DICER_MOUSE
ID DICER_MOUSE Reviewed; 1916 AA.
AC Q8R418; Q8R419;
DT 25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Endoribonuclease Dicer;
DE EC=3.1.26.3;
DE AltName: Full=Double-strand-specific ribonuclease mDCR-1;
GN Name=Dicer1; Synonyms=Dicer, Mdcr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [GENOMIC
RP DNA] OF 17-1916.
RC STRAIN=C57BL/6J;
RX PubMed=11889553; DOI=10.1007/s00335-001-2119-6;
RA Nicholson R.H., Nicholson A.W.;
RT "Molecular characterization of a mouse cDNA encoding Dicer, a ribonuclease
RT III ortholog involved in RNA interference.";
RL Mamm. Genome 13:67-73(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12526743; DOI=10.1016/s0960-9822(02)01394-5;
RA Doi N., Zenno S., Ueda R., Ohki-Hamazaki H., Ui-Tei K., Saigo K.;
RT "Short-interfering-RNA-mediated gene silencing in mammalian cells requires
RT Dicer and eIF2C translation initiation factors.";
RL Curr. Biol. 13:41-46(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Czech II;
RX PubMed=15081373; DOI=10.1016/j.ydbio.2004.01.028;
RA Svoboda P., Stein P., Anger M., Bernstein E., Hannon G.J., Schultz R.M.;
RT "RNAi and expression of retrotransposons MuERV-L and IAP in preimplantation
RT mouse embryos.";
RL Dev. Biol. 269:276-285(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1464, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP IDENTIFICATION OF ISOFORM 2, FUNCTION (ISOFORMS 1 AND 2), DISRUPTION
RP PHENOTYPE (ISOFORM 2), AND TISSUE SPECIFICITY (ISOFORMS 1 AND 2).
RX PubMed=24209619; DOI=10.1016/j.cell.2013.10.001;
RA Flemr M., Malik R., Franke V., Nejepinska J., Sedlacek R., Vlahovicek K.,
RA Svoboda P.;
RT "A retrotransposon-driven dicer isoform directs endogenous small
RT interfering RNA production in mouse oocytes.";
RL Cell 155:807-816(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 1647-1910, AND MUTAGENESIS OF
RP LYS-1800.
RX PubMed=18268334; DOI=10.1073/pnas.0711506105;
RA Du Z., Lee J.K., Tjhen R., Stroud R.M., James T.L.;
RT "Structural and biochemical insights into the dicing mechanism of mouse
RT Dicer: a conserved lysine is critical for dsRNA cleavage.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:2391-2396(2008).
CC -!- FUNCTION: Double-stranded RNA (dsRNA) endoribonuclease playing a
CC central role in short dsRNA-mediated post-transcriptional gene
CC silencing. Cleaves naturally occurring long dsRNAs and short hairpin
CC pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three
CC nucleotides with 3' overhang of two nucleotides, producing respectively
CC short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs
CC serve as guide to direct the RNA-induced silencing complex (RISC) to
CC complementary RNAs to degrade them or prevent their translation. Gene
CC silencing mediated by siRNAs, also called RNA interference, controls
CC the elimination of transcripts from mobile and repetitive DNA elements
CC of the genome but also the degradation of exogenous RNA of viral origin
CC for instance. The miRNA pathway on the other side is a mean to
CC specifically regulate the expression of target genes (By similarity).
CC {ECO:0000250|UniProtKB:Q9UPY3}.
CC -!- FUNCTION: [Isoform 2]: More active than isoform 1 to process long
CC double-stranded RNA into siRNAs. Responsible for the accumulation of
CC endogenous siRNAs observed in mouse oocytes compared to somatic cells
CC and it regulates meiotic spindle organization in female germline.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000305};
CC Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000305};
CC -!- SUBUNIT: Component of the RISC loading complex (RLC), or micro-RNA
CC (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and
CC TARBP2; DICER1 and TARBP2 are required to process precursor miRNAs
CC (pre-miRNAs) to mature miRNAs and then load them onto AGO2. Note that
CC the trimeric RLC/miRLC is also referred to as RISC. Interacts with
CC DHX9, AGO1, PIWIL1 and PRKRA. Interacts with AGO2, TARBP2, EIF6, MOV10
CC and RPL7A (60S ribosome subunit); they form a large RNA-induced
CC silencing complex (RISC). Interacts with BCDIN3D (By similarity).
