GGT6_HUMAN
ID GGT6_HUMAN Reviewed; 493 AA.
AC Q6P531; B4DUH4; Q8NCM0;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Glutathione hydrolase 6 {ECO:0000303|PubMed:18357469};
DE EC=3.4.19.13 {ECO:0000250|UniProtKB:P19440};
DE AltName: Full=Gamma-glutamyltransferase 6;
DE Short=GGT 6;
DE EC=2.3.2.2 {ECO:0000250|UniProtKB:P19440};
DE AltName: Full=Gamma-glutamyltranspeptidase 6;
DE Contains:
DE RecName: Full=Glutathione hydrolase 6 heavy chain;
DE Contains:
DE RecName: Full=Glutathione hydrolase 6 light chain;
DE Flags: Precursor;
GN Name=GGT6 {ECO:0000312|HGNC:HGNC:26891};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP TRP-40 AND VAL-58.
RC TISSUE=Mammary gland, and Rectum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-58.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-58.
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NOMENCLATURE.
RX PubMed=18357469; DOI=10.1007/s00439-008-0487-7;
RA Heisterkamp N., Groffen J., Warburton D., Sneddon T.P.;
RT "The human gamma-glutamyltransferase gene family.";
RL Hum. Genet. 123:321-332(2008).
CC -!- FUNCTION: Hydrolyzes and transfers gamma-glutamyl moieties from
CC glutathione and other gamma-glutamyl compounds to acceptors.
CC {ECO:0000250|UniProtKB:P19440}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-amino acid + an N-terminal (5-L-glutamyl)-[peptide] =
CC 5-L-glutamyl amino acid + N-terminal L-alpha-aminoacyl-[peptide];
CC Xref=Rhea:RHEA:23904, Rhea:RHEA-COMP:9780, Rhea:RHEA-COMP:9795,
CC ChEBI:CHEBI:77644, ChEBI:CHEBI:78597, ChEBI:CHEBI:78599,
CC ChEBI:CHEBI:78608; EC=2.3.2.2;
CC Evidence={ECO:0000250|UniProtKB:P19440};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23905;
CC Evidence={ECO:0000250|UniProtKB:P19440};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + H2O = L-cysteinylglycine + L-glutamate;
CC Xref=Rhea:RHEA:28807, ChEBI:CHEBI:15377, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:61694; EC=3.4.19.13;
CC Evidence={ECO:0000250|UniProtKB:P19440};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28808;
CC Evidence={ECO:0000250|UniProtKB:P19440};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted glutathione + H2O = an S-substituted L-
CC cysteinylglycine + L-glutamate; Xref=Rhea:RHEA:59468,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:29985, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:143103; EC=3.4.19.13;
CC Evidence={ECO:0000250|UniProtKB:P19440};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59469;
CC Evidence={ECO:0000250|UniProtKB:P19440};
CC -!- PATHWAY: Sulfur metabolism; glutathione metabolism.
CC {ECO:0000250|UniProtKB:P19440}.
CC -!- SUBUNIT: Heterodimer composed of the light and heavy chains. The active
CC site is located in the light chain. {ECO:0000250|UniProtKB:P19440}.
CC -!- INTERACTION:
CC Q6P531; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-2868927, EBI-10225815;
CC Q6P531; O95393: BMP10; NbExp=3; IntAct=EBI-2868927, EBI-3922513;
CC Q6P531; O75355-2: ENTPD3; NbExp=3; IntAct=EBI-2868927, EBI-12279764;
CC Q6P531; Q9BWQ8: FAIM2; NbExp=3; IntAct=EBI-2868927, EBI-9056723;
CC Q6P531; Q92520: FAM3C; NbExp=3; IntAct=EBI-2868927, EBI-2876774;
CC Q6P531; Q7Z429: GRINA; NbExp=3; IntAct=EBI-2868927, EBI-2832909;
CC Q6P531; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-2868927, EBI-8652744;
CC Q6P531; Q969X1: TMBIM1; NbExp=3; IntAct=EBI-2868927, EBI-2820569;
CC Q6P531; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-2868927, EBI-12003398;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P19440}; Single-
CC pass type II membrane protein {ECO:0000250|UniProtKB:P07314}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6P531-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6P531-2; Sequence=VSP_030451;
CC -!- PTM: Cleaved by autocatalysis into a large and a small subunit and the
CC autocatalytic cleavage is essential to the functional activation of the
CC enzyme. {ECO:0000250|UniProtKB:P19440}.
CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AK074646; BAC11110.1; -; mRNA.
DR EMBL; AK300648; BAG62336.1; -; mRNA.
DR EMBL; CH471108; EAW90433.1; -; Genomic_DNA.
DR EMBL; BC063111; AAH63111.1; -; mRNA.
DR CCDS; CCDS11047.1; -. [Q6P531-2]
DR CCDS; CCDS45582.1; -. [Q6P531-1]
DR RefSeq; NP_001116362.1; NM_001122890.2. [Q6P531-1]
DR RefSeq; NP_001275631.1; NM_001288702.1.
DR RefSeq; NP_001275632.1; NM_001288703.1.
DR RefSeq; NP_001275633.1; NM_001288704.1.
DR RefSeq; NP_699169.2; NM_153338.3. [Q6P531-2]
DR AlphaFoldDB; Q6P531; -.
