UGPA_HUMAN
ID UGPA_HUMAN Reviewed; 508 AA.
AC Q16851; Q07131; Q0P6K2; Q86Y81; Q9BU15;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=UTP--glucose-1-phosphate uridylyltransferase {ECO:0000305|PubMed:8354390};
DE EC=2.7.7.9 {ECO:0000269|PubMed:31820119, ECO:0000269|PubMed:8354390, ECO:0000269|PubMed:8631325};
DE AltName: Full=UDP-glucose pyrophosphorylase;
DE Short=UDPGP;
DE Short=UGPase;
GN Name=UGP2 {ECO:0000312|HGNC:HGNC:12527};
GN Synonyms=UGP1 {ECO:0000312|HGNC:HGNC:12527};
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ILE-268, AND CAUTION.
RC TISSUE=Liver;
RX PubMed=8354390; DOI=10.1016/0014-5793(93)80213-e;
RA Peng H.-L., Chang H.-Y.;
RT "Cloning of a human liver UDP-glucose pyrophosphorylase cDNA by
RT complementation of the bacterial galU mutation.";
RL FEBS Lett. 329:153-158(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP VARIANT ILE-268, AND CAUTION.
RC TISSUE=Skeletal muscle;
RX PubMed=8631325; DOI=10.1111/j.1432-1033.1996.00173.x;
RA Duggleby R.G., Chao Y.C., Huang J.G., Peng H.-L., Chang H.-Y.;
RT "Sequence differences between human muscle and liver cDNAs for UDPglucose
RT pyrophosphorylase and kinetic properties of the recombinant enzymes
RT expressed in Escherichia coli.";
RL Eur. J. Biochem. 235:173-179(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cervix, Lymph, 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 [4]
RP MUTAGENESIS.
RX PubMed=8612650; DOI=10.1111/j.1432-1033.1996.t01-1-00723.x;
RA Chang H.-Y., Peng H.-L., Chao Y.C., Duggleby R.G.;
RT "The importance of conserved residues in human liver UDPglucose
RT pyrophosphorylase.";
RL Eur. J. Biochem. 236:723-728(1996).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-438, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(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 ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-13, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP SER-2 (ISOFORM 2), CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]
RP (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF
RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION
RP 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13; THR-426; SER-434; SER-448
RP AND SER-461, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [13]
RP INVOLVEMENT IN DEE83, VARIANT DEE83 VAL-12, CHARACTERIZATION OF VARIANT
RP DEE83 VAL-12, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE (ISOFORM 2).
RX PubMed=31820119; DOI=10.1007/s00401-019-02109-6;
RA Perenthaler E., Nikoncuk A., Yousefi S., Berdowski W.M., Alsagob M.,
RA Capo I., van der Linde H.C., van den Berg P., Jacobs E.H., Putar D.,
RA Ghazvini M., Aronica E., van Ijcken W.F.J., de Valk W.G.,
RA Medici-van den Herik E., van Slegtenhorst M., Brick L., Kozenko M.,
RA Kohler J.N., Bernstein J.A., Monaghan K.G., Begtrup A., Torene R.,
RA Al Futaisi A., Al Murshedi F., Mani R., Al Azri F., Kamsteeg E.J.,
RA Mojarrad M., Eslahi A., Khazaei Z., Darmiyan F.M., Doosti M.,
RA Karimiani E.G., Vandrovcova J., Zafar F., Rana N., Kandaswamy K.K.,
RA Hertecant J., Bauer P., Almuhaizea M.A., Salih M.A., Aldosary M.,
RA Almass R., Al-Quait L., Qubbaj W., Coskun S., Alahmadi K.O., Hamad M.H.A.,
RA Alwadaee S., Awartani K., Dababo A.M., Almohanna F., Colak D., Dehghani M.,
RA Mehrjardi M.Y.V., Gunel M., Ercan-Sencicek A.G., Passi G.R., Cheema H.A.,
RA Efthymiou S., Houlden H., Bertoli-Avella A.M., Brooks A.S., Retterer K.,
RA Maroofian R., Kaya N., van Ham T.J., Barakat T.S.;
RT "Loss of UGP2 in brain leads to a severe epileptic encephalopathy,
RT emphasizing that bi-allelic isoform-specific start-loss mutations of
RT essential genes can cause genetic diseases.";
RL Acta Neuropathol. 139:415-442(2020).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.57 ANGSTROMS), SUBUNIT, AND MUTAGENESIS OF
RP 502-ASP--LEU-503.