CC Interacts (via Dicer dsRNA-binding fold domain) with ALOX5 (via PLAT
CC domain); this interaction enhances arachidonate 5-lipoxygenase activity
CC and modifies the miRNA precursor processing activity of DICER1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9UPY3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UPY3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=DicerS;
CC IsoId=Q8R418-1; Sequence=Displayed;
CC Name=2; Synonyms=DicerO;
CC IsoId=Q8R418-2; Sequence=VSP_053586;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in a wide variety of
CC tissues. Isoform 2 is specifically expressed in oocytes during their
CC growth (at protein level).
CC -!- DISRUPTION PHENOTYPE: [Isoform 2]: Mice lacking isoform 2 are viable
CC and males are fertile. However, females are sterile, their oocytes
CC displaying meiotic spindle defects.
CC -!- MISCELLANEOUS: [Isoform 2]: An MT-C retrotransposon in intron 6 of the
CC mouse DICER gene functions as a promoter producing a transcript lacking
CC exons 1 to 6. A new alternative first exon is directly derived from the
CC retrotransposon. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the helicase family. Dicer subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-11 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM21495.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC15765.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC15765.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF484523; AAL84637.1; -; Genomic_DNA.
DR EMBL; AF484524; AAL84638.1; -; Genomic_DNA.
DR EMBL; AB081470; BAC15765.1; ALT_INIT; mRNA.
DR EMBL; AF430845; AAM21495.1; ALT_FRAME; mRNA.
DR PDB; 3C4B; X-ray; 1.68 A; A=1648-1910.
DR PDB; 3C4T; X-ray; 2.80 A; A=1648-1910.
DR PDBsum; 3C4B; -.
DR PDBsum; 3C4T; -.
DR AlphaFoldDB; Q8R418; -.
DR SMR; Q8R418; -.
DR ComplexPortal; CPX-1073; RISC-loading complex, PRKRA variant.
DR ComplexPortal; CPX-135; RISC-loading complex, TARBP2 variant.
DR DIP; DIP-29721N; -.
DR IntAct; Q8R418; 4.
DR STRING; 10090.ENSMUSP00000043676; -.
DR iPTMnet; Q8R418; -.
DR PhosphoSitePlus; Q8R418; -.
DR EPD; Q8R418; -.
DR jPOST; Q8R418; -.
DR MaxQB; Q8R418; -.
DR PaxDb; Q8R418; -.
DR PeptideAtlas; Q8R418; -.
DR PRIDE; Q8R418; -.
DR ProteomicsDB; 279660; -. [Q8R418-1]
DR ProteomicsDB; 279661; -. [Q8R418-2]
DR MGI; MGI:2177178; Dicer1.
DR eggNOG; KOG0701; Eukaryota.
DR InParanoid; Q8R418; -.
DR PhylomeDB; Q8R418; -.
DR BRENDA; 3.1.26.3; 3474.
DR Reactome; R-MMU-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-MMU-426486; Small interfering RNA (siRNA) biogenesis.
DR ChiTaRS; Dicer1; mouse.
DR EvolutionaryTrace; Q8R418; -.
DR PRO; PR:Q8R418; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8R418; protein.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0016442; C:RISC complex; IDA:MGI.
DR GO; GO:0070578; C:RISC-loading complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004530; F:deoxyribonuclease I activity; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0004521; F:endoribonuclease activity; ISO:MGI.
DR GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035198; F:miRNA binding; IDA:MGI.
DR GO; GO:0070883; F:pre-miRNA binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0004525; F:ribonuclease III activity; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0035197; F:siRNA binding; ISO:MGI.
DR GO; GO:0048856; P:anatomical structure development; IMP:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; IBA:GO_Central.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:MGI.
DR GO; GO:0055013; P:cardiac muscle cell development; IMP:MGI.
DR GO; GO:0061309; P:cardiac neural crest cell development involved in outflow tract morphogenesis; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; IMP:MGI.
DR GO; GO:0048565; P:digestive tract development; IMP:MGI.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IMP:MGI.
DR GO; GO:0048730; P:epidermis morphogenesis; IMP:MGI.
DR GO; GO:0061548; P:ganglion development; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0098795; P:global gene silencing by mRNA cleavage; ISS:UniProtKB.
DR GO; GO:0071335; P:hair follicle cell proliferation; IMP:MGI.
DR GO; GO:0001942; P:hair follicle development; IMP:MGI.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI.
DR GO; GO:0060119; P:inner ear receptor cell development; IMP:MGI.
DR GO; GO:0060576; P:intestinal epithelial cell development; IGI:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0000212; P:meiotic spindle organization; IMP:UniProtKB.
