SPCS_HUMAN
ID SPCS_HUMAN Reviewed; 501 AA.
AC Q9HD40; A8K8W1; Q0D2P3; Q17RT1; Q9NXZ5; Q9UGM9; Q9Y353;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=O-phosphoseryl-tRNA(Sec) selenium transferase;
DE EC=2.9.1.2 {ECO:0000269|PubMed:17142313};
DE AltName: Full=Liver-pancreas antigen;
DE Short=LP;
DE AltName: Full=SLA-p35;
DE AltName: Full=SLA/LP autoantigen;
DE AltName: Full=Selenocysteine synthase;
DE Short=Sec synthase;
DE AltName: Full=Selenocysteinyl-tRNA(Sec) synthase;
DE AltName: Full=Sep-tRNA:Sec-tRNA synthase;
DE Short=SepSecS;
DE AltName: Full=Soluble liver antigen;
DE Short=SLA;
DE AltName: Full=UGA suppressor tRNA-associated protein;
DE AltName: Full=tRNA(Ser/Sec)-associated antigenic protein;
GN Name=SEPSECS; Synonyms=TRNP48;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Muscle;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-501 (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 29-501 (ISOFORM 2).
RC TISSUE=Liver, and T-cell lymphoma;
RX PubMed=10801173; DOI=10.1016/s0140-6736(00)02166-8;
RA Wies I., Brunner S., Henninger J., Herkel J., Kanzler S.,
RA Meyer zum Bueschenfelde K.-H., Lohse A.W.;
RT "Identification of target antigen for SLA/LP autoantibodies in autoimmune
RT hepatitis.";
RL Lancet 355:1510-1515(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-501 (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=10931155; DOI=10.1046/j.1365-2249.2000.01280.x;
RA Costa M., Rodriguez-Sanchez J.L., Czaja A.J., Gelpi C.;
RT "Isolation and characterization of cDNA encoding the antigenic protein of
RT the human tRNP(Ser)Sec complex recognized by autoantibodies from patients
RT with type-1 autoimmune hepatitis.";
RL Clin. Exp. Immunol. 121:364-374(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 61-501 (ISOFORM 1).
RC TISSUE=Liver;
RA Seelig H.-P., Wiemann C., Plaikner M., Schranz P., Seelig R., Renz M.;
RT "Coding sequence of the human SLA/LP autoantigen.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 208-501.
RX PubMed=11230739; DOI=10.1053/jhep.2001.22218;
RA Volkmann M., Martin L., Baeurle A., Heid H., Strassburg C.P., Trautwein C.,
RA Fiehn W., Manns M.P.;
RT "Soluble liver antigen: isolation of a 35-kd recombinant protein (SLA-p35)
RT specifically recognizing sera from patients with autoimmune hepatitis.";
RL Hepatology 33:591-596(2001).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 434-493, AND SLA/LP EPITOPE MAPPING.
RX PubMed=11826415; DOI=10.1053/jhep.2002.30699;
RA Herkel J., Heidrich B., Nieraad N., Wies I., Rother M., Lohse A.W.;
RT "Fine specificity of autoantibodies to soluble liver antigen and
RT liver/pancreas.";
RL Hepatology 35:403-408(2002).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, COFACTOR, AND MUTAGENESIS OF
RP LYS-284.
RX PubMed=17142313; DOI=10.1073/pnas.0609703104;
RA Yuan J., Palioura S., Salazar J.C., Su D., O'Donoghue P., Hohn M.J.,
RA Cardoso A.M., Whitman W.B., Soell D.;
RT "RNA-dependent conversion of phosphoserine forms selenocysteine in
RT eukaryotes and archaea.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18923-18927(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) IN COMPLEX WITH TRNA AND PYRIDOXAL
RP PHOSPHATE, SUBUNIT, SUBSTRATE-BINDING SITES, COFACTOR, MUTAGENESIS OF
RP ARG-75; ARG-97; GLN-105; LYS-173 AND ARG-313, AND REGION.
RX PubMed=19608919; DOI=10.1126/science.1173755;
RA Palioura S., Sherrer R.L., Steitz T.A., Soll D., Simonovic M.;
RT "The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine
RT formation.";
RL Science 325:321-325(2009).
