GSHB_HUMAN
ID GSHB_HUMAN Reviewed; 474 AA.
AC P48637; B2R697; B6F210; E1P5P9; Q4TTD9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Glutathione synthetase {ECO:0000303|PubMed:7646467};
DE Short=GSH synthetase;
DE Short=GSH-S;
DE EC=6.3.2.3 {ECO:0000269|PubMed:7646467, ECO:0000269|PubMed:9215686};
DE AltName: Full=Glutathione synthase;
GN Name=GSS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RC TISSUE=Brain;
RX PubMed=7646467; DOI=10.1042/bj3100353;
RA Gali R.R., Board P.G.;
RT "Sequencing and expression of a cDNA for human glutathione synthetase.";
RL Biochem. J. 310:353-358(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=19672693; DOI=10.1007/s11033-009-9675-3;
RA Uchida M., Sugaya M., Kanamaru T., Hisatomi H.;
RT "Alternative RNA splicing in expression of the glutathione synthetase gene
RT in human cells.";
RL Mol. Biol. Rep. 37:2105-2109(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Shi Z.-Z., Galang R.L., Habib G.M., Lebovitz R.M., Lieberman M.W.;
RL Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-437.
RC TISSUE=Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-236 AND GLU-437.
RG NIEHS SNPs program;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 26-34; 113-125; 142-158; 222-230; 254-267; 274-283;
RP 294-305; 419-434 AND 453-474, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-474 IN COMPLEX WITH ADP AND
RP GLUTATHIONE, FUNCTION, COFACTOR, AND SUBUNIT.
RX PubMed=10369661; DOI=10.1093/emboj/18.12.3204;
RA Polekhina G., Board P.G., Gali R.R., Rossjohn J., Parker M.W.;
RT "Molecular basis of glutathione synthetase deficiency and a rare gene
RT permutation event.";
RL EMBO J. 18:3204-3213(1999).
RN [16]
RP VARIANTS GSS DEFICIENCY GLY-219; TRP-267 AND CYS-283.
RX PubMed=8896573; DOI=10.1038/ng1196-361;
RA Shi Z.-Z., Habib G.M., Rhead W.J., Gahl W.A., He X., Sazer S.,
RA Lieberman M.W.;
RT "Mutations in the glutathione synthetase gene cause 5-oxoprolinuria.";
RL Nat. Genet. 14:361-365(1996).
RN [17]
RP VARIANTS GSS DEFICIENCY ASP-26; PRO-188; GLY-219; ARG-254; TRP-267;
RP CYS-270; HIS-270; CYS-283; GLN-286; CYS-330; VAL-464 AND GLU-469,
RP CHARACTERIZATION OF VARIANTS GSS DEFICIENCY PRO-188; CYS-270; HIS-270 AND
RP CYS-283, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=9215686; DOI=10.1093/hmg/6.7.1147;
RA Dahl N., Pigg M., Ristoff E., Gali R., Carlsson B., Mannervik B.,
RA Larsson A., Board P.;
RT "Missense mutations in the human glutathione synthetase gene result in
RT severe metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and
RT neurological dysfunction.";
RL Hum. Mol. Genet. 6:1147-1152(1997).
RN [18]
RP VARIANTS GSS DEFICIENCY GLY-219 AND PRO-301.
RX PubMed=27581854; DOI=10.1542/peds.2015-4324;
RA Signolet I., Chenouard R., Oca F., Barth M., Reynier P., Denis M.C.,
RA Simard G.;
RT "Recurrent isolated neonatal hemolytic anemia: think about glutathione
RT synthetase deficiency.";
RL Pediatrics 138:0-0(2016).
CC -!- FUNCTION: Catalyzes the production of glutathione from gamma-
CC glutamylcysteine and glycine in an ATP-dependent manner
CC (PubMed:7646467, PubMed:9215686). Glutathione (gamma-
CC glutamylcysteinylglycine, GSH) is the most abundant intracellular thiol
CC in living aerobic cells and is required for numerous processes
CC including the protection of cells against oxidative damage, amino acid
CC transport, the detoxification of foreign compounds, the maintenance of
CC protein sulfhydryl groups in a reduced state and acts as a cofactor for
CC a number of enzymes (PubMed:10369661). {ECO:0000269|PubMed:7646467,
CC ECO:0000269|PubMed:9215686, ECO:0000303|PubMed:10369661}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP +
CC glutathione + H(+) + phosphate; Xref=Rhea:RHEA:13557,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57925, ChEBI:CHEBI:58173,
CC ChEBI:CHEBI:456216; EC=6.3.2.3; Evidence={ECO:0000269|PubMed:7646467,
CC ECO:0000269|PubMed:9215686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13558;
CC Evidence={ECO:0000269|PubMed:9215686};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10369661};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:10369661};
CC -!- PATHWAY: Sulfur metabolism; glutathione biosynthesis; glutathione from
CC L-cysteine and L-glutamate: step 2/2. {ECO:0000305|PubMed:9215686}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10369661,
CC ECO:0000269|PubMed:7646467}.
