ID   DHE3_PIG                Reviewed;         558 AA.
AC   P42174;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   07-OCT-2020, sequence version 2.
DT   24-JAN-2024, entry version 91.
DE   RecName: Full=Glutamate dehydrogenase 1, mitochondrial;
DE            Short=GDH 1;
DE            EC=1.4.1.3 {ECO:0000269|PubMed:8240242};
DE   AltName: Full=Membrane protein 50 {ECO:0000303|PubMed:8240242};
DE            Short=MP50 {ECO:0000303|PubMed:8240242};
DE   Flags: Precursor;
GN   Name=GLUD1; Synonyms=GLUD;
OS   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG   Porcine genome sequencing project;
RL   Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 54-73 AND 364-381, CATALYTIC ACTIVITY, FUNCTION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=8240242; DOI=10.1042/bj2950447;
RA   Rajas F., Rousset B.;
RT   "A membrane-bound form of glutamate dehydrogenase possesses an ATP-
RT   dependent high-affinity microtubule-binding activity.";
RL   Biochem. J. 295:447-455(1993).
CC   -!- FUNCTION: Mitochondrial glutamate dehydrogenase that converts L-
CC       glutamate into alpha-ketoglutarate. Plays a key role in glutamine
CC       anaplerosis by producing alpha-ketoglutarate, an important intermediate
CC       in the tricarboxylic acid cycle (PubMed:8240242). Plays a role in
CC       insulin homeostasis (By similarity). May be involved in learning and
CC       memory reactions by increasing the turnover of the excitatory
CC       neurotransmitter glutamate (By similarity).
CC       {ECO:0000250|UniProtKB:P10860, ECO:0000250|UniProtKB:P26443,
CC       ECO:0000269|PubMed:8240242}.
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=1.4.1.3;
CC         Evidence={ECO:0000269|PubMed:8240242};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH +
CC         NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.3;
CC         Evidence={ECO:0000250|UniProtKB:P00367};
CC   -!- ACTIVITY REGULATION: Subject to allosteric regulation. Activated by
CC       ADP. Inhibited by GTP and ATP. ADP can occupy the NADH binding site and
CC       activate the enzyme. Inhibited by SIRT4 (By similarity). Inhibited by
CC       HADH (By similarity). {ECO:0000250|UniProtKB:P00367,
CC       ECO:0000250|UniProtKB:P26443}.
CC   -!- SUBUNIT: Homohexamer (By similarity). Interacts with HADH; this
CC       interaction inhibits the activation of GLUD1 (By similarity).
CC       {ECO:0000250|UniProtKB:P00366, ECO:0000250|UniProtKB:P26443}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P00367}.
CC       Endoplasmic reticulum {ECO:0000250|UniProtKB:P00367}. Note=Mostly
CC       translocates into the mitochondria, only a small amount of the protein
CC       localizes to the endoplasmic reticulum. {ECO:0000250|UniProtKB:P00367}.
CC   -!- TISSUE SPECIFICITY: Liver, brain and thyroid.
CC       {ECO:0000269|PubMed:8240242}.
CC   -!- PTM: ADP-ribosylated by SIRT4, leading to inactivate glutamate
CC       dehydrogenase activity. Stoichiometry shows that ADP-ribosylation
CC       occurs in one subunit per catalytically active homohexamer.
CC       {ECO:0000250|UniProtKB:P00367}.
CC   -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC       {ECO:0000305}.
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DR   EMBL; AEMK02000096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; S39010; S39010.
DR   RefSeq; NP_001231430.1; NM_001244501.1.
DR   AlphaFoldDB; P42174; -.
DR   SMR; P42174; -.
DR   STRING; 9823.ENSSSCP00000011056; -.
DR   PeptideAtlas; P42174; -.
DR   Ensembl; ENSSSCT00025034039.1; ENSSSCP00025014172.1; ENSSSCG00025025117.1.
DR   Ensembl; ENSSSCT00030091528.1; ENSSSCP00030042102.1; ENSSSCG00030065447.1.
DR   Ensembl; ENSSSCT00035079984.1; ENSSSCP00035032921.1; ENSSSCG00035059666.1.
DR   Ensembl; ENSSSCT00045058193.1; ENSSSCP00045040681.1; ENSSSCG00045033938.1.
DR   Ensembl; ENSSSCT00050091367.1; ENSSSCP00050039305.1; ENSSSCG00050067038.1.
DR   Ensembl; ENSSSCT00055054205.1; ENSSSCP00055043253.1; ENSSSCG00055027367.1.
DR   Ensembl; ENSSSCT00060082867.1; ENSSSCP00060035914.1; ENSSSCG00060060739.1.
DR   Ensembl; ENSSSCT00065050932.1; ENSSSCP00065022079.1; ENSSSCG00065037327.1.
DR   Ensembl; ENSSSCT00070048400.1; ENSSSCP00070040872.1; ENSSSCG00070024230.1.
DR   GeneID; 100157162; -.
DR   KEGG; ssc:100157162; -.
DR   CTD; 2746; -.
DR   eggNOG; KOG2250; Eukaryota.
DR   InParanoid; P42174; -.
DR   OrthoDB; 45283at2759; -.
DR   Reactome; R-SSC-2151201; Transcriptional activation of mitochondrial biogenesis.
DR   Reactome; R-SSC-8964539; Glutamate and glutamine metabolism.
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Chromosome 14.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
DR   Bgee; ENSSSCG00000010368; Expressed in Ammon's horn and 43 other cell types or tissues.
