SPS2_HUMAN
ID SPS2_HUMAN Reviewed; 448 AA.
AC Q99611; Q9BUQ2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Selenide, water dikinase 2;
DE EC=2.7.9.3 {ECO:0000250|UniProtKB:P49903};
DE AltName: Full=Selenium donor protein 2;
DE AltName: Full=Selenophosphate synthase 2;
GN Name=SEPHS2; Synonyms=SPS2;
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].
RX PubMed=7588067; DOI=10.1242/dev.121.10.3335;
RA Guimaraes M.J., Bazan J.F., Zlotnik A., Wiles M.V., Grimaldi J.C., Lee F.,
RA McClanahan T.;
RT "A new approach to the study of haematopoietic development in the yolk sac
RT and embryoid bodies.";
RL Development 121:3335-3346(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8986768; DOI=10.1073/pnas.93.26.15086;
RA Guimaraes M.J., Peterson D., Vicari A., Cocks B.G., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Ferrick D.A., Kastelein R., Bazan J.F.,
RA Zlotnik A.;
RT "Identification of a novel selD homolog from eukaryotes, bacteria, and
RT archaea: is there an autoregulatory mechanism in selenocysteine
RT metabolism?";
RL Proc. Natl. Acad. Sci. U.S.A. 93:15086-15091(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle, and Skin;
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 [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=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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97, AND IDENTIFICATION BY
RP 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 [7]
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).
CC -!- FUNCTION: Synthesizes selenophosphate from selenide and ATP.
CC {ECO:0000250|UniProtKB:P49903}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + hydrogenselenide = AMP + 2 H(+) + phosphate +
CC selenophosphate; Xref=Rhea:RHEA:18737, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16144, ChEBI:CHEBI:29317,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456215; EC=2.7.9.3;
CC Evidence={ECO:0000250|UniProtKB:P49903};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P49903};
CC Note=Binds 1 Mg(2+) ion per monomer. {ECO:0000250|UniProtKB:P49903};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P49903}.
CC -!- PTM: Truncated SEPHS2 proteins produced by failed UGA/Sec decoding are
CC ubiquitinated by the CRL2(KLHDC3) complex, which recognizes the glycine
CC (Gly) at the C-terminus of truncated SEPHS2 proteins.
CC {ECO:0000269|PubMed:26138980}.
CC -!- SIMILARITY: Belongs to the selenophosphate synthase 1 family. Class I
CC subfamily. {ECO:0000305}.
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DR EMBL; U43286; AAC50958.2; -; mRNA.
DR EMBL; AC116348; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002381; AAH02381.3; -; mRNA.
DR EMBL; BC016643; AAH16643.1; -; mRNA.
DR CCDS; CCDS42150.1; -.
DR RefSeq; NP_036380.2; NM_012248.3.
DR BioGRID; 116588; 19.
DR CORUM; Q99611; -.
DR IntAct; Q99611; 7.
DR MINT; Q99611; -.
DR STRING; 9606.ENSP00000418669; -.
DR iPTMnet; Q99611; -.
DR PhosphoSitePlus; Q99611; -.
DR BioMuta; SEPHS2; -.
DR DMDM; 172044671; -.
DR EPD; Q99611; -.
DR jPOST; Q99611; -.
DR MassIVE; Q99611; -.
DR MaxQB; Q99611; -.
DR PaxDb; Q99611; -.
DR PeptideAtlas; Q99611; -.
DR PRIDE; Q99611; -.
DR ProteomicsDB; 78354; -.
DR Antibodypedia; 43619; 112 antibodies from 22 providers.
DR DNASU; 22928; -.
DR Ensembl; ENST00000478753.5; ENSP00000418669.3; ENSG00000179918.19.
DR GeneID; 22928; -.
DR KEGG; hsa:22928; -.
DR MANE-Select; ENST00000478753.5; ENSP00000418669.3; NM_012248.4; NP_036380.2.
DR CTD; 22928; -.
DR DisGeNET; 22928; -.
DR GeneCards; SEPHS2; -.
DR HGNC; HGNC:19686; SEPHS2.
