GLUD2_DICDI
ID GLUD2_DICDI Reviewed; 1042 AA.
AC Q54VI3;
DT 03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 25-MAY-2022, entry version 95.
DE RecName: Full=Glutamate dehydrogenase 2;
DE EC=1.4.1.2 {ECO:0000269|PubMed:1952936, ECO:0000269|PubMed:33476647};
DE AltName: Full=NAD-specific glutamate dehydrogenase;
DE Short=NAD-GDH;
GN Name=glud2; ORFNames=DDB_G0280319;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP PROTEIN SEQUENCE OF 115-130; 191-204; 238-246; 254-265; 344-356; 428-440;
RP 462-476; 514-522; 692-703; 790-803 AND 1009-1018, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=AX2;
RA Bienvenut W.V., Ura S., Insall R.H.;
RL Submitted (JUL-2009) to UniProtKB.
RN [3]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1952936; DOI=10.1016/0003-9861(91)90127-5;
RA Pamula F., Wheldrake J.F.;
RT "The NAD-dependent glutamate dehydrogenase from Dictyostelium discoideum:
RT purification and properties.";
RL Arch. Biochem. Biophys. 291:225-230(1991).
RN [4]
RP ACTIVITY REGULATION.
RX PubMed=1402793; DOI=10.1099/00221287-138-9-1935;
RA Pamula F., Wheldrake J.F.;
RT "The effect of AMP on the NAD-dependent glutamate dehydrogenase during
RT activation and morphogenesis in the cellular slime moulds.";
RL J. Gen. Microbiol. 138:1935-1940(1992).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=8728102;
RA Pamula F., Wheldrake J.F.;
RT "Kinetic properties and the mechanism of activation of NAD-dependent
RT glutamate dehydrogenase from Dictyostelium discoideum.";
RL Biochem. Mol. Biol. Int. 38:729-738(1996).
RN [6]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION (MICROBIAL INFECTION),
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ADP-RIBOSYLATION AT ARG-763
RP (MICROBIAL INFECTION), AND MUTAGENESIS OF ARG-763.
RX PubMed=33476647; DOI=10.1016/j.jbc.2021.100301;
RA Black M.H., Osinski A., Park G.J., Gradowski M., Servage K.A.,
RA Pawlowski K., Tagliabracci V.S.;
RT "A Legionella effector ADP-ribosyltransferase inactivates glutamate
RT dehydrogenase.";
RL J. Biol. Chem. 296:100301-100301(2021).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH +
CC NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.4.1.2;
CC Evidence={ECO:0000269|PubMed:1952936, ECO:0000269|PubMed:33476647};
CC -!- ACTIVITY REGULATION: Activity is stimulated by AMP.
CC {ECO:0000269|PubMed:1402793, ECO:0000269|PubMed:1952936,
CC ECO:0000269|PubMed:8728102}.
CC -!- ACTIVITY REGULATION: (Microbial infection) Inhibited by ADP-
CC ribosylation. {ECO:0000269|PubMed:33476647}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18.53 mM for glutamate {ECO:0000269|PubMed:33476647};
CC KM=0.36 mM for alpha-ketoglutarate {ECO:0000269|PubMed:1952936,
CC ECO:0000269|PubMed:8728102};
CC KM=16 uM for NADH {ECO:0000269|PubMed:1952936,
CC ECO:0000269|PubMed:8728102};
CC KM=35.4 mM for ammonium ions {ECO:0000269|PubMed:1952936,
CC ECO:0000269|PubMed:8728102};
CC pH dependence:
CC Optimum pH is 7.25-7.5. {ECO:0000269|PubMed:1952936,
CC ECO:0000269|PubMed:8728102};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:33476647}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: (Microbial infection) ADP-ribosylated at Arg-763 by the Legionella
CC pneumophila effector Lart1, which inhibits the glutamate dehydrogenase
CC activity. Amoeba are natural hosts of Legionella, and ADP-ribosylation
CC by Lart1 may promote Legionella parasitism.
CC {ECO:0000269|PubMed:33476647}.
CC -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC {ECO:0000305}.
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DR EMBL; AAFI02000035; EAL67386.2; -; Genomic_DNA.
DR RefSeq; XP_641372.4; XM_636280.3.
DR AlphaFoldDB; Q54VI3; -.
