ID EPT1_HUMAN Reviewed; 397 AA.
AC Q9C0D9; Q63ZE3;
DT 22-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 27-MAR-2024, entry version 159.
DE RecName: Full=Ethanolaminephosphotransferase 1 {ECO:0000305};
DE Short=hEPT1;
DE EC=2.7.8.1 {ECO:0000269|PubMed:17132865, ECO:0000269|PubMed:28052917, ECO:0000269|PubMed:29500230};
DE AltName: Full=Selenoprotein I {ECO:0000303|PubMed:27645994, ECO:0000312|HGNC:HGNC:29361};
DE Short=SelI {ECO:0000303|PubMed:27645994};
GN Name=SELENOI {ECO:0000312|HGNC:HGNC:29361};
GN Synonyms=EPT1 {ECO:0000312|HGNC:HGNC:29361},
GN KIAA1724 {ECO:0000312|EMBL:BAB21815.1}, SELI {ECO:0000303|PubMed:27645994};
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 SELENOCYSTEINE.
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=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [3]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, COFACTOR,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17132865; DOI=10.1194/jlr.c600019-jlr200;
RA Horibata Y., Hirabayashi Y.;
RT "Identification and characterization of human
RT ethanolaminephosphotransferase1.";
RL J. Lipid Res. 48:503-508(2007).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [6]
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 [7]
RP INVOLVEMENT IN SPG81, VARIANT SPG81 PRO-112, CHARACTERIZATION OF VARIANT
RP SPG81 PRO-112, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION,
RP AND TOPOLOGY.
RX PubMed=28052917; DOI=10.1093/brain/aww318;
RA Ahmed M.Y., Al-Khayat A., Al-Murshedi F., Al-Futaisi A., Chioza B.A.,
RA Pedro Fernandez-Murray J., Self J.E., Salter C.G., Harlalka G.V.,
RA Rawlins L.E., Al-Zuhaibi S., Al-Azri F., Al-Rashdi F., Cazenave-Gassiot A.,
RA Wenk M.R., Al-Salmi F., Patton M.A., Silver D.L., Baple E.L.,
RA McMaster C.R., Crosby A.H.;
RT "A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway
RT phospholipid biosynthesis.";
RL Brain 140:547-554(2017).
RN [8]
RP INVOLVEMENT IN SPG81, CATALYTIC ACTIVITY, FUNCTION, AND PATHWAY.
RX PubMed=29500230; DOI=10.1194/jlr.p081620;
RA Horibata Y., Elpeleg O., Eran A., Hirabayashi Y., Savitzki D., Tal G.,
RA Mandel H., Sugimoto H.;
RT "EPT1 (selenoprotein I) is critical for the neural development and
RT maintenance of plasmalogen in humans.";
RL J. Lipid Res. 59:1015-1026(2018).
CC -!- FUNCTION: Ethanolaminephosphotransferase that catalyzes the transfer of
CC phosphoethanolamine/PE from CDP-ethanolamine to lipid acceptors, the
CC final step in the synthesis of PE via the 'Kennedy' pathway
CC (PubMed:17132865, PubMed:28052917, PubMed:29500230). PE is the second
CC most abundant phospholipid of membranes in mammals and is involved in
CC various membrane-related cellular processes (PubMed:17132865). The
CC enzyme is critical for the synthesis of several PE species and could
CC also catalyze the synthesis of ether-linked phospholipids like
CC plasmanyl- and plasmenyl-PE which could explain it is required for
CC proper myelination and neurodevelopment (PubMed:29500230).