DR   ExpressionAtlas; P42174; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004352; F:glutamate dehydrogenase (NAD+) activity; IBA:GO_Central.
DR   GO; GO:0004354; F:glutamate dehydrogenase (NADP+) activity; IEA:RHEA.
DR   GO; GO:0004353; F:glutamate dehydrogenase [NAD(P)+] activity; ISS:UniProtKB.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0006538; P:glutamate catabolic process; IBA:GO_Central.
DR   GO; GO:0006541; P:glutamine metabolic process; ISS:UniProtKB.
DR   GO; GO:0072350; P:tricarboxylic acid metabolic process; ISS:UniProtKB.
DR   CDD; cd01076; NAD_bind_1_Glu_DH; 1.
DR   Gene3D; 1.10.287.140; -; 1.
DR   Gene3D; 3.40.50.10860; Leucine Dehydrogenase, chain A, domain 1; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR046346; Aminoacid_DH-like_N_sf.
DR   InterPro; IPR006095; Glu/Leu/Phe/Val/Trp_DH.
DR   InterPro; IPR006096; Glu/Leu/Phe/Val/Trp_DH_C.
DR   InterPro; IPR006097; Glu/Leu/Phe/Val/Trp_DH_dimer.
DR   InterPro; IPR033524; Glu/Leu/Phe/Val_DH_AS.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR033922; NAD_bind_Glu_DH.
DR   PANTHER; PTHR11606; GLUTAMATE DEHYDROGENASE; 1.
DR   PANTHER; PTHR11606:SF13; GLUTAMATE DEHYDROGENASE 1, MITOCHONDRIAL; 1.
DR   Pfam; PF00208; ELFV_dehydrog; 1.
DR   Pfam; PF02812; ELFV_dehydrog_N; 1.
DR   PRINTS; PR00082; GLFDHDRGNASE.
DR   SMART; SM00839; ELFV_dehydrog; 1.
DR   SUPFAM; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00074; GLFV_DEHYDROGENASE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ADP-ribosylation; ATP-binding; Direct protein sequencing;
KW   Endoplasmic reticulum; GTP-binding; Hydroxylation; Mitochondrion; NAD;
KW   NADP; Nucleotide-binding; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..53
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P00367"
FT   CHAIN           54..558
FT                   /note="Glutamate dehydrogenase 1, mitochondrial"
FT                   /id="PRO_0000182741"
FT   REGION          34..58
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        183
FT                   /evidence="ECO:0000250|UniProtKB:P10860"
FT   BINDING         141..143
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         147
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         171
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         176
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         252
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         266
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         270
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         319
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         322
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         438
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         444
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         450
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   BINDING         516
FT                   /ligand="ADP"
FT                   /ligand_id="ChEBI:CHEBI:456216"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         68
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         79
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P10860"
FT   MOD_RES         84
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         84
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         90
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         110
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         110
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         128
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P10860"
FT   MOD_RES         135
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         147
FT                   /note="N6-(2-hydroxyisobutyryl)lysine"
FT                   /evidence="ECO:0000250|UniProtKB:P00367"
FT   MOD_RES         162
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         162
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         171
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         172
FT                   /note="ADP-ribosylcysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P00367"
FT   MOD_RES         183
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         183
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         187
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         191
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         191
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         200
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         211
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         227
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00367"
FT   MOD_RES         326
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         346
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         346
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         352
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         352
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         363
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         363
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         365
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         365
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         384
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00367"
FT   MOD_RES         386
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         390
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         390
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         399
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         410
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P10860"
FT   MOD_RES         415
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         415
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         457
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         457
FT                   /note="N6-malonyllysine; alternate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         457
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         477
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         477
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         480
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         480
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
FT   MOD_RES         503
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         503
FT                   /note="N6-malonyllysine; alternate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         503
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         512
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P00367"
FT   MOD_RES         527
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         527
FT                   /note="N6-malonyllysine; alternate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         527
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         545
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         545
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P00366"
FT   MOD_RES         548
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P26443"
SQ   SEQUENCE   558 AA;  61308 MW;  B0096993A9A7F225 CRC64;
     MYRCLGEALL LSRAGPAALG SAAADSAALL GRTRGQPATA PQPGLAPPAR RHYSEAAADR
     EDDPNFFKMV EGFFDRGASI VEDKLVEDLK TRESEEQKRN RVRGILRIIK PCNHVLSLSF
     PIRRDDGSWE VIEGYRAQHS QHRTPCKGGI RYSTDVSVDE VKALASLMTY KCAVVDVPFG
     GAKAGVKINP KNYTDNELEK ITRRFTMELA KKGFIGPGID VPAPDMSTGE REMSWIADTY
     ASTIGHYDIN AHACVTGKPI SQGGIHGRIS ATGRGVFHGI ENFINEASYM SILGMTPGFG
     DKTFVVQGFG NVGLHSMRYL HRFGAKCVGV GESDGSIWNP DGIDPKELED FKLQHGTILG
     FPKAKIYEGS ILEADCDILI PAASEKQLTK SNAPRVKAKI IAEGANGPTT PEADKIFLER
     NIMVIPDLYL NAGGVTVSYF EWLKNLNHVS YGRLTFKYER DSNYHLLMSV QESLERKFGK
     HGGTIPIVPT AEFQDRISGA SEKDIVHSGL AYTMERSARQ IMRTAMKYNL GLDLRTAAYV
     NAIEKVFKVY NEAGVTFT
//