DR STRING; 44689.DDB0233691; -.
DR PaxDb; Q54VI3; -.
DR GeneID; 8622506; -.
DR KEGG; ddi:DDB_G0280319; -.
DR dictyBase; DDB_G0280319; glud2.
DR eggNOG; KOG2250; Eukaryota.
DR HOGENOM; CLU_005220_0_0_1; -.
DR InParanoid; Q54VI3; -.
DR OMA; LYCLPQN; -.
DR PhylomeDB; Q54VI3; -.
DR PRO; PR:Q54VI3; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004352; F:glutamate dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0006538; P:glutamate catabolic process; IBA:GO_Central.
DR GO; GO:0019551; P:glutamate catabolic process to 2-oxoglutarate; IEA:InterPro.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR006096; Glu/Leu/Phe/Val_DH_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR016210; NAD-GDH_euk.
DR Pfam; PF00208; ELFV_dehydrog; 1.
DR PIRSF; PIRSF000184; GDH_NAD; 1.
DR SMART; SM00839; ELFV_dehydrog; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Cytoplasm; Direct protein sequencing; NAD;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..1042
FT /note="Glutamate dehydrogenase 2"
FT /id="PRO_0000388369"
FT ACT_SITE 596
FT /evidence="ECO:0000250"
FT MOD_RES 763
FT /note="ADP-ribosylarginine; by Legionella Lart1"
FT /evidence="ECO:0000269|PubMed:33476647"
FT MUTAGEN 763
FT /note="R->A: Abolishes ADP-ribosylation by Lart1."
FT /evidence="ECO:0000269|PubMed:33476647"
SQ SEQUENCE 1042 AA; 117144 MW; BB9F1819F5D3F79A CRC64;
MLNQNLTISQ EIAAQPKTQY FTKEDGDALA NLLESNPYKE QAVEVKSLLK SERLIESSRV
EPEVDWFYCK LGLDSNYFDS TPSIVIARHI LSLYAAKMVS HATGAKLEVH LHSKNEGSAT
FITPSNPGKR DSPAMMIEHA IESHYFGEGY HQDQQLLSPQ QVAVAPFPVS PKPPTGTNLP
PHGFRLACYR TTGTVSNSSP VHLRLYYLTK PVFPQATNDL SASKNDEILA TETDLFKIGD
ISFIEKSSEL TKKIYQEVMN EVVGKQGPVI KHYPYQTNGA RLVIAYRRGS THSYWSAIGE
LYHFHQMYAT HKYVEQFSNG ITIYSIYLRP LHPDVDINTK ISKIAEQASL VYVLPRTSLT
PLFLSHQLSF PEVTYAYVCW KFAYQFLNRY ATEYSALAAA IGDDSTKQSM LAQLKTRLSK
DTFTEGRVRD AVLQYPELIK ILYQDFEKFH FSGSNSNNTQ KYDVQHGSEI LASIKKTVNN
ELDSQIFSAI LSFNRHLLKT NFYKQTKTAL SFRLDPGFLS TKEYVSTPYA VFFVVGSEFR
GFHIRFRDIS RGGIRIIRSG NSTQYDHNSS SLFDENYNLA NTQQSKNKDI AEGGSKGTIL
LSADHQSKAE VAFHKYIDGL LDLLLPNHEI VDHFAKPEIL FLGPDEGTAD FMNWASSHAK
DRGAHFWKAF TTGKSLSRGG IPHDLYGMTT RSIHQYVLGT LAKLGRNEAD CTKFQTGGPD
GDLGSNEIKI SKDKTIGIVD GSGVLLDPQG LNRDEIGRLA SKRQMARYFD KSKLSPQGFF
VDVAENDVKL PNGDIVESGL IFRNNFHLNP LCNADIFVPC GGRPESVQLT NVDKMFTATG
ESRFPIIVEG ANLFFTQKAR LMIEEKGAII FKDASANKGG VTSSSLEVLA ALALNDEEFD
RHMCVKDNVV PEFYENYIKD VHHTIESNAR LEFECIWSEH ESTKTPRSIL SDLLSNKINS
LNDSIQTSSL WTDQSLRRKI ISAACPKVLL NLLGVDKIME RVPEPYVKAI FGSYLASRFV
YKYGLNSNEF AFYTYMETLK QQ
