GLUL (glutamate-ammonia ligase)

Gene

• Entrez ID: 2752
• Gene name: Glutamate-ammonia ligase
• Gene symbol: GLUL
• Synonyms: GLNS, GS, PIG43, PIG59
• Chromosome: 1
• Chromosome location: 1q25.3
• Summary: The protein encoded by this gene belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. This protein plays a role in ammonia and glutamate detoxification, acid-base homeostasis, cell signaling, and cell proliferation. Glutamine is an abundant amino acid, and is important to the biosynthesis of several amino acids, pyrimidines, and purines. Mutations in this gene are associated with congenital glutamine deficiency, and overexpression of this gene was observed in some primary liver cancer samples. There are six pseudogenes of this gene found on chromosomes 2, 5, 9, 11, and 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs80358214	G>A,T	Pathogenic	Missense variant, coding sequence variant
rs80358215	G>A	Pathogenic	Missense variant, coding sequence variant
rs1131691970	T>A	Likely-pathogenic	Initiator codon variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004021	hsa-miR-29a-3p	Immunoblot, Luciferase reporter assay, Microarray, qRT-PCR	19951903
MIRT021141	hsa-miR-186-5p	Sequencing	20371350
MIRT025018	hsa-miR-183-5p	Sequencing	20371350
MIRT030540	hsa-miR-24-3p	Sequencing	20371350
MIRT036244	hsa-miR-320b	CLASH	23622248
MIRT036638	hsa-miR-937-3p	CLASH	23622248
MIRT036966	hsa-miR-877-3p	CLASH	23622248
MIRT037273	hsa-miR-877-5p	CLASH	23622248
MIRT038153	hsa-miR-423-5p	CLASH	23622248
MIRT038394	hsa-miR-296-3p	CLASH	23622248
MIRT038640	hsa-miR-125a-3p	CLASH	23622248
MIRT040016	hsa-miR-615-3p	CLASH	23622248
MIRT041957	hsa-miR-484	CLASH	23622248
MIRT044856	hsa-miR-320a	CLASH	23622248
MIRT045330	hsa-miR-185-5p	CLASH	23622248
MIRT045626	hsa-miR-149-5p	CLASH	23622248
MIRT048155	hsa-miR-196a-5p	CLASH	23622248
MIRT051362	hsa-let-7f-5p	CLASH	23622248
MIRT051664	hsa-let-7e-5p	CLASH	23622248
MIRT052399	hsa-let-7a-5p	CLASH	23622248
MIRT523509	hsa-miR-6728-5p	PAR-CLIP	23446348
MIRT523510	hsa-miR-6788-5p	PAR-CLIP	23446348
MIRT523510	hsa-miR-6788-5p	HITS-CLIP	23313552
MIRT523511	hsa-miR-30c-2-3p	PAR-CLIP	23446348
MIRT523511	hsa-miR-30c-2-3p	HITS-CLIP	23313552
MIRT523512	hsa-miR-30c-1-3p	PAR-CLIP	23446348
MIRT523512	hsa-miR-30c-1-3p	HITS-CLIP	23313552
MIRT523513	hsa-miR-4309	PAR-CLIP	23446348
MIRT523514	hsa-miR-3198	PAR-CLIP	23446348
MIRT523515	hsa-miR-4769-5p	PAR-CLIP	23446348
MIRT523516	hsa-miR-4654	PAR-CLIP	23446348
MIRT523517	hsa-miR-625-5p	PAR-CLIP	23446348
MIRT523518	hsa-miR-6780b-5p	PAR-CLIP	23446348
MIRT523519	hsa-miR-4725-3p	PAR-CLIP	23446348
MIRT523520	hsa-miR-4271	PAR-CLIP	23446348
MIRT523521	hsa-miR-5187-5p	PAR-CLIP	23446348
MIRT523522	hsa-miR-8085	PAR-CLIP	23446348
MIRT523522	hsa-miR-8085	HITS-CLIP	23313552
MIRT523523	hsa-miR-6731-5p	PAR-CLIP	23446348
MIRT523523	hsa-miR-6731-5p	HITS-CLIP	23313552
MIRT523524	hsa-miR-6878-5p	PAR-CLIP	23446348
MIRT523524	hsa-miR-6878-5p	HITS-CLIP	23313552
MIRT523525	hsa-miR-122-5p	PAR-CLIP	23446348
MIRT523526	hsa-miR-504-3p	PAR-CLIP	23446348
MIRT523527	hsa-miR-571	PAR-CLIP	23446348
MIRT523528	hsa-miR-4745-5p	PAR-CLIP	23446348
MIRT523529	hsa-miR-4481	PAR-CLIP	23446348
MIRT523530	hsa-miR-549a	PAR-CLIP	23446348
MIRT523531	hsa-miR-3185	PAR-CLIP	23446348
MIRT523532	hsa-miR-3192-5p	PAR-CLIP	23446348
MIRT523532	hsa-miR-3192-5p	HITS-CLIP	23313552
MIRT523533	hsa-miR-6794-5p	PAR-CLIP	23446348
MIRT523534	hsa-miR-4716-3p	PAR-CLIP	23446348
MIRT523535	hsa-miR-4511	PAR-CLIP	23446348
MIRT663719	hsa-miR-5047	HITS-CLIP	23824327
