P97494 (GSH1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate--cysteine ligase catalytic subunit
EC=6.3.2.2

Alternative name(s):
GCS heavy chain
Gamma-ECS
Gamma-glutamylcysteine synthetase

Gene names

Name:	Gclc
Synonyms:	Glclc

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	637 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Catalytic activity	ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine.
Enzyme regulation	Feedback inhibition by glutathione.
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.
Sequence similarities	Belongs to the glutamate--cysteine ligase type 3 family.

Ontologies

Keywords
Biological process	Glutathione biosynthesis
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	L-ascorbic acid metabolic process Inferred from mutant phenotype. Source: MGI anti-apoptosis Inferred from sequence or structural similarity. Source: UniProtKB cell redox homeostasis Inferred from sequence or structural similarity. Source: UniProtKB cysteine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glutamate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glutathione biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of protein ubiquitination Inferred from mutant phenotype. Source: MGI negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype. Source: MGI regulation of blood vessel size Inferred from sequence or structural similarity. Source: UniProtKB regulation of mitochondrial depolarization Inferred from genetic interaction. Source: MGI response to arsenic-containing substance Inferred from mutant phenotype. Source: MGI response to heat Inferred from sequence or structural similarity. Source: UniProtKB response to hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB response to xenobiotic stimulus Inferred from mutant phenotype. Source: MGI
Cellular component	cytosol Inferred from direct assay. Source: MGI glutamate-cysteine ligase complex Inferred from direct assay. Source: MGI
Molecular function	ADP binding Inferred from sequence or structural similarity. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW coenzyme binding Inferred from sequence or structural similarity. Source: UniProtKB glutamate binding Inferred from sequence or structural similarity. Source: UniProtKB glutamate-cysteine ligase activity Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB protein heterodimerization activity Inferred from physical interaction. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Probable
	Chain	2 – 637	636	Glutamate--cysteine ligase catalytic subunit		PRO_0000192564
Experimental info
	Sequence conflict	6	1	Q → H in AAB42020. Ref.1
	Sequence conflict	25 – 26	2	HG → RD in AAB42020. Ref.1
	Sequence conflict	32	1	H → Q in AAH19374. Ref.3
	Sequence conflict	500	1	G → E in AAB42020. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P97494 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 8A176CD1DE49094C	FASTA	637	72,571
	10 20 30 40 50 60 MGLLSQGSPL SWEETQRHAD HVRRHGILQF LHIYHAVKDR HKDVLKWGDE VEYMLVSFDH 70 80 90 100 110 120 ENRKVQLLLN GGDVLETLQE KGERTNPNHP TLWRPEYGSY MIEGTPGQPY GGTMSEFNTV 130 140 150 160 170 180 EANMRKRRKE ATSVLGEHQA LCTITSFPRL GCPGFTLPEH RPNPEEGGAS KSLFFPDEAI 190 200 210 220 230 240 NKHPRFGTLT RNIRHRRGEK VVINVPIFKD KNTPSPFVET FPEDAEASKA SQPDHIYMDA 250 260 270 280 290 300 MGFGMGNCCL QVTFQACSIS EARYLYDQLA TICPIVMALS AASPFYRGYV SDIDCRWGVI 310 320 330 340 350 360 SASVDDRTRE ERGLEPLKNN RFRISKSRYD SIDSYLSKCG EKYNDIDLTI DKEIYEQLLE 370 380 390 400 410 420 EGIDHLLAQH VAHLFIRDPL TLFEEKIHLD DANESDHFEN IQSTNWQTMR FKPPPPNSDI 430 440 450 460 470 480 GWRVEFRPME VQLTDFENSA YVVFVVLLTR VILSYKLDFL IPLSKVDENM KVAQKRDAVL 490 500 510 520 530 540 QGMFYFRKDI CKGGNAVVDG CSKAQSSSEP AAEEYTLMSI DTIINGKEGV FPGLIPILNS 550 560 570 580 590 600 YLENMEVDVD TRCSILNYLK LIKKRASGEL MTVARWMREF IANHPDYKQD SVITDEINYS 610 620 630 LIWKCNQIAD ELCECPELLG SGFRKAKYSG GKSDPSA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning/brain localization of mouse glutamylcysteine synthetase heavy chain mRNA." Kang Y., Oiao X., Jurma O., Knusel B., Andersen J.K. NeuroReport 8:2053-2060(1997) [PubMed: 9223101] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Molecular cloning and sequencing of the cDNA encoding the catalytic subunit of mouse glutamate-cysteine ligase." Reid L.L., Botta D., Lu Y., Gallagher E.P., Kavanagh T.J. Biochim. Biophys. Acta 1352:233-237(1997) [PubMed: 9224945] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Kidney.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U85414 mRNA. Translation: AAB42020.1. U85498 mRNA. Translation: AAB52542.1. BC019374 mRNA. Translation: AAH19374.1.
IPI	IPI00125658.
RefSeq	NP_034425.1. NM_010295.2.
UniGene	Mm.485389.
3D structure databases
ProteinModelPortal	P97494.
SMR	P97494. Positions 2-624.
ModBase	Search...
Protein-protein interaction databases
STRING	P97494.
PTM databases
PhosphoSite	P97494.
Proteomic databases
PRIDE	P97494.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000034905; ENSMUSP00000034905; ENSMUSG00000032350.
GeneID	14629.
KEGG	mmu:14629.
Organism-specific databases
CTD	2729.
MGI	MGI:104990. Gclc.
Phylogenomic databases
eggNOG	roNOG09927.
HOGENOM	HBG331200.
HOVERGEN	HBG005924.
InParanoid	P97494.
OMA	QVTFQAC.
OrthoDB	EOG47M1XB.
PhylomeDB	P97494.
Enzyme and pathway databases
BRENDA	6.3.2.2. 3474.
Gene expression databases
ArrayExpress	P97494.
Bgee	P97494.
CleanEx	MM_GCLC.
Genevestigator	P97494.
GermOnline	ENSMUSG00000032350. Mus musculus.
Family and domain databases
InterPro	IPR004308. GCS. [Graphical view]
KO	K11204.
PANTHER	PTHR11164. GCS. 1 hit.
Pfam	PF03074. GCS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	286474.
SOURCE	Search...

Entry information

Entry name

GSH1_MOUSE

Accession

Primary (citable) accession number: P97494
Secondary accession number(s): O09166, Q8VCS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 95 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program