GLUD1

Protein identityUniProt · HPA

UniProt accession

P00367

Gene

GLUD1

Ensembl

ENSG00000148672

Chromosome

10

Canonical length

558 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homohexamer

OverviewNCBI Gene

This gene encodes glutamate dehydrogenase, which is a mitochondrial matrix enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate and ammonia. This enzyme has an important role in regulating amino acid-induced insulin secretion. It is allosterically activated by ADP and inhibited by GTP and ATP. Activating mutations in this gene are a common cause of congenital hyperinsulinism. Alternative splicing of this gene results in multiple transcript variants. The related glutamate dehydrogenase 2 gene on the human X-chromosome originated from this gene via retrotransposition and encodes a soluble form of glutamate dehydrogenase. Related pseudogenes have been identified on chromosomes 10, 18 and X. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

558 residues, UniProt reviewed canonical sequence.

>P00367|GLUD1
     1  MYRYLGEALL LSRAGPAALG SASADSAALL GWARGQPAAA PQPGLALAAR RHYSEAVADR
    61  EDDPNFFKMV EGFFDRGASI VEDKLVEDLR TRESEEQKRN RVRGILRIIK PCNHVLSLSF
   121  PIRRDDGSWE VIEGYRAQHS QHRTPCKGGI RYSTDVSVDE VKALASLMTY KCAVVDVPFG
   181  GAKAGVKINP KNYTDNELEK ITRRFTMELA KKGFIGPGID VPAPDMSTGE REMSWIADTY
   241  ASTIGHYDIN AHACVTGKPI SQGGIHGRIS ATGRGVFHGI ENFINEASYM SILGMTPGFG
   301  DKTFVVQGFG NVGLHSMRYL HRFGAKCIAV GESDGSIWNP DGIDPKELED FKLQHGSILG
   361  FPKAKPYEGS ILEADCDILI PAASEKQLTK SNAPRVKAKI IAEGANGPTT PEADKIFLER
   421  NIMVIPDLYL NAGGVTVSYF EWLKNLNHVS YGRLTFKYER DSNYHLLMSV QESLERKFGK
   481  HGGTIPIVPT AEFQDRISGA SEKDIVHSGL AYTMERSARQ IMRTAMKYNL GLDLRTAAYV
   541  NAIEKVFKVY NEAGVTFT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLUD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

860 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLUD1.

Disease | AllUniProt

Conditions GLUD1 is implicated in, by any mechanism.

• Hyperinsulinemic hypoglycemia, familial, 6 (HHF6) MIM:606762

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 319 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyperinsulinism-hyperammonemia syndrome
• Familial hyperinsulinemia
• Familial hyperinsulinism
• GLUD1-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.61

gnomAD pLI

0.01

gnomAD missense Z

3.06

DepMap mean gene effect

0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glutamate biosynthetic process
• glutamine metabolic process
• L-glutamate catabolic process
• positive regulation of insulin secretion
• substantia nigra development
• tricarboxylic acid metabolic process

Molecular functions

• ADP binding
• ATP binding
• glutamate dehydrogenase (NAD+) activity
• glutamate dehydrogenase (NADP+) activity
• glutamate dehydrogenase [NAD(P)+] activity
• GTP binding
• L-leucine binding
• NAD+ binding
• protein homodimerization activity

Cellular components

• cytoplasm
• endoplasmic reticulum
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase
• Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase, C-terminal
• Glutamate/phenylalanine/leucine/valine/L-tryptophan dehydrogenase, dimerisation domain
• Leu/Phe/Val dehydrogenases active site
• NAD(P) binding domain of glutamate dehydrogenase
• NAD(P)-binding domain superfamily
• Aminoacid dehydrogenase-like, N-terminal domain superfamily
• Glutamate/Leucine/Phenylalanine/Valine dehydrogenase
• Glu/Leu/Phe/Val dehydrogenase, dimerisation domain

KeywordsUniProt

• Acetylation
• ADP-ribosylation
• ATP-binding
• Endoplasmic reticulum
• GTP-binding
• Hydroxylation
• Mitochondrion
• NADP
• Nucleotide-binding
• Oxidoreductase
• Phosphoprotein
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of GLUD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HADH
• SIRT4
• RIPK3
• CUL3
• GLUD2
• KLHL22