DR SMR; Q6P531; -.
DR BioGRID; 125906; 12.
DR IntAct; Q6P531; 10.
DR STRING; 9606.ENSP00000370962; -.
DR MEROPS; T03.024; -.
DR GlyGen; Q6P531; 2 sites.
DR iPTMnet; Q6P531; -.
DR PhosphoSitePlus; Q6P531; -.
DR BioMuta; GGT6; -.
DR DMDM; 166221586; -.
DR jPOST; Q6P531; -.
DR MassIVE; Q6P531; -.
DR PaxDb; Q6P531; -.
DR PeptideAtlas; Q6P531; -.
DR PRIDE; Q6P531; -.
DR ProteomicsDB; 66987; -. [Q6P531-1]
DR ProteomicsDB; 66988; -. [Q6P531-2]
DR Antibodypedia; 11242; 129 antibodies from 15 providers.
DR DNASU; 124975; -.
DR Ensembl; ENST00000301395.7; ENSP00000301395.3; ENSG00000167741.11. [Q6P531-2]
DR Ensembl; ENST00000574154.5; ENSP00000458307.1; ENSG00000167741.11. [Q6P531-1]
DR GeneID; 124975; -.
DR KEGG; hsa:124975; -.
DR UCSC; uc002fyc.6; human. [Q6P531-1]
DR CTD; 124975; -.
DR DisGeNET; 124975; -.
DR GeneCards; GGT6; -.
DR HGNC; HGNC:26891; GGT6.
DR HPA; ENSG00000167741; Tissue enhanced (esophagus, intestine, salivary gland, skin).
DR MIM; 612341; gene.
DR neXtProt; NX_Q6P531; -.
DR OpenTargets; ENSG00000167741; -.
DR PharmGKB; PA142671739; -.
DR VEuPathDB; HostDB:ENSG00000167741; -.
DR eggNOG; KOG2410; Eukaryota.
DR GeneTree; ENSGT00940000161883; -.
DR InParanoid; Q6P531; -.
DR OrthoDB; 1209764at2759; -.
DR PhylomeDB; Q6P531; -.
DR TreeFam; TF338758; -.
DR PathwayCommons; Q6P531; -.
DR Reactome; R-HSA-174403; Glutathione synthesis and recycling.
DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SignaLink; Q6P531; -.
DR UniPathway; UPA00204; -.
DR BioGRID-ORCS; 124975; 16 hits in 1070 CRISPR screens.
DR GenomeRNAi; 124975; -.
DR Pharos; Q6P531; Tbio.
DR PRO; PR:Q6P531; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q6P531; protein.
DR Bgee; ENSG00000167741; Expressed in pancreatic ductal cell and 109 other tissues.
DR ExpressionAtlas; Q6P531; baseline and differential.
DR Genevisible; Q6P531; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0036374; F:glutathione hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0102953; F:hypoglycin A gamma-glutamyl transpeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0103068; F:leukotriene C4 gamma-glutamyl transferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006750; P:glutathione biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:1901750; P:leukotriene D4 biosynthetic process; ISS:UniProtKB.
DR Gene3D; 3.60.20.40; -; 1.
DR InterPro; IPR043137; GGT_ssub.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR SUPFAM; SSF56235; SSF56235; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative splicing; Glutathione biosynthesis;
KW Glycoprotein; Hydrolase; Membrane; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix; Zymogen.
FT CHAIN 1..?
FT /note="Glutathione hydrolase 6 heavy chain"
FT /id="PRO_0000314954"
FT CHAIN ?..493
FT /note="Glutathione hydrolase 6 light chain"
FT /id="PRO_0000314955"
FT TOPO_DOM 1..54
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P07314"
FT TRANSMEM 55..75
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 76..493
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P07314"
FT REGION 19..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 83..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 442..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 116..147
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_030451"
FT VARIANT 40
FT /note="R -> W (in dbSNP:rs7216284)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_038138"
FT VARIANT 58
FT /note="A -> V (in dbSNP:rs11657054)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_038139"
SQ SEQUENCE 493 AA; 50509 MW; BBC8ECC544C0D1A2 CRC64;
MERAEEPVVY QKLLPWEPSL ESEEEVEEEE TSEALVLNPR RHQDSSRNKA GGLPGTWARV
VAALLLLAVG CSLAVRQLQN QGRSTGSLGS VAPPPGGHSH GPGVYHHGAI ISPAGRELLV
AGGNVVDAGV GAALCLAVVH PHATGLGAMF WGLFHDSSSG NSTALTSGPA QTLAPGLGLP
AALPTLHLLH ARFGRLPWPR LLVGPTTLAQ EGFLVDTPLA RALVARGTEG LCPLLCHADG
TPLGAGARAT NPQLAAVLRS AALAPTSDLA GDALLSLLAG DLGVEVPSAV PRPTLEPAEQ
LPVPQGILFT TPSPSAGPEL LALLEAALRS GAPIPDPCPP FLQTAVSPES SALAAVDSSG
SVLLLTSSLN CSFGSAHLSP STGVLLSNLV AKSTTSAWAC PLILRGSLDD TEADVLGLVA
SGTPDVARAM THTLLRHLAA RPPTQAQHQH QGQQEPTEHP STCGQGTLLQ VAAHTEHAHV
SSVPHACCPF QGF
