VIMP on SELS, selenoproteiini S ja kuuluu ERAD -koneistoon

VIMP proteiinia koodautuu geenistä nimeltä SELENOS.VIMP proteiini sijoitautuu endoplasmiseen verkostoon ja osallistuu viallisten proteiinien hajoittamiseen ja sillä voi olla merkitystä tulehduksenkin hallinnassa. Esim. tutkijat ovat havainneet (2017) , että SELS (VIMP) vaaditaan , jotta enteroviruspolypeptidi C99 saadaan puhdistettua ERAD-teitse ja samalla inhiboituu amyloidibeta tuotantokin. C99 on 2210 aminohappoa sisältävä polypeptidi. Selenoproteiini S (SELS) vähentää myös ER stressin aiheutyamaa tau-fosforylaatiota ja vaikuttanee selenaattien aiheutaman lievennyksen tau-patologiaan. Selenoproteiini S pitoisuus aivossa korreloi käänteisesti taufosforylaatioon. Maksan ja seerumin Selenoproteiini S (SELS) pitoisuuden sääteleminen voi olla uutta strategiaa 2-tyypin diabeteksen ja ateroskleroosin makrovaskulaaristen muutosten ehkäisyyn ja hoitoon. ERAD-funktiossa on välttämätöntä selenoproteiinista riippuva Selenoproteiini-K-sitoutuminen p97(VCP). Interaktio SELS – p97(VCP) SelK omaa tärkeän osan ERAD:issa ja ER-stressissä. SELS on uusia glukoosin säätelemiä proteiineja (2004). Arvellaan jo 2002 että on yhteyttä tämän geenin Tanis ja tyypin 2DM sekä tulehduksen kesken. Tämä on sikäli erikoinen proteiini, että siinä on poikekuksellinen koodautuminen. Se koodautuu UGA kodonilla, joka yleensä on STOP-signaali. Selenoproteiini mRNA:n 3´prim UTR sisältää consensus stem-loop rakenteet, SECIS- elementin, joka on vaatimus, jotta UGA tunnistautuu Sec-kodoniksi eikä STOP-signaaliksi. On transkripit variantti josta SECIS-elementti puuttuu, mutta tähän liitän linkin vallitsevasta isoformista, jossa on Se-cysteiiniä sisältävä kohta.

 http://genomics.unl.edu/RBC_EDU/IMAGES/sel2.jpg

Tämän proteiinin VIMP- nimi tarkoittaa valosiinia sisältävän proteiinin kanssa vuorovaikutuksen tekevä kalvoproteiini. (ERAD koneiston komplekseissa interaktion keskenään tekevät mm. SELS, p97, Seleno-K SelK, HRD1, gp78), p97 joista erikseen asiaa) .

(Kts. myös tämä artikkeli https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022850/ )

Geeni: SELENOS, (Kr. 15q26.3)

Also known as SELS; VIMP; ADO15; SBBI8; SEPS1; AD-015

Preferred

Names

selenoprotein S

Names

VCP interacting membrane selenoprotein

VCP-interacting membrane protein

tanis

valosin-containing protein-interacting membrane protein

Summary: This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017] Expression Ubiquitous expression in testis (RPKM 27.4), colon (RPKM 26.5) and 25 other tissues See more

https://www.ncbi.nlm.nih.gov/pubmed/22700979

Peptide structure and history: Selenoproteiini S isoformi 1

https://www.ncbi.nlm.nih.gov/protein/NP_060915.2

selenoprotein S isoform 1 [Homo sapiens]

