UniProtKB - P48637 (GSHB_HUMAN)
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Protein
Glutathione synthetase
Gene
GSS
Organism
Homo sapiens (Human)
Status
Functioni
Catalytic activityi
ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione.
Cofactori
Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.1 Publication
: glutathione biosynthesis Pathwayi
This protein is involved in step 2 of the subpathway that synthesizes glutathione from L-cysteine and L-glutamate.Proteins known to be involved in the 2 steps of the subpathway in this organism are:
- Glutamate--cysteine ligase regulatory subunit (GCLM), Glutamate--cysteine ligase catalytic subunit (GCLC)
- Glutathione synthetase, Glutathione synthetase (GSS), Glutathione synthetase, Glutathione synthetase (HEL-S-64p)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes glutathione from L-cysteine and L-glutamate, the pathway glutathione biosynthesis and in Sulfur metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 125 | Substrate | 1 | |
Metal bindingi | 144 | Magnesium | 1 | |
Binding sitei | 144 | ATP | 1 | |
Metal bindingi | 146 | Magnesium | 1 | |
Binding sitei | 220 | Substrate | 1 | |
Binding sitei | 305 | ATP | 1 | |
Metal bindingi | 368 | Magnesium | 1 | |
Binding sitei | 375 | ATP | 1 | |
Binding sitei | 425 | ATP | 1 | |
Binding sitei | 450 | Substrate | 1 | |
Binding sitei | 452 | ATP | 1 | |
Binding sitei | 458 | ATP; via carbonyl oxygen | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 364 – 373 | ATP | 10 | |
Nucleotide bindingi | 398 – 401 | ATP | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- glutathione binding Source: UniProtKB
- glutathione synthase activity Source: GO_Central
- glycine binding Source: Ensembl
- identical protein binding Source: IntAct
- magnesium ion binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
GO - Biological processi
- aging Source: Ensembl
- cellular amino acid metabolic process Source: ProtInc
- glutathione biosynthetic process Source: Reactome
- nervous system development Source: ProtInc
- response to amino acid Source: Ensembl
- response to cadmium ion Source: Ensembl
- response to nutrient levels Source: Ensembl
- response to oxidative stress Source: ProtInc
- response to tumor necrosis factor Source: Ensembl
- response to xenobiotic stimulus Source: Ensembl
Keywordsi
Molecular function | Ligase |
Biological process | Glutathione biosynthesis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS02174-MONOMER. |
BRENDAi | 6.3.2.3. 2681. |
Reactomei | R-HSA-174403. Glutathione synthesis and recycling. R-HSA-5579006. Defective GSS causes Glutathione synthetase deficiency (GSS deficiency). |
SABIO-RKi | P48637. |
UniPathwayi | UPA00142; UER00210. |
Names & Taxonomyi
Protein namesi | Recommended name: Glutathione synthetase (EC:6.3.2.3)Short name: GSH synthetase Short name: GSH-S Alternative name(s): Glutathione synthase |
Gene namesi | Name:GSS |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100983.9. |
HGNCi | HGNC:4624. GSS. |
MIMi | 601002. gene. |
neXtProti | NX_P48637. |
Subcellular locationi
Pathology & Biotechi
Involvement in diseasei
Glutathione synthetase deficiency (GSS deficiency)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionSevere form characterized by an increased rate of hemolysis and defective function of the central nervous system.
See also OMIM:266130Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_003602 | 26 | A → D in GSS deficiency. Corresponds to variant dbSNP:rs759253242Ensembl. | 1 | |
Natural variantiVAR_003603 | 188 | L → P in GSS deficiency; 100-fold reduction of activity. | 1 | |
Natural variantiVAR_003604 | 219 | D → A in GSS deficiency. | 1 | |
Natural variantiVAR_003605 | 219 | D → G in GSS deficiency. 2 PublicationsCorresponds to variant dbSNP:rs28938472Ensembl. | 1 | |
Natural variantiVAR_003606 | 254 | L → R in GSS deficiency. | 1 | |
Natural variantiVAR_003607 | 267 | R → W in GSS deficiency. 1 PublicationCorresponds to variant dbSNP:rs121909308Ensembl. | 1 | |
Natural variantiVAR_003608 | 270 | Y → C in GSS deficiency; 100-fold reduction of activity. | 1 | |
Natural variantiVAR_003609 | 270 | Y → H in GSS deficiency; 100-fold reduction of activity. | 1 | |
Natural variantiVAR_003610 | 283 | R → C in GSS deficiency; 10-fold reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs121909309Ensembl. | 1 | |
Natural variantiVAR_003611 | 286 | L → Q in GSS deficiency. | 1 | |
Natural variantiVAR_078567 | 301 | L → P in GSS deficiency. 1 Publication | 1 | |
Natural variantiVAR_003612 | 330 | R → C in GSS deficiency. Corresponds to variant dbSNP:rs148640446Ensembl. | 1 | |
Natural variantiVAR_003613 | 464 | G → V in GSS deficiency. | 1 | |
Natural variantiVAR_003614 | 469 | D → E in GSS deficiency. | 1 |
Glutathione synthetase deficiency of erythrocytes (GLUSYNDE)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMild form causing hemolytic anemia.