RN [16]
RP VARIANTS PCH2D THR-239 AND CYS-334, AND CHARACTERIZATION OF VARIANTS PCH2D
RP THR-239 AND CYS-334.
RX PubMed=20920667; DOI=10.1016/j.ajhg.2010.09.007;
RA Agamy O., Ben Zeev B., Lev D., Marcus B., Fine D., Su D., Narkis G.,
RA Ofir R., Hoffmann C., Leshinsky-Silver E., Flusser H., Sivan S., Soll D.,
RA Lerman-Sagie T., Birk O.S.;
RT "Mutations disrupting selenocysteine formation cause progressive cerebello-
RT cerebral atrophy.";
RL Am. J. Hum. Genet. 87:538-544(2010).
RN [17]
RP VARIANT PCH2D SER-325.
RX PubMed=26115735; DOI=10.1212/wnl.0000000000001787;
RA Anttonen A.K., Hilander T., Linnankivi T., Isohanni P., French R.L.,
RA Liu Y., Simonovic M., Soell D., Somer M., Muth-Pawlak D., Corthals G.L.,
RA Laari A., Ylikallio E., Laehde M., Valanne L., Loennqvist T., Pihko H.,
RA Paetau A., Lehesjoki A.E., Suomalainen A., Tyynismaa H.;
RT "Selenoprotein biosynthesis defect causes progressive encephalopathy with
RT elevated lactate.";
RL Neurology 85:306-315(2015).
CC -!- FUNCTION: Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-
CC tRNA(Sec) required for selenoprotein biosynthesis.
CC {ECO:0000269|PubMed:17142313}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-seryl-tRNA(Sec) + selenophosphate = L-
CC selenocysteinyl-tRNA(Sec) + 2 phosphate; Xref=Rhea:RHEA:25041,
CC Rhea:RHEA-COMP:9743, Rhea:RHEA-COMP:9947, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16144, ChEBI:CHEBI:43474, ChEBI:CHEBI:78551,
CC ChEBI:CHEBI:78573; EC=2.9.1.2;
CC Evidence={ECO:0000269|PubMed:17142313};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:17142313, ECO:0000269|PubMed:19608919};
CC -!- PATHWAY: Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec)
CC biosynthesis; selenocysteinyl-tRNA(Sec) from L-seryl-tRNA(Sec)
CC (archaeal/eukaryal route): step 2/2. {ECO:0000269|PubMed:17142313}.
CC -!- SUBUNIT: Homotetramer formed by a catalytic dimer and a non-catalytic
CC dimer serving as a binding platform that orients tRNASec for catalysis.
CC Each tetramer binds the CCA ends of two tRNAs which point to the active
CC sites of the catalytic dimer. {ECO:0000269|PubMed:19608919}.
CC -!- INTERACTION:
CC Q9HD40; P04591: gag; Xeno; NbExp=3; IntAct=EBI-6163446, EBI-6163428;
CC Q9HD40; PRO_0000038593 [P04591]: gag; Xeno; NbExp=5; IntAct=EBI-6163446, EBI-6179719;
CC Q9HD40-3; Q86UW9: DTX2; NbExp=3; IntAct=EBI-12190001, EBI-740376;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9HD40-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HD40-2; Sequence=VSP_038078, VSP_038079;
CC Name=3;
CC IsoId=Q9HD40-3; Sequence=VSP_038080;
CC -!- TISSUE SPECIFICITY: Primarily expressed in liver, pancreas, kidney and
CC lung. Overexpressed in PHA-stimulated T-cells.
CC -!- DISEASE: Pontocerebellar hypoplasia 2D (PCH2D) [MIM:613811]: A disorder
CC characterized by postnatal onset of progressive atrophy of the cerebrum
CC and cerebellum, microcephaly, profound intellectual disability,
CC spasticity, and variable seizures. {ECO:0000269|PubMed:20920667,
CC ECO:0000269|PubMed:26115735}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Possible diagnostic marker for autoimmune hepatitis
CC (AIH).
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the SepSecS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD33963.2; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=AAH23539.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=CAB62209.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB89517.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK292476; BAF85165.1; -; mRNA.