MIRT663720	hsa-miR-1301-3p	HITS-CLIP	23824327
MIRT663721	hsa-miR-653-3p	HITS-CLIP	23824327
MIRT663722	hsa-miR-4420	HITS-CLIP	23824327
MIRT663723	hsa-miR-181b-3p	HITS-CLIP	23824327
MIRT663724	hsa-miR-181b-2-3p	HITS-CLIP	23824327
MIRT663725	hsa-miR-4660	HITS-CLIP	23824327
MIRT663726	hsa-miR-1184	HITS-CLIP	23824327
MIRT663727	hsa-miR-6890-3p	HITS-CLIP	23824327
MIRT663728	hsa-miR-509-5p	HITS-CLIP	23824327
MIRT663729	hsa-miR-509-3-5p	HITS-CLIP	23824327
MIRT663730	hsa-miR-4418	HITS-CLIP	23824327
MIRT688044	hsa-miR-548s	HITS-CLIP	23313552
MIRT688045	hsa-miR-3926	HITS-CLIP	23313552
MIRT688046	hsa-miR-4683	HITS-CLIP	23313552
MIRT688047	hsa-miR-4772-5p	HITS-CLIP	23313552
MIRT688048	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT688049	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT688050	hsa-miR-4433a-3p	HITS-CLIP	23313552
MIRT688051	hsa-miR-4459	HITS-CLIP	23313552
MIRT688052	hsa-miR-4768-3p	HITS-CLIP	23313552
MIRT688053	hsa-miR-383-5p	HITS-CLIP	23313552
MIRT688054	hsa-miR-6771-3p	HITS-CLIP	23313552
MIRT688055	hsa-miR-665	HITS-CLIP	23313552
MIRT688056	hsa-miR-6516-5p	HITS-CLIP	23313552
MIRT688057	hsa-miR-6780a-5p	HITS-CLIP	23313552
MIRT688058	hsa-miR-6779-5p	HITS-CLIP	23313552
MIRT688059	hsa-miR-3689c	HITS-CLIP	23313552
MIRT688060	hsa-miR-3689b-3p	HITS-CLIP	23313552
MIRT688061	hsa-miR-3689a-3p	HITS-CLIP	23313552
MIRT688062	hsa-miR-30b-3p	HITS-CLIP	23313552
MIRT688063	hsa-miR-1273h-5p	HITS-CLIP	23313552
MIRT688064	hsa-miR-455-3p	HITS-CLIP	23313552
MIRT688065	hsa-miR-4314	HITS-CLIP	23313552
MIRT688066	hsa-miR-6799-5p	HITS-CLIP	23313552
MIRT688067	hsa-miR-6883-5p	HITS-CLIP	23313552
MIRT688068	hsa-miR-6785-5p	HITS-CLIP	23313552
MIRT688069	hsa-miR-4728-5p	HITS-CLIP	23313552
MIRT688070	hsa-miR-149-3p	HITS-CLIP	23313552
MIRT688071	hsa-miR-7106-5p	HITS-CLIP	23313552
MIRT688072	hsa-miR-650	HITS-CLIP	23313552
MIRT688073	hsa-miR-3612	HITS-CLIP	23313552
MIRT688074	hsa-miR-7160-5p	HITS-CLIP	23313552
MIRT688075	hsa-miR-4722-5p	HITS-CLIP	23313552
MIRT688076	hsa-miR-298	HITS-CLIP	23313552
MIRT688077	hsa-miR-6884-5p	HITS-CLIP	23313552
MIRT688078	hsa-miR-485-5p	HITS-CLIP	23313552
MIRT688079	hsa-miR-1827	HITS-CLIP	23313552
MIRT688080	hsa-miR-4646-5p	HITS-CLIP	23313552
MIRT688081	hsa-miR-204-3p	HITS-CLIP	23313552
MIRT688082	hsa-miR-4649-3p	HITS-CLIP	23313552
MIRT688083	hsa-miR-1298-3p	HITS-CLIP	23313552
MIRT688084	hsa-miR-4478	HITS-CLIP	23313552
MIRT688085	hsa-miR-4419b	HITS-CLIP	23313552
MIRT688086	hsa-miR-3929	HITS-CLIP	23313552
MIRT688087	hsa-miR-940	HITS-CLIP	23313552
MIRT688088	hsa-miR-6893-5p	HITS-CLIP	23313552
MIRT688089	hsa-miR-6808-5p	HITS-CLIP	23313552
MIRT688090	hsa-miR-6511a-5p	HITS-CLIP	23313552
MIRT688091	hsa-miR-1910-3p	HITS-CLIP	23313552
MIRT688092	hsa-miR-495-5p	HITS-CLIP	23313552
MIRT710637	hsa-miR-129-5p	HITS-CLIP	19536157
MIRT710638	hsa-miR-8055	HITS-CLIP	19536157
MIRT710639	hsa-miR-4446-5p	HITS-CLIP	19536157
MIRT710640	hsa-miR-5006-3p	HITS-CLIP	19536157
MIRT710641	hsa-miR-4755-5p	HITS-CLIP	19536157
MIRT710642	hsa-miR-744-3p	HITS-CLIP	19536157
MIRT710643	hsa-miR-642a-5p	HITS-CLIP	19536157
MIRT710644	hsa-miR-4653-3p	HITS-CLIP	19536157
MIRT710645	hsa-miR-8082	HITS-CLIP	19536157
MIRT710646	hsa-miR-4534	HITS-CLIP	19536157
MIRT710647	hsa-miR-1273f	HITS-CLIP	19536157
MIRT710648	hsa-miR-4708-5p	HITS-CLIP	19536157
MIRT710649	hsa-miR-6088	HITS-CLIP	19536157
MIRT710650	hsa-miR-4770	HITS-CLIP	19536157
MIRT710651	hsa-miR-143-3p	HITS-CLIP	19536157
MIRT710652	hsa-miR-2276-5p	HITS-CLIP	19536157
MIRT710653	hsa-miR-6892-3p	HITS-CLIP	19536157
MIRT710654	hsa-miR-6514-5p	HITS-CLIP	19536157

