Glutamate--cysteine ligase catalytic subunit

Details

Name
Glutamate--cysteine ligase catalytic subunit
Synonyms
  • 6.3.2.2
  • Gamma-ECS
  • Gamma-glutamylcysteine synthetase
  • GCS heavy chain
  • GLCL
  • GLCLC
Gene Name
GCLC
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010186|Glutamate--cysteine ligase catalytic subunit
MGLLSQGSPLSWEETKRHADHVRRHGILQFLHIYHAVKDRHKDVLKWGDEVEYMLVSFDH
ENKKVRLVLSGEKVLETLQEKGERTNPNHPTLWRPEYGSYMIEGTPGQPYGGTMSEFNTV
EANMRKRRKEATSILEENQALCTITSFPRLGCPGFTLPEVKPNPVEGGASKSLFFPDEAI
NKHPRFSTLTRNIRHRRGEKVVINVPIFKDKNTPSPFIETFTEDDEASRASKPDHIYMDA
MGFGMGNCCLQVTFQACSISEARYLYDQLATICPIVMALSAASPFYRGYVSDIDCRWGVI
SASVDDRTREERGLEPLKNNNYRISKSRYDSIDSYLSKCGEKYNDIDLTIDKEIYEQLLQ
EGIDHLLAQHVAHLFIRDPLTLFEEKIHLDDANESDHFENIQSTNWQTMRFKPPPPNSDI
GWRVEFRPMEVQLTDFENSAYVVFVVLLTRVILSYKLDFLIPLSKVDENMKVAQKRDAVL
QGMFYFRKDICKGGNAVVDGCGKAQNSTELAAEEYTLMSIDTIINGKEGVFPGLIPILNS
YLENMEVDVDTRCSILNYLKLIKKRASGELMTVARWMREFIANHPDYKQDSVITDEMNYS
LILKCNQIANELCECPELLGSAFRKVKYSGSKTDSSN
Number of residues
637
Molecular Weight
72765.14
Theoretical pI
5.98
GO Classification
Functions
ADP binding / ATP binding / coenzyme binding / glutamate binding / glutamate-cysteine ligase activity / magnesium ion binding
Processes
apoptotic mitochondrial changes / cell redox homeostasis / cellular nitrogen compound metabolic process / cysteine metabolic process / glutamate metabolic process / glutathione biosynthetic process / glutathione derivative biosynthetic process / L-ascorbic acid metabolic process / negative regulation of apoptotic process / negative regulation of extrinsic apoptotic signaling pathway / negative regulation of neuron apoptotic process / negative regulation of protein ubiquitination / negative regulation of transcription, DNA-templated / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / regulation of blood vessel size / regulation of mitochondrial depolarization / response to arsenic-containing substance / response to heat / response to hormone / response to nitrosative stress / response to oxidative stress / small molecule metabolic process / sulfur amino acid metabolic process / xenobiotic metabolic process
Components
cytosol / glutamate-cysteine ligase complex
General Function
Magnesium ion binding
Specific Function
Not Available
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0010187|Glutamate--cysteine ligase catalytic subunit (GCLC)
ATGGGGCTGCTGTCCCAGGGCTCGCCGCTGAGCTGGGAGGAAACCAAGCGCCATGCCGAC
CACGTGCGGCGGCACGGGATCCTCCAGTTCCTGCACATCTACCACGCCGTCAAGGACCGG
CACAAGGACGTTCTCAAGTGGGGCGATGAGGTGGAATACATGTTGGTATCTTTTGATCAT
GAAAATAAAAAAGTCCGGTTGGTCCTGTCTGGGGAGAAAGTTCTTGAAACTCTGCAAGAG
AAGGGGGAAAGGACAAACCCAAACCATCCTACCCTTTGGAGACCAGAGTATGGGAGTTAC
