UGDH_MOUSE
ID UGDH_MOUSE Reviewed; 493 AA.
AC O70475;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=UDP-glucose 6-dehydrogenase;
DE Short=UDP-Glc dehydrogenase;
DE Short=UDP-GlcDH;
DE Short=UDPGDH;
DE EC=1.1.1.22 {ECO:0000269|PubMed:9737970};
GN Name=Ugdh;
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], CATALYTIC ACTIVITY, FUNCTION, PATHWAY, ACTIVITY
RP REGULATION, AND DEVELOPMENTAL STAGE.
RX PubMed=9737970; DOI=10.1074/jbc.273.39.25117;
RA Spicer A.P., Kaback L.A., Smith T.J., Seldin M.F.;
RT "Molecular cloning and characterization of the human and mouse UDP-glucose
RT dehydrogenase genes.";
RL J. Biol. Chem. 273:25117-25124(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP FUNCTION, MUTAGENESIS OF GLN-302, AND DEVELOPMENTAL STAGE.
RX PubMed=14505572; DOI=10.1016/s0092-8674(03)00715-3;
RA Garcia-Garcia M.J., Anderson K.V.;
RT "Essential role of glycosaminoglycans in Fgf signaling during mouse
RT gastrulation.";
RL Cell 114:727-737(2003).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-474, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-474, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-474, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-107, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Catalyzes the formation of UDP-alpha-D-glucuronate, a
CC constituent of complex glycosaminoglycans (PubMed:9737970). Required
CC for the biosynthesis of chondroitin sulfate and heparan sulfate.
CC Required for embryonic development via its role in the biosynthesis of
CC glycosaminoglycans (PubMed:14505572). Required for proper brain and
CC neuronal development (By similarity). {ECO:0000250|UniProtKB:O60701,
CC ECO:0000269|PubMed:14505572, ECO:0000269|PubMed:9737970}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + 2 NAD(+) + UDP-alpha-D-glucose = 3 H(+) + 2 NADH + UDP-
CC alpha-D-glucuronate; Xref=Rhea:RHEA:23596, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58885; EC=1.1.1.22;
CC Evidence={ECO:0000269|PubMed:9737970};
CC -!- ACTIVITY REGULATION: UDP-alpha-D-xylose (UDX) acts as a feedback
CC inhibitor (PubMed:9737970). It binds at the same site as the substrate,
CC but functions as allosteric inhibitor by triggering a conformation
CC change that disrupts the active hexameric ring structure and gives rise
CC to an inactive, horseshoe-shaped hexamer (By similarity).
CC {ECO:0000250|UniProtKB:O60701, ECO:0000269|PubMed:9737970}.
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; UDP-alpha-D-glucuronate
CC biosynthesis; UDP-alpha-D-glucuronate from UDP-alpha-D-glucose: step
CC 1/1. {ECO:0000269|PubMed:9737970}.
CC -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:O60701}.
CC -!- DEVELOPMENTAL STAGE: Detected in embryos from 7.5 to 17.5 dpc
CC (PubMed:9737970, PubMed:14505572). Detected in the epiblast at 7.5 dpc,
CC in the cardiac region and tail bud at 8.5 dpc, in otic vesicle and
CC branchial arches at 9.5 dpc, and in forebrain, branchial arches and
CC limb buds at 10.5 dpc (PubMed:14505572). {ECO:0000269|PubMed:14505572,
CC ECO:0000269|PubMed:9737970}.
CC -!- DOMAIN: The protein goes through several conformation states during the
CC reaction cycle, giving rise to hysteresis. In the initial state, the
CC ligand-free protein is in an inactive conformation (E*). Substrate
CC binding triggers a change to the active conformation (E). UDP-xylose
CC binding triggers the transition to a distinct, inhibited conformation.
CC The presence of an intrinsically disordered C-terminus promotes a more
CC dynamic protein structure and favors a conformation with high affinity
CC for UPD-xylose. {ECO:0000250|UniProtKB:O60701}.
CC -!- DOMAIN: The allosteric switch region moves by about 5 Angstroms when
CC UDP-xylose is bound, and occupies part of the UDP-glucose binding site.
CC At the same time it promotes domain movements that disrupt the active
CC hexameric ring structure and lead to the formation of a horseshoe-
CC shaped, inactive hexamer. {ECO:0000250|UniProtKB:O60701}.
CC -!- SIMILARITY: Belongs to the UDP-glucose/GDP-mannose dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; AF061017; AAC36096.1; -; mRNA.
DR EMBL; BC006749; AAH06749.1; -; mRNA.
DR CCDS; CCDS19308.1; -.
DR RefSeq; NP_033492.1; NM_009466.2.
DR RefSeq; XP_006503925.1; XM_006503862.3.
DR AlphaFoldDB; O70475; -.
DR SMR; O70475; -.
DR BioGRID; 204433; 21.
DR IntAct; O70475; 1.
DR STRING; 10090.ENSMUSP00000031103; -.
DR iPTMnet; O70475; -.
DR PhosphoSitePlus; O70475; -.
DR SwissPalm; O70475; -.
DR EPD; O70475; -.
DR jPOST; O70475; -.
DR PaxDb; O70475; -.
