Reactome | UniProt:P19440 GGT1

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UniProt:P19440 GGT1 Show undefined attributes

chain	chain:1-380 chain:381-569
checksum	71AE12485239A69F
comment	FUNCTION Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as leukotriene C4, LTC4) (PubMed:17924658, PubMed:21447318, PubMed:27791009). The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases (PubMed:27791009). In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound (PubMed:17924658, PubMed:7673200, PubMed:7759490, PubMed:8095045, PubMed:8827453, PubMed:21447318). Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4.FUNCTION Seems to be inactive.CATALYTIC ACTIVITY an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] = 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide]CATALYTIC ACTIVITY glutathione + H2O = L-cysteinylglycine + L-glutamateCATALYTIC ACTIVITY an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamateCATALYTIC ACTIVITY H2O + leukotriene C4 = L-glutamate + leukotriene D4CATALYTIC ACTIVITY (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + H2O = (13R)-S-cysteinylglycyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + L-glutamateACTIVITY REGULATION Activated by autocatalytic cleavage (PubMed:23682772). Inhibited by serine-borate (PubMed:21447318).BIOPHYSICOCHEMICAL PROPERTIES Lipid metabolism; leukotriene D4 biosynthesis.PATHWAY Sulfur metabolism; glutathione metabolism.SUBUNIT Heterodimer composed of the light and heavy chains. The active site is located in the light chain.INTERACTION Detected in fetal and adult kidney and liver, adult pancreas, stomach, intestine, placenta and lung. There are several other tissue-specific forms that arise from alternative promoter usage but that produce the same protein.TISSUE SPECIFICITY Lung-specific.PTM N-glycosylated on both chains. Contains hexoses, hexosamines and sialic acid residues. Glycosylation profiles tested in kidney and liver tissues reveal the presence of tissue-specific and site-specific glycan composition, despite the overlap in composition among the N-glycans. A total of 36 glycan compositions, with 40 unique structures are observed. Up to 15 different glycans are observed at a single site, with site-specific variation in glycan composition. The difference in glycosylation profiles in the 2 tissues do not affect the enzyme activity.PTM Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.DISEASE The disease is caused by variants affecting the gene represented in this entry. A large homozygous deletion that removes several exons of all isoforms of GGT1 has been found in one family affected by glutathionuria.MISCELLANEOUS Cys-454 was thought to bind the gamma-glutamyl moiety, but mutagenesis of this residue had no effect on activity.MISCELLANEOUS Chloride ions bound in the active site cavity may contribute to stabilize the protein fold.MISCELLANEOUS Produced by alternative promoter usage.MISCELLANEOUS Produced by alternative splicing of isoform 1.MISCELLANEOUS Produced by alternative promoter usage.SIMILARITY Belongs to the gamma-glutamyltransferase family.SEQUENCE CAUTION Extended N-terminus.ONLINE INFORMATION Gamma-glutamyl transpeptidase entry
crossReference	[DatabaseIdentifier:10971987] Pharos - Targets:P19440 [DatabaseIdentifier:11055161] OpenTargets:ENSG00000100031 [DatabaseIdentifier:11596658] RefSeq:NP_001275762.1 [DatabaseIdentifier:11596672] RefSeq:NP_038265.2 [DatabaseIdentifier:11596687] RefSeq:NP_038347.2 [DatabaseIdentifier:11719439] PDB:4GDX [DatabaseIdentifier:11719453] PDB:4GG2 [DatabaseIdentifier:11719464] PDB:4Z9O [DatabaseIdentifier:11719470] PDB:4ZBK [DatabaseIdentifier:11719483] PDB:4ZC6 [DatabaseIdentifier:11719494] PDB:4ZCG [DatabaseIdentifier:11719506] PDB:5V4Q [DatabaseIdentifier:11811723] PRO:P19440 [DatabaseIdentifier:11842919] GeneCards:P19440 [DatabaseIdentifier:11863814] ZINC target:P19440 [DatabaseIdentifier:11882830] Orphanet:26453 [DatabaseIdentifier:11889111] HMDB Protein:HMDBP00730 [DatabaseIdentifier:11894833] HPA:ENSG00000100031-GGT1 [DatabaseIdentifier:11978395] Ensembl:ENSP00000383232 [DatabaseIdentifier:11978396] Ensembl:ENSP00000385445 [DatabaseIdentifier:11978397] Ensembl:ENSP00000383231 [DatabaseIdentifier:11978398] Ensembl:ENSP00000387499 [DatabaseIdentifier:11978399] Ensembl:ENST00000400382 [DatabaseIdentifier:11978400] Ensembl:ENSP00000384381 [DatabaseIdentifier:11978401] Ensembl:ENST00000400380 [DatabaseIdentifier:11978402] Ensembl:ENST00000425895 [DatabaseIdentifier:11978403] Ensembl:ENST00000401885 [DatabaseIdentifier:11978404] Ensembl:ENST00000404532 [DatabaseIdentifier:11978405] Ensembl:ENSP00000384820 [DatabaseIdentifier:11978406] Ensembl:ENSG00000100031 [DatabaseIdentifier:11978407] Ensembl:ENST00000403838