See also OMIM:231900Keywords - Diseasei
Disease mutation, Hereditary hemolytic anemiaOrganism-specific databases
DisGeNETi | 2937. |
MalaCardsi | GSS. |
MIMi | 231900. phenotype. 266130. phenotype. |
OpenTargetsi | ENSG00000100983. |
Orphaneti | 289846. Glutathione synthetase deficiency with 5-oxoprolinuria. 289849. Glutathione synthetase deficiency without 5-oxoprolinuria. |
PharmGKBi | PA29015. |
Chemistry databases
DrugBanki | DB06151. Acetylcysteine. DB03408. gamma-Glutamylcysteine. DB00143. Glutathione. DB00145. Glycine. DB00151. L-Cysteine. DB04395. Phosphoaminophosphonic Acid-Adenylate Ester. |
Polymorphism and mutation databases
BioMutai | GSS. |
DMDMi | 1346191. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000211260 | 2 – 474 | Glutathione synthetaseAdd BLAST | 473 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 415 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P48637. |
PaxDbi | P48637. |
PeptideAtlasi | P48637. |
PRIDEi | P48637. |
2D gel databases
OGPi | P48637. |
REPRODUCTION-2DPAGEi | IPI00010706. |
PTM databases
iPTMneti | P48637. |
PhosphoSitePlusi | P48637. |
Expressioni
Gene expression databases
Bgeei | ENSG00000100983. |
CleanExi | HS_GSS. |
ExpressionAtlasi | P48637. baseline and differential. |
Genevisiblei | P48637. HS. |
Organism-specific databases
HPAi | HPA054508. HPA059315. |
Interactioni
Subunit structurei
Homodimer.1 Publication
Binary interactionsi
GO - Molecular functioni
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGridi | 109192. 27 interactors. |
IntActi | P48637. 3 interactors. |
MINTi | P48637. |
STRINGi | 9606.ENSP00000216951. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 6 – 9 | Combined sources | 4 | |
Helixi | 12 – 28 | Combined sources | 17 | |
Beta strandi | 32 – 34 | Combined sources | 3 | |
Beta strandi | 43 – 47 | Combined sources | 5 | |
Beta strandi | 50 – 53 | Combined sources | 4 | |
Beta strandi | 56 – 58 | Combined sources | 3 | |
Helixi | 59 – 67 | Combined sources | 9 | |
Helixi | 69 – 81 | Combined sources | 13 | |
Helixi | 83 – 91 | Combined sources | 9 | |
Helixi | 93 – 96 | Combined sources | 4 | |
Helixi | 98 – 113 | Combined sources | 16 | |
Beta strandi | 119 – 132 | Combined sources | 14 | |
Beta strandi | 134 – 136 | Combined sources | 3 | |
Beta strandi | 138 – 146 | Combined sources | 9 | |
Helixi | 153 – 158 | Combined sources | 6 | |
Helixi | 160 – 169 | Combined sources | 10 | |
Helixi | 173 – 176 | Combined sources | 4 | |
Helixi | 184 – 199 | Combined sources | 16 | |
Beta strandi | 205 – 209 | Combined sources | 5 | |
Helixi | 217 – 228 | Combined sources | 12 | |
Turni | 229 – 231 | Combined sources | 3 | |
Beta strandi | 234 – 237 | Combined sources | 4 | |
Helixi | 239 – 245 | Combined sources | 7 | |
Beta strandi | 246 – 248 | Combined sources | 3 | |
Beta strandi | 254 – 256 | Combined sources | 3 | |
Beta strandi | 259 – 268 | Combined sources | 10 | |
Helixi | 272 – 274 | Combined sources | 3 | |
Helixi | 277 – 288 | Combined sources | 12 | |
Beta strandi | 289 – 295 | Combined sources | 7 | |
Helixi | 297 – 301 | Combined sources | 5 | |