DR HPA; ENSG00000179918; Tissue enhanced (liver).
DR MIM; 606218; gene.
DR neXtProt; NX_Q99611; -.
DR OpenTargets; ENSG00000179918; -.
DR PharmGKB; PA134868765; -.
DR VEuPathDB; HostDB:ENSG00000179918; -.
DR eggNOG; KOG3939; Eukaryota.
DR GeneTree; ENSGT00390000000950; -.
DR InParanoid; Q99611; -.
DR OMA; RWNKINM; -.
DR OrthoDB; 1166567at2759; -.
DR PhylomeDB; Q99611; -.
DR TreeFam; TF313811; -.
DR BRENDA; 2.7.9.3; 2681.
DR PathwayCommons; Q99611; -.
DR Reactome; R-HSA-2408557; Selenocysteine synthesis.
DR SignaLink; Q99611; -.
DR BioGRID-ORCS; 22928; 344 hits in 1049 CRISPR screens.
DR ChiTaRS; SEPHS2; human.
DR GenomeRNAi; 22928; -.
DR Pharos; Q99611; Tdark.
DR PRO; PR:Q99611; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q99611; protein.
DR Bgee; ENSG00000179918; Expressed in jejunal mucosa and 205 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004756; F:selenide, water dikinase activity; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0001887; P:selenium compound metabolic process; IEA:Ensembl.
DR GO; GO:0016260; P:selenocysteine biosynthetic process; IBA:GO_Central.
DR GO; GO:0016259; P:selenocysteine metabolic process; TAS:Reactome.
DR CDD; cd02195; SelD; 1.
DR Gene3D; 3.30.1330.10; -; 1.
DR Gene3D; 3.90.650.10; -; 1.
DR InterPro; IPR010918; PurM-like_C_dom.
DR InterPro; IPR036676; PurM-like_C_sf.
DR InterPro; IPR016188; PurM-like_N.
DR InterPro; IPR036921; PurM-like_N_sf.
DR InterPro; IPR004536; SPS/SelD.
DR PANTHER; PTHR10256; PTHR10256; 1.
DR Pfam; PF00586; AIRS; 1.
DR Pfam; PF02769; AIRS_C; 1.
DR SUPFAM; SSF55326; SSF55326; 1.
DR SUPFAM; SSF56042; SSF56042; 1.
DR TIGRFAMs; TIGR00476; selD; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Selenium;
KW Selenocysteine; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..448
FT /note="Selenide, water dikinase 2"
FT /id="PRO_0000127650"
FT REGION 84..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 60
FT /evidence="ECO:0000255"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 118..120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 120
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 138
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 161
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 161
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 212..215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT BINDING 316
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P49903"
FT SITE 63
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:P16456"
FT NON_STD 60
FT /note="Selenocysteine"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97364"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 269
FT /note="P -> A (in dbSNP:rs1804600)"
FT /id="VAR_052345"
SQ SEQUENCE 448 AA; 47305 MW; 309520C0CAE770F7 CRC64;
MAEASATGAC GEAMAAAEGS SGPAGLTLGR SFSNYRPFEP QALGLSPSWR LTGFSGMKGU
GCKVPQEALL KLLAGLTRPD VRPPLGRGLV GGQEEASQEA GLPAGAGPSP TFPALGIGMD
SCVIPLRHGG LSLVQTTDFF YPLVEDPYMM GRIACANVLS DLYAMGITEC DNMLMLLSVS
QSMSEEEREK VTPLMVKGFR DAAEEGGTAV TGGQTVVNPW IIIGGVATVV CQPNEFIMPD
SAVVGDVLVL TKPLGTQVAV NAHQWLDNPE RWNKVKMVVS REEVELAYQE AMFNMATLNR
TAAGLMHTFN AHAATDITGF GILGHSQNLA KQQRNEVSFV IHNLPIIAKM AAVSKASGRF
GLLQGTSAET SGGLLICLPR EQAARFCSEI KSSKYGEGHQ AWIVGIVEKG NRTARIIDKP
RVIEVLPRGA TAAVLAPDSS NASSEPSS
