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 13-SEP-2023, entry version 101. 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}. 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; 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; 167209at2759; -. 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 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 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 //