   SELENOP [ SEEK ]   SELENOP [ MEM ]
Gene Expression Viewer (FireBrowse)SELENOP [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6414
GTEX Portal (Tissue expression)SELENOP
Protein : pattern, domain, 3D structure
UniProt/SwissProtP49908   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP49908  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP49908
Splice isoforms : SwissVarP49908
PhosPhoSitePlusP49908
Domains : Interpro (EBI)Selenoprotein-P_N    SelP_C   
Domain families : Pfam (Sanger)SelP_C (PF04593)    SelP_N (PF04592)   
Domain families : Pfam (NCBI)pfam04593    pfam04592   
Conserved Domain (NCBI)SELENOP
DMDM Disease mutations6414
Blocks (Seattle)SELENOP
SuperfamilyP49908
Human Protein AtlasENSG00000250722
Peptide AtlasP49908
HPRD03286
IPIIPI00029061   IPI00847381   IPI00967366   IPI00964354   
Protein Interaction databases
DIP (DOE-UCLA)P49908
IntAct (EBI)P49908
FunCoupENSG00000250722
BioGRIDSELENOP
STRING (EMBL)SELENOP
ZODIACSELENOP
Ontologies - Pathways
QuickGOP49908
Ontology : AmiGOselenium compound metabolic process  platelet degranulation  extracellular region  extracellular region  extracellular space  response to oxidative stress  brain development  locomotory behavior  selenium binding  post-embryonic development  sexual reproduction  platelet dense granule lumen  growth  extracellular exosome  
Ontology : EGO-EBIselenium compound metabolic process  platelet degranulation  extracellular region  extracellular region  extracellular space  response to oxidative stress  brain development  locomotory behavior  selenium binding  post-embryonic development  sexual reproduction  platelet dense granule lumen  growth  extracellular exosome  
NDEx NetworkSELENOP
Atlas of Cancer Signalling NetworkSELENOP
Wikipedia pathwaysSELENOP
Orthology - Evolution
OrthoDB6414
GeneTree (enSembl)ENSG00000250722
Phylogenetic Trees/Animal Genes : TreeFamSELENOP
HOVERGENP49908
HOGENOMP49908
Homologs : HomoloGeneSELENOP
Homology/Alignments : Family Browser (UCSC)SELENOP
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSELENOP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SELENOP
dbVarSELENOP
ClinVarSELENOP
1000_GenomesSELENOP 
Exome Variant ServerSELENOP
ExAC (Exome Aggregation Consortium)SELENOP (select the gene name)
Genetic variants : HAPMAP6414
Genomic Variants (DGV)SELENOP [DGVbeta]
DECIPHERSELENOP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSELENOP 
Mutations
ICGC Data PortalSELENOP 
TCGA Data PortalSELENOP 
Broad Tumor PortalSELENOP
OASIS PortalSELENOP [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDSELENOP
BioMutasearch SELENOP
DgiDB (Drug Gene Interaction Database)SELENOP
DoCM (Curated mutations)SELENOP (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SELENOP (select a term)
intoGenSELENOP
NCG5 (London)SELENOP
Cancer3DSELENOP(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601484   
Orphanet
MedgenSELENOP
Genetic Testing Registry SELENOP
NextProtP49908 [Medical]
TSGene6414
GENETestsSELENOP
Target ValidationSELENOP
Huge Navigator SELENOP [HugePedia]
snp3D : Map Gene to Disease6414
BioCentury BCIQSELENOP
ClinGenSELENOP
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6414
Chemical/Pharm GKB GenePA35672
Clinical trialSELENOP
Miscellaneous
canSAR (ICR)SELENOP (select the gene name)
Other databaseIHOP
Probes
Litterature
PubMed93 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSELENOP
EVEXSELENOP
GoPubMedSELENOP
iHOPSELENOP
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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