GPD2_CANAL
ID GPD2_CANAL Reviewed; 371 AA.
AC Q59W33;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Glycerol-3-phosphate dehydrogenase [NAD(+)] 2 {ECO:0000305};
DE EC=1.1.1.8 {ECO:0000255|RuleBase:RU361243};
GN Name=GPD2 {ECO:0000312|CGD:CAL0000176146};
GN OrderedLocusNames=orf19.691 {ECO:0000312|CGD:CAL0000176146};
GN ORFNames=CAALFM_C602010CA {ECO:0000312|EMBL:AOW30137.1};
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561 {ECO:0000312|Proteomes:UP000000559};
RN [1] {ECO:0000312|Proteomes:UP000000559}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876 {ECO:0000312|Proteomes:UP000000559};
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2] {ECO:0000312|Proteomes:UP000000559}
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876 {ECO:0000312|Proteomes:UP000000559};
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3] {ECO:0000312|Proteomes:UP000000559}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HUMAN CFH; CFHR1 AND PLASMINOGEN, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23204165; DOI=10.1093/infdis/jis718;
RA Luo S., Hoffmann R., Skerka C., Zipfel P.F.;
RT "Glycerol-3-phosphate dehydrogenase 2 is a novel factor H-, factor H-like
RT protein 1-, and plasminogen-binding surface protein of Candida albicans.";
RL J. Infect. Dis. 207:594-603(2013).
RN [5] {ECO:0000305}
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=34986357; DOI=10.1016/j.celrep.2021.110183;
RA Kumwenda P., Cottier F., Hendry A.C., Kneafsey D., Keevan B., Gallagher H.,
RA Tsai H.J., Hall R.A.;
RT "Estrogen promotes innate immune evasion of Candida albicans through
RT inactivation of the alternative complement system.";
RL Cell Rep. 38:110183-110183(2022).
CC -!- FUNCTION: May catalyze the production and accumulation of glycerol
CC during hyperosmotic stress conditions (By similarity). Glycerol acts as
CC a osmoregulator that prevents loss of water and turgor of the cells (By
CC similarity). Mediates evasion of the host innate immune system by
CC binding inhibitory components of the host alternative complement
CC system, in a manner dependent on estrogen-induced inhibition of EBP1
CC (PubMed:34986357, PubMed:23204165). {ECO:0000250|UniProtKB:Q00055,
CC ECO:0000269|PubMed:23204165, ECO:0000269|PubMed:34986357}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + sn-glycerol 3-phosphate = dihydroxyacetone phosphate
CC + H(+) + NADH; Xref=Rhea:RHEA:11092, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57597, ChEBI:CHEBI:57642,
CC ChEBI:CHEBI:57945; EC=1.1.1.8;
CC Evidence={ECO:0000255|RuleBase:RU361243};
CC -!- SUBUNIT: Interacts with human CFH/complement factor H; the interaction
CC is direct and enables the pathogen to evade the host innate immune
CC system (PubMed:23204165). Interacts with human CFHR1/complement factor
CC H-related protein 1; the interaction is direct (PubMed:23204165).
CC Interacts with human PLG/plasminogen; the interaction is direct and
CC provides active plasmin on the surface of fungal cells
CC (PubMed:23204165). {ECO:0000269|PubMed:23204165}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:23204165}. Secreted {ECO:0000269|PubMed:23204165}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q00055}. Peroxisome
CC {ECO:0000250|UniProtKB:Q00055}. Note=Localizes to the cell wall in both
CC yeast and hyphae. {ECO:0000269|PubMed:23204165}.
CC -!- INDUCTION: Mildly induced by estrogen (17beta-estradiol).
CC {ECO:0000269|PubMed:34986357}.
CC -!- DISRUPTION PHENOTYPE: In presence of estrogen; decreases binding of
CC host complement factor H protein and increases phagocytosis of the
CC fungus by host (PubMed:34986357). Decreases virulence in presence of
CC estrogen in a zebrafish larval model of infection (PubMed:34986357).
CC {ECO:0000269|PubMed:34986357}.