DR GO; GO:0035196; P:miRNA processing; IMP:BHF-UCL.
DR GO; GO:0048255; P:mRNA stabilization; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0014835; P:myoblast differentiation involved in skeletal muscle regeneration; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IMP:MGI.
DR GO; GO:0010626; P:negative regulation of Schwann cell proliferation; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0021675; P:nerve development; IMP:BHF-UCL.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:BHF-UCL.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; IMP:MGI.
DR GO; GO:0031508; P:pericentric heterochromatin assembly; IMP:MGI.
DR GO; GO:0032290; P:peripheral nervous system myelin formation; IMP:BHF-UCL.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:1904906; P:positive regulation of endothelial cell-matrix adhesion via fibronectin; ISO:MGI.
DR GO; GO:1903142; P:positive regulation of establishment of endothelial barrier; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:1904899; P:positive regulation of hepatic stellate cell proliferation; ISO:MGI.
DR GO; GO:2000630; P:positive regulation of miRNA metabolic process; IMP:MGI.
DR GO; GO:0031643; P:positive regulation of myelination; IMP:BHF-UCL.
DR GO; GO:0014040; P:positive regulation of Schwann cell differentiation; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0035194; P:post-transcriptional gene silencing by RNA; IMP:MGI.
DR GO; GO:0031054; P:pre-miRNA processing; IDA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:MGI.
DR GO; GO:0070173; P:regulation of enamel mineralization; IMP:MGI.
DR GO; GO:0030856; P:regulation of epithelial cell differentiation; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI.
DR GO; GO:2000628; P:regulation of miRNA metabolic process; IMP:MGI.
DR GO; GO:0010660; P:regulation of muscle cell apoptotic process; IMP:MGI.
DR GO; GO:0031641; P:regulation of myelination; IMP:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; IMP:MGI.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:MGI.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IC:BHF-UCL.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IMP:MGI.
DR GO; GO:0048713; P:regulation of oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IMP:MGI.
DR GO; GO:0051252; P:regulation of RNA metabolic process; IMP:MGI.
DR GO; GO:2000736; P:regulation of stem cell differentiation; IMP:MGI.
DR GO; GO:0045069; P:regulation of viral genome replication; IMP:MGI.
DR GO; GO:0048608; P:reproductive structure development; IMP:MGI.
DR GO; GO:0070922; P:RISC complex assembly; ISO:MGI.
DR GO; GO:0090501; P:RNA phosphodiester bond hydrolysis; IBA:GO_Central.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; ISO:MGI.
DR GO; GO:0006396; P:RNA processing; IDA:MGI.
DR GO; GO:0006364; P:rRNA processing; IEA:InterPro.
DR GO; GO:0030422; P:siRNA processing; IDA:MGI.
DR GO; GO:0007284; P:spermatogonial cell division; IMP:MGI.
DR GO; GO:0021522; P:spinal cord motor neuron differentiation; IMP:MGI.
DR GO; GO:0051225; P:spindle assembly; IMP:MGI.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR GO; GO:0019827; P:stem cell population maintenance; IMP:MGI.
DR GO; GO:0001834; P:trophectodermal cell proliferation; IMP:MGI.
DR GO; GO:0010070; P:zygote asymmetric cell division; IMP:MGI.
DR CDD; cd10843; DSRM_DICER; 1.
DR CDD; cd00593; RIBOc; 2.
DR Gene3D; 1.10.1520.10; -; 2.
DR Gene3D; 3.30.160.380; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR HAMAP; MF_00104; RNase_III; 1.
DR InterPro; IPR038248; Dicer_dimer_sf.
DR InterPro; IPR005034; Dicer_dimerisation_dom.
DR InterPro; IPR044441; DICER_DSRM.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR006935; Helicase/UvrB_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR003100; PAZ_dom.
DR InterPro; IPR036085; PAZ_dom_sf.
DR InterPro; IPR011907; RNase_III.
DR InterPro; IPR000999; RNase_III_dom.
DR InterPro; IPR036389; RNase_III_sf.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF02170; PAZ; 1.
DR Pfam; PF04851; ResIII; 1.
DR Pfam; PF00636; Ribonuclease_3; 2.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00358; DSRM; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00949; PAZ; 1.
DR SMART; SM00535; RIBOc; 2.
DR SUPFAM; SSF101690; SSF101690; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF69065; SSF69065; 2.
DR PROSITE; PS51327; DICER_DSRBF; 1.
DR PROSITE; PS50137; DS_RBD; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS50821; PAZ; 1.
DR PROSITE; PS00517; RNASE_3_1; 1.
