SELK_HUMAN
ID SELK_HUMAN Reviewed; 94 AA.
AC Q9Y6D0; Q8IZQ3; Q9P085;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Selenoprotein K {ECO:0000303|PubMed:27645994};
DE Short=SelK {ECO:0000303|PubMed:12775843};
GN Name=SELENOK {ECO:0000303|PubMed:27645994, ECO:0000312|HGNC:HGNC:30394};
GN Synonyms=SELK {ECO:0000303|PubMed:12775843};
GN ORFNames=HSPC030 {ECO:0000312|EMBL:AAD40194.1},
GN HSPC297 {ECO:0000312|EMBL:AAF28975.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=12775843; DOI=10.1126/science.1083516;
RA Kryukov G.V., Castellano S., Novoselov S.V., Lobanov A.V., Zehtab O.,
RA Guigo R., Gladyshev V.N.;
RT "Characterization of mammalian selenoproteomes.";
RL Science 300:1439-1443(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal cortex;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-13 AND 60-72, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16962588; DOI=10.1016/j.febslet.2006.08.065;
RA Lu C., Qiu F., Zhou H., Peng Y., Hao W., Xu J., Yuan J., Wang S., Qiang B.,
RA Xu C., Peng X.;
RT "Identification and characterization of selenoprotein K: an antioxidant in
RT cardiomyocytes.";
RL FEBS Lett. 580:5189-5197(2006).
RN [6]
RP FUNCTION, AND INDUCTION.
RX PubMed=20692228; DOI=10.1016/j.abb.2010.08.001;
RA Du S., Zhou J., Jia Y., Huang K.;
RT "SelK is a novel ER stress-regulated protein and protects HepG2 cells from
RT ER stress agent-induced apoptosis.";
RL Arch. Biochem. Biophys. 502:137-143(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DERL1; DERL2; DERL3; VCP
RP AND SELENOS, AND INDUCTION.
RX PubMed=22016385; DOI=10.1074/jbc.m111.310920;
RA Shchedrina V.A., Everley R.A., Zhang Y., Gygi S.P., Hatfield D.L.,
RA Gladyshev V.N.;
RT "Selenoprotein K binds multiprotein complexes and is involved in the
RT regulation of endoplasmic reticulum homeostasis.";
RL J. Biol. Chem. 286:42937-42948(2011).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=21220695; DOI=10.4049/jimmunol.1002878;
RA Verma S., Hoffmann F.W., Kumar M., Huang Z., Roe K., Nguyen-Wu E.,
RA Hashimoto A.S., Hoffmann P.R.;
RT "Selenoprotein K knockout mice exhibit deficient calcium flux in immune
RT cells and impaired immune responses.";
RL J. Immunol. 186:2127-2137(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ZDHHC6.
RX PubMed=25368151; DOI=10.1073/pnas.1417176111;
RA Fredericks G.J., Hoffmann F.W., Rose A.H., Osterheld H.J., Hess F.M.,
RA Mercier F., Hoffmann P.R.;
RT "Stable expression and function of the inositol 1,4,5-triphosphate receptor
RT requires palmitoylation by a DHHC6/selenoprotein K complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:16478-16483(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP UBIQUITINATION.
RX PubMed=26138980; DOI=10.1126/science.aab0515;
RA Lin H.C., Ho S.C., Chen Y.Y., Khoo K.H., Hsu P.H., Yen H.C.;
RT "SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced
RT by failed UGA/Sec decoding.";
RL Science 349:91-95(2015).
RN [14]
RP NOMENCLATURE.
RX PubMed=27645994; DOI=10.1074/jbc.m116.756155;
RA Gladyshev V.N., Arner E.S., Berry M.J., Brigelius-Flohe R., Bruford E.A.,
RA Burk R.F., Carlson B.A., Castellano S., Chavatte L., Conrad M.,
RA Copeland P.R., Diamond A.M., Driscoll D.M., Ferreiro A., Flohe L.,
RA Green F.R., Guigo R., Handy D.E., Hatfield D.L., Hesketh J., Hoffmann P.R.,
RA Holmgren A., Hondal R.J., Howard M.T., Huang K., Kim H.Y., Kim I.Y.,
RA Koehrle J., Krol A., Kryukov G.V., Lee B.J., Lee B.C., Lei X.G., Liu Q.,
RA Lescure A., Lobanov A.V., Loscalzo J., Maiorino M., Mariotti M.,
RA Sandeep Prabhu K., Rayman M.P., Rozovsky S., Salinas G., Schmidt E.E.,
RA Schomburg L., Schweizer U., Simonovic M., Sunde R.A., Tsuji P.A.,
RA Tweedie S., Ursini F., Whanger P.D., Zhang Y.;
RT "Selenoprotein gene nomenclature.";
RL J. Biol. Chem. 291:24036-24040(2016).
RN [15] {ECO:0007744|PDB:6DO3}
RP X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 85-91 IN COMPLEX WITH KLHDC2, AND
RP UBIQUITINATION.
RX PubMed=30526872; DOI=10.1016/j.molcel.2018.10.021;
RA Rusnac D.V., Lin H.C., Canzani D., Tien K.X., Hinds T.R., Tsue A.F.,
RA Bush M.F., Yen H.S., Zheng N.;
RT "Recognition of the diglycine C-end degron by CRL2(KLHDC2) ubiquitin
RT ligase.";
RL Mol. Cell 72:813-822(2018).
CC -!- FUNCTION: Required for Ca(2+) flux in immune cells and plays a role in
CC T-cell proliferation and in T-cell and neutrophil migration (By
CC similarity). Involved in endoplasmic reticulum-associated degradation
CC (ERAD) of soluble glycosylated proteins (PubMed:22016385). Required for
CC palmitoylation and cell surface expression of CD36 and involved in
CC macrophage uptake of low-density lipoprotein and in foam cell formation
CC (By similarity). Together with ZDHHC6, required for palmitoylation of
CC ITPR1 in immune cells, leading to regulate ITPR1 stability and function
CC (PubMed:25368151). Plays a role in protection of cells from ER stress-
CC induced apoptosis (PubMed:20692228). Protects cells from oxidative
CC stress when overexpressed in cardiomyocytes (PubMed:16962588).
CC {ECO:0000250|UniProtKB:Q9JLJ1, ECO:0000269|PubMed:16962588,
CC ECO:0000269|PubMed:20692228, ECO:0000269|PubMed:22016385,
CC ECO:0000269|PubMed:25368151}.
CC -!- SUBUNIT: Interacts with DERL1, DERL2, DERL3 and SELENOS
CC (PubMed:22016385). The SELENOK-SELENOS complex interacts with VCP
CC (PubMed:22016385). Interacts with ZDHHC6 (PubMed:25368151).
CC {ECO:0000269|PubMed:22016385, ECO:0000269|PubMed:25368151}.
CC -!- INTERACTION:
CC Q9Y6D0; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-9679163, EBI-19125216;
CC Q9Y6D0; Q13520: AQP6; NbExp=3; IntAct=EBI-9679163, EBI-13059134;
CC Q9Y6D0; Q13323: BIK; NbExp=3; IntAct=EBI-9679163, EBI-700794;
CC Q9Y6D0; O95873: C6orf47; NbExp=3; IntAct=EBI-9679163, EBI-719613;
CC Q9Y6D0; P34972: CNR2; NbExp=3; IntAct=EBI-9679163, EBI-2835940;
CC Q9Y6D0; P21964: COMT; NbExp=3; IntAct=EBI-9679163, EBI-372265;
CC Q9Y6D0; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-9679163, EBI-18013275;
CC Q9Y6D0; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-9679163, EBI-781551;
CC Q9Y6D0; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-9679163, EBI-18304435;
CC Q9Y6D0; O15552: FFAR2; NbExp=3; IntAct=EBI-9679163, EBI-2833872;
CC Q9Y6D0; Q5T7V8: GORAB; NbExp=3; IntAct=EBI-9679163, EBI-3917143;
CC Q9Y6D0; Q8TED1: GPX8; NbExp=3; IntAct=EBI-9679163, EBI-11721746;