Helixi | 305 – 310 | Combined sources | 6 | |
Helixi | 316 – 320 | Combined sources | 5 | |
Helixi | 325 – 333 | Combined sources | 9 | |
Beta strandi | 338 – 340 | Combined sources | 3 | |
Beta strandi | 342 – 344 | Combined sources | 3 | |
Helixi | 345 – 356 | Combined sources | 12 | |
Helixi | 358 – 360 | Combined sources | 3 | |
Beta strandi | 361 – 366 | Combined sources | 6 | |
Beta strandi | 369 – 371 | Combined sources | 3 | |
Helixi | 376 – 386 | Combined sources | 11 | |
Helixi | 390 – 394 | Combined sources | 5 | |
Beta strandi | 395 – 399 | Combined sources | 5 | |
Beta strandi | 406 – 411 | Combined sources | 6 | |
Beta strandi | 418 – 435 | Combined sources | 18 | |
Beta strandi | 438 – 453 | Combined sources | 16 | |
Turni | 461 – 464 | Combined sources | 4 | |
Beta strandi | 467 – 469 | Combined sources | 3 | |
Beta strandi | 472 – 474 | Combined sources | 3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2HGS | X-ray | 2.10 | A | 1-474 | [»] | |
ProteinModelPortali | P48637. | |||||
SMRi | P48637. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P48637. |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 148 – 151 | Substrate binding | 4 | |
Regioni | 214 – 216 | Substrate binding | 3 | |
Regioni | 267 – 270 | Substrate binding | 4 | |
Regioni | 461 – 462 | Substrate binding | 2 |
Sequence similaritiesi
Belongs to the eukaryotic GSH synthase family.Curated
Phylogenomic databases
eggNOGi | KOG0021. Eukaryota. ENOG410XPHH. LUCA. |
GeneTreei | ENSGT00390000013764. |
HOGENOMi | HOG000172641. |
HOVERGENi | HBG002458. |
InParanoidi | P48637. |
KOi | K21456. |
OMAi | FRSDYMV. |
OrthoDBi | EOG091G05V8. |
PhylomeDBi | P48637. |
TreeFami | TF105187. |
Family and domain databases
CDDi | cd00228. eu-GS. 1 hit. |
Gene3Di | 1.10.1080.10. 2 hits. 3.30.1490.50. 1 hit. 3.30.1490.80. 3 hits. 3.40.50.1760. 1 hit. |
InterProi | View protein in InterPro IPR005615. Glutathione_synthase. IPR014042. Glutathione_synthase_a-hlx. IPR014709. Glutathione_synthase_C_euk. IPR014049. Glutathione_synthase_N_euk. IPR037013. GSH-S_sub-bd_sf. IPR004887. GSH_synth_subst-bd. IPR016185. PreATP-grasp_dom_sf. |
PANTHERi | PTHR11130. PTHR11130. 1 hit. |
Pfami | View protein in Pfam PF03917. GSH_synth_ATP. 1 hit. PF03199. GSH_synthase. 1 hit. |
PIRSFi | PIRSF001558. GSHase. 1 hit. |
SUPFAMi | SSF52440. SSF52440. 1 hit. |
TIGRFAMsi | TIGR01986. glut_syn_euk. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: P48637-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MATNWGSLLQ DKQQLEELAR QAVDRALAEG VLLRTSQEPT SSEVVSYAPF
60 70 80 90 100
TLFPSLVPSA LLEQAYAVQM DFNLLVDAVS QNAAFLEQTL SSTIKQDDFT
110 120 130 140 150
ARLFDIHKQV LKEGIAQTVF LGLNRSDYMF QRSADGSPAL KQIEINTISA
160 170 180 190 200
SFGGLASRTP AVHRHVLSVL SKTKEAGKIL SNNPSKGLAL GIAKAWELYG
210 220 230 240 250
SPNALVLLIA QEKERNIFDQ RAIENELLAR NIHVIRRTFE DISEKGSLDQ
260 270 280 290 300
DRRLFVDGQE IAVVYFRDGY MPRQYSLQNW EARLLLERSH AAKCPDIATQ
310 320 330 340 350
LAGTKKVQQE LSRPGMLEML LPGQPEAVAR LRATFAGLYS LDVGEEGDQA
360 370 380 390 400
IAEALAAPSR FVLKPQREGG GNNLYGEEMV QALKQLKDSE ERASYILMEK
410 420 430 440 450
