UGDH_PONAB
ID UGDH_PONAB Reviewed; 494 AA.
AC Q5R7B3;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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; CR860205; CAH92347.1; -; mRNA.
DR RefSeq; NP_001127543.1; NM_001134071.1.
DR AlphaFoldDB; Q5R7B3; -.
DR SMR; Q5R7B3; -.
DR STRING; 9601.ENSPPYP00000016396; -.
DR GeneID; 100174620; -.
DR KEGG; pon:100174620; -.
DR CTD; 7358; -.
DR eggNOG; KOG2666; Eukaryota.
DR InParanoid; Q5R7B3; -.
DR OrthoDB; 915490at2759; -.
DR UniPathway; UPA00038; UER00491.
DR Proteomes; UP000001595; Unplaced.
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:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Allosteric enzyme; Carbohydrate metabolism; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..494
FT /note="UDP-glucose 6-dehydrogenase"
FT /id="PRO_0000317477"
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"
SQ SEQUENCE 494 AA; 55077 MW; 9584347DAD728943 CRC64;
MFEIKKICCI GAGYVGGPTC SVIAHMRPEI RVTVVDVNES RINAWNSPTL PIYEPGLKEV
VESCRGKNLF FSTNIDDAIK EADLVFISVN TPTKTYGMGK GRAADLKYIE ACARRIVQNS
NGYKIVTEKS TVPVRAAESI RRIFDANTKP NLNLQVLSNP EFLAEGTAIK DLKNPDRVLI
GGDETPEGQR AVQALCAVYE HWVPREKILT TNTWSSELSK LAANAFLAQR ISSINSISAL
CEATGADVEE VATAIGMDQR IGNKFLKASV GFGGSCFQKD VLNLVYLCEA LNLPEVARYW
QQVIDMNDYQ RRRFASRIID SLFNTVTDKK IAILGFAFKK DTGDTRESSS IYISKYLMDE
GAHLHIYDPK VPREQIVVDL SHPGVSEDDQ VSRLVTISKD PYEACDGAHA VVICTEWDMF
KELDYERIHK KMLKPAFIFD GRRVLDGLHN ELQTIGFQIE TIGKKVSSKR IPYAPSGEIP
KFSLQDPPNK KPKV