CC Q9Y6D0; Q13651: IL10RA; NbExp=3; IntAct=EBI-9679163, EBI-1031656;
CC Q9Y6D0; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-9679163, EBI-2858252;
CC Q9Y6D0; Q15546: MMD; NbExp=3; IntAct=EBI-9679163, EBI-17873222;
CC Q9Y6D0; Q6IN84: MRM1; NbExp=3; IntAct=EBI-9679163, EBI-5454865;
CC Q9Y6D0; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-9679163, EBI-3923617;
CC Q9Y6D0; P15941-11: MUC1; NbExp=3; IntAct=EBI-9679163, EBI-17263240;
CC Q9Y6D0; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-9679163, EBI-7545592;
CC Q9Y6D0; Q6ZMZ0: RNF19B; NbExp=3; IntAct=EBI-9679163, EBI-2466594;
CC Q9Y6D0; Q9Y6D0: SELENOK; NbExp=2; IntAct=EBI-9679163, EBI-9679163;
CC Q9Y6D0; Q14973: SLC10A1; NbExp=3; IntAct=EBI-9679163, EBI-3923031;
CC Q9Y6D0; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-9679163, EBI-10262251;
CC Q9Y6D0; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-9679163, EBI-17295964;
CC Q9Y6D0; Q7Z769: SLC35E3; NbExp=3; IntAct=EBI-9679163, EBI-13389236;
CC Q9Y6D0; Q9H169-2: STMN4; NbExp=3; IntAct=EBI-9679163, EBI-20117546;
CC Q9Y6D0; P27105: STOM; NbExp=3; IntAct=EBI-9679163, EBI-1211440;
CC Q9Y6D0; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-9679163, EBI-12345267;
CC Q9Y6D0; Q9Y320: TMX2; NbExp=3; IntAct=EBI-9679163, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16962588, ECO:0000269|PubMed:21220695,
CC ECO:0000269|PubMed:22016385, ECO:0000269|PubMed:25368151}; Single-pass
CC membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:12775843}; Single-pass membrane protein
CC {ECO:0000255}. Note=Probably mainly localized in the ER.
CC {ECO:0000269|PubMed:21220695}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart.
CC {ECO:0000269|PubMed:16962588}.
CC -!- INDUCTION: By ER stress (at protein level). Displays a slow increase
CC with a lag phase of 6 hours but exhibits a dramatic increase after
CC incubation with ER stress agents for more than 12 hours with maximum
CC induction at 24 hours. Also induced by accumulation of misfolded
CC proteins in the ER. {ECO:0000269|PubMed:20692228,
CC ECO:0000269|PubMed:22016385}.
CC -!- PTM: Cleaved by CAPN2/m-calpain in resting macrophages but not in
CC activated macrophages. Macrophage activation up-regulates expression of
CC the calpain inhibitor CAST/calpastatin, resulting in inhibition of
CC CAPN2 activity (By similarity). {ECO:0000250|UniProtKB:Q9JLJ1}.
CC -!- PTM: Truncated SELENOK proteins produced by failed UGA/Sec decoding are
CC ubiquitinated by the CRL2(KLHDC2) complex, which recognizes the
CC diglycine (Gly-Gly) at the C-terminus of truncated SELENOK proteins.
CC {ECO:0000269|PubMed:26138980, ECO:0000269|PubMed:30526872}.
CC -!- SIMILARITY: Belongs to the selenoprotein K family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD40194.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF28975.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF537132; AAN61473.1; -; mRNA.
DR EMBL; AF085359; AAD40194.1; ALT_SEQ; mRNA.
DR EMBL; AF161415; AAF28975.1; ALT_SEQ; mRNA.
DR EMBL; BC013162; AAH13162.2; -; mRNA.
DR CCDS; CCDS54597.1; -.
DR RefSeq; NP_067060.2; NM_021237.4.
DR PDB; 6DO3; X-ray; 2.17 A; C/D=85-91.
DR PDBsum; 6DO3; -.
DR SMR; Q9Y6D0; -.
DR BioGRID; 121841; 48.
DR CORUM; Q9Y6D0; -.
DR IntAct; Q9Y6D0; 38.
DR MINT; Q9Y6D0; -.
DR STRING; 9606.ENSP00000418813; -.