CC {ECO:0000269|PubMed:17132865, ECO:0000269|PubMed:28052917,
CC ECO:0000269|PubMed:29500230, ECO:0000303|PubMed:17132865}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + CDP-ethanolamine = a 1,2-diacyl-sn-
CC glycero-3-phosphoethanolamine + CMP + H(+); Xref=Rhea:RHEA:32943,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:57876,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:64612; EC=2.7.8.1;
CC Evidence={ECO:0000269|PubMed:17132865, ECO:0000269|PubMed:28052917,
CC ECO:0000269|PubMed:29500230};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32944;
CC Evidence={ECO:0000269|PubMed:17132865, ECO:0000269|PubMed:28052917,
CC ECO:0000269|PubMed:29500230};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17132865};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:17132865};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.8 uM for CDP-ethanolamine {ECO:0000269|PubMed:17132865};
CC Vmax=76.3 pmol/min/mg enzyme with CDP-ethanolamine as substrate
CC {ECO:0000269|PubMed:17132865};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylethanolamine
CC biosynthesis; phosphatidylethanolamine from ethanolamine: step 3/3.
CC {ECO:0000269|PubMed:28052917, ECO:0000269|PubMed:29500230}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:17132865, ECO:0000305|PubMed:28052917}; Multi-pass
CC membrane protein {ECO:0000305|PubMed:28052917}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Abundant in brain, placenta,
CC liver and pancreas, followed by heart, skeletal muscle, lung and
CC kidney. In brain it is strongly expressed in cerebellum, followed by
CC the occipital pole and the frontal lobe. {ECO:0000269|PubMed:17132865}.
CC -!- DISEASE: Spastic paraplegia 81, autosomal recessive (SPG81)
CC [MIM:618768]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body. SPG81 is a complicated
CC form characterized by white matter abnormalities, hypomyelination with
CC progressive white matter loss, delayed motor development, progressive
CC spasticity, and impaired intellectual development and speech delay.
CC Additional features may include bifid uvula, microcephaly, seizures,
CC and variable ocular anomalies. {ECO:0000269|PubMed:28052917,
CC ECO:0000269|PubMed:29500230}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CDP-alcohol phosphatidyltransferase class-I
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB21815.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; BK001426; DAA01514.1; -; mRNA.
DR EMBL; AB051511; BAB21815.1; ALT_SEQ; mRNA.
DR CCDS; CCDS46240.1; -.
DR RefSeq; NP_277040.1; NM_033505.3.
DR BioGRID; 124549; 26.
DR IntAct; Q9C0D9; 4.
DR STRING; 9606.ENSP00000260585; -.
DR iPTMnet; Q9C0D9; -.
DR PhosphoSitePlus; Q9C0D9; -.
DR SwissPalm; Q9C0D9; -.
DR BioMuta; SELENOI; -.
DR DMDM; 172046233; -.
DR EPD; Q9C0D9; -.
DR jPOST; Q9C0D9; -.
DR MassIVE; Q9C0D9; -.
DR MaxQB; Q9C0D9; -.
DR PaxDb; 9606-ENSP00000260585; -.
DR PeptideAtlas; Q9C0D9; -.
DR ProteomicsDB; 80018; -.
DR Pumba; Q9C0D9; -.
DR Antibodypedia; 60801; 14 antibodies from 7 providers.
DR DNASU; 85465; -.
DR Ensembl; ENST00000260585.12; ENSP00000260585.7; ENSG00000138018.19.
DR GeneID; 85465; -.
DR KEGG; hsa:85465; -.
DR MANE-Select; ENST00000260585.12; ENSP00000260585.7; NM_033505.4; NP_277040.1.
DR UCSC; uc021veu.2; human.
DR AGR; HGNC:29361; -.
DR CTD; 85465; -.
DR DisGeNET; 85465; -.
DR GeneCards; SELENOI; -.
DR HGNC; HGNC:29361; SELENOI.
DR HPA; ENSG00000138018; Low tissue specificity.
DR MalaCards; SELENOI; -.
DR MIM; 607915; gene.
DR MIM; 618768; phenotype.
DR neXtProt; NX_Q9C0D9; -.
DR OpenTargets; ENSG00000138018; -.
DR Orphanet; 506353; Autosomal recessive complex spastic paraplegia due to Kennedy pathway dysfunction.
DR PharmGKB; PA165696581; -.
DR VEuPathDB; HostDB:ENSG00000138018; -.
DR eggNOG; KOG2877; Eukaryota.
DR GeneTree; ENSGT00950000183117; -.
DR HOGENOM; CLU_035066_2_0_1; -.