DR PROSITE; PS50142; RNASE_3_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; ATP-binding; Cytoplasm;
KW Endonuclease; Helicase; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Nuclease; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; RNA-mediated gene silencing.
FT CHAIN 1..1916
FT /note="Endoribonuclease Dicer"
FT /id="PRO_0000180471"
FT DOMAIN 51..227
FT /note="Helicase ATP-binding"
FT DOMAIN 433..602
FT /note="Helicase C-terminal"
FT DOMAIN 630..722
FT /note="Dicer dsRNA-binding fold"
FT DOMAIN 891..1042
FT /note="PAZ"
FT DOMAIN 1276..1403
FT /note="RNase III 1"
FT DOMAIN 1660..1818
FT /note="RNase III 2"
FT DOMAIN 1843..1908
FT /note="DRBM"
FT REGION 256..595
FT /note="Required for interaction with PRKRA and TARBP2"
FT /evidence="ECO:0000250"
FT REGION 409..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 726..745
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1598..1626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 175..178
FT /note="DECH box"
FT COMPBIAS 412..427
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1600..1616
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 64..71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1316
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1395
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1398
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1699
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT BINDING 1804
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT BINDING 1807
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT SITE 1800
FT /note="Important for activity"
FT /evidence="ECO:0000269|PubMed:18268334"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1016
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT MOD_RES 1862
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UPY3"
FT VAR_SEQ 1..245
FT /note="MKSPALQPLSMAGLQLMTPASSPMGPFFGLPWQQEAIHDNIYTPRKYQVELL
FT EAALDHNTIVCLNTGSGKTFIAVLLTKELAHQIRGDLNPHAKRTVFLVNSANQVAQQVS
FT AVRTHSDLKVGEYSDLEVNASWTKERWSQEFTKHQVLIMTCYVALTVLKNGYLSLSDIN
FT LLVFDECHLAILDHPYREIMKLCESCPSCPRILGLTASILNGKCDPEELEEKIQKLERI
FT LRSDAETATDLVVLDR -> MSRDTEV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053586"
FT MUTAGEN 1800
FT /note="K->A,R,S,T: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18268334"
FT CONFLICT 1
FT /note="M -> L (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="A -> C (in Ref. 3; AAM21495)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="S -> P (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="H -> Y (in Ref. 3; AAM21495)"
FT /evidence="ECO:0000305"
FT CONFLICT 610
FT /note="A -> T (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 759
FT /note="E -> D (in Ref. 3; AAM21495)"
FT /evidence="ECO:0000305"
FT CONFLICT 837
FT /note="T -> I (in Ref. 3; AAM21495)"
FT /evidence="ECO:0000305"
FT CONFLICT 888
FT /note="G -> S (in Ref. 1; AAL84638)"
FT /evidence="ECO:0000305"
FT CONFLICT 965
FT /note="Y -> C (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 993
FT /note="T -> A (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 1090
FT /note="R -> G (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 1110
FT /note="T -> S (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 1336
FT /note="P -> H (in Ref. 1; AAL84638)"
FT /evidence="ECO:0000305"
FT CONFLICT 1619
FT /note="A -> S (in Ref. 1; AAL84637 and 2; BAC15765)"
