Glutamine synthetase

Details

Name
Glutamine synthetase
Kind
protein
Synonyms
  • 6.3.1.2
  • GLNS
  • Glutamate--ammonia ligase
  • GS
  • Palmitoyltransferase GLUL
Gene Name
GLUL
UniProtKB Entry
P15104Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0019251|Glutamine synthetase
MTTSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKCVEELPEW
NFDGSSTLQSEGSNSDMYLVPAAMFRDPFRKDPNKLVLCEVFKYNRRPAETNLRHTCKRI
MDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADRAYGRDIVEAHY
RACLYAGVKIAGTNAEVMPAQWEFQIGPCEGISMGDHLWVARFILHRVCEDFGVIATFDP
KPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIEKLSKRHQYHIRAYDPKGGLDNARRL
TGFHETSNINDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCL
LNETGDEPFQYKN
Number of residues
373
Molecular Weight
42064.15
Theoretical pI
6.88
GO Classification
Functions
glutamine synthetase activity / metal ion binding / protein-cysteine S-palmitoyltransferase activity
Processes
angiogenesis / cell population proliferation / protein palmitoylation / regulation of endothelial cell migration / regulation of protein localization to nucleolus / regulation of sprouting angiogenesis / ribosome biogenesis
Components
cell body / endoplasmic reticulum / plasma membrane
General Function
Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:16267323, PubMed:30158707, PubMed:36289327). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). Through the interaction with BEST2, inhibits BEST2 channel activity by affecting the gating at the aperture in the absence of intracellular L-glutamate, but sensitizes BEST2 to intracellular L-glutamate, which promotes the opening of BEST2 and thus relieves its inhibitory effect on BEST2 (PubMed:36289327)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytosol
Gene sequence
>lcl|BSEQ0019252|Glutamine synthetase (GLUL)
ATGACCACCTCAGCAAGTTCCCACTTAAATAAAGGCATCAAGCAGGTGTACATGTCCCTG
CCTCAGGGTGAGAAAGTCCAGGCCATGTATATCTGGATCGATGGTACTGGAGAAGGACTG
CGCTGCAAGACCCGGACCCTGGACAGTGAGCCCAAGTGTGTGGAAGAGTTGCCTGAGTGG
AATTTCGATGGCTCTAGTACTTTACAGTCTGAGGGTTCCAACAGTGACATGTATCTCGTG
CCTGCTGCCATGTTTCGGGACCCCTTCCGTAAGGACCCTAACAAGCTGGTGTTATGTGAA
GTTTTCAAGTACAATCGAAGGCCTGCAGAGACCAATTTGAGGCACACCTGTAAACGGATA
ATGGACATGGTGAGCAACCAGCACCCCTGGTTTGGCATGGAGCAGGAGTATACCCTCATG
GGGACAGATGGGCACCCCTTTGGTTGGCCTTCCAACGGCTTCCCAGGGCCCCAGGGTCCA
TATTACTGTGGTGTGGGAGCAGACAGAGCCTATGGCAGGGACATCGTGGAGGCCCATTAC
CGGGCCTGCTTGTATGCTGGAGTCAAGATTGCGGGGACTAATGCCGAGGTCATGCCTGCC
CAGTGGGAATTTCAGATTGGACCTTGTGAAGGAATCAGCATGGGAGATCATCTCTGGGTG
GCCCGTTTCATCTTGCATCGTGTGTGTGAAGACTTTGGAGTGATAGCAACCTTTGATCCT
AAGCCCATTCCTGGGAACTGGAATGGTGCAGGCTGCCATACCAACTTCAGCACCAAGGCC
ATGCGGGAGGAGAATGGTCTGAAGTACATCGAGGAGGCCATTGAGAAACTAAGCAAGCGG
CACCAGTACCACATCCGTGCCTATGATCCCAAGGGAGGCCTGGACAATGCCCGACGTCTA
ACTGGATTCCATGAAACCTCCAACATCAACGACTTTTCTGCTGGTGTAGCCAATCGTAGC
GCCAGCATACGCATTCCCCGGACTGTTGGCCAGGAGAAGAAGGGTTACTTTGAAGATCGT
CGCCCCTCTGCCAACTGCGACCCCTTTTCGGTGACAGAAGCCCTCATCCGCACGTGTCTT
CTCAATGAAACCGGCGATGAGCCCTTCCAGTACAAAAATTAA
Chromosome Location
1
Locus
1q25.3
External Identifiers
ResourceLink
UniProtKB IDP15104
UniProtKB Entry NameGLNA_HUMAN
GenBank Protein ID31833
GenBank Gene IDY00387
GeneCard IDGLUL
GenAtlas IDGLUL
HGNC IDHGNC:4341
PDB ID(s)2OJW, 2QC8, 7EVT, 8DNU
KEGG IDhsa:2752
NCBI Gene ID2752
General References
  1. Gibbs CS, Campbell KE, Wilson RH: Sequence of a human glutamine synthetase cDNA. Nucleic Acids Res. 1987 Aug 11;15(15):6293. [Article]
  2. Van den Hoff MJ, Geerts WJ, Das AT, Moorman AF, Lamers WH: cDNA sequence of the long mRNA for human glutamine synthase. Biochim Biophys Acta. 1991 Oct 8;1090(2):249-51. [Article]
  3. Christa L, Simon MT, Flinois JP, Gebhardt R, Brechot C, Lasserre C: Overexpression of glutamine synthetase in human primary liver cancer. Gastroenterology. 1994 May;106(5):1312-20. [Article]
  4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
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  7. Boksha IS, Schonfeld HJ, Langen H, Muller F, Tereshkina EB, Burbaeva GSh: Glutamine synthetase isolated from human brain: octameric structure and homology of partial primary structure with human liver glutamine synthetase. Biochemistry (Mosc). 2002 Sep;67(9):1012-20. [Article]
  8. Vermeulen T, Gorg B, Vogl T, Wolf M, Varga G, Toutain A, Paul R, Schliess F, Haussinger D, Haberle J: Glutamine synthetase is essential for proliferation of fetal skin fibroblasts. Arch Biochem Biophys. 2008 Oct 1;478(1):96-102. doi: 10.1016/j.abb.2008.07.009. Epub 2008 Jul 17. [Article]
  9. Olkku A, Mahonen A: Wnt and steroid pathways control glutamate signalling by regulating glutamine synthetase activity in osteoblastic cells. Bone. 2008 Sep;43(3):483-93. doi: 10.1016/j.bone.2008.04.016. Epub 2008 May 7. [Article]
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  11. 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]
  12. 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]
  13. Haberle J, Gorg B, Rutsch F, Schmidt E, Toutain A, Benoist JF, Gelot A, Suc AL, Hohne W, Schliess F, Haussinger D, Koch HG: Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005 Nov 3;353(18):1926-33. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
L-Glutamineapproved, investigational, nutraceuticalunknowntargetproduct ofDetails
Glutamic acidapproved, nutraceuticalunknowntargetDetails
Methionineapproved, nutraceuticalunknownenzymeinhibitorDetails
CapsaicinapprovedunknownenzymeinducerDetails
CeftriaxoneapprovedunknownenzymeinducerDetails
PegvisomantapprovedunknownenzymeinhibitorDetails
PicrotoxinexperimentalunknownenzymeinhibitorDetails
Ethyl biscoumacetatewithdrawnunknownenzymeinhibitorDetails
AmmoniaapprovedunknownenzymesubstrateDetails
Manganese cationapproved, nutraceuticalunknowntargetDetails