DR InParanoid; Q9C0D9; -.
DR OMA; QNMGQGW; -.
DR OrthoDB; 5482983at2759; -.
DR PhylomeDB; Q9C0D9; -.
DR TreeFam; TF313270; -.
DR BioCyc; MetaCyc:HS06434-MONOMER; -.
DR BRENDA; 2.7.8.1; 2681.
DR PathwayCommons; Q9C0D9; -.
DR Reactome; R-HSA-1483213; Synthesis of PE.
DR SABIO-RK; Q9C0D9; -.
DR SignaLink; Q9C0D9; -.
DR UniPathway; UPA00558; UER00743.
DR BioGRID-ORCS; 85465; 45 hits in 1168 CRISPR screens.
DR ChiTaRS; SELENOI; human.
DR GenomeRNAi; 85465; -.
DR Pharos; Q9C0D9; Tbio.
DR PRO; PR:Q9C0D9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9C0D9; Protein.
DR Bgee; ENSG00000138018; Expressed in ileal mucosa and 167 other cell types or tissues.
DR ExpressionAtlas; Q9C0D9; baseline and differential.
DR Genevisible; Q9C0D9; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0004307; F:ethanolaminephosphotransferase activity; IDA:HGNC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; IDA:HGNC.
DR Gene3D; 1.20.120.1760; -; 1.
DR InterPro; IPR000462; CDP-OH_P_trans.
DR InterPro; IPR043130; CDP-OH_PTrfase_TM_dom.
DR InterPro; IPR048254; CDP_ALCOHOL_P_TRANSF_CS.
DR InterPro; IPR014472; CHOPT.
DR PANTHER; PTHR10414; ETHANOLAMINEPHOSPHOTRANSFERASE; 1.
DR PANTHER; PTHR10414:SF47; ETHANOLAMINEPHOSPHOTRANSFERASE 1; 1.
DR Pfam; PF01066; CDP-OH_P_transf; 1.
DR PIRSF; PIRSF015665; CHOPT; 1.
DR PROSITE; PS00379; CDP_ALCOHOL_P_TRANSF; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disease variant; Endoplasmic reticulum;
KW Hereditary spastic paraplegia; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Manganese; Membrane; Metal-binding; Neurodegeneration;
KW Phospholipid biosynthesis; Phospholipid metabolism; Reference proteome;
KW Selenocysteine; Transferase; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..397
FT /note="Ethanolaminephosphotransferase 1"
FT /id="PRO_0000056813"
FT TRANSMEM 47..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..145
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..201
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 221..243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 317..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT NON_STD 387
FT /note="Selenocysteine"
FT /evidence="ECO:0000269|PubMed:12775843"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT VARIANT 112
FT /note="R -> P (in SPG81; loss of
FT ethanolaminephosphotransferase activity;
FT dbSNP:rs933233143)"
FT /evidence="ECO:0000269|PubMed:28052917"
FT /id="VAR_083878"
SQ SEQUENCE 397 AA; 45229 MW; 24CDB1F19EFE4202 CRC64;
MAGYEYVSPE QLAGFDKYKY SAVDTNPLSL YVMHPFWNTI VKVFPTWLAP NLITFSGFLL
VVFNFLLMAY FDPDFYASAP GHKHVPDWVW IVVGILNFVA YTLDGVDGKQ ARRTNSSTPL
GELFDHGLDS WSCVYFVVTV YSIFGRGSTG VSVFVLYLLL WVVLFSFILS HWEKYNTGIL
FLPWGYDISQ VTISFVYIVT AVVGVEAWYE PFLFNFLYRD LFTAMIIGCA LCVTLPMSLL
NFFRSYKNNT LKLNSVYEAM VPLFSPCLLF ILSTAWILWS PSDILELHPR VFYFMVGTAF
ANSTCQLIVC QMSSTRCPTL NWLLVPLFLV VLVVNLGVAS YVESILLYTL TTAFTLAHIH
YGVRVVKQLS SHFQIYPFSL RKPNSDULGM EEKNIGL
//