RX PubMed=22132858; DOI=10.1042/bj20111598;
RA Yu Q., Zheng X.;
RT "The crystal structure of human UDP-glucose pyrophosphorylase reveals a
RT latch effect that influences enzymatic activity.";
RL Biochem. J. 442:283-291(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) OF 2-508 IN COMPLEX WITH
RP UDP-GLUCOSE.
RX PubMed=25860585; DOI=10.1038/srep09618;
RA Fuhring J.I., Cramer J.T., Schneider J., Baruch P., Gerardy-Schahn R.,
RA Fedorov R.;
RT "A quaternary mechanism enables the complex biological functions of
RT octameric human UDP-glucose pyrophosphorylase, a key enzyme in cell
RT metabolism.";
RL Sci. Rep. 5:9618-9618(2015).
CC -!- FUNCTION: UTP--glucose-1-phosphate uridylyltransferase catalyzing the
CC conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor
CC for the production of glycogen. {ECO:0000269|PubMed:31820119,
CC ECO:0000269|PubMed:8354390, ECO:0000269|PubMed:8631325}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha-D-glucose 1-phosphate + H(+) + UTP = diphosphate + UDP-
CC alpha-D-glucose; Xref=Rhea:RHEA:19889, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:46398, ChEBI:CHEBI:58601,
CC ChEBI:CHEBI:58885; EC=2.7.7.9; Evidence={ECO:0000269|PubMed:31820119,
CC ECO:0000269|PubMed:8354390, ECO:0000269|PubMed:8631325};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19890;
CC Evidence={ECO:0000269|PubMed:31820119};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC Kinetic parameters:
CC KM=917 uM for MgUTP {ECO:0000269|PubMed:31820119};
CC KM=404 uM for Glc1P {ECO:0000269|PubMed:31820119};
CC KM=63 uM for UDP-Glc {ECO:0000269|PubMed:31820119};
CC KM=384 uM for MgPPi {ECO:0000269|PubMed:31820119};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]:
CC Kinetic parameters:
CC KM=301 uM for MgUTP {ECO:0000269|PubMed:31820119};
CC KM=207 uM for Glc1P {ECO:0000269|PubMed:31820119};
CC KM=41 uM for UDP-Glc {ECO:0000269|PubMed:31820119};
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC {ECO:0000305|PubMed:31820119}.
CC -!- SUBUNIT: Homooctamer. {ECO:0000269|PubMed:22132858}.
CC -!- INTERACTION:
CC Q16851; O95376: ARIH2; NbExp=7; IntAct=EBI-743729, EBI-711158;
CC Q16851; O76003: GLRX3; NbExp=3; IntAct=EBI-743729, EBI-374781;
CC Q16851; P62993: GRB2; NbExp=2; IntAct=EBI-743729, EBI-401755;
CC Q16851; O14901: KLF11; NbExp=3; IntAct=EBI-743729, EBI-948266;
CC Q16851; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-743729, EBI-742388;
CC Q16851; Q16851: UGP2; NbExp=6; IntAct=EBI-743729, EBI-743729;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31820119,
CC ECO:0000269|PubMed:8354390}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Muscle-II {ECO:0000303|PubMed:8631325}, long
CC {ECO:0000303|PubMed:31820119};
CC IsoId=Q16851-1; Sequence=Displayed;
CC Name=2; Synonyms=Muscle-I {ECO:0000303|PubMed:8631325}, short
CC {ECO:0000303|PubMed:31820119};
CC IsoId=Q16851-2; Sequence=VSP_012834;
CC -!- TISSUE SPECIFICITY: Highly expressed in various brain regions.
CC Expressed in amygdala, anterior cingulate cortex, caudate, cerebellar
CC hemisphere, cerebellum, cortex, frontal cortex, hippocampus,
CC hypothalamus, nucleus accumbens, putamen, spinal cord and substantia
CC nigra (PubMed:31820119). Also widely expressed among other tissues,
CC including liver, heart, placenta, lung, kidney, pancreas and skeletal
CC muscle (PubMed:8354390, PubMed:8631325). {ECO:0000269|PubMed:31820119,
CC ECO:0000269|PubMed:8354390, ECO:0000269|PubMed:8631325}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 2]: Predominantly expressed in developing
CC brain (PubMed:31820119). Preferentially expressed in the developing
CC cortex and cerebellum from gestational weeks 14, 20 and 28 and in the
CC frontal cortex of brains from weeks 21 and 23 (at protein level)
CC (PubMed:31820119). {ECO:0000269|PubMed:31820119}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 83 (DEE83)
CC [MIM:618744]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE83 is an autosomal recessive form characterized by
CC onset of frequent, intractable seizures in the first days to months of
CC life. Affected individuals have profound developmental delay with no
CC motor or language skill acquisition, and poor or absent visual
CC tracking. Many patients die in the first years of life.