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001504	Process	Neurotransmitter uptake	TAS
GO:0001525	Process	Angiogenesis	IEA
GO:0004356	Function	Glutamate-ammonia ligase activity	IBA	21873635
GO:0004356	Function	Glutamate-ammonia ligase activity	IDA	30158707
GO:0005515	Function	Protein binding	IPI	21994455, 25910212, 30158707
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005739	Component	Mitochondrion	IDA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005829	Component	Cytosol	IDA	30158707
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	30158707
GO:0006538	Process	Glutamate catabolic process	TAS	21757002
GO:0006542	Process	Glutamine biosynthetic process	IBA	21873635
GO:0006542	Process	Glutamine biosynthetic process	TAS	21757002
GO:0008283	Process	Cell population proliferation	IDA	18662667
GO:0008652	Process	Cellular amino acid biosynthetic process	TAS
GO:0010594	Process	Regulation of endothelial cell migration	IDA	30158707
GO:0018215	Process	Protein phosphopantetheinylation	IEA
GO:0018345	Process	Protein palmitoylation	IDA	30158707
GO:0019706	Function	Protein-cysteine S-palmitoyltransferase activity	IDA	30158707
GO:0042254	Process	Ribosome biogenesis	IMP	26711351
GO:0042802	Function	Identical protein binding	IPI	16189514, 19447967, 21988832, 25416956, 25502805, 31515488
GO:0046872	Function	Metal ion binding	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:1903670	Process	Regulation of sprouting angiogenesis	IDA	30158707
GO:1904749	Process	Regulation of protein localization to nucleolus	IMP	26711351

Other IDs

• MIM: 138290
• HGNC: 4341
• e!Ensembl: ENSG00000135821

Protein

• UniProt ID: P15104
• Protein name: Glutamine synthetase (GS) (EC 6.3.1.2) (Glutamate--ammonia ligase) (Palmitoyltransferase GLUL) (EC 2.3.1.225)
• Protein function: Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:30158707, PubMed:16267323). 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).
• PDB: 2OJW, 2QC8
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03951	Gln-synt_N	24 → 104	Glutamine synthetase, beta-Grasp domain	Domain
  PF00120	Gln-synt_C	110 → 361	Glutamine synthetase, catalytic domain	Domain

• Sequence:

  MTTSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKCVEELPEW
  NFDGSSTLQSEGSNSDMYLVPAAMFRDPFRKDPNKLVLCEVFKYNRRPAETNLRHTCKRI
  MDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADRAYGRDIVEAHY
  RACLYAGVKIAGTNAEVMPAQWEFQIGPCEGISMGDHLWVARFILHRVCEDFGVIATFDP
  KPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIEKLSKRHQYHIRAYDPKGGLDNARRL
  TGFHETSNINDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCL
  LNETGDEPFQYKN

• Sequence length: 373