You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP00512
Secondary Accession Numbers
  • 5759
  • HMDBP04093
Name Glutamate--cysteine ligase catalytic subunit
Synonyms
  1. GCS heavy chain
  2. Gamma-ECS
  3. Gamma-glutamylcysteine synthetase
Gene Name GCLC
Protein Type Enzyme
Biological Properties
General Function Involved in glutamate-cysteine ligase activity
Specific Function Not Available
Pathways
  • 2-Hydroxyglutric Aciduria (D And L Form)
  • 4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency
  • 5-oxoprolinase deficiency
  • 5-Oxoprolinuria
  • Beta-mercaptolactate-cysteine disulfiduria
  • Cysteine Metabolism
  • Cystinosis, ocular nonnephropathic
  • Gamma-glutamyl-transpeptidase deficiency
  • Gamma-Glutamyltransferase Deficiency
  • Glutamate Metabolism
  • glutathione biosynthesis
  • Glutathione Metabolism
  • Glutathione metabolism
  • Glutathione Synthetase Deficiency
  • Homocarnosinosis
  • Hyperinsulinism-Hyperammonemia Syndrome
  • Succinic semialdehyde dehydrogenase deficiency
Reactions
Adenosine triphosphate + L-Glutamic acid + L-Cysteine → ADP + Phosphate + gamma-Glutamylcysteine details
GO Classification
Biological Process
cell redox homeostasis
response to arsenic-containing substance
L-ascorbic acid metabolic process
negative regulation of protein ubiquitination
negative regulation of neuron apoptotic process
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
cysteine metabolic process
regulation of mitochondrial depolarization
negative regulation of apoptotic process
response to heat
response to hormone stimulus
response to nitrosative stress
response to oxidative stress
glutamate metabolic process
xenobiotic metabolic process
negative regulation of transcription, DNA-dependent
glutathione biosynthetic process
regulation of blood vessel size
Cellular Component
cytosol
glutamate-cysteine ligase complex
Function
glutamate-cysteine ligase activity
catalytic activity
ligase activity
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
Molecular Function
magnesium ion binding
glutamate-cysteine ligase activity
ATP binding
glutamate binding
ADP binding
coenzyme binding
Process
glutathione biosynthetic process
metabolic process
cellular metabolic process
peptide metabolic process
glutathione metabolic process
Cellular Location Not Available
Gene Properties
Chromosome Location 6
Locus 6p12
SNPs GCLC
Gene Sequence
>1914 bp
ATGGGGCTGCTGTCCCAGGGCTCGCCGCTGAGCTGGGAGGAAACCAAGCGCCATGCCGAC
CACGTGCGGCGGCACGGGATCCTCCAGTTCCTGCACATCTACCACGCCGTCAAGGACCGG
CACAAGGACGTTCTCAAGTGGGGCGATGAGGTGGAATACATGTTGGTATCTTTTGATCAT
GAAAATAAAAAAGTCCGGTTGGTCCTGTCTGGGGAGAAAGTTCTTGAAACTCTGCAAGAG
AAGGGGGAAAGGACAAACCCAAACCATCCTACCCTTTGGAGACCAGAGTATGGGAGTTAC
ATGATTGAAGGGACACCAGGACAGCCCTACGGAGGAACAATGTCCGAGTTCAATACAGTT
GAGGCCAACATGCGAAAACGCCGGAAGGAGGCTACTTCTATATTAGAAGAAAATCAGGCT
CTTTGCACAATAACTTCATTTCCCAGATTAGGCTGTCCTGGGTTCACACTGCCCGAGGTC
AAACCCAACCCAGTGGAAGGAGGAGCTTCCAAGTCCCTCTTCTTTCCAGATGAAGCAATA
AACAAGCACCCTCGCTTCAGTACCTTAACAAGAAATATCCGACATAGGAGAGGAGAAAAG
GTTGTCATCAATGTACCAATATTTAAGGACAAGAATACACCATCTCCATTTATAGAAACA
TTTACTGAGGATGATGAAGCTTCAAGGGCTTCTAAGCCGGATCATATTTACATGGATGCC
ATGGGATTTGGAATGGGCAATTGCTGTCTCCAGGTGACATTCCAAGCCTGCAGTATATCT
GAGGCCAGATACCTTTATGATCAGTTGGCTACTATCTGTCCAATTGTTATGGCTTTGAGT
GCTGCATCTCCCTTTTACCGAGGCTATGTGTCAGACATTGATTGTCGCTGGGGAGTGATT
