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UniProtKB - P48637 (GSHB_HUMAN)

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Protein

Glutathione synthetase

Gene

GSS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Pathwayi: glutathione biosynthesis

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:
  1. Glutamate--cysteine ligase regulatory subunit (GCLM), Glutamate--cysteine ligase catalytic subunit (GCLC)
  2. Glutathione synthetase, Glutathione synthetase (GSS), Glutathione synthetase, Glutathione synthetase (HEL-S-64p)
This subpathway is part of the pathway glutathione biosynthesis, which is itself part of Sulfur metabolism.
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei125Substrate1
Metal bindingi144Magnesium1
Binding sitei144ATP1
Metal bindingi146Magnesium1
Binding sitei220Substrate1
Binding sitei305ATP1
Metal bindingi368Magnesium1
Binding sitei375ATP1
Binding sitei425ATP1
Binding sitei450Substrate1
Binding sitei452ATP1
Binding sitei458ATP; via carbonyl oxygen1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi364 – 373ATP10
Nucleotide bindingi398 – 401ATP4

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • glutathione binding Source: UniProtKB
  • glutathione synthase activity Source: GO_Central
  • identical protein binding Source: IntAct
  • magnesium ion binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cellular amino acid metabolic process Source: ProtInc
  • glutathione biosynthetic process Source: Reactome
  • nervous system development Source: ProtInc
  • response to oxidative stress Source: ProtInc
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionLigase
Biological processGlutathione biosynthesis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02174-MONOMER
BRENDAi6.3.2.3 2681
ReactomeiR-HSA-174403 Glutathione synthesis and recycling
R-HSA-5579006 Defective GSS causes Glutathione synthetase deficiency (GSS deficiency)
SABIO-RKiP48637
UniPathwayiUPA00142; 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000100983.9
HGNCiHGNC:4624 GSS
MIMi601002 gene
neXtProtiNX_P48637

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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:266130
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00360226A → D in GSS deficiency. Corresponds to variant dbSNP:rs759253242Ensembl.1
Natural variantiVAR_003603188L → P in GSS deficiency; 100-fold reduction of activity. 1
Natural variantiVAR_003604219D → A in GSS deficiency. 1
Natural variantiVAR_003605219D → G in GSS deficiency. 2 PublicationsCorresponds to variant dbSNP:rs28938472EnsemblClinVar.1
Natural variantiVAR_003606254L → R in GSS deficiency. 1
Natural variantiVAR_003607267R → W in GSS deficiency. 1 PublicationCorresponds to variant dbSNP:rs121909308EnsemblClinVar.1
Natural variantiVAR_003608270Y → C in GSS deficiency; 100-fold reduction of activity. 1
Natural variantiVAR_003609270Y → H in GSS deficiency; 100-fold reduction of activity. 1
Natural variantiVAR_003610283R → C in GSS deficiency; 10-fold reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs121909309EnsemblClinVar.1
Natural variantiVAR_003611286L → Q in GSS deficiency. 1
Natural variantiVAR_078567301L → P in GSS deficiency. 1 Publication1
Natural variantiVAR_003612330R → C in GSS deficiency. Corresponds to variant dbSNP:rs148640446Ensembl.1
Natural variantiVAR_003613464G → V in GSS deficiency. 1
Natural variantiVAR_003614469D → 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:231900

Keywords - Diseasei

Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

DisGeNETi2937
MalaCardsiGSS
MIMi231900 phenotype
266130 phenotype
OpenTargetsiENSG00000100983
Orphaneti289846 Glutathione synthetase deficiency with 5-oxoprolinuria
289849 Glutathione synthetase deficiency without 5-oxoprolinuria
PharmGKBiPA29015

Chemistry databases

DrugBankiDB06151 Acetylcysteine
DB03408 gamma-Glutamylcysteine
DB00143 Glutathione
DB00145 Glycine
DB00151 L-Cysteine
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester

Polymorphism and mutation databases

BioMutaiGSS
DMDMi1346191

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002112602 – 474Glutathione synthetaseAdd BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei415PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP48637
PaxDbiP48637
PeptideAtlasiP48637
PRIDEiP48637

2D gel databases

OGPiP48637
REPRODUCTION-2DPAGEiIPI00010706

PTM databases

iPTMnetiP48637
PhosphoSitePlusiP48637

Expressioni

Gene expression databases

BgeeiENSG00000100983
CleanExiHS_GSS
ExpressionAtlasiP48637 baseline and differential
GenevisibleiP48637 HS

Organism-specific databases

HPAiHPA054508
HPA059315

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi109192, 27 interactors
IntActiP48637, 3 interactors
MINTiP48637
STRINGi9606.ENSP00000216951

