ID   UGDH_BOVIN              Reviewed;         494 AA.
AC   P12378; A6QR10; O77806;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-1998, sequence version 2.
DT   27-MAR-2024, entry version 159.
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:0000250|UniProtKB:O60701};
GN   Name=UGDH;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RX   PubMed=10336992; DOI=10.1093/glycob/9.6.595;
RA   Lind T., Falk E., Hjertson E., Kusche-Gullberg M., Lidholt K.;
RT   "cDNA cloning and expression of UDP-glucose dehydrogenase from bovine
RT   kidney.";
RL   Glycobiology 9:595-600(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Ascending colon;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 1-469.
RC   TISSUE=Liver;
RX   PubMed=7920253; DOI=10.1002/pro.5560030710;
RA   Hempel J., Perozich J., Romovacek H., Hinich A., Kuo I., Feingold D.S.;
RT   "UDP-glucose dehydrogenase from bovine liver: primary structure and
RT   relationship to other dehydrogenases.";
RL   Protein Sci. 3:1074-1080(1994).
RN   [4]
RP   PROTEIN SEQUENCE OF 268-281.
RC   TISSUE=Liver;
RX   PubMed=6896145; DOI=10.1042/bj1990599;
RA   Franzen B., Carrubba C., Feingold D.S., Ashcom J., Franzen J.S.;
RT   "Amino acid sequence of the tryptic peptide containing the catalytic-site
RT   thiol group of bovine liver uridine diphosphate glucose dehydrogenase.";
RL   Biochem. J. 199:599-602(1981).
CC   -!- FUNCTION: Catalyzes the formation of UDP-alpha-D-glucuronate, a
CC       constituent of complex glycosaminoglycans (By similarity). Required for
CC       the biosynthesis of chondroitin sulfate and heparan sulfate. Required
CC       for embryonic development via its role in the biosynthesis of
CC       glycosaminoglycans (By similarity). Required for proper brain and
CC       neuronal development (By similarity). {ECO:0000250|UniProtKB:O60701,
CC       ECO:0000250|UniProtKB:O70475}.
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:0000250|UniProtKB:O60701};
CC   -!- ACTIVITY REGULATION: UDP-alpha-D-xylose (UDX) acts as a feedback
CC       inhibitor. It binds at the same site as the substrate, but functions as
CC       allosteric inhibitor by triggering a conformation change that disrupts
CC       the active hexameric ring structure and gives rise to an inactive,
CC       horseshoe-shaped hexamer. {ECO:0000250|UniProtKB:O60701}.
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:0000250|UniProtKB:O60701}.
CC   -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:O60701}.
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}.
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; AF095792; AAC64183.1; -; mRNA.
DR   EMBL; BC150068; AAI50069.1; -; mRNA.
DR   PIR; A17150; A17150.
DR   RefSeq; NP_776636.1; NM_174211.3.
DR   RefSeq; XP_005207890.1; XM_005207833.2.
DR   AlphaFoldDB; P12378; -.
DR   SMR; P12378; -.
DR   STRING; 9913.ENSBTAP00000019302; -.
DR   PaxDb; 9913-ENSBTAP00000019302; -.
DR   PeptideAtlas; P12378; -.
DR   Ensembl; ENSBTAT00000019302.5; ENSBTAP00000019302.4; ENSBTAG00000014521.5.
DR   GeneID; 281564; -.
DR   KEGG; bta:281564; -.
DR   CTD; 7358; -.
DR   VEuPathDB; HostDB:ENSBTAG00000014521; -.
DR   VGNC; VGNC:36648; UGDH.
DR   eggNOG; KOG2666; Eukaryota.
DR   GeneTree; ENSGT00390000015355; -.
DR   HOGENOM; CLU_023810_7_0_1; -.
DR   InParanoid; P12378; -.
DR   OMA; CFIAVGT; -.
DR   OrthoDB; 167209at2759; -.
DR   TreeFam; TF105671; -.
DR   Reactome; R-BTA-173599; Formation of the active cofactor, UDP-glucuronate.
DR   UniPathway; UPA00038; UER00491.
DR   Proteomes; UP000009136; Chromosome 6.
DR   Bgee; ENSBTAG00000014521; Expressed in liver and 105 other cell types or tissues.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0003979; F:UDP-glucose 6-dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0030206; P:chondroitin sulfate biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0001702; P:gastrulation with mouth forming second; ISS:AgBase.
DR   GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IBA:GO_Central.
DR   GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; ISS: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   Gene3D; 1.20.5.100; Cytochrome c1, transmembrane anchor, C-terminal; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
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   NCBIfam; TIGR03026; NDP-sugDHase; 1.
DR   PANTHER; PTHR11374:SF59; UDP-GLUCOSE 6-DEHYDROGENASE; 1.
DR   PANTHER; PTHR11374; UDP-GLUCOSE DEHYDROGENASE/UDP-MANNAC DEHYDROGENASE; 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; 6-phosphogluconate dehydrogenase C-terminal domain-like; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   SUPFAM; SSF52413; UDP-glucose/GDP-mannose dehydrogenase C-terminal domain; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Allosteric enzyme; Carbohydrate metabolism;
KW   Direct protein sequencing; NAD; Oxidoreductase; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..494
FT                   /note="UDP-glucose 6-dehydrogenase"
FT                   /id="PRO_0000074059"
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..494
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:0000250|UniProtKB:O60701"
FT   MOD_RES         476
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60701"
FT   CONFLICT        157
FT                   /note="Missing (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        278..281
FT                   /note="QKDV -> ZZGK (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   494 AA;  55136 MW;  8560E27089C4D03E CRC64;
     MFEIKKICCI GAGYVGGPTC SVIAHMCPEI RVTVVDINES RINAWNSPTL PIYEPGLKEV
     VESCRGKNLF FSTNIDDAIK EADLVFISVN TPTKTYGMGK GRAADLKYIE ACARRIVQNS
     HGYKIVTEKS TVPVRAAESI RRIFDANTKP NLNLQVLSNP EFLAEGTAIK DLKNPDRVLI
     GGDETPEGQR AVQALCAVYE HWVPREKILT TNTWSSELSK LTANAFLAQR ISSINSISAL
     CEATGADVEE VATAIGMDQR IGNKFLKASV GFGGSCFQKD VLNLVYLCEA LNLPEVARYW
     QQVIDMNDYQ RRRFASRIID SLFNTVTDKK IAILGFAFKK DTGDTRESSS IYISKYLMDE
     GAHLHIYDPK VPREQIVVDL SHPGVSKDDQ VARLVTISKD PYEACDGAHA VVICTEWDMF
     KELDYERIHK KMLKPAFIFD GRRVLDGLHN ELQTIGFQIE TIGKKVSSKR IPYAPSGEIP
     KFSLQDMPNK KPRV
//