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Protein

Glutamate--cysteine ligase regulatory subunit

Gene

GCLM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Pathwayi: glutathione biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes glutathione from L-cysteine and L-glutamate.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Glutamate--cysteine ligase regulatory subunit (GCLM), Glutamate--cysteine ligase catalytic subunit (GCLC)
  2. Glutathione synthetase, Glutathione synthetase (GSS), Glutathione synthetase, Glutathione synthetase (HEL-S-64p)
This subpathway is part of the pathway glutathione biosynthesis, which is itself part of Sulfur metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes glutathione from L-cysteine and L-glutamate, the pathway glutathione biosynthesis and in Sulfur metabolism.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Glutathione biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000023909-MONOMER.
ZFISH:ENSG00000023909-MONOMER.
BRENDAi6.3.2.2. 2681.
ReactomeiR-HSA-1614635. Sulfur amino acid metabolism.
R-HSA-174403. Glutathione synthesis and recycling.
UniPathwayiUPA00142; UER00209.

Names & Taxonomyi

Protein namesi
Recommended name:
Glutamate--cysteine ligase regulatory subunit
Alternative name(s):
GCS light chain
Gamma-ECS regulatory subunit
Gamma-glutamylcysteine synthetase regulatory subunit
Glutamate--cysteine ligase modifier subunit
Gene namesi
Name:GCLM
Synonyms:GLCLR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:4312. GCLM.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • glutamate-cysteine ligase complex Source: GO_Central
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi2730.
MalaCardsiGCLM.
MIMi601176. gene+phenotype.
OpenTargetsiENSG00000023909.
PharmGKBiPA28613.

Chemistry databases

DrugBankiDB00151. L-Cysteine.

Polymorphism and mutation databases

BioMutaiGCLM.
DMDMi1346188.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001925731 – 274Glutamate--cysteine ligase regulatory subunitAdd BLAST274

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei263N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP48507.
MaxQBiP48507.
PaxDbiP48507.
PeptideAtlasiP48507.
PRIDEiP48507.

2D gel databases

OGPiP48507.

PTM databases

iPTMnetiP48507.
PhosphoSitePlusiP48507.

Expressioni

Tissue specificityi

In all tissues examined. Highest levels in skeletal muscle.

Gene expression databases

BgeeiENSG00000023909.
CleanExiHS_GCLM.
GenevisibleiP48507. HS.

Organism-specific databases

HPAiCAB009568.
CAB040554.
HPA023696.
HPA053656.

Interactioni

Subunit structurei

Heterodimer of a catalytic heavy chain and a regulatory light chain.

GO - Molecular functioni

  • glutamate-cysteine ligase catalytic subunit binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108992. 18 interactors.
IntActiP48507. 4 interactors.
STRINGi9606.ENSP00000359258.

Structurei

3D structure databases

ProteinModelPortaliP48507.
SMRiP48507.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3023. Eukaryota.
COG0656. LUCA.
GeneTreeiENSGT00510000047658.
HOGENOMiHOG000007111.
HOVERGENiHBG005923.
InParanoidiP48507.
KOiK11205.
OMAiEYLQPYW.
OrthoDBiEOG091G0DYU.
PhylomeDBiP48507.
TreeFamiTF105986.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR032963. Gclm.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR13295. PTHR13295. 1 hit.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMiSSF51430. SSF51430. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P48507-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGTDSRAAKA LLARARTLHL QTGNLLNWGR LRKKCPSTHS EELHDCIQKT
60 70 80 90 100
LNEWSSQINP DLVREFPDVL ECTVSHAVEK INPDEREEMK VSAKLFIVES
110 120 130 140 150
NSSSSTRSAV DMACSVLGVA QLDSVIIASP PIEDGVNLSL EHLQPYWEEL
160 170 180 190 200
ENLVQSKKIV AIGTSDLDKT QLEQLYQWAQ VKPNSNQVNL ASCCVMPPDL
210 220 230 240 250
TAFAKQFDIQ LLTHNDPKEL LSEASFQEAL QESIPDIQAH EWVPLWLLRY
260 270
SVIVKSRGII KSKGYILQAK RRGS
Length:274
Mass (Da):30,727
Last modified:February 1, 1996 - v1
Checksum:i88F73E22322E40B2
GO
Isoform 2 (identifier: P48507-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     43-64: Missing.

