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547  structures 2982  species 13  interactions 12627  sequences 129  architectures

Clan: GCS (CL0286)


gamma-glutamylcysteine synthetase/glutamine synthetase clan Add an annotation

This clan represents a superfamily of carboxylate-amine/ammonia ligases [1] that includes Gamma-Glutamylcysteine synthetase (gamma-GCS) and glutamine synthetase (GS). Gamma-Glutamylcysteine synthetase (gamma-GCS) catalyses the first step in the de novo biosynthesis of glutathione.

This clan contains 8 families and the total number of domains in the clan is 12627. The clan was built by A Bateman and J Pei.

Literature references

  1. Abbott JJ, Pei J, Ford JL, Qi Y, Grishin VN, Pitcher LA, Phillips MA, Grishin NV; , J Biol Chem. 2001;276:42099-42107.: Structure prediction and active site analysis of the metal binding determinants in gamma -glutamylcysteine synthetase. PUBMED:11527962 EPMC:11527962


This clan contains the following 8 member families:

Amidoligase_2 ATP-gua_Ptrans DUF2126 GCS GCS2 Gln-synt_C Glu_cys_ligase Pup_ligase

External database links

Domain organisation

Below is a listing of the unique domain organisations or architectures from this clan. More...

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The table below shows the number of occurrences of each domain throughout the sequence database. More...

Pfam family Num. domains Alignment
Gln-synt_C (PF00120) 6903 (54.7%) View
GCS2 (PF04107) 1669 (13.2%) View
ATP-gua_Ptrans (PF00217) 1182 (9.4%) View
Amidoligase_2 (PF12224) 664 (5.3%) View
GCS (PF03074) 657 (5.2%) View
Glu_cys_ligase (PF04262) 614 (4.9%) View
Pup_ligase (PF03136) 610 (4.8%) View
DUF2126 (PF09899) 328 (2.6%) View
Total: 8 Total: 12627 Clan alignment

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Family relationships

This diagram shows the relationships between members of this clan. More...

Species distribution

Tree controls


This tree shows the occurrence of the domains in this clan across different species. More...



There are 13 interactions for this clan. More...

Interacting families
ATP-grasp_4 Glu_cys_ligase
ATP-gua_Ptrans ATP-gua_Ptrans
ATP-gua_PtransN ATP-gua_Ptrans
Gln-synt_C Gln-synt_C
Gln-synt_N Gln-synt_C
Glu_cys_ligase ATP-grasp_4
GSIII_N Gln-synt_C
Pup_ligase Pup


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt three-dimensional structures. The table below shows the mapping between the Pfam families in this clan, the corresponding UniProt entries, and the region of the three-dimensional structures that are available for that sequence.

Loading structure mapping...