DR EMBL; BX648976; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC007073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104662; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW92832.1; -; Genomic_DNA.
DR EMBL; BC023539; AAH23539.1; ALT_SEQ; mRNA.
DR EMBL; BC117202; AAI17203.1; -; mRNA.
DR EMBL; AF146396; AAD33963.2; ALT_SEQ; mRNA.
DR EMBL; AJ277541; CAB89517.1; ALT_FRAME; mRNA.
DR EMBL; AJ238617; CAB62209.1; ALT_INIT; mRNA.
DR EMBL; AF282065; AAG00491.1; -; mRNA.
DR CCDS; CCDS3432.2; -. [Q9HD40-1]
DR RefSeq; NP_058651.3; NM_016955.3. [Q9HD40-1]
DR RefSeq; XP_011512148.1; XM_011513846.2. [Q9HD40-3]
DR RefSeq; XP_011512150.1; XM_011513848.1.
DR PDB; 3HL2; X-ray; 2.81 A; A/B/C/D=1-501.
DR PDB; 4ZDL; X-ray; 2.26 A; A/B=1-501.
DR PDB; 4ZDO; X-ray; 2.65 A; A/B/C/D=1-501.
DR PDB; 4ZDP; X-ray; 2.70 A; A/B/C/D=1-501.
DR PDB; 7L1T; X-ray; 2.25 A; A=1-501.
DR PDBsum; 3HL2; -.
DR PDBsum; 4ZDL; -.
DR PDBsum; 4ZDO; -.
DR PDBsum; 4ZDP; -.
DR PDBsum; 7L1T; -.
DR AlphaFoldDB; Q9HD40; -.
DR SMR; Q9HD40; -.
DR BioGRID; 119280; 16.
DR CORUM; Q9HD40; -.
DR IntAct; Q9HD40; 13.
DR MINT; Q9HD40; -.
DR STRING; 9606.ENSP00000371535; -.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR iPTMnet; Q9HD40; -.
DR PhosphoSitePlus; Q9HD40; -.
DR BioMuta; SEPSECS; -.
DR DMDM; 62287911; -.
DR EPD; Q9HD40; -.
DR jPOST; Q9HD40; -.
DR MassIVE; Q9HD40; -.
DR MaxQB; Q9HD40; -.
DR PaxDb; Q9HD40; -.
DR PeptideAtlas; Q9HD40; -.
DR PRIDE; Q9HD40; -.
DR ProteomicsDB; 81825; -. [Q9HD40-1]
DR ProteomicsDB; 81826; -. [Q9HD40-2]
DR ProteomicsDB; 81827; -. [Q9HD40-3]
DR Antibodypedia; 10200; 172 antibodies from 28 providers.
DR DNASU; 51091; -.
DR Ensembl; ENST00000382103.7; ENSP00000371535.2; ENSG00000109618.13. [Q9HD40-1]
DR Ensembl; ENST00000514585.5; ENSP00000421880.1; ENSG00000109618.13. [Q9HD40-2]
DR GeneID; 51091; -.
DR KEGG; hsa:51091; -.
DR MANE-Select; ENST00000382103.7; ENSP00000371535.2; NM_016955.4; NP_058651.3.
DR UCSC; uc003grg.4; human. [Q9HD40-1]
DR CTD; 51091; -.
DR DisGeNET; 51091; -.
DR GeneCards; SEPSECS; -.
DR HGNC; HGNC:30605; SEPSECS.
DR HPA; ENSG00000109618; Tissue enhanced (liver).
DR MalaCards; SEPSECS; -.
DR MIM; 613009; gene.
DR MIM; 613811; phenotype.
DR neXtProt; NX_Q9HD40; -.
DR OpenTargets; ENSG00000109618; -.
DR Orphanet; 2524; Pontocerebellar hypoplasia type 2.
DR Orphanet; 247198; Progressive cerebello-cerebral atrophy.
DR PharmGKB; PA162402915; -.
DR VEuPathDB; HostDB:ENSG00000109618; -.
DR eggNOG; KOG3843; Eukaryota.
DR GeneTree; ENSGT00390000007332; -.
DR HOGENOM; CLU_022508_0_0_1; -.
DR InParanoid; Q9HD40; -.