FT /evidence="ECO:0000305"
FT CONFLICT 1860
FT /note="K -> E (in Ref. 2; BAC15765)"
FT /evidence="ECO:0000305"
FT HELIX 1649..1656
FT /evidence="ECO:0007829|PDB:3C4B"
FT TURN 1657..1659
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1660..1667
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1674..1681
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1696..1716
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1723..1733
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1736..1745
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1748..1750
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1757..1774
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1800..1816
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1821..1842
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1847..1854
FT /evidence="ECO:0007829|PDB:3C4B"
FT TURN 1856..1858
FT /evidence="ECO:0007829|PDB:3C4B"
FT STRAND 1859..1861
FT /evidence="ECO:0007829|PDB:3C4B"
FT STRAND 1872..1878
FT /evidence="ECO:0007829|PDB:3C4B"
FT TURN 1879..1881
FT /evidence="ECO:0007829|PDB:3C4B"
FT STRAND 1882..1890
FT /evidence="ECO:0007829|PDB:3C4B"
FT HELIX 1891..1908
FT /evidence="ECO:0007829|PDB:3C4B"
SQ SEQUENCE 1916 AA; 216821 MW; D97EA17922D7E79C CRC64;
MKSPALQPLS MAGLQLMTPA SSPMGPFFGL PWQQEAIHDN IYTPRKYQVE LLEAALDHNT
IVCLNTGSGK TFIAVLLTKE LAHQIRGDLN PHAKRTVFLV NSANQVAQQV SAVRTHSDLK
VGEYSDLEVN ASWTKERWSQ EFTKHQVLIM TCYVALTVLK NGYLSLSDIN LLVFDECHLA
ILDHPYREIM KLCESCPSCP RILGLTASIL NGKCDPEELE EKIQKLERIL RSDAETATDL
VVLDRYTSQP CEIVVDCGPF TDRSGLYERL LMELEAALDF INDCNVAVHS KERDSTLISK
QILSDCRAVL VVLGPWCADK VAGMMVRELQ KYIKHEQEEL HRKFLLFTDT LLRKIHALCE
EYFSPASLDL KYVTPKVMKL LEILRKYKPY ERQQFESVEW YNNRNQDNYV SWSDSEDDDD
DEEIEEKEKP ETNFPSPFTN ILCGIIFVER RYTAVVLNRL IKEAGKQDPE LAYISSNFIT
GHGIGKNQPR SKQMEAEFRK QEEVLRKFRA HETNLLIATS VVEEGVDIPK CNLVVRFDLP
TEYRSYVQSK GRARAPISNY VMLADTDKIK SFEEDLKTYK AIEKILRNKC SKSADGAEAD
VHAGVDDEDA FPPYVLRPDD GGPRVTINTA IGHINRYCAR LPSDPFTHLA PKCRTRELPD
GTFYSTLYLP INSPLRASIV GPPMDSVRLA ERVVALICCE KLHKIGELDE HLMPVGKETV
KYEEELDLHD EEETSVPGRP GSTKRRQCYP KAIPECLRES YPKPDQPCYL YVIGMVLTTP
LPDELNFRRR KLYPPEDTTR CFGILTAKPI PQIPHFPVYT RSGEVTISIE LKKSGFTLSQ
QMLELITRLH QYIFSHILRL EKPALEFKPT GAESAYCVLP LNVVNDSGTL DIDFKFMEDI
EKSEARIGIP STKYSKETPF VFKLEDYQDA VIIPRYRNFD QPHRFYVADV YTDLTPLSKF
PSPEYETFAE YYKTKYNLDL TNLNQPLLDV DHTSSRLNLL TPRHLNQKGK ALPLSSAEKR
KAKWESLQNK QILVPELCAI HPIPASLWRK AVCLPSILYR LHCLLTAEEL RAQTASDAGV
GVRSLPVDFR YPNLDFGWKK SIDSKSFIST CNSSLAESDN YCKHSTTVVP EHAAHQGATR
PSLENHDQMS VNCKRLPAES PAKLQSEVST DLTAINGLSY NKNLANGSYD LVNRDFCQGN
QLNYFKQEIP VQPTTSYPIQ NLYNYENQPK PSNECPLLSN TYLDGNANTS TSDGSPAVST
MPAMMNAVKA LKDRMDSEQS PSVGYSSRTL GPNPGLILQA LTLSNASDGF NLERLEMLGD
SFLKHAITTY LFCTYPDAHE GRLSYMRSKK VSNCNLYRLG KKKGLPSRMV VSIFDPPVNW
LPPGYVVNQD KSNSEKWEKD EMTKDCLLAN GKLGEACEEE EDLTWRAPKE EAEDEDDFLE
YDQEHIQFID SMLMGSGAFV RKISLSPFSA SDSAYEWKMP KKASLGSMPF ASGLEDFDYS
SWDAMCYLDP SKAVEEDDFV VGFWNPSEEN CGVDTGKQSI SYDLHTEQCI ADKSIADCVE
ALLGCYLTSC GERAAQLFLC SLGLKVLPVI KRTSREKALD PAQENGSSQQ KSLSGSCAAP
VGPRSSAGKD LEYGCLKIPP RCMFDHPDAE KTLNHLISGF ETFEKKINYR FKNKAYLLQA
FTHASYHYNT ITDCYQRLEF LGDAILDYLI TKHLYEDPRQ HSPGVLTDLR SALVNNTIFA
SLAVKYDYHK YFKAVSPELF HVIDDFVKFQ LEKNEMQGMD SELRRSEEDE EKEEDIEVPK
AMGDIFESLA GAIYMDSGMS LEVVWQVYYP MMQPLIEKFS ANVPRSPVRE LLEMEPETAK
FSPAERTYDG KVRVTVEVVG KGKFKGVGRS YRIAKSAAAR RALRSLKANQ PQVPNS
