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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

Pathway:iglutathione 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.
BRENDAi6.3.2.2. 2681.
ReactomeiREACT_115639. Sulfur amino acid metabolism.
REACT_6960. 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
ProteomesiUP000005640 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

MIMi601176. gene+phenotype.
PharmGKBiPA28613.

Chemistry

DrugBankiDB00151. L-Cysteine.

Polymorphism and mutation databases

BioMutaiGCLM.
DMDMi1346188.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 274274Glutamate--cysteine ligase regulatory subunitPRO_0000192573Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei263 – 2631N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP48507.
PaxDbiP48507.
PeptideAtlasiP48507.
PRIDEiP48507.

2D gel databases

OGPiP48507.

PTM databases

PhosphoSiteiP48507.

Expressioni

Tissue specificityi

In all tissues examined. Highest levels in skeletal muscle.

Gene expression databases

BgeeiP48507.
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.

Protein-protein interaction databases

BioGridi108992. 14 interactions.
IntActiP48507. 3 interactions.
STRINGi9606.ENSP00000359258.

Structurei

3D structure databases

ProteinModelPortaliP48507.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0656.
GeneTreeiENSGT00510000047658.
HOGENOMiHOG000007111.
HOVERGENiHBG005923.
InParanoidiP48507.
KOiK11205.
OMAiEYLQPYW.
OrthoDBiEOG7B5WWG.
PhylomeDBiP48507.
TreeFamiTF105986.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR023210. NADP_OxRdtase_dom.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti209 – 2091I → M.1 Publication
Corresponds to variant rs17880087 [ dbSNP | Ensembl ].
VAR_021063

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei43 – 6422Missing in isoform 2. 1 PublicationVSP_057008Add
BLAST

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]
PIRiJC2474.
RefSeqiNP_002052.1. NM_002061.3. [P48507-1]
UniGeneiHs.315562.

Genome annotation databases

EnsembliENST00000370238; ENSP00000359258; ENSG00000023909.
ENST00000615724; ENSP00000484507; ENSG00000023909. [P48507-2]
GeneIDi2730.
KEGGihsa:2730.
UCSCiuc001dqg.1. 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]
PIRiJC2474.
RefSeqiNP_002052.1. NM_002061.3. [P48507-1]
UniGeneiHs.315562.

3D structure databases

ProteinModelPortaliP48507.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108992. 14 interactions.
IntActiP48507. 3 interactions.
STRINGi9606.ENSP00000359258.

Chemistry

DrugBankiDB00151. L-Cysteine.

PTM databases

PhosphoSiteiP48507.

Polymorphism and mutation databases

BioMutaiGCLM.
DMDMi1346188.

2D gel databases

OGPiP48507.

Proteomic databases

MaxQBiP48507.
PaxDbiP48507.
PeptideAtlasiP48507.
PRIDEiP48507.

Protocols and materials databases

DNASUi2730.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2730.
GeneCardsiGC01M094351.
HGNCiHGNC:4312. GCLM.
HPAiCAB009568.
CAB040554.
HPA023696.
HPA053656.
MIMi601176. gene+phenotype.
neXtProtiNX_P48507.
PharmGKBiPA28613.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0656.
GeneTreeiENSGT00510000047658.
HOGENOMiHOG000007111.
HOVERGENiHBG005923.
InParanoidiP48507.
KOiK11205.
OMAiEYLQPYW.
OrthoDBiEOG7B5WWG.
PhylomeDBiP48507.
TreeFamiTF105986.

Enzyme and pathway databases

UniPathwayiUPA00142; UER00209.
BioCyciMetaCyc:ENSG00000023909-MONOMER.
BRENDAi6.3.2.2. 2681.
ReactomeiREACT_115639. Sulfur amino acid metabolism.
REACT_6960. Glutathione synthesis and recycling.

Miscellaneous databases

ChiTaRSiGCLM. human.
GeneWikiiGCLM.
GenomeRNAii2730.
NextBioi10760.
PROiP48507.
SOURCEiSearch...

Gene expression databases

BgeeiP48507.
CleanExiHS_GCLM.
GenevisibleiP48507. HS.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR023210. NADP_OxRdtase_dom.
[Graphical view]
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
SUPFAMiSSF51430. SSF51430. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequencing of the cDNA for the light subunit of human liver gamma-glutamylcysteine synthetase and relative mRNA levels for heavy and light subunits in human normal tissues."
    Gipp J.J., Bailey H.H., Mulcahy R.T.
    Biochem. Biophys. Res. Commun. 206:584-589(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Liver.
  2. "Homo sapiens GCLM mRNA for glutamate-cysteine ligase, modifier subunit delta2 alternative splicing variant, complete cds."
    Sawada Y., Sudo M., Fujii A., Mizuochi A., Hisatomi H.
    Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  4. NIEHS SNPs program
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-209.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  6. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  9. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-263, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: July 22, 2015
This is version 136 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

External Data

Dasty 3

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 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.