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Protein

Glutamate--cysteine ligase regulatory subunit

Gene

GCLM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (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

Keywordsi

Biological processGlutathione biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000023909-MONOMER
BRENDAi6.3.2.2 2681
ReactomeiR-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

EuPathDBiHostDB:ENSG00000023909.9
HGNCiHGNC:4312 GCLM
MIMi601176 gene+phenotype
neXtProtiNX_P48507

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi2730
MalaCardsiGCLM
MIMi601176 gene+phenotype
OpenTargetsiENSG00000023909
PharmGKBiPA28613

Chemistry databases

DrugBankiDB00151 L-Cysteine
DB00142 L-Glutamic Acid

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
ProteomicsDBi55897

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

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108992, 22 interactors
IntActiP48507, 12 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
InterProiView protein in InterPro
IPR032963 Gclm
IPR023210 NADP_OxRdtase_dom
IPR036812 NADP_OxRdtase_dom_sf
PANTHERiPTHR13295 PTHR13295, 1 hit
PfamiView protein in Pfam
PF00248 Aldo_ket_red, 1 hit
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 → M1 PublicationCorresponds to variant dbSNP:rs17880087Ensembl.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 Genomic DNA No translation available.
AL117351 Genomic DNA No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiGSH0_HUMAN
AccessioniPrimary (citable) accession number: P48507
Secondary accession number(s): A8K334
, D3DT45, M5A959, Q6FHC1, Q9NPX9, Q9NU74
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 18, 2018
This is version 163 of the entry and version 1 of the sequence. See 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

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