DR PeptideAtlas; O70475; -.
DR PRIDE; O70475; -.
DR ProteomicsDB; 298195; -.
DR Antibodypedia; 23464; 330 antibodies from 31 providers.
DR DNASU; 22235; -.
DR Ensembl; ENSMUST00000031103; ENSMUSP00000031103; ENSMUSG00000029201.
DR GeneID; 22235; -.
DR KEGG; mmu:22235; -.
DR UCSC; uc008xns.1; mouse.
DR CTD; 7358; -.
DR MGI; MGI:1306785; Ugdh.
DR VEuPathDB; HostDB:ENSMUSG00000029201; -.
DR eggNOG; KOG2666; Eukaryota.
DR GeneTree; ENSGT00390000015355; -.
DR HOGENOM; CLU_023810_7_2_1; -.
DR InParanoid; O70475; -.
DR OMA; CECLNLP; -.
DR OrthoDB; 915490at2759; -.
DR PhylomeDB; O70475; -.
DR TreeFam; TF105671; -.
DR BRENDA; 1.1.1.22; 3474.
DR Reactome; R-MMU-173599; Formation of the active cofactor, UDP-glucuronate.
DR UniPathway; UPA00038; UER00491.
DR BioGRID-ORCS; 22235; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Ugdh; mouse.
DR PRO; PR:O70475; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O70475; protein.
DR Bgee; ENSMUSG00000029201; Expressed in olfactory epithelium and 145 other tissues.
DR ExpressionAtlas; O70475; baseline and differential.
DR Genevisible; O70475; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0003979; F:UDP-glucose 6-dehydrogenase activity; IDA:CACAO.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IMP:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IMP:UniProtKB.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IBA:GO_Central.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR GO; GO:0006065; P:UDP-glucuronate biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR017476; UDP-Glc/GDP-Man.
DR InterPro; IPR014027; UDP-Glc/GDP-Man_DH_C.
DR InterPro; IPR036220; UDP-Glc/GDP-Man_DH_C_sf.
DR InterPro; IPR014026; UDP-Glc/GDP-Man_DH_dimer.
DR InterPro; IPR001732; UDP-Glc/GDP-Man_DH_N.
DR InterPro; IPR028356; UDPglc_DH_euk.
DR PANTHER; PTHR11374; PTHR11374; 1.
DR Pfam; PF00984; UDPG_MGDP_dh; 1.
DR Pfam; PF03720; UDPG_MGDP_dh_C; 1.
DR Pfam; PF03721; UDPG_MGDP_dh_N; 1.
DR PIRSF; PIRSF500133; UDPglc_DH_euk; 1.
DR PIRSF; PIRSF000124; UDPglc_GDPman_dh; 1.
DR SMART; SM00984; UDPG_MGDP_dh_C; 1.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52413; SSF52413; 1.
DR TIGRFAMs; TIGR03026; NDP-sugDHase; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allosteric enzyme; Carbohydrate metabolism; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..493
FT /note="UDP-glucose 6-dehydrogenase"
FT /id="PRO_0000074061"
FT REGION 88..110
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT REGION 129..135
FT /note="Allosteric switch region"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT REGION 321..325
FT /note="Important for formation of active hexamer structure"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT REGION 466..493
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT ACT_SITE 161
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT ACT_SITE 220
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT ACT_SITE 276
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 11..16
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 36
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 41
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 89..93
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 130..132
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 161..165
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 165
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 220..224
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 267..273
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 276..279
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 338..339
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 346
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT BINDING 442
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O60701"
FT MOD_RES 107
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 474
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MUTAGEN 302
FT /note="Q->QFQ: In lzme; causes arrest of embryonic
FT development during gastrulation due to chondroitin sulfate
FT and heparan sulfate deficiency, impaired FGF signaling and
FT impaired migration of mesoderm and endoderm."
FT /evidence="ECO:0000269|PubMed:14505572"
SQ SEQUENCE 493 AA; 54832 MW; C6234F3C1D7480C7 CRC64;
MVEIKKICCI GAGYVGGPTC SVIAHMCPEI RVTVVDVNEA RINAWNSPTL PIYEPGLKEV
VESCRGKNLF FSTNIDDAIR EADLVFISVN TPTKTYGMGK GRAADLKYIE ACARRIVQNS
NGYKIVTEKS TVPVRAAESI RRIFDANTKP NLNLQVLSNP EFLAEGTAIK DLKNPDRVLI
GGDETPEGQK AVRALCAVYE HWVPKEKILT TNTWSSELSK LAANAFLAQR ISSINSISAL
CEATGADVEE VATAIGMDQR IGNKFLKASV GFGGSCFQKD VLNLVYLCEA LNLPEVARYW
QQVIDMNDYQ RRRFASRIID SLFNTVTDKK IAILGFAFKK DTGDTRESSS IYISKYLMDE
GAHLHIYDPK VPREQIVVDL SHPGVSADDQ VSRLVTISKD PYEACDGAHA LVICTEWDMF
KELDYERIHK KMLKPAFIFD GRRVLDGLHS ELQTIGFQIE TIGKKVSSKR IPYTPGEIPK
FSLQDPPNKK PKV