IEPEPFENCL LRPGSPARVV QCISELGIFG VYVRQEKTLV MNKHVGHLLR
460 470
TKAIEHADGG VAAGVAVLDN PYPV
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_003602 | 26 | A → D in GSS deficiency. Corresponds to variant dbSNP:rs759253242Ensembl. | 1 | |
Natural variantiVAR_003603 | 188 | L → P in GSS deficiency; 100-fold reduction of activity. | 1 | |
Natural variantiVAR_003604 | 219 | D → A in GSS deficiency. | 1 | |
Natural variantiVAR_003605 | 219 | D → G in GSS deficiency. 2 PublicationsCorresponds to variant dbSNP:rs28938472Ensembl. | 1 | |
Natural variantiVAR_025047 | 236 | R → Q1 PublicationCorresponds to variant dbSNP:rs34239729Ensembl. | 1 | |
Natural variantiVAR_003606 | 254 | L → R in GSS deficiency. | 1 | |
Natural variantiVAR_003607 | 267 | R → W in GSS deficiency. 1 PublicationCorresponds to variant dbSNP:rs121909308Ensembl. | 1 | |
Natural variantiVAR_003608 | 270 | Y → C in GSS deficiency; 100-fold reduction of activity. | 1 | |
Natural variantiVAR_003609 | 270 | Y → H in GSS deficiency; 100-fold reduction of activity. | 1 | |
Natural variantiVAR_003610 | 283 | R → C in GSS deficiency; 10-fold reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs121909309Ensembl. | 1 | |
Natural variantiVAR_003611 | 286 | L → Q in GSS deficiency. | 1 | |
Natural variantiVAR_078567 | 301 | L → P in GSS deficiency. 1 Publication | 1 | |
Natural variantiVAR_003612 | 330 | R → C in GSS deficiency. Corresponds to variant dbSNP:rs148640446Ensembl. | 1 | |
Natural variantiVAR_025048 | 437 | K → E2 PublicationsCorresponds to variant dbSNP:rs34852238Ensembl. | 1 | |
Natural variantiVAR_003613 | 464 | G → V in GSS deficiency. | 1 | |
Natural variantiVAR_003614 | 469 | D → E in GSS deficiency. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_047617 | 93 – 203 | Missing in isoform 2. 1 PublicationAdd BLAST | 111 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L42531 mRNA. Translation: AAA69492.1. AB459500 mRNA. Translation: BAG75452.1. U34683 mRNA. Translation: AAB62390.1. AK312492 mRNA. Translation: BAG35394.1. DQ074975 Genomic DNA. Translation: AAY57328.1. AL133324 Genomic DNA. No translation available. CH471077 Genomic DNA. Translation: EAW76239.1. CH471077 Genomic DNA. Translation: EAW76240.1. BC007927 mRNA. Translation: AAH07927.1. |
CCDSi | CCDS13245.1. [P48637-1] |
PIRi | S56748. |
RefSeqi | NP_000169.1. NM_000178.3. [P48637-1] NP_001309423.1. NM_001322494.1. [P48637-1] NP_001309424.1. NM_001322495.1. [P48637-1] |
UniGenei | Hs.82327. |
Genome annotation databases
Ensembli | ENST00000216951; ENSP00000216951; ENSG00000100983. [P48637-1] ENST00000451957; ENSP00000407517; ENSG00000100983. [P48637-2] |
GeneIDi | 2937. |
KEGGi | hsa:2937. |
UCSCi | uc010zuo.3. human. [P48637-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | GSHB_HUMAN | |
Accessioni | P48637Primary (citable) accession number: P48637 Secondary accession number(s): B2R697 Q4TTD9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1996 |
Last sequence update: | February 1, 1996 | |
Last modified: | February 28, 2018 | |
This is version 184 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |