Reviewed,
UniProtKB/Swiss-Prot P48506 (GSH1_HUMAN)
Last modified
November 24, 2009.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Glutamate--cysteine ligase catalytic subunit EC=6.3.2.2 Alternative name(s): Gamma-glutamylcysteine synthetase Gamma-ECS GCS heavy chain | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
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 protein 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. |
| Involvement in disease | Defects in GCLC are the cause of hemolytic anemia [MIM:230450]. Ref.6 Ref.9 Ref.10 |
| Sequence similarities | Belongs to the glutamate--cysteine ligase type 3 family. |
Ontologies
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_0000192563 | |||||
Natural variations | |||||||||
| Natural variant | 55 | 1 | L → S: dbSNP rs2066512. | VAR_014884 | |||||
| Natural variant | 127 | 1 | R → C in hemolytic anemia. Ref.10 | VAR_021110 | |||||
| Natural variant | 158 | 1 | P → L in hemolytic anemia. Ref.9 | VAR_015403 | |||||
| Natural variant | 370 | 1 | H → L in hemolytic anemia. Ref.6 | VAR_013514 | |||||
| Natural variant | 462 | 1 | P → S: dbSNP rs17883718. Ref.2 | VAR_021100 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase." Gipp J.J., Chang C., Mulcahy R.T. Biochem. Biophys. Res. Commun. 185:29-35(1992) [PubMed: 1350904] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver. |
| [2] | NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-462. |
| [3] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "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: Hippocampus and Testis. |
| [5] | "Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene." Mulcahy R.T., Gipp J.J. Biochem. Biophys. Res. Commun. 209:227-233(1995) [PubMed: 7726839] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27. Tissue: Foreskin fibroblast. |
| [6] | "The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency." Beutler E., Gelbart T., Kondo T., Matsunaga A.T. Blood 94:2890-2894(1999) [PubMed: 10515893] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 341-440, VARIANT HEMOLYTIC ANEMIA LEU-370. |
| [7] | "Expression and purification of human gamma-glutamylcysteine synthetase." Misra I., Griffith O.W. Protein Expr. Purif. 13:268-276(1998) [PubMed: 9675072] [Abstract] Cited for: CHARACTERIZATION. |
| [8] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [9] | "A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia." Ristoff E., Augustson C., Geissler J., de Rijk T., Carlsson K., Luo J.-L., Andersson K., Weening R.S., van Zwieten R., Larsson A., Roos D. Blood 95:2193-2196(2000) [PubMed: 10733484] [Abstract] Cited for: VARIANT HEMOLYTIC ANEMIA LEU-158. |
| [10] | "A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production." Hamilton D., Wu J.H., Alaoui-Jamali M., Batist G. Blood 102:725-730(2003) [PubMed: 12663448] [Abstract] Cited for: VARIANT HEMOLYTIC ANEMIA CYS-127. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| M90656 mRNA. Translation: AAA58499.1. AY780794 Genomic DNA. Translation: AAV31778.1. AL033397 Genomic DNA. No translation available. BC022487 mRNA. Translation: AAH22487.1. BC039894 mRNA. Translation: AAH39894.1. L39773 Genomic DNA. Translation: AAC41751.1. AF118846 Genomic DNA. Translation: AAD18031.1. | |
| IPI | IPI00215768. |
| PIR | JH0611. |
| RefSeq | NP_001489.1. |
| UniGene | Hs.654465 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P48506. |
PTM databases | |
| PhosphoSite | P48506. |
Proteomic databases | |
| PeptideAtlas | P48506. |
| PRIDE | P48506. |
Genome annotation databases | |
| Ensembl | ENST00000229416; ENSP00000229416; ENSG00000001084; Homo sapiens. [Genome view] |
| GeneID | 2729. |
| KEGG | hsa:2729. |
| UCSC | uc003pbw.1. human. |
Organism-specific databases | |
| CTD | 2729. |
| GeneCards | GC06M053470. |
| H-InvDB | HIX0025084. |
| HGNC | HGNC:4311. GCLC. |
| HPA | CAB009569. |
| MIM | 230450. phenotype. 606857. gene+phenotype. |
| Orphanet | 33574. Gamma-glutamylcysteine synthetase deficiency. |
| PharmGKB | PA28612. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | P48506. |
| HOVERGEN | P48506. |
| OMA | DNMRKRR |
| OrthoDB | EOG9M94BX |
Enzyme and pathway databases | |
| BRENDA | 6.3.2.2. 247. |
| Reactome | REACT_13433. Biological oxidations. |
Gene expression databases | |
| ArrayExpress | P48506. |
| Bgee | P48506. |
| CleanEx | HS_GCLC. |
| Genevestigator | P48506. |
| GermOnline | ENSG00000001084. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR004308. GCS. [Graphical view] |
| PANTHER | PTHR11164. GCS. 1 hit. |
| Pfam | PF03074. GCS. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00151. L-Cysteine. DB00142. L-Glutamic Acid. |
| NextBio | 10756. |
| PMAP-CutDB | P48506. |
| SOURCE | Search... |
Entry information
| Entry name | GSH1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P48506 Secondary accession number(s): Q14399 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with