DR OMA; HIINGAY; -.
DR OrthoDB; 680116at2759; -.
DR PhylomeDB; Q9HD40; -.
DR TreeFam; TF314381; -.
DR BRENDA; 2.9.1.2; 2681.
DR PathwayCommons; Q9HD40; -.
DR Reactome; R-HSA-2408557; Selenocysteine synthesis.
DR SignaLink; Q9HD40; -.
DR UniPathway; UPA00906; UER00898.
DR BioGRID-ORCS; 51091; 332 hits in 1089 CRISPR screens.
DR ChiTaRS; SEPSECS; human.
DR EvolutionaryTrace; Q9HD40; -.
DR GeneWiki; SEPSECS; -.
DR GenomeRNAi; 51091; -.
DR Pharos; Q9HD40; Tbio.
DR PRO; PR:Q9HD40; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9HD40; protein.
DR Bgee; ENSG00000109618; Expressed in ileal mucosa and 150 other tissues.
DR ExpressionAtlas; Q9HD40; baseline and differential.
DR Genevisible; Q9HD40; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:HGNC-UCL.
DR GO; GO:0098621; F:phosphoseryl-selenocysteinyl-tRNA selenium transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0000049; F:tRNA binding; ISS:HGNC-UCL.
DR GO; GO:0001514; P:selenocysteine incorporation; ISS:HGNC-UCL.
DR GO; GO:0097056; P:selenocysteinyl-tRNA(Sec) biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.640.10; -; 1.
DR InterPro; IPR019793; Peroxidases_heam-ligand_BS.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR019872; Sec-tRNA_Se_transferase.
DR InterPro; IPR008829; SepSecS/SepCysS.
DR PANTHER; PTHR12944; PTHR12944; 1.
DR Pfam; PF05889; SepSecS; 1.
DR PIRSF; PIRSF017689; SepSecS; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR03531; selenium_SpcS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Epilepsy;
KW Intellectual disability; Neurodegeneration; Phosphoprotein;
KW Protein biosynthesis; Pyridoxal phosphate; Reference proteome; RNA-binding;
KW Selenium; Transferase; tRNA-binding.
FT CHAIN 1..501
FT /note="O-phosphoseryl-tRNA(Sec) selenium transferase"
FT /id="PRO_0000219875"
FT REGION 1..44
FT /note="Tetramerization"
FT /evidence="ECO:0000269|PubMed:19608919"
FT REGION 96..106
FT /note="Phosphate loop (P-loop)"
FT /evidence="ECO:0000269|PubMed:19608919"
FT REGION 474..493
FT /note="SLA/LP epitope"
FT /evidence="ECO:0000269|PubMed:11826415"
FT BINDING 75
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 271
FT /ligand="tRNA"
FT /ligand_id="ChEBI:CHEBI:17843"
FT /ligand_part="tRNA variable arm"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 313
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 398
FT /ligand="tRNA"
FT /ligand_id="ChEBI:CHEBI:17843"
FT /ligand_part="tRNA discriminator base"
FT /evidence="ECO:0000269|PubMed:19608919"
FT BINDING 463
FT /ligand="tRNA"
FT /ligand_id="ChEBI:CHEBI:17843"
FT /ligand_part="tRNA acceptor arm"
FT /evidence="ECO:0000269|PubMed:19608919"
FT SITE 74
FT /note="May act as a substrate filter by repelling compounds
FT with a negatively charged alpha-carboxylate"
FT /evidence="ECO:0000250|UniProtKB:Q6P6M7"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 284
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:19608919"
FT VAR_SEQ 1..38
FT /note="MNRESFAAGERLVSPAYVRQGCEARRSHEHLIRLLLEK -> MQCDDLGSLQ
FT PPPPGFTPFACLSLPSSWDYRRPPPHP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038080"
FT VAR_SEQ 39..47
FT /note="GKCPENGWD -> VHSWHWTIR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10801173,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_038078"
FT VAR_SEQ 48..501
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10801173,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_038079"
FT VARIANT 239
FT /note="A -> T (in PCH2D; abrogates enzyme activity;
FT dbSNP:rs267607035)"
FT /evidence="ECO:0000269|PubMed:20920667"
FT /id="VAR_065585"
FT VARIANT 325
FT /note="T -> S (in PCH2D; dbSNP:rs1461368206)"
FT /evidence="ECO:0000269|PubMed:26115735"
FT /id="VAR_074163"
FT VARIANT 334
FT /note="Y -> C (in PCH2D; abrogates enzyme activity;
FT dbSNP:rs267607036)"
FT /evidence="ECO:0000269|PubMed:20920667"
FT /id="VAR_065586"
FT MUTAGEN 75
FT /note="R->A: Inactive in vivo."