ATGATTGAAGGGACACCAGGACAGCCCTACGGAGGAACAATGTCCGAGTTCAATACAGTT
GAGGCCAACATGCGAAAACGCCGGAAGGAGGCTACTTCTATATTAGAAGAAAATCAGGCT
CTTTGCACAATAACTTCATTTCCCAGTACCTTAACAAGAAATATCCGACATAGGAGAGGA
GAAAAGGTTGTCATCAATGTACCAATATTTAAGGACAAGAATACACCATCTCCATTTATA
GAAACATTTACTGAGGATGATGAAGCTTCAAGGGCTTCTAAGCCGGATCATATTTACATG
GATGCCATGGGATTTGGAATGGGCAATTGCTGTCTCCAGGTGACATTCCAAGCCTGCAGT
ATATCTGAGGCCAGATACCTTTATGATCAGTTGGCTACTATCTGTCCAATTGTTATGGCT
TTGAGTGCTGCATCTCCCTTTTACCGAGGCTATGTGTCAGACATTGATTGTCGCTGGGGA
GTGATTTCTGCATCTGTAGATGATAGAACTCGGGAGGAGCGAGGACTGGAGCCATTGAAG
AACAATAACTATAGGATCAGTAAATCCCGATATGACTCAATAGACAGCTATTTATCTAAG
TGTGGTGAGAAATATAATGACATCGACTTGACGATAGATAAAGAGATCTACGAACAGCTG
TTGCAGGAAGGCATTGATCATCTCCTGGCCCAGCATGTTGCTCATCTCTTTATTAGAGAC
CCACTGACACTGTTTGAAGAGAAAATACACCTGGATGATGCTAATGAGTCTGACCATTTT
GAGAATATTCAGTCCACAAATTGGCAGACAATGAGATTTAAGCCCCCTCCTCCAAACTCA
GACATTGGATGGAGAGTAGAATTTCGACCCATGGAGGTGCAATTAACAGACTTTGAGAAC
TCTGCCTATGTGGTGTTTGTGGTACTGCTCACCAGAGTGATCCTTTCCTACAAATTGGAT
TTTCTCATTCCACTGTCAAAGGTTGATGAGAACATGAAGGTAGCACAGAAAAGAGATGCT
GTCTTGCAGGGAATGTTTTATTTCAGGAAAGATATTTGCAAAGGTGGCAATGCAGTGGTG
GATGGTTGTGGCAAGGCCCAGAACAGCACGGAGCTCGCTGCAGAGGAGTACACCCTCATG
AGCATAGACACCATCATCAATGGGAAGGAAGGTGTGTTTCCTGGACTGATCCCAATTCTG
AACTCTTACCTTGAAAACATGGAAGTGGATGTGGACACCAGATGTAGTATTCTGAACTAC
CTAAAGCTAATTAAGAAGAGAGCATCTGGAGAACTAATGACAGTTGCCAGATGGATGAGG
GAGTTTATCGCAAACCATCCTGACTACAAGCAAGACAGTGTCATAACTGATGAAATGAAT
TATAGCCTTATTTTGAAGTGTAACCAAATTGCAAATGAATTATGTGAATGCCCAGAGTTA
CTTGGATCAGCATTTAGGAAAGTAAAATATAGTGGAAGTAAAACTGACTCATCCAACTAG
Chromosome Location
6
Locus
6p12
External Identifiers
ResourceLink
UniProtKB IDP48506
UniProtKB Entry NameGSH1_HUMAN
GenBank Protein ID183039
GenBank Gene IDM90656
GenAtlas IDGCLC
HGNC IDHGNC:4311
General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  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. [Article]
  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. [Article]
  6. Misra I, Griffith OW: Expression and purification of human gamma-glutamylcysteine synthetase. Protein Expr Purif. 1998 Jul;13(2):268-76. [Article]
  7. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  8. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  9. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  10. 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. [Article]
  11. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00151Cysteineapproved, nutraceuticalunknownDetails
DB00142Glutamic acidapproved, nutraceuticalunknownsubstrateDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknowninducerDetails
DB14001alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknowninducerDetails
DB14002D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknowninducerDetails