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
- Functionsglutamine synthetase activity / metal ion binding / protein-cysteine S-palmitoyltransferase activityProcessesangiogenesis / cell population proliferation / protein palmitoylation / regulation of endothelial cell migration / regulation of protein localization to nucleolus / regulation of sprouting angiogenesis / ribosome biogenesisComponentscell 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
Resource Link UniProtKB ID P15104 UniProtKB Entry Name GLNA_HUMAN GenBank Protein ID 31833 GenBank Gene ID Y00387 GeneCard ID GLUL GenAtlas ID GLUL HGNC ID HGNC:4341 PDB ID(s) 2OJW, 2QC8, 7EVT, 8DNU KEGG ID hsa:2752 NCBI Gene ID 2752 - General References
- Gibbs CS, Campbell KE, Wilson RH: Sequence of a human glutamine synthetase cDNA. Nucleic Acids Res. 1987 Aug 11;15(15):6293. [Article]
- 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]
- 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]
- 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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- 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]
- 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]
- 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]
- 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]
- 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]
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- 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
Drug Drug group Pharmacological action? Type Actions Details L-Glutamine approved, investigational, nutraceutical unknown target product of Details Glutamic acid approved, nutraceutical unknown target Details Methionine approved, nutraceutical unknown enzyme inhibitor Details Capsaicin approved unknown enzyme inducer Details Ceftriaxone approved unknown enzyme inducer Details Pegvisomant approved unknown enzyme inhibitor Details Picrotoxin experimental unknown enzyme inhibitor Details Ethyl biscoumacetate withdrawn unknown enzyme inhibitor Details Ammonia approved unknown enzyme substrate Details Manganese cation approved, nutraceutical unknown target Details