Structurei

Secondary structure

1474
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 9Combined sources4
Helixi12 – 28Combined sources17
Beta strandi32 – 34Combined sources3
Beta strandi43 – 47Combined sources5
Beta strandi50 – 53Combined sources4
Beta strandi56 – 58Combined sources3
Helixi59 – 67Combined sources9
Helixi69 – 81Combined sources13
Helixi83 – 91Combined sources9
Helixi93 – 96Combined sources4
Helixi98 – 113Combined sources16
Beta strandi119 – 132Combined sources14
Beta strandi134 – 136Combined sources3
Beta strandi138 – 146Combined sources9
Helixi153 – 158Combined sources6
Helixi160 – 169Combined sources10
Helixi173 – 176Combined sources4
Helixi184 – 199Combined sources16
Beta strandi205 – 209Combined sources5
Helixi217 – 228Combined sources12
Turni229 – 231Combined sources3
Beta strandi234 – 237Combined sources4
Helixi239 – 245Combined sources7
Beta strandi246 – 248Combined sources3
Beta strandi254 – 256Combined sources3
Beta strandi259 – 268Combined sources10
Helixi272 – 274Combined sources3
Helixi277 – 288Combined sources12
Beta strandi289 – 295Combined sources7
Helixi297 – 301Combined sources5
Helixi305 – 310Combined sources6
Helixi316 – 320Combined sources5
Helixi325 – 333Combined sources9
Beta strandi338 – 340Combined sources3
Beta strandi342 – 344Combined sources3
Helixi345 – 356Combined sources12
Helixi358 – 360Combined sources3
Beta strandi361 – 366Combined sources6
Beta strandi369 – 371Combined sources3
Helixi376 – 386Combined sources11
Helixi390 – 394Combined sources5
Beta strandi395 – 399Combined sources5
Beta strandi406 – 411Combined sources6
Beta strandi418 – 435Combined sources18
Beta strandi438 – 453Combined sources16
Turni461 – 464Combined sources4
Beta strandi467 – 469Combined sources3
Beta strandi472 – 474Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HGSX-ray2.10A1-474[»]
ProteinModelPortaliP48637
SMRiP48637
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP48637

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni148 – 151Substrate binding4
Regioni214 – 216Substrate binding3
Regioni267 – 270Substrate binding4
Regioni461 – 462Substrate binding2

Sequence similaritiesi

Belongs to the eukaryotic GSH synthase family.Curated

Phylogenomic databases

eggNOGiKOG0021 Eukaryota
ENOG410XPHH LUCA
GeneTreeiENSGT00390000013764
HOGENOMiHOG000172641
HOVERGENiHBG002458
InParanoidiP48637
KOiK21456
OMAiFRSDYMV
OrthoDBiEOG091G05V8
PhylomeDBiP48637
TreeFamiTF105187

Family and domain databases

CDDicd00228 eu-GS, 1 hit
Gene3Di1.10.1080.10, 2 hits
3.30.1490.50, 1 hit
3.30.1490.80, 3 hits
3.40.50.1760, 1 hit
InterProiView 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
PANTHERiPTHR11130 PTHR11130, 1 hit
PfamiView protein in Pfam
PF03917 GSH_synth_ATP, 1 hit
PF03199 GSH_synthase, 1 hit
PIRSFiPIRSF001558 GSHase, 1 hit
SUPFAMiSSF52440 SSF52440, 1 hit
TIGRFAMsiTIGR01986 glut_syn_euk, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative 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.

« Hide

        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
Length:474
Mass (Da):52,385
Last modified:February 1, 1996 - v1
Checksum:i3C25EF7072EFE058
GO
Isoform 2 (identifier: P48637-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     93-203: Missing.

Note: Detected in colon, kidney, lung, liver, placenta, peripheral blood and uterus, but not in heart, skeletal muscle and spleen.
Show »
Length:363
Mass (Da):40,349
Checksum:i931DA0F137EE1634
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00360226A → D in GSS deficiency. Corresponds to variant dbSNP:rs759253242Ensembl.1
Natural variantiVAR_003603188L → P in GSS deficiency; 100-fold reduction of activity. 1
Natural variantiVAR_003604219D → A in GSS deficiency. 1
Natural variantiVAR_003605219D → G in GSS deficiency. 2 PublicationsCorresponds to variant dbSNP:rs28938472EnsemblClinVar.1
Natural variantiVAR_025047236R → Q1 PublicationCorresponds to variant dbSNP:rs34239729Ensembl.1
Natural variantiVAR_003606254L → R in GSS deficiency. 1
Natural variantiVAR_003607267R → W in GSS deficiency. 1 PublicationCorresponds to variant dbSNP:rs121909308EnsemblClinVar.1
Natural variantiVAR_003608270Y → C in GSS deficiency; 100-fold reduction of activity. 1
Natural variantiVAR_003609270Y → H in GSS deficiency; 100-fold reduction of activity. 1
Natural variantiVAR_003610283R → C in GSS deficiency; 10-fold reduction of activity. 1 PublicationCorresponds to variant dbSNP:rs121909309EnsemblClinVar.1
Natural variantiVAR_003611286L → Q in GSS deficiency. 1
Natural variantiVAR_078567301L → P in GSS deficiency. 1 Publication1
Natural variantiVAR_003612330R → C in GSS deficiency. Corresponds to variant dbSNP:rs148640446Ensembl.1
Natural variantiVAR_025048437K → E2 PublicationsCorresponds to variant dbSNP:rs34852238Ensembl.1
Natural variantiVAR_003613464G → V in GSS deficiency. 1
Natural variantiVAR_003614469D → E in GSS deficiency. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04761793 – 203Missing in isoform 2. 1 PublicationAdd BLAST111

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
CCDSiCCDS13245.1 [P48637-1]
PIRiS56748
RefSeqiNP_000169.1, NM_000178.3 [P48637-1]
NP_001309423.1, NM_001322494.1 [P48637-1]
NP_001309424.1, NM_001322495.1 [P48637-1]
UniGeneiHs.82327

Genome annotation databases

EnsembliENST00000216951; ENSP00000216951; ENSG00000100983 [P48637-1]
ENST00000451957; ENSP00000407517; ENSG00000100983 [P48637-2]
GeneIDi2937
KEGGihsa:2937
UCSCiuc010zuo.3 human [P48637-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGSHB_HUMAN
AccessioniPrimary (citable) accession number: P48637
Secondary accession number(s): B2R697
, B6F210, E1P5P9, Q4TTD9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 25, 2018
This is version 185 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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