P48507 (GSH0_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	GCLM
Synonyms:	GLCLR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	274 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Pathway	Sulfur metabolism; glutathione biosynthesis; glutathione from L-cysteine and L-glutamate: step 1/2.
Subunit structure	Heterodimer of a catalytic heavy chain and a regulatory light chain.
Tissue specificity	In all tissues examined. Highest levels in skeletal muscle.
Sequence similarities	Belongs to the aldo/keto reductase family. Glutamate--cysteine ligase light chain subfamily.

Ontologies

Keywords
Biological process	Glutathione biosynthesis
Coding sequence diversity	Polymorphism
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cysteine metabolic process Inferred from electronic annotation. Source: Compara glutamate metabolic process Inferred from direct assay PubMed 9841880PubMed 9895302. Source: UniProtKB glutathione biosynthetic process Inferred from direct assay PubMed 10395918. Source: UniProtKB negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of glutamate-cysteine ligase activity Inferred from electronic annotation. Source: Compara regulation of blood vessel size Inferred from mutant phenotype PubMed 12975258. Source: UniProtKB regulation of mitochondrial depolarization Inferred from electronic annotation. Source: Compara response to drug Inferred from direct assay PubMed 9895302. Source: UniProtKB response to nitrosative stress Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from direct assay PubMed 10395918. Source: UniProtKB sulfur amino acid metabolic process Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Non-traceable author statement PubMed 9895302. Source: UniProtKB glutamate-cysteine ligase complex Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 274	274	Glutamate--cysteine ligase regulatory subunit		PRO_0000192573
Amino acid modifications
	Modified residue	263	1	N6-acetyllysine Ref.8
Natural variations
	Natural variant	209	1	I → M. Ref.3 Corresponds to variant rs17880087 [ dbSNP | Ensembl ].		VAR_021063

Sequences

	Sequence		Length	Mass (Da)
	P48507 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 88F73E22322E40B2	FASTA	274	30,727
	10 20 30 40 50 60 MGTDSRAAKA LLARARTLHL QTGNLLNWGR LRKKCPSTHS EELHDCIQKT LNEWSSQINP 70 80 90 100 110 120 DLVREFPDVL ECTVSHAVEK INPDEREEMK VSAKLFIVES NSSSSTRSAV DMACSVLGVA 130 140 150 160 170 180 QLDSVIIASP PIEDGVNLSL EHLQPYWEEL ENLVQSKKIV AIGTSDLDKT QLEQLYQWAQ 190 200 210 220 230 240 VKPNSNQVNL ASCCVMPPDL TAFAKQFDIQ LLTHNDPKEL LSEASFQEAL QESIPDIQAH 250 260 270 EWVPLWLLRY SVIVKSRGII KSKGYILQAK RRGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]. Tissue: Liver.
[2]	"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].
[3]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-209.
[4]	"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]. Tissue: Brain.
[5]	"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].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Brain.
[8]	"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, MASS SPECTROMETRY.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	L35546 mRNA. Translation: AAA65028.1. 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.
IPI	IPI00010090.
PIR	JC2474.
RefSeq	NP_002052.1. NM_002061.2.
UniGene	Hs.315562.
3D structure databases
ProteinModelPortal	P48507.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48507. 3 interactions.
STRING	9606.ENSP00000359258.
PTM databases
PhosphoSite	P48507.
Polymorphism databases
DMDM	1346188.
2D gel databases
OGP	P48507.
Proteomic databases
PaxDb	P48507.
PeptideAtlas	P48507.
PRIDE	P48507.
Protocols and materials databases
DNASU	2730.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370238; ENSP00000359258; ENSG00000023909.
GeneID	2730.
KEGG	hsa:2730.
UCSC	uc001dqg.1. human.
Organism-specific databases
CTD	2730.
GeneCards	GC01M094351.
HGNC	HGNC:4312. GCLM.
HPA	CAB009568. CAB040554. HPA023696.
MIM	601176. gene+phenotype.
neXtProt	NX_P48507.
PharmGKB	PA28613.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0656.
HOGENOM	HOG000007111.
HOVERGEN	HBG005923.
InParanoid	P48507.
KO	K11205.
OMA	LEWVLRY.
OrthoDB	EOG4QNMWW.
PhylomeDB	P48507.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000023909-MONOMER.
BRENDA	6.3.2.2. 2681.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00142; UER00209.
Gene expression databases
ArrayExpress	P48507.
Bgee	P48507.
CleanEx	HS_GCLM.
Genevestigator	P48507.
GermOnline	ENSG00000023909. Homo sapiens.
Family and domain databases
Gene3D	3.20.20.100. 1 hit.
InterPro	IPR023210. NADP_OxRdtase_dom. [Graphical view]
Pfam	PF00248. Aldo_ket_red. 1 hit. [Graphical view]
SUPFAM	SSF51430. Aldo/ket_red. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	GCLM. human.
DrugBank	DB00151. L-Cysteine. DB00142. L-Glutamic Acid.
GenomeRNAi	2730.
NextBio	10760.
SOURCE	Search...

Entry information

Entry name

GSH0_HUMAN

Accession

Primary (citable) accession number: P48507
Secondary accession number(s): A8K334 , D3DT45, Q6FHC1, Q9NPX9, Q9NU74

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.