UGDH_BOVIN
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 03-AUG-2022, entry version 152.
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}.
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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; P12378; -.
DR PeptideAtlas; P12378; -.
DR PRIDE; P12378; -.
DR Ensembl; ENSBTAT00000019302; ENSBTAP00000019302; ENSBTAG00000014521.
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; CECLNLP; -.
DR OrthoDB; 915490at2759; -.
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 tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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 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;
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