CC {ECO:0000269|PubMed:31820119}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. A recurrent, pathogenic
CC variant affecting the translation initiation codon of isoform 2 has
CC been found in multiple DEE83 families. The variant results in the
CC absence of isoform 2 and leads to reduced levels of functional UGP2
CC enzyme in neural stem cells. The absence of isoform 2 is compensated by
CC an increased abundance of a functional isoform 1, carrying variant
CC p.Met12Val, which may explain the survival of the patients. A complete
CC absence of functional UGP2 in all cells would be embryonic lethal.
CC {ECO:0000269|PubMed:31820119}.
CC -!- SIMILARITY: Belongs to the UDPGP type 1 family. {ECO:0000305}.
CC -!- CAUTION: The human genome was initially thought to contain 2 genes for
CC UTP--glucose-1-phosphate uridylyltransferase: UGP1 and UGP2
CC (PubMed:8354390, PubMed:8631325). However, the sequence defined as UGP1
CC (PubMed:8354390) probably does not exist and corresponds to UGP2.
CC {ECO:0000269|PubMed:8354390, ECO:0000269|PubMed:8631325,
CC ECO:0000305|PubMed:8354390, ECO:0000305|PubMed:8631325}.
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DR EMBL; U27460; AAB05640.1; -; mRNA.
DR EMBL; BC000173; AAH00173.2; -; mRNA.
DR EMBL; BC002954; AAH02954.1; -; mRNA.
DR EMBL; BC047004; AAH47004.1; -; mRNA.
DR CCDS; CCDS1875.1; -. [Q16851-1]
DR CCDS; CCDS42690.1; -. [Q16851-2]
DR PIR; S35692; S35692.
DR RefSeq; NP_001001521.1; NM_001001521.1. [Q16851-2]
DR RefSeq; NP_006750.3; NM_006759.3. [Q16851-1]
DR RefSeq; XP_005264594.1; XM_005264537.2.
DR RefSeq; XP_005264595.1; XM_005264538.1.
DR PDB; 3R2W; X-ray; 3.60 A; A/B/C/D=1-508.
DR PDB; 3R3I; X-ray; 3.57 A; A/B/C/D=1-508.
DR PDB; 4R7P; X-ray; 3.35 A; A/B/C/D=2-508.
DR PDBsum; 3R2W; -.
DR PDBsum; 3R3I; -.
DR PDBsum; 4R7P; -.
DR AlphaFoldDB; Q16851; -.
DR SMR; Q16851; -.
DR BioGRID; 113207; 79.
DR IntAct; Q16851; 18.
DR MINT; Q16851; -.
DR STRING; 9606.ENSP00000338703; -.
DR GlyGen; Q16851; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q16851; -.
DR MetOSite; Q16851; -.
DR PhosphoSitePlus; Q16851; -.
DR SwissPalm; Q16851; -.
DR BioMuta; UGP2; -.
DR DMDM; 59803098; -.
DR REPRODUCTION-2DPAGE; IPI00395676; -.
DR UCD-2DPAGE; Q16851; -.
DR CPTAC; CPTAC-291; -.
DR CPTAC; CPTAC-292; -.
DR EPD; Q16851; -.
DR jPOST; Q16851; -.
DR MassIVE; Q16851; -.
DR MaxQB; Q16851; -.
DR PaxDb; Q16851; -.
DR PeptideAtlas; Q16851; -.
DR PRIDE; Q16851; -.
DR ProteomicsDB; 61103; -. [Q16851-1]
DR ProteomicsDB; 61104; -. [Q16851-2]
DR Antibodypedia; 30782; 213 antibodies from 24 providers.
DR DNASU; 7360; -.