CC -!- INTERACTION:
CC P48637; P48637: GSS; NbExp=8; IntAct=EBI-2969145, EBI-2969145;
CC P48637; P54274: TERF1; NbExp=2; IntAct=EBI-2969145, EBI-710997;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48637-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48637-2; Sequence=VSP_047617;
CC -!- DISEASE: Glutathione synthetase deficiency (GSS deficiency)
CC [MIM:266130]: Severe form characterized by an increased rate of
CC hemolysis and defective function of the central nervous system.
CC {ECO:0000269|PubMed:27581854, ECO:0000269|PubMed:8896573,
CC ECO:0000269|PubMed:9215686}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Glutathione synthetase deficiency of erythrocytes (GLUSYNDE)
CC [MIM:231900]: Mild form causing hemolytic anemia. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Detected in colon, kidney, lung, liver,
CC placenta, peripheral blood and uterus, but not in heart, skeletal
CC muscle and spleen. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the eukaryotic GSH synthase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gss/";
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DR EMBL; L42531; AAA69492.1; -; mRNA.
DR EMBL; AB459500; BAG75452.1; -; mRNA.
DR EMBL; U34683; AAB62390.1; -; mRNA.
DR EMBL; AK312492; BAG35394.1; -; mRNA.
DR EMBL; DQ074975; AAY57328.1; -; Genomic_DNA.
DR EMBL; AL133324; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76239.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76240.1; -; Genomic_DNA.
DR EMBL; BC007927; AAH07927.1; -; mRNA.
DR CCDS; CCDS13245.1; -. [P48637-1]
DR PIR; S56748; S56748.
DR RefSeq; NP_000169.1; NM_000178.3. [P48637-1]
DR RefSeq; NP_001309423.1; NM_001322494.1. [P48637-1]
DR RefSeq; NP_001309424.1; NM_001322495.1. [P48637-1]
DR PDB; 2HGS; X-ray; 2.10 A; A=1-474.
DR PDBsum; 2HGS; -.
DR AlphaFoldDB; P48637; -.
DR SMR; P48637; -.
DR BioGRID; 109192; 33.
DR IntAct; P48637; 5.
DR MINT; P48637; -.
DR STRING; 9606.ENSP00000216951; -.
DR DrugBank; DB06151; Acetylcysteine.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00151; Cysteine.
DR DrugBank; DB03408; gamma-Glutamylcysteine.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR iPTMnet; P48637; -.
DR PhosphoSitePlus; P48637; -.
DR BioMuta; GSS; -.
DR DMDM; 1346191; -.
DR OGP; P48637; -.
DR REPRODUCTION-2DPAGE; IPI00010706; -.
DR CPTAC; CPTAC-210; -.
DR CPTAC; CPTAC-211; -.
DR EPD; P48637; -.
DR jPOST; P48637; -.
DR MassIVE; P48637; -.
DR MaxQB; P48637; -.
DR PaxDb; P48637; -.
DR PeptideAtlas; P48637; -.
DR PRIDE; P48637; -.
DR ProteomicsDB; 55917; -. [P48637-1]
DR ProteomicsDB; 6247; -.
DR Antibodypedia; 25920; 439 antibodies from 34 providers.
DR DNASU; 2937; -.
DR Ensembl; ENST00000451957.2; ENSP00000407517.2; ENSG00000100983.12. [P48637-2]
DR Ensembl; ENST00000643188.1; ENSP00000493903.1; ENSG00000100983.12. [P48637-1]
DR Ensembl; ENST00000644793.1; ENSP00000495750.1; ENSG00000100983.12. [P48637-1]
DR Ensembl; ENST00000646735.1; ENSP00000493763.1; ENSG00000100983.12. [P48637-2]
DR Ensembl; ENST00000651619.1; ENSP00000498303.1; ENSG00000100983.12. [P48637-1]
DR GeneID; 2937; -.