databaseName	UniProt
dbId	55624
description	recommendedName: Glutathione hydrolase 1 proenzyme ecNumber evidence="4 10 16"3.4.19.13 alternativeName: Gamma-glutamyltransferase 1 alternativeName: Gamma-glutamyltranspeptidase 1 shortName: GGT 1 ecNumber evidence="4 10 11 21 23 24 25"2.3.2.2 alternativeName: Leukotriene-C4 hydrolase ecNumber evidence="10"3.4.19.14 cdAntigenNameCD224/cdAntigenName component recommendedName: Glutathione hydrolase 1 heavy chain /component component recommendedName: Glutathione hydrolase 1 light chain /component
displayName	UniProt:P19440 GGT1
geneName	GGT1 GGT
identifier	P19440
isSequenceChanged	false
keyword	3D-structure Acyltransferase Alternative promoter usage Alternative splicing Cell membrane Direct protein sequencing Disease variant Disulfide bond Glutathione biosynthesis Glycoprotein Hydrolase Intellectual disability Lipid metabolism Membrane Protease Reference proteome Sialic acid Signal-anchor Transferase Transmembrane Transmembrane helix Zymogen
modified	[InstanceEdit:12187927] Wright, Adam, 2024-03-12
name	GGT1
otherIdentifier	11741396_s_at 16928293 17122238 17122240 17122242 17123034 17123036 17123038 207131_3p_x_at 207131_PM_x_at 207131_x_at 208284_3p_x_at 208284_PM_x_at 208284_x_at 209919_3p_x_at 209919_PM_x_at 209919_x_at 211417_3p_x_at 211417_PM_x_at 211417_x_at 215603_PM_x_at 215603_x_at 2493558 2493560 2493561 2493565 2493567 2678 32893_s_at 3901449 3901453 3901460 3937463 3937464 3937483 3939018 3939019 3939020 3939920 3939921 3939924 3939925 3939926 3939927 3939929 3939930 3939931 3939932 3939933 3939934 3939935 3939936 3939937 3939938 3939939 3939941 3939942 3939943 3939944 3939945 3939946 3939949 3939950 3939951 3940233 3940235 3940237 3952072 3952076 3952079 3952082 3952085 3952090 3952091 3952093 3952094 3952095 3953225 3953257 3953259 3953972 3953979 3953980 3953983 3953985 3953988 3953989 3953990 3953991 3953992 3954823 3955210 3955213 4038554 4038557 4038589 4038591 4038599 4038603 4038611 4038615 4038621 4038629 4038631 41868_at 715_s_at 76993_f_at 8071927 8074316 A_21_P0012281 A_23_P154986 GO:0000048 GO:0002376 GO:0002682 GO:0002951 GO:0003824 GO:0005515 GO:0005576 GO:0005615 GO:0005886 GO:0006508 GO:0006520 GO:0006536 GO:0006575 GO:0006629 GO:0006631 GO:0006691 GO:0006749 GO:0006750 GO:0006751 GO:0006790 GO:0006954 GO:0007283 GO:0008233 GO:0016020 GO:0016740 GO:0016746 GO:0016787 GO:0019344 GO:0022414 GO:0031179 GO:0031638 GO:0036374 GO:0043226 GO:0050727 GO:0051604 GO:0070062 GO:0103068 GO:0140096 GO:1901750 HMNXSV003008629 HMNXSV003013451 HMNXSV003039302 Hs.314108.0.A1_3p_s_at ILMN_1652604 ILMN_1686531 ILMN_1787180 ILMN_1813658 ILMN_2368585 PH_hs_0028212 PH_hs_0032802 PH_hs_0033869 PH_hs_0040704 TC22001026.hg TC22001235.hg g306748_3p_s_at g306752_3p_s_at g306752_3p_x_at g306754_3p_s_at g306754_3p_x_at g9845490_3p_s_at g9845492_3p_s_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-5602938] GGT1(381-569) S452A [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5602862] GGT1(381-569) D423E [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5602863] GGT1(1-380) R107H [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1247924] GGT1(381-569) S451A [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5602961] GGT1(1-380) R107Q [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5602869] GGT1(381-569) D423A [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8943263] GGT1(381-569) [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1247889] GGT1(1-380) [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8991285] ENSEMBL:ENSG00000100031 GGT1 [ReferenceDNASequence:11029569] KEGG Gene (Homo sapiens):2678 GGT1 [ReferenceDNASequence:11262834] NCBI Gene:2678 GGT1 [ReferenceDNASequence:11262835] BioGPS Gene:2678 GGT1 [ReferenceDNASequence:11262836] CTD Gene:2678 GGT1 [ReferenceDNASequence:11262837] dbSNP Gene:2678 GGT1 [ReferenceDNASequence:11262838] Monarch:2678 GGT1 [ReferenceDNASequence:11350840] ENSEMBL_homo_sapiens_GENE:ENSG00000100031.19 GGT1 [ReferenceDNASequence:11513198] UCSC:P19440 GGT1 [ReferenceDNASequence:11799992] OMIM:612346 GGT1 [ReferenceDNASequence:11870277] HGNC:4250 GGT1 [ReferenceDNASequence:12195510] COSMIC (genes):GGT1 GGT1
referenceTranscript	[ReferenceRNASequence:11450901] RefSeq:NM_001288833.1 GGT1 [ReferenceRNASequence:11450918] RefSeq:NM_013421.2 GGT1 [ReferenceRNASequence:11450932] RefSeq:NM_013430.2 GGT1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	GGT1_HUMAN Q08247 Q14404 Q8TBS1 Q9UMK1
sequenceLength	569
species	[Species:48887] Homo sapiens
url	https://purl.uniprot.org/uniprot/P19440

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