DR Ensembl; ENST00000337130.10; ENSP00000338703.5; ENSG00000169764.16. [Q16851-1]
DR Ensembl; ENST00000394417.7; ENSP00000377939.2; ENSG00000169764.16. [Q16851-2]
DR Ensembl; ENST00000467648.6; ENSP00000420793.2; ENSG00000169764.16. [Q16851-2]
DR GeneID; 7360; -.
DR KEGG; hsa:7360; -.
DR MANE-Select; ENST00000337130.10; ENSP00000338703.5; NM_006759.4; NP_006750.3.
DR UCSC; uc002scl.4; human. [Q16851-1]
DR CTD; 7360; -.
DR DisGeNET; 7360; -.
DR GeneCards; UGP2; -.
DR HGNC; HGNC:12527; UGP2.
DR HPA; ENSG00000169764; Tissue enhanced (liver, tongue).
DR MalaCards; UGP2; -.
DR MIM; 191750; gene.
DR MIM; 191760; gene.
DR MIM; 618744; phenotype.
DR neXtProt; NX_Q16851; -.
DR OpenTargets; ENSG00000169764; -.
DR PharmGKB; PA37172; -.
DR VEuPathDB; HostDB:ENSG00000169764; -.
DR eggNOG; KOG2638; Eukaryota.
DR GeneTree; ENSGT00940000153464; -.
DR HOGENOM; CLU_023632_3_0_1; -.
DR InParanoid; Q16851; -.
DR OMA; TNNLWAK; -.
DR OrthoDB; 503037at2759; -.
DR PhylomeDB; Q16851; -.
DR TreeFam; TF300567; -.
DR BioCyc; MetaCyc:HS10006-MON; -.
DR BRENDA; 2.7.7.9; 2681.
DR PathwayCommons; Q16851; -.
DR Reactome; R-HSA-173599; Formation of the active cofactor, UDP-glucuronate.
DR Reactome; R-HSA-3322077; Glycogen synthesis.
DR SABIO-RK; Q16851; -.
DR SignaLink; Q16851; -.
DR SIGNOR; Q16851; -.
DR UniPathway; UPA00164; -.
DR BioGRID-ORCS; 7360; 125 hits in 1085 CRISPR screens.
DR ChiTaRS; UGP2; human.
DR GenomeRNAi; 7360; -.
DR Pharos; Q16851; Tbio.
DR PRO; PR:Q16851; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q16851; protein.
DR Bgee; ENSG00000169764; Expressed in skeletal muscle tissue of biceps brachii and 208 other tissues.
DR ExpressionAtlas; Q16851; baseline and differential.
DR Genevisible; Q16851; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032557; F:pyrimidine ribonucleotide binding; IEA:Ensembl.
DR GO; GO:0003983; F:UTP:glucose-1-phosphate uridylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0019255; P:glucose 1-phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0005978; P:glycogen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IBA:GO_Central.
DR GO; GO:0006011; P:UDP-glucose metabolic process; IDA:UniProtKB.
DR CDD; cd00897; UGPase_euk; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR002618; UDPGP_fam.
DR InterPro; IPR016267; UDPGP_trans.
DR PANTHER; PTHR43511; PTHR43511; 1.
DR Pfam; PF01704; UDPGP; 1.
