UGDH_CHICK
ID UGDH_CHICK Reviewed; 494 AA.
AC Q5F3T9;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
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; ORFNames=RCJMB04_7d7;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
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). {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; AJ851561; CAH65195.1; -; mRNA.
DR RefSeq; NP_001012599.1; NM_001012581.1.
DR AlphaFoldDB; Q5F3T9; -.
DR SMR; Q5F3T9; -.
DR STRING; 9031.ENSGALP00000023101; -.
DR PaxDb; Q5F3T9; -.
DR Ensembl; ENSGALT00000090339; ENSGALP00000060119; ENSGALG00000041993.
DR GeneID; 422792; -.
DR KEGG; gga:422792; -.
DR CTD; 7358; -.
DR VEuPathDB; HostDB:geneid_422792; -.
DR eggNOG; KOG2666; Eukaryota.
DR GeneTree; ENSGT00390000015355; -.
DR HOGENOM; CLU_023810_7_2_1; -.
DR InParanoid; Q5F3T9; -.
DR OMA; CECLNLP; -.
DR OrthoDB; 915490at2759; -.
DR PhylomeDB; Q5F3T9; -.
DR Reactome; R-GGA-173599; Formation of the active cofactor, UDP-glucuronate.
DR UniPathway; UPA00038; UER00491.
DR PRO; PR:Q5F3T9; -.
DR Proteomes; UP000000539; Chromosome 4.
DR Bgee; ENSGALG00000041993; Expressed in liver and 13 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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: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 Allosteric enzyme; Carbohydrate metabolism; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..494
FT /note="UDP-glucose 6-dehydrogenase"
FT /id="PRO_0000317478"
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"
SQ SEQUENCE 494 AA; 55064 MW; B5D9F2590D366122 CRC64;
MFEIKKICCI GAGYVGGPTC SVIAQMCPKI QVTVVDVNEA RINAWNSDTL PIYEPGLKEV
VESCRGRNLF FSTSIDDAIR EADLVFISVN TPTKTYGMGK GRAADLKYIE ACARRIVQNS
NGYKIVTEKS TVPVRAAESI RRIFDANTKP NLDLQVLSNP EFLAEGTAIK DLKNPDRVLI
GGDDSPEGQK AVRALCAVYE HWVPKEKILT TNTWSSELSK LAANAFLAQR ISSINSISAL
CEATGADVEE VARAIGTDQR IGNKFLKASV GFGGSCFQKD VLNLVYLCEA LNLPEVARYW
QQVIDMNDYQ RRRFASRIID SLFNTVTDKK IAILGFAFKK DTGDTRESSS IYISKYLMDE
GAKLHIYDPK VPKEQIILDL SHPGVSEDNQ VSRLVTISQD PYEACDGAHA LVICTEWDMF
KELDYERIHK KMLKPAFIFD GRRVLDDLHN ELQVIGFQIE TIGKKVSAKR IPFASSCEIP
KFSLQDPPVK KPRV