FT /evidence="ECO:0000269|PubMed:19608919"
FT MUTAGEN 97
FT /note="R->A: Indistinguishable from wild-type."
FT /evidence="ECO:0000269|PubMed:19608919"
FT MUTAGEN 97
FT /note="R->Q: Indistinguishable from wild-type."
FT /evidence="ECO:0000269|PubMed:19608919"
FT MUTAGEN 105
FT /note="Q->A: Inactive in vivo."
FT /evidence="ECO:0000269|PubMed:19608919"
FT MUTAGEN 173
FT /note="K->A: Indistinguishable from wild-type."
FT /evidence="ECO:0000269|PubMed:19608919"
FT MUTAGEN 173
FT /note="K->M: Indistinguishable from wild-type."
FT /evidence="ECO:0000269|PubMed:19608919"
FT MUTAGEN 284
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17142313"
FT MUTAGEN 313
FT /note="R->A: Inactive in vivo."
FT /evidence="ECO:0000269|PubMed:19608919"
FT CONFLICT 98
FT /note="S -> P (in Ref. 8; AAG00491)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="H -> R (in Ref. 1; BAF85165)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="R -> K (in Ref. 6; AAD33963/CAB89517)"
FT /evidence="ECO:0000305"
FT CONFLICT 452
FT /note="K -> N (in Ref. 6; AAD33963/CAB89517)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="K -> R (in Ref. 8; AAG00491)"
FT /evidence="ECO:0000305"
FT HELIX 3..10
FT /evidence="ECO:0007829|PDB:4ZDO"
FT HELIX 22..38
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 48..59
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 82..87
FT /evidence="ECO:0007829|PDB:4ZDL"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 109..128
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 144..158
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 173..181
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 197..200
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 202..212
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 217..225
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 235..244
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 260..272
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 282..286
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 293..298
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 300..308
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 317..357
FT /evidence="ECO:0007829|PDB:4ZDL"
FT TURN 358..360
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 370..376
FT /evidence="ECO:0007829|PDB:4ZDL"
FT TURN 382..384
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 388..397
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 411..414
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 417..420
FT /evidence="ECO:0007829|PDB:4ZDL"
FT TURN 421..425
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:4ZDL"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:4ZDL"
FT HELIX 444..461
FT /evidence="ECO:0007829|PDB:4ZDL"
SQ SEQUENCE 501 AA; 55726 MW; 7136FB390B18760B CRC64;
MNRESFAAGE RLVSPAYVRQ GCEARRSHEH LIRLLLEKGK CPENGWDEST LELFLHELAI
MDSNNFLGNC GVGEREGRVA SALVARRHYR FIHGIGRSGD ISAVQPKAAG SSLLNKITNS
LVLDIIKLAG VHTVANCFVV PMATGMSLTL CFLTLRHKRP KAKYIIWPRI DQKSCFKSMI
TAGFEPVVIE NVLEGDELRT DLKAVEAKVQ ELGPDCILCI HSTTSCFAPR VPDRLEELAV
ICANYDIPHI VNNAYGVQSS KCMHLIQQGA RVGRIDAFVQ SLDKNFMVPV GGAIIAGFND
SFIQEISKMY PGRASASPSL DVLITLLSLG SNGYKKLLKE RKEMFSYLSN QIKKLSEAYN
ERLLHTPHNP ISLAMTLKTL DEHRDKAVTQ LGSMLFTRQV SGARVVPLGS MQTVSGYTFR
GFMSHTNNYP CAYLNAASAI GMKMQDVDLF IKRLDRCLKA VRKERSKESD DNYDKTEDVD
IEEMALKLDN VLLDTYQDAS S