NCBI Reference Sequence: NP_060915.2
Identical Proteins FASTA Graphics

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LOCUS       NP_060915                189 aa            linear   PRI 30-APR-2018
DEFINITION  selenoprotein S isoform 1 [Homo sapiens].
ACCESSION   NP_060915
VERSION     NP_060915.2
DBSOURCE    REFSEQ: accession NM_018445.5
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 189)
  AUTHORS   Jang JK, Park KJ, Lee JH, Ko KY, Kang S and Kim IY.
  TITLE     Selenoprotein S is required for clearance of C99 through
            endoplasmic reticulum-associated degradation
  JOURNAL   Biochem. Biophys. Res. Commun. 486 (2), 444-450 (2017)
   PUBMED   28315680
  REMARK    GeneRIF: The results suggest that SelS is required for C99
            degradation through endoplasmic reticulum-associated degradation,
            resulting in inhibition of amyloid beta production.
REFERENCE   2  (residues 1 to 189)
  AUTHORS   Rueli RH, Torres DJ, Dewing AS, Kiyohara AC, Barayuga SM, Bellinger
            MT, Uyehara-Lock JH, White LR, Moreira PI, Berry MJ, Perry G and
            Bellinger FP.
  TITLE     Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced
            Phosphorylation of Tau: Potential Role in Selenate Mitigation of
            Tau Pathology
  JOURNAL   J. Alzheimers Dis. 55 (2), 749-762 (2017)
   PUBMED   27802219
  REMARK    GeneRIF: In these studies found that SelS increases in negative
            correlation with tau phosphorylation in brain.
REFERENCE   3  (residues 1 to 189)
  AUTHORS   Yu SS, Men LL, Wu JL, Huang LW, Xing Q, Yao JJ, Wang YB, Song GR,
            Guo HS, Sun GH, Zhang YH, Li H and Du JL.
  TITLE     The source of circulating selenoprotein S and its association with
            type 2 diabetes mellitus and atherosclerosis: a preliminary study
  JOURNAL   Cardiovasc Diabetol 15, 70 (2016)
   PUBMED   27121097
  REMARK    GeneRIF: regulating liver and serum Selenoprotein S levels might
            become a new strategy for the prevention and treatment of DM and
            its macrovascular complications
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 189)
  AUTHORS   Lee JH, Park KJ, Jang JK, Jeon YH, Ko KY, Kwon JH, Lee SR and Kim
            IY.
  TITLE     Selenoprotein S-dependent Selenoprotein K Binding to p97(VCP)
            Protein Is Essential for Endoplasmic Reticulum-associated
            Degradation
  JOURNAL   J. Biol. Chem. 290 (50), 29941-29952 (2015)
   PUBMED   26504085
  REMARK    GeneRIF: interaction between SelK and p97(VCP) is SelS-dependent,
            and the resulting ERAD complex (SelS-p97(VCP)-SelK) plays an
            important role in ERAD and ER stress
REFERENCE   5  (residues 1 to 189)
  AUTHORS   Bubenik JL, Miniard AC and Driscoll DM.
  TITLE     Alternative transcripts and 3'UTR elements govern the incorporation
            of selenocysteine into selenoprotein S
  JOURNAL   PLoS ONE 8 (4), e62102 (2013)
   PUBMED   23614019
  REMARK    Publication Status: Online-Only
REFERENCE   6  (residues 1 to 189)
  AUTHORS   Gao Y, Feng HC, Walder K, Bolton K, Sunderland T, Bishara N, Quick
            M, Kantham L and Collier GR.
  TITLE     Regulation of the selenoprotein SelS by glucose deprivation and
            endoplasmic reticulum stress - SelS is a novel glucose-regulated
            protein
  JOURNAL   FEBS Lett. 563 (1-3), 185-190 (2004)
   PUBMED   15063746
  REMARK    GeneRIF: SELS is regulated by glucose deprivation and endoplasmic
            reticulum stress.  It is a glucose-regulated protein.
REFERENCE   7  (residues 1 to 189)
  AUTHORS   Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo
            R and Gladyshev VN.
  TITLE     Characterization of mammalian selenoproteomes
  JOURNAL   Science 300 (5624), 1439-1443 (2003)
   PUBMED   12775843
REFERENCE   8  (residues 1 to 189)
  AUTHORS   Gao Y, Walder K, Sunderland T, Kantham L, Feng HC, Quick M, Bishara
            N, de Silva A, Augert G, Tenne-Brown J and Collier GR.
  TITLE     Elevation in Tanis expression alters glucose metabolism and insulin
            sensitivity in H4IIE cells
  JOURNAL   Diabetes 52 (4), 929-934 (2003)
   PUBMED   12663463
REFERENCE   9  (residues 1 to 189)
  AUTHORS   Walder K, Kantham L, McMillan JS, Trevaskis J, Kerr L, De Silva A,
            Sunderland T, Godde N, Gao Y, Bishara N, Windmill K, Tenne-Brown J,
            Augert G, Zimmet PZ and Collier GR.
  TITLE     Tanis: a link between type 2 diabetes and inflammation?
  JOURNAL   Diabetes 51 (6), 1859-1866 (2002)
   PUBMED   12031974
REFERENCE   10 (residues 1 to 189)
  AUTHORS   Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH,
            Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong
            R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM,
            Huang GY, Chen Z, Chen MD and Chen JL.
  TITLE     Gene expression profiling in the human
            hypothalamus-pituitary-adrenal axis and full-length cDNA cloning
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 97 (17), 9543-9548 (2000)
   PUBMED   10931946
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BG829960.1, BC005840.2,
            AK097011.1 and AK225955.1.
            This sequence is a reference standard in the RefSeqGene project.
            On Jul 26, 2003 this sequence version replaced NP_060915.1.
            