DR PIRSF; PIRSF000806; UDPGP; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Disease variant; Epilepsy; Magnesium; Metal-binding;
KW Nucleotidyltransferase; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..508
FT /note="UTP--glucose-1-phosphate uridylyltransferase"
FT /id="PRO_0000185752"
FT REGION 457..508
FT /note="Oligomerization"
FT REGION 502..503
FT /note="Critical for end-to-end subunit interaction"
FT ACT_SITE 396
FT /evidence="ECO:0000250"
FT BINDING 113..116
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000250|UniProtKB:Q9M9P3"
FT BINDING 115..116
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25860585,
FT ECO:0007744|PDB:4R7P"
FT BINDING 127
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000250|UniProtKB:Q9M9P3"
FT BINDING 190
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000250|UniProtKB:Q9M9P3"
FT BINDING 222
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000250|UniProtKB:Q9M9P3"
FT BINDING 223
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25860585,
FT ECO:0007744|PDB:4R7P"
FT BINDING 251..253
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25860585,
FT ECO:0007744|PDB:4R7P"
FT BINDING 253
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 253
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000250|UniProtKB:Q9M9P3"
FT BINDING 330
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:25860585,
FT ECO:0007744|PDB:4R7P"
FT BINDING 396
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000250|UniProtKB:Q9M9P3"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 426
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 438
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..11
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8631325"
FT /id="VSP_012834"
FT VARIANT 12
FT /note="M -> V (in DEE83; the nucleotide substitution also
FT alters the translation of other alternatively spliced
FT products of the gene globally reducing functional enzyme
FT levels and causing reduced synthesis of UDP-glucose and
FT decreased glycogen biosynthetic process; no effect on
FT protein localization; no effect on UTP:glucose-1-phosphate
FT uridylyltransferase activity; dbSNP:rs768305634)"
FT /evidence="ECO:0000269|PubMed:31820119"
FT /id="VAR_083746"
FT VARIANT 268
FT /note="M -> I (in dbSNP:rs1130982)"
FT /evidence="ECO:0000269|PubMed:8354390,
FT ECO:0000269|PubMed:8631325"
FT /id="VAR_033042"
FT MUTAGEN 123
FT /note="C->S: No significant loss of activity."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 218
FT /note="W->S: No significant loss of activity."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 266
FT /note="H->R: No significant loss of activity."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 333
FT /note="W->S: Loss of activity; possibly due to folding
FT defect."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 389
FT /note="R->H: No significant loss of activity."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 391
FT /note="R->H: Loss of activity; possibly due to folding
FT defect."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 422
FT /note="R->H: No significant loss of activity."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 445
FT /note="R->H: No significant loss of activity."
FT /evidence="ECO:0000269|PubMed:8612650"
FT MUTAGEN 502..503
FT /note="NL->PE: Abolishes oligomerization and significantly
FT increases enzymatic activity."
FT /evidence="ECO:0000269|PubMed:22132858"
FT CONFLICT 25
FT /note="R -> L (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 44
FT /note="S -> T (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="F -> Y (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="F -> Y (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="T -> S (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="L -> R (in Ref. 1 and 2; AAB05640)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="Y -> S (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="N -> S (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 240..241
FT /note="IG -> LE (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="A -> P (in Ref. 1)"
FT /evidence="ECO:0000305"
FT HELIX 25..41
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 49..65
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 89..95
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 101..105
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:4R7P"
FT TURN 118..122
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 138..153
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:4R7P"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 168..172
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 179..182
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 226..232
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 235..241
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 246..254
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 261..268
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 277..284
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 301..305
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 315..319
FT /evidence="ECO:0007829|PDB:4R7P"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 326..335
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 336..344
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 353..359
FT /evidence="ECO:0007829|PDB:4R7P"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 363..369
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 372..378
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 398..405
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 409..412
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 415..418
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 423..426
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:4R7P"
FT HELIX 439..445
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 446..448
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 455..460
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 462..466
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 471..480
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 485..488
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 493..496
FT /evidence="ECO:0007829|PDB:4R7P"
FT STRAND 498..501
FT /evidence="ECO:0007829|PDB:4R7P"
FT INIT_MET Q16851-2:1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES Q16851-2:2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES Q16851-2:2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
SQ SEQUENCE 508 AA; 56940 MW; 60E54806807AB470 CRC64;
MSRFVQDLSK AMSQDGASQF QEVIRQELEL SVKKELEKIL TTASSHEFEH TKKDLDGFRK
LFHRFLQEKG PSVDWGKIQR PPEDSIQPYE KIKARGLPDN ISSVLNKLVV VKLNGGLGTS
MGCKGPKSLI GVRNENTFLD LTVQQIEHLN KTYNTDVPLV LMNSFNTDED TKKILQKYNH
CRVKIYTFNQ SRYPRINKES LLPVAKDVSY SGENTEAWYP PGHGDIYASF YNSGLLDTFI
GEGKEYIFVS NIDNLGATVD LYILNHLMNP PNGKRCEFVM EVTNKTRADV KGGTLTQYEG
KLRLVEIAQV PKAHVDEFKS VSKFKIFNTN NLWISLAAVK RLQEQNAIDM EIIVNAKTLD
GGLNVIQLET AVGAAIKSFE NSLGINVPRS RFLPVKTTSD LLLVMSNLYS LNAGSLTMSE
KREFPTVPLV KLGSSFTKVQ DYLRRFESIP DMLELDHLTV SGDVTFGKNV SLKGTVIIIA
NHGDRIDIPP GAVLENKIVS GNLRILDH