TCTGCATCTGTAGATGATAGAACTCGGGAGGAGCGAGGACTGGAGCCATTGAAGAACAAT
AACTATAGGATCAGTAAATCCCGATATGACTCAATAGACAGCTATTTATCTAAGTGTGGT
GAGAAATATAATGACATCGACTTGACGATAGATAAAGAGATCTACGAACAGCTGTTGCAG
GAAGGCATTGATCATCTCCTGGCCCAGCATGTTGCTCATCTCTTTATTAGAGACCCACTG
ACACTGTTTGAAGAGAAAATACACCTGGATGATGCTAATGAGTCTGACCATTTTGAGAAT
ATTCAGTCCACAAATTGGCAGACAATGAGATTTAAGCCCCCTCCTCCAAACTCAGACATT
GGATGGAGAGTAGAATTTCGACCCATGGAGGTGCAATTAACAGACTTTGAGAACTCTGCC
TATGTGGTGTTTGTGGTACTGCTCACCAGAGTGATCCTTTCCTACAAATTGGATTTTCTC
ATTCCACTGTCAAAGGTTGATGAGAACATGAAGGTAGCACAGAAAAGAGATGCTGTCTTG
CAGGGAATGTTTTATTTCAGGAAAGATATTTGCAAAGGTGGCAATGCAGTGGTGGATGGT
TGTGGCAAGGCCCAGAACAGCACGGAGCTCGCTGCAGAGGAGTACACCCTCATGAGCATA
GACACCATCATCAATGGGAAGGAAGGTGTGTTTCCTGGACTGATCCCAATTCTGAACTCT
TACCTTGAAAACATGGAAGTGGATGTGGACACCAGATGTAGTATTCTGAACTACCTAAAG
CTAATTAAGAAGAGAGCATCTGGAGAACTAATGACAGTTGCCAGATGGATGAGGGAGTTT
ATCGCAAACCATCCTGACTACAAGCAAGACAGTGTCATAACTGATGAAATGAATTATAGC
CTTATTTTGAAGTGTAACCAAATTGCAAATGAATTATGTGAATGCCCAGAGTTACTTGGA
TCAGCATTTAGGAAAGTAAAATATAGTGGAAGTAAAACTGACTCATCCAACTAG
Protein Properties
Number of Residues 637
Molecular Weight 68629.42
Theoretical pI 5.935
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Glutamate--cysteine ligase catalytic subunit
MGLLSQGSPLSWEETKRHADHVRRHGILQFLHIYHAVKDRHKDVLKWGDEVEYMLVSFDH
ENKKVRLVLSGEKVLETLQEKGERTNPNHPTLWRPEYGSYMIEGTPGQPYGGTMSEFNTV
EANMRKRRKEATSILEENQALCTITSFPRLGCPGFTLPEVKPNPVEGGASKSLFFPDEAI
NKHPRFSTLTRNIRHRRGEKVVINVPIFKDKNTPSPFIETFTEDDEASRASKPDHIYMDA
MGFGMGNCCLQVTFQACSISEARYLYDQLATICPIVMALSAASPFYRGYVSDIDCRWGVI
SASVDDRTREERGLEPLKNNNYRISKSRYDSIDSYLSKCGEKYNDIDLTIDKEIYEQLLQ
EGIDHLLAQHVAHLFIRDPLTLFEEKIHLDDANESDHFENIQSTNWQTMRFKPPPPNSDI
GWRVEFRPMEVQLTDFENSAYVVFVVLLTRVILSYKLDFLIPLSKVDENMKVAQKRDAVL
QGMFYFRKDICKGGNAVVDGCGKAQNSTELAAEEYTLMSIDTIINGKEGVFPGLIPILNS
YLENMEVDVDTRCSILNYLKLIKKRASGELMTVARWMREFIANHPDYKQDSVITDEMNYS
LILKCNQIANELCECPELLGSAFRKVKYSGSKTDSSN
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P48506
UniProtKB/Swiss-Prot Entry Name GSH1_HUMAN
PDB IDs Not Available
GenBank Gene ID M90656
GeneCard ID GCLC
GenAtlas ID GCLC
HGNC ID HGNC:4311
References
General References
  1. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed:14574404 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Gipp JJ, Chang C, Mulcahy RT: Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase. Biochem Biophys Res Commun. 1992 May 29;185(1):29-35. [PubMed:1350904 ]
  4. Mulcahy RT, Gipp JJ: Identification of a putative antioxidant response element in the 5'-flanking region of the human gamma-glutamylcysteine synthetase heavy subunit gene. Biochem Biophys Res Commun. 1995 Apr 6;209(1):227-33. [PubMed:7726839 ]
  5. Beutler E, Gelbart T, Kondo T, Matsunaga AT: The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency. Blood. 1999 Oct 15;94(8):2890-4. [PubMed:10515893 ]
  6. Misra I, Griffith OW: Expression and purification of human gamma-glutamylcysteine synthetase. Protein Expr Purif. 1998 Jul;13(2):268-76. [PubMed:9675072 ]
  7. Ristoff E, Augustson C, Geissler J, de Rijk T, Carlsson K, Luo JL, Andersson K, Weening RS, van Zwieten R, Larsson A, Roos D: A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia. Blood. 2000 Apr 1;95(7):2193-6. [PubMed:10733484 ]
  8. Hamilton D, Wu JH, Alaoui-Jamali M, Batist G: A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production. Blood. 2003 Jul 15;102(2):725-30. Epub 2003 Mar 27. [PubMed:12663448 ]