CC -!- SIMILARITY: Belongs to the NAD-dependent glycerol-3-phosphate
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; CP017628; AOW30137.1; -; Genomic_DNA.
DR RefSeq; XP_713824.1; XM_708731.2.
DR SMR; Q59W33; -.
DR STRING; 237561.Q59W33; -.
DR PRIDE; Q59W33; -.
DR EnsemblFungi; KHC73342; KHC73342; W5Q_04780.
DR EnsemblFungi; KHC82605; KHC82605; I503_04763.
DR GeneID; 3644563; -.
DR KEGG; cal:CAALFM_C602010CA; -.
DR CGD; CAL0000176146; GPD2.
DR VEuPathDB; FungiDB:C6_02010C_A; -.
DR eggNOG; KOG2711; Eukaryota.
DR HOGENOM; CLU_033449_2_3_1; -.
DR OMA; INCVNET; -.
DR OrthoDB; 476066at2759; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0009986; C:cell surface; IDA:CGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:UniProtKB.
DR GO; GO:0009331; C:glycerol-3-phosphate dehydrogenase complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004367; F:glycerol-3-phosphate dehydrogenase [NAD+] activity; IBA:GO_Central.
DR GO; GO:0051287; F:NAD binding; IEA:UniProtKB-UniRule.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0042784; P:evasion of host immune response via regulation of host complement system; IMP:UniProtKB.
DR GO; GO:0046168; P:glycerol-3-phosphate catabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006072; P:glycerol-3-phosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006116; P:NADH oxidation; IBA:GO_Central.
DR Gene3D; 1.10.1040.10; -; 1.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR013328; 6PGD_dom2.
DR InterPro; IPR006168; G3P_DH_NAD-dep.
DR InterPro; IPR006109; G3P_DH_NAD-dep_C.
DR InterPro; IPR017751; G3P_DH_NAD-dep_euk.
DR InterPro; IPR011128; G3P_DH_NAD-dep_N.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF07479; NAD_Gly3P_dh_C; 1.
DR Pfam; PF01210; NAD_Gly3P_dh_N; 1.
DR PIRSF; PIRSF000114; Glycerol-3-P_dh; 1.
DR PRINTS; PR00077; GPDHDRGNASE.
DR SUPFAM; SSF48179; SSF48179; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR03376; glycerol3P_DH; 1.
DR PROSITE; PS00957; NAD_G3PDH; 1.
PE 1: Evidence at protein level;
KW Cell wall; Cytoplasm; NAD; Oxidoreductase; Peroxisome; Reference proteome;
KW Secreted; Virulence.
FT CHAIN 1..371
FT /note="Glycerol-3-phosphate dehydrogenase [NAD(+)] 2"
FT /id="PRO_0000456035"
FT ACT_SITE 222
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-1"
FT BINDING 18..23
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-3"
FT BINDING 50
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-3"
FT BINDING 106
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-3"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-2"
FT BINDING 162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-3"
FT BINDING 294..295
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-2"
FT BINDING 294
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-3"
FT BINDING 323
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|PIRSR:PIRSR000114-3"
SQ SEQUENCE 371 AA; 40801 MW; 4224FCCB1253BDA3 CRC64;
MTTSPYPIET PFKVCIVGSG NWGTAVAKLV AENCAEKPNI FQRDVKMWVF EEEIEGRKLT
EIINTEHENV KYLPEIKLPT NLVANPDIVD TVQDADLIVF NIPHQFLGRI VKQIEGKVKP
TARAISCLKG LDVSPEGCKL LSTSITDTLK IYCGVLSGAN IANEVAKGNW SETSIAYTVP
EDFRGAGKDI DPFILKEAFH RPYFHVRVIE DVVGASIAGA LKNVIACSVG FVEGAGWGDN
AKAAIMRIGI KETIRFASYW ELFKIKALSP PNPKTFTEES AGVADLITTC SGGRNVKVAR
YMIKNNVDAF EAEKIVLKGQ SSQGILTAKE VHELLTNFNL QDEFPLLEAT YKVIYENGSV
DDFPQLLEGD Q