            Summary: This gene encodes a transmembrane protein that is
            localized in the endoplasmic reticulum (ER). It is involved in the
            degradation process of misfolded proteins in the ER, and may also
            have a role in inflammation control. This protein is a
            selenoprotein, containing the rare amino acid selenocysteine (Sec).
            Sec is encoded by the UGA codon, which normally signals translation
            termination. The 3' UTRs of selenoprotein mRNAs contain a conserved
            stem-loop structure, designated the Sec insertion sequence (SECIS)
            element, that is necessary for the recognition of UGA as a Sec
            codon, rather than as a stop signal. Two additional
            phylogenetically conserved stem-loop structures (Stem-loop 1 and
            Stem-loop 2) in the 3' UTR of this mRNA have been shown to function
            as modulators of Sec insertion. An alternatively spliced transcript
            variant, lacking the SECIS element and encoding a non-Sec
            containing shorter isoform, has been described for this gene
            (PMID:23614019). [provided by RefSeq, Jul 2017].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript, and encodes a selenocysteine-containing longer isoform
            (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK225955.1, SRR1803617.201092.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            protein contains selenocysteine :: PMID: 12775843, 23614019
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..189
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q26.3"
     Protein         1..189
                     /product="selenoprotein S isoform 1"
                     /note="VCP-interacting membrane protein;
                     valosin-containing protein-interacting membrane protein;
                     VCP interacting membrane selenoprotein; tanis"
                     /calculated_mol_wt=21032
     Region          1..187
                     /region_name="Selenoprotein_S"
                     /note="Selenoprotein S (SelS); pfam06936"
                     /db_xref="CDD:284376"
     Site            28..48
                     /site_type="transmembrane region"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BQE4.3)"
     Region          78..90
                     /region_name="VCP/p97-interacting motif (VIM).
                     {ECO:0000269|PubMed:21896481}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9BQE4.3)"
     Site            140
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:23186163}; propagated from
                     UniProtKB/Swiss-Prot (Q9BQE4.3)"
     Site            188
                     /site_type="other"
                     /note="Selenocysteine"
     CDS             1..189
                     /gene="SELENOS"
                     /gene_synonym="AD-015; ADO15; SBBI8; SELS; SEPS1; VIMP"
                     /coded_by="NM_018445.5:104..673"
                     /note="UGA stop codon recoded as selenocysteine; isoform 1
                     is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS53979.1"
                     /db_xref="GeneID:55829"
                     /db_xref="HGNC:HGNC:30396"
                     /db_xref="MIM:607918"
ORIGIN      
        1 merqeeslsa rpaleteglr flhttvgsll atygwyivfs cillyvvfqk lsarlralrq
       61 rqldraaaav epdvvvkrqe alaaarlkmq eelnaqvekh keklkqleee krrqkiemwd
      121 smqegksykg nakkpqeeds pgpstssvlk rksdrkplrg ggynplsgeg ggacswrpgr
      181 rgpssggug
//

Related articles in PubMed

1. Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology. Rueli RH, et al. J Alzheimers Dis, 2017. PMID 27802219, Free PMC Article
2. The source of circulating selenoprotein S and its association with type 2 diabetes mellitus and atherosclerosis: a preliminary study. Yu SS, et al. Cardiovasc Diabetol, 2016 Apr 28. PMID 27121097, Free PMC Article
3. Single nucleotide polymorphism in the SEPS1 gene may contribute to the risk of various human diseases: a meta-analysis. Sun HY, et al. Ann Hum Biol, 2016 Sep. PMID 26382012
4. Association studies of SEPS1 gene polymorphisms with Hashimoto's thyroiditis in Han Chinese. Li M, et al. J Hum Genet, 2015 Aug. PMID 26016409
5. Role of selenoprotein S (SEPS1) -105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease. Du XA, et al. Osteoarthritis Cartilage, 2015 Feb. PMID 25433273
   

See all (79) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. In these studies found that SelS increases in negative correlation with tau phosphorylation in brain.
2. The results suggest that SelS is required for C99 degradation through endoplasmic reticulum-associated degradation, resulting in inhibition of amyloid beta production.
3. regulating liver and serum Selenoprotein S levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications
4. SEPS1 may be a potential gene marker for disease diagnosis and prognosis.
5. interaction between SelK and p97(VCP) is SelS-dependent, and the resulting ERAD complex (SelS-p97(VCP)-SelK) plays an important role in ERAD and ER stress
6. Potential roles of the SEPS1 gene in the pathogenesis and etiology of Hashimoto's thyroiditis.
7. SNP rs4965814 of SELS may affect the susceptibility to ischemic stroke.
8. The SEPS1 -105G>A is associated with an increased risk of Kashin-Beck disease and influences the expression of PI3K/Akt signaling pathway in Kashin-Beck disease patients
9. Although VIMP can interact with CLIMP-63 and Syn5L, it does not interact with MT-binding ER proteins (such as Reep1) that shape the tubular smooth ER
10. Selenoprotein S is a marker but not a regulator of endoplasmic reticulum stress in intestinal epithelial cells in inflammatory bowel diseases.
    

Submit: New GeneRIF Correction See all GeneRIFs (38)