Show »
Length:252
Mass (Da):28,135
Checksum:i8626F088B6BD810B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021063209I → M.1 PublicationCorresponds to variant rs17880087dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05700843 – 64Missing in isoform 2. 1 PublicationAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L35546 mRNA. Translation: AAA65028.1.
AB809606 mRNA. Translation: BAN05309.1.
CR541833 mRNA. Translation: CAG46632.1.
AY773965 Genomic DNA. Translation: AAV28733.1.
AK290449 mRNA. Translation: BAF83138.1.
AL049796, AL117351 Genomic DNA. Translation: CAI21813.1.
AL117351, AL049796 Genomic DNA. Translation: CAI22976.1.
CH471097 Genomic DNA. Translation: EAW73060.1.
CH471097 Genomic DNA. Translation: EAW73061.1.
BC041809 mRNA. Translation: AAH41809.1.
CCDSiCCDS746.1. [P48507-1]
CCDS81352.1. [P48507-2]
PIRiJC2474.
RefSeqiNP_001295182.1. NM_001308253.1. [P48507-2]
NP_002052.1. NM_002061.3. [P48507-1]
UniGeneiHs.315562.
Hs.596052.
Hs.711318.

Genome annotation databases

EnsembliENST00000370238; ENSP00000359258; ENSG00000023909. [P48507-1]
ENST00000615724; ENSP00000484507; ENSG00000023909. [P48507-2]
GeneIDi2730.
KEGGihsa:2730.
UCSCiuc001dqg.2. human. [P48507-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L35546 mRNA. Translation: AAA65028.1.
AB809606 mRNA. Translation: BAN05309.1.
CR541833 mRNA. Translation: CAG46632.1.
AY773965 Genomic DNA. Translation: AAV28733.1.
AK290449 mRNA. Translation: BAF83138.1.
AL049796, AL117351 Genomic DNA. Translation: CAI21813.1.
AL117351, AL049796 Genomic DNA. Translation: CAI22976.1.
CH471097 Genomic DNA. Translation: EAW73060.1.
CH471097 Genomic DNA. Translation: EAW73061.1.
BC041809 mRNA. Translation: AAH41809.1.
CCDSiCCDS746.1. [P48507-1]
CCDS81352.1. [P48507-2]
PIRiJC2474.
RefSeqiNP_001295182.1. NM_001308253.1. [P48507-2]
NP_002052.1. NM_002061.3. [P48507-1]
UniGeneiHs.315562.
Hs.596052.
Hs.711318.

3D structure databases

ProteinModelPortaliP48507.
SMRiP48507.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108992. 18 interactors.
IntActiP48507. 4 interactors.
STRINGi9606.ENSP00000359258.

Chemistry databases

DrugBankiDB00151. L-Cysteine.

PTM databases

iPTMnetiP48507.
PhosphoSitePlusiP48507.

Polymorphism and mutation databases

BioMutaiGCLM.
DMDMi1346188.

2D gel databases

OGPiP48507.

Proteomic databases

EPDiP48507.
MaxQBiP48507.
PaxDbiP48507.
PeptideAtlasiP48507.
PRIDEiP48507.

Protocols and materials databases

DNASUi2730.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370238; ENSP00000359258; ENSG00000023909. [P48507-1]
ENST00000615724; ENSP00000484507; ENSG00000023909. [P48507-2]
GeneIDi2730.
KEGGihsa:2730.
UCSCiuc001dqg.2. human. [P48507-1]

Organism-specific databases

CTDi2730.
DisGeNETi2730.
GeneCardsiGCLM.
HGNCiHGNC:4312. GCLM.
HPAiCAB009568.
CAB040554.
HPA023696.
HPA053656.
MalaCardsiGCLM.
MIMi601176. gene+phenotype.
neXtProtiNX_P48507.
OpenTargetsiENSG00000023909.
PharmGKBiPA28613.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3023. Eukaryota.
COG0656. LUCA.
GeneTreeiENSGT00510000047658.
HOGENOMiHOG000007111.
HOVERGENiHBG005923.
InParanoidiP48507.
KOiK11205.
OMAiEYLQPYW.
OrthoDBiEOG091G0DYU.
PhylomeDBiP48507.
TreeFamiTF105986.

Enzyme and pathway databases

UniPathwayiUPA00142; UER00209.
BioCyciMetaCyc:ENSG00000023909-MONOMER.
ZFISH:ENSG00000023909-MONOMER.
BRENDAi6.3.2.2. 2681.
ReactomeiR-HSA-1614635. Sulfur amino acid metabolism.
R-HSA-174403. Glutathione synthesis and recycling.

Miscellaneous databases

ChiTaRSiGCLM. human.
GeneWikiiGCLM.
GenomeRNAii2730.
PROiP48507.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000023909.
CleanExiHS_GCLM.
GenevisibleiP48507. HS.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR032963. Gclm.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR13295. PTHR13295. 1 hit.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMiSSF51430. SSF51430. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiGSH0_HUMAN
AccessioniPrimary (citable) accession number: P48507
Secondary accession number(s): A8K334
, D3DT45, M5A959, Q6FHC1, Q9NPX9, Q9NU74
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.