GCLM

Protein identityUniProt · HPA

UniProt accession

P48507

Gene

GCLM

Ensembl

ENSG00000023909

Chromosome

1

Canonical length

274 aa

Protein class

Cancer-related genes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane,Cytosol

OverviewNCBI Gene

Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

Canonical amino-acid sequenceUniProt

274 residues, UniProt reviewed canonical sequence.

>P48507|GCLM
     1  MGTDSRAAKA LLARARTLHL QTGNLLNWGR LRKKCPSTHS EELHDCIQKT LNEWSSQINP
    61  DLVREFPDVL ECTVSHAVEK INPDEREEMK VSAKLFIVES NSSSSTRSAV DMACSVLGVA
   121  QLDSVIIASP PIEDGVNLSL EHLQPYWEEL ENLVQSKKIV AIGTSDLDKT QLEQLYQWAQ
   181  VKPNSNQVNL ASCCVMPPDL TAFAKQFDIQ LLTHNDPKEL LSEASFQEAL QESIPDIQAH
   241  EWVPLWLLRY SVIVKSRGII KSKGYILQAK RRGS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GCLM 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)

0.27

Highest tissue expression

45 nTPM

Expression across tissuesHPA

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)

0.22

gnomAD pLI

0.99

gnomAD missense Z

1.36

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic mitochondrial changes
• blood vessel diameter maintenance
• cellular response to fibroblast growth factor stimulus
• cellular response to follicle-stimulating hormone stimulus
• cellular response to glucose stimulus
• cellular response to hepatocyte growth factor stimulus
• cellular response to leukemia inhibitory factor
• cellular response to thyroxine stimulus
• cysteine metabolic process
• glutamate metabolic process
• glutathione biosynthetic process
• hepatic stellate cell activation
• negative regulation of extrinsic apoptotic signaling pathway
• negative regulation of neuron apoptotic process
• regulation of mitochondrial depolarization
• response to activity
• response to human chorionic gonadotropin
• response to nitrosative stress
• response to nutrient
• response to oxidative stress
• response to xenobiotic stimulus

Molecular functions

• glutamate-cysteine ligase activity
• protein-containing complex binding
• glutamate-cysteine ligase catalytic subunit binding
• glutamate-cysteine ligase regulator activity

Cellular components

• cytosol
• glutamate-cysteine ligase complex

Protein domainsUniProt · Pfam · InterPro

• NADP-dependent oxidoreductase domain
• NAD(P)-dependent oxidoreductase domain superfamily
• Aldo/keto reductase family
• Glutamate--cysteine ligase regulatory subunit

KeywordsUniProt

• Acetylation
• Glutathione biosynthesis

InteractionsUniProt · HPA

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

• GCLC