GLUL

Protein identityUniProt · HPA

UniProt accession

P15104

Gene

GLUL

Ensembl

ENSG00000135821

Chromosome

1

Canonical length

373 aa

Protein class

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

Subcellular location

Plasma membrane,Mitochondria,Cytosol,Connecting piece

OverviewNCBI Gene

The protein encoded by this gene belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. This protein plays a role in ammonia and glutamate detoxification, acid-base homeostasis, cell signaling, and cell proliferation. Glutamine is an abundant amino acid, and is important to the biosynthesis of several amino acids, pyrimidines, and purines. Mutations in this gene are associated with congenital glutamine deficiency, and overexpression of this gene was observed in some primary liver cancer samples. There are six pseudogenes of this gene found on chromosomes 2, 5, 9, 11, and 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

373 residues, UniProt reviewed canonical sequence.

>P15104|GLUL
     1  MTTSASSHLN KGIKQVYMSL PQGEKVQAMY IWIDGTGEGL RCKTRTLDSE PKCVEELPEW
    61  NFDGSSTLQS EGSNSDMYLV PAAMFRDPFR KDPNKLVLCE VFKYNRRPAE TNLRHTCKRI
   121  MDMVSNQHPW FGMEQEYTLM GTDGHPFGWP SNGFPGPQGP YYCGVGADRA YGRDIVEAHY
   181  RACLYAGVKI AGTNAEVMPA QWEFQIGPCE GISMGDHLWV ARFILHRVCE DFGVIATFDP
   241  KPIPGNWNGA GCHTNFSTKA MREENGLKYI EEAIEKLSKR HQYHIRAYDP KGGLDNARRL
   301  TGFHETSNIN DFSAGVANRS ASIRIPRTVG QEKKGYFEDR RPSANCDPFS VTEALIRTCL
   361  LNETGDEPFQ YKN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLUL 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

1,349 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLUL.

Disease | AllUniProt

Conditions GLUL is implicated in, by any mechanism.

• Glutamine deficiency, congenital (GLND) MIM:610015
• Developmental and epileptic encephalopathy 116 (DEE116) MIM:620806

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 283 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy 116
• Congenital brain dysgenesis due to glutamine synthetase deficiency
• Glutamine synthetase stabilization 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)

0.19

gnomAD pLI

1

gnomAD missense Z

1.6

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• cell population proliferation
• cellular response to starvation
• L-glutamate catabolic process
• positive regulation of erythrocyte differentiation
• protein palmitoylation
• regulation of endothelial cell migration
• regulation of protein localization to nucleolus
• regulation of sprouting angiogenesis
• response to glucose
• ribosome biogenesis
• glutamine biosynthetic process
• intracellular ammonium homeostasis

Molecular functions

• ATP binding
• identical protein binding
• metal ion binding
• protein-cysteine S-palmitoyltransferase activity
• glutamine synthetase activity

Cellular components

• cell body
• cytoplasm
• cytosol
• extracellular exosome
• glial cell projection
• mitochondrion
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Glutamine synthetase, catalytic domain
• Glutamine synthetase, N-terminal domain
• Glutamine synthetase/guanido kinase, catalytic domain
• Glutamine synthetase, N-terminal domain superfamily
• Glutamine synthetase, catalytic domain
• Glutamine synthetase, N-terminal conserved site
• Glutamine synthetase, glycine-rich site
• Glutamine Synthetase
• Glutamine synthetase, beta-Grasp domain

KeywordsUniProt

• Acetylation
• Angiogenesis
• ATP-binding
• Cell membrane
• Cytoplasm
• Endoplasmic reticulum
• Epilepsy
• Intellectual disability
• Ligase
• Lipoprotein
• Magnesium
• Manganese
• Membrane
• Metal-binding
• Microsome
• Mitochondrion
• Nucleotide-binding
• Palmitate
• Phosphoprotein
• Transferase
• Ubl conjugation

InteractionsUniProt · HPA

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

• BEST2
• PALMD
• RHOJ
• ZNRF1
• RIPK3
• HNRNPH1