DR KEGG; hsa:2937; -.
DR MANE-Select; ENST00000651619.1; ENSP00000498303.1; NM_000178.4; NP_000169.1.
DR UCSC; uc010zuo.3; human. [P48637-1]
DR CTD; 2937; -.
DR DisGeNET; 2937; -.
DR GeneCards; GSS; -.
DR HGNC; HGNC:4624; GSS.
DR HPA; ENSG00000100983; Low tissue specificity.
DR MalaCards; GSS; -.
DR MIM; 231900; phenotype.
DR MIM; 266130; phenotype.
DR MIM; 601002; gene.
DR neXtProt; NX_P48637; -.
DR OpenTargets; ENSG00000100983; -.
DR Orphanet; 289846; Glutathione synthetase deficiency with 5-oxoprolinuria.
DR Orphanet; 289849; Glutathione synthetase deficiency without 5-oxoprolinuria.
DR PharmGKB; PA29015; -.
DR VEuPathDB; HostDB:ENSG00000100983; -.
DR eggNOG; KOG0021; Eukaryota.
DR GeneTree; ENSGT00390000013764; -.
DR HOGENOM; CLU_025152_2_1_1; -.
DR InParanoid; P48637; -.
DR OMA; NGLVMYP; -.
DR PhylomeDB; P48637; -.
DR TreeFam; TF105187; -.
DR BioCyc; MetaCyc:HS02174-MON; -.
DR BRENDA; 6.3.2.3; 2681.
DR PathwayCommons; P48637; -.
DR Reactome; R-HSA-174403; Glutathione synthesis and recycling.
DR Reactome; R-HSA-5579006; Defective GSS causes GSS deficiency.
DR SABIO-RK; P48637; -.
DR SignaLink; P48637; -.
DR UniPathway; UPA00142; UER00210.
DR BioGRID-ORCS; 2937; 39 hits in 1091 CRISPR screens.
DR ChiTaRS; GSS; human.
DR EvolutionaryTrace; P48637; -.
DR GenomeRNAi; 2937; -.
DR Pharos; P48637; Tbio.
DR PRO; PR:P48637; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P48637; protein.
DR Bgee; ENSG00000100983; Expressed in frontal pole and 204 other tissues.
DR ExpressionAtlas; P48637; baseline and differential.
DR Genevisible; P48637; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0043295; F:glutathione binding; IDA:UniProtKB.
DR GO; GO:0004363; F:glutathione synthase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006520; P:cellular amino acid metabolic process; TAS:ProtInc.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; TAS:ProtInc.
DR CDD; cd00228; eu-GS; 1.
DR Gene3D; 1.10.1080.10; -; 1.
DR Gene3D; 3.30.1490.50; -; 1.
DR Gene3D; 3.30.1490.80; -; 1.
DR Gene3D; 3.40.50.1760; -; 1.
DR InterPro; IPR005615; Glutathione_synthase.
DR InterPro; IPR014042; Glutathione_synthase_a-hlx.
DR InterPro; IPR014709; Glutathione_synthase_C_euk.
DR InterPro; IPR014049; Glutathione_synthase_N_euk.
DR InterPro; IPR037013; GSH-S_sub-bd_sf.
DR InterPro; IPR004887; GSH_synth_subst-bd.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR PANTHER; PTHR11130; PTHR11130; 1.
DR Pfam; PF03917; GSH_synth_ATP; 1.
DR Pfam; PF03199; GSH_synthase; 1.