DR iPTMnet; Q9Y6D0; -.
DR PhosphoSitePlus; Q9Y6D0; -.
DR BioMuta; SELENOK; -.
DR DMDM; 190352222; -.
DR EPD; Q9Y6D0; -.
DR jPOST; Q9Y6D0; -.
DR MassIVE; Q9Y6D0; -.
DR MaxQB; Q9Y6D0; -.
DR PaxDb; Q9Y6D0; -.
DR PeptideAtlas; Q9Y6D0; -.
DR PRIDE; Q9Y6D0; -.
DR ProteomicsDB; 86653; -.
DR Antibodypedia; 1553; 86 antibodies from 21 providers.
DR DNASU; 58515; -.
DR Ensembl; ENST00000495461.6; ENSP00000418813.1; ENSG00000113811.12.
DR GeneID; 58515; -.
DR KEGG; hsa:58515; -.
DR MANE-Select; ENST00000495461.6; ENSP00000418813.1; NM_021237.5; NP_067060.2.
DR CTD; 58515; -.
DR DisGeNET; 58515; -.
DR GeneCards; SELENOK; -.
DR HGNC; HGNC:30394; SELENOK.
DR HPA; ENSG00000113811; Low tissue specificity.
DR MIM; 607916; gene.
DR neXtProt; NX_Q9Y6D0; -.
DR OpenTargets; ENSG00000113811; -.
DR VEuPathDB; HostDB:ENSG00000113811; -.
DR eggNOG; ENOG502S3PW; Eukaryota.
DR GeneTree; ENSGT00390000016119; -.
DR InParanoid; Q9Y6D0; -.
DR OMA; FWGIADF; -.
DR OrthoDB; 1566291at2759; -.
DR PhylomeDB; Q9Y6D0; -.
DR PathwayCommons; Q9Y6D0; -.
DR SignaLink; Q9Y6D0; -.
DR BioGRID-ORCS; 58515; 41 hits in 1034 CRISPR screens.
DR ChiTaRS; SELENOK; human.
DR GenomeRNAi; 58515; -.
DR Pharos; Q9Y6D0; Tbio.
DR PRO; PR:Q9Y6D0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y6D0; protein.
DR Bgee; ENSG00000113811; Expressed in left ventricle myocardium and 185 other tissues.
DR ExpressionAtlas; Q9Y6D0; baseline and differential.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006816; P:calcium ion transport; IBA:GO_Central.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0010742; P:macrophage derived foam cell differentiation; IEA:Ensembl.
DR GO; GO:1990266; P:neutrophil migration; IEA:Ensembl.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IEA:Ensembl.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; IEA:Ensembl.
DR GO; GO:2000406; P:positive regulation of T cell migration; IEA:Ensembl.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0018345; P:protein palmitoylation; IDA:UniProtKB.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0051223; P:regulation of protein transport; IEA:Ensembl.
DR GO; GO:0045728; P:respiratory burst after phagocytosis; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0072678; P:T cell migration; IEA:Ensembl.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR InterPro; IPR024491; Se_SelK/SelG.
DR PANTHER; PTHR16875; PTHR16875; 1.
DR Pfam; PF10961; SelK_SelG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Calcium transport; Cell membrane;
KW Direct protein sequencing; Endoplasmic reticulum; Ion transport; Membrane;
KW Reference proteome; Selenocysteine; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4"
FT CHAIN 2..94
FT /note="Selenoprotein K"
FT /id="PRO_0000097669"
FT TRANSMEM 20..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 48..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 81..82
FT /note="Cleavage; by CAPN2"
FT /evidence="ECO:0000250"
FT NON_STD 92
FT /note="Selenocysteine"
FT VARIANT 50
FT /note="R -> S (in dbSNP:rs11562)"
FT /id="VAR_053921"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:6DO3"
SQ SEQUENCE 94 AA; 10645 MW; D26F13E90BEC6807 CRC64;
MVYISNGQVL DSRSQSPWRL SLITDFFWGI AEFVVLFFKT LLQQDVKKRR SYGNSSDSRY
DDGRGPPGNP PRRMGRINHL RGPSPPPMAG GUGR