DR PIRSF; PIRSF001558; GSHase; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR TIGRFAMs; TIGR01986; glut_syn_euk; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Direct protein sequencing; Disease variant; Glutathione biosynthesis;
KW Hereditary hemolytic anemia; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..474
FT /note="Glutathione synthetase"
FT /id="PRO_0000211260"
FT BINDING 125
FT /ligand="substrate"
FT BINDING 144
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 144
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 146
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 148..151
FT /ligand="substrate"
FT BINDING 214..216
FT /ligand="substrate"
FT BINDING 220
FT /ligand="substrate"
FT BINDING 267..270
FT /ligand="substrate"
FT BINDING 305
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 364..373
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 368
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 375
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 398..401
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 425
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 450
FT /ligand="substrate"
FT BINDING 452
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 458
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 461..462
FT /ligand="substrate"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 93..203
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19672693"
FT /id="VSP_047617"
FT VARIANT 26
FT /note="A -> D (in GSS deficiency; dbSNP:rs759253242)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003602"
FT VARIANT 188
FT /note="L -> P (in GSS deficiency; 100-fold decreased
FT glutathione synthase activity)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003603"
FT VARIANT 219
FT /note="D -> A (in GSS deficiency; dbSNP:rs28938472)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003604"
FT VARIANT 219
FT /note="D -> G (in GSS deficiency; dbSNP:rs28938472)"
FT /evidence="ECO:0000269|PubMed:27581854,
FT ECO:0000269|PubMed:8896573, ECO:0000269|PubMed:9215686"
FT /id="VAR_003605"
FT VARIANT 236
FT /note="R -> Q (in dbSNP:rs34239729)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025047"
FT VARIANT 254
FT /note="L -> R (in GSS deficiency)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003606"
FT VARIANT 267
FT /note="R -> W (in GSS deficiency; dbSNP:rs121909308)"
FT /evidence="ECO:0000269|PubMed:8896573,
FT ECO:0000269|PubMed:9215686"
FT /id="VAR_003607"
FT VARIANT 270
FT /note="Y -> C (in GSS deficiency; 100-fold decreased
FT glutathione synthase activity; dbSNP:rs1325986563)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003608"
FT VARIANT 270
FT /note="Y -> H (in GSS deficiency; 100-fold decreased
FT glutathione synthase activity)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003609"
FT VARIANT 283
FT /note="R -> C (in GSS deficiency; 10-fold decreased
FT glutathione synthase activity; dbSNP:rs121909309)"
FT /evidence="ECO:0000269|PubMed:8896573,
FT ECO:0000269|PubMed:9215686"
FT /id="VAR_003610"
FT VARIANT 286
FT /note="L -> Q (in GSS deficiency; dbSNP:rs1296000099)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003611"
FT VARIANT 301
FT /note="L -> P (in GSS deficiency)"
FT /evidence="ECO:0000269|PubMed:27581854"
FT /id="VAR_078567"
FT VARIANT 330
FT /note="R -> C (in GSS deficiency; dbSNP:rs148640446)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003612"
FT VARIANT 437
FT /note="K -> E (in dbSNP:rs34852238)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.5"
FT /id="VAR_025048"
FT VARIANT 464
FT /note="G -> V (in GSS deficiency)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003613"
FT VARIANT 469
FT /note="D -> E (in GSS deficiency; dbSNP:rs1419704426)"
FT /evidence="ECO:0000269|PubMed:9215686"
FT /id="VAR_003614"
FT HELIX 6..9
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 12..28
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 59..67
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 69..81
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 98..113
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 119..132
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 138..146
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 160..169
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 184..199
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 205..209
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:2HGS"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 239..245
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 259..268
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 277..288
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 289..295
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 297..301
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 305..310
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 316..320
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 325..333
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 345..356
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 361..366
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 376..386
FT /evidence="ECO:0007829|PDB:2HGS"
FT HELIX 390..394
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 395..399
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 406..411
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 418..435
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 438..453
FT /evidence="ECO:0007829|PDB:2HGS"
FT TURN 461..464
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 467..469
FT /evidence="ECO:0007829|PDB:2HGS"
FT STRAND 472..474
FT /evidence="ECO:0007829|PDB:2HGS"
SQ SEQUENCE 474 AA; 52385 MW; 3C25EF7072EFE058 CRC64;
MATNWGSLLQ DKQQLEELAR QAVDRALAEG VLLRTSQEPT SSEVVSYAPF TLFPSLVPSA
LLEQAYAVQM DFNLLVDAVS QNAAFLEQTL SSTIKQDDFT ARLFDIHKQV LKEGIAQTVF
LGLNRSDYMF QRSADGSPAL KQIEINTISA SFGGLASRTP AVHRHVLSVL SKTKEAGKIL
SNNPSKGLAL GIAKAWELYG SPNALVLLIA QEKERNIFDQ RAIENELLAR NIHVIRRTFE
DISEKGSLDQ DRRLFVDGQE IAVVYFRDGY MPRQYSLQNW EARLLLERSH AAKCPDIATQ
LAGTKKVQQE LSRPGMLEML LPGQPEAVAR LRATFAGLYS LDVGEEGDQA IAEALAAPSR
FVLKPQREGG GNNLYGEEMV QALKQLKDSE ERASYILMEK IEPEPFENCL LRPGSPARVV
QCISELGIFG VYVRQEKTLV MNKHVGHLLR TKAIEHADGG VAAGVAVLDN PYPV
