ID GGT2_HUMAN Reviewed; 569 AA.
AC P36268;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 3.
DT 24-JAN-2024, entry version 175.
DE RecName: Full=Inactive glutathione hydrolase 2;
DE AltName: Full=Gamma-glutamyltransferase 2 pseudogene {ECO:0000312|HGNC:HGNC:4251};
DE AltName: Full=Inactive gamma-glutamyltranspeptidase 2;
DE Short=GGT 2;
DE Flags: Precursor;
GN Name=GGT2P {ECO:0000312|HGNC:HGNC:4251}; Synonyms=GGT2;
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 GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 362-569 (ISOFORM 2).
RX PubMed=2573352; DOI=10.1016/0006-291x(89)91545-3;
RA Pawlak A., Wu S.-J., Bulle F., Suzuki A., Chikhi N., Ferry N., Baik J.-H.,
RA Siegrist S., Guellaen G.;
RT "Different gamma-glutamyl transpeptidase mRNAs are expressed in human liver
RT and kidney.";
RL Biochem. Biophys. Res. Commun. 164:912-918(1989).
RN [3]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-511.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [4]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3), ABSENCE OF CATALYTIC ACTIVITY
RP AND AUTOCATALYTIC CLEAVAGE, SUBCELLULAR LOCATION, GLYCOSYLATION, AND
RP MUTAGENESIS OF TRP-192 AND TYR-193.
RX PubMed=23682772; DOI=10.1089/ars.2012.4997;
RA West M.B., Wickham S., Parks E.E., Sherry D.M., Hanigan M.H.;
RT "Human GGT2 does not autocleave into a functional enzyme: a cautionary tale
RT for interpretation of microarray data on redox signaling.";
RL Antioxid. Redox Signal. 19:1877-1888(2013).
CC -!- FUNCTION: [Isoform 1]: Lacks catalytic activity due to its inability to
CC undergo the autocatalytic cleavage needed to produce a mature,
CC enzymatically active heterodimer. {ECO:0000269|PubMed:23682772}.
CC -!- FUNCTION: [Isoform 2]: Lacks catalytic activity due to its inability to
CC undergo the autocatalytic cleavage needed to produce a mature,
CC enzymatically active heterodimer. {ECO:0000269|PubMed:23682772}.
CC -!- FUNCTION: [Isoform 3]: Lacks catalytic activity due to its inability to
CC undergo the autocatalytic cleavage needed to produce a mature,
CC enzymatically active heterodimer. {ECO:0000269|PubMed:23682772}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:23682772}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:23682772}. Note=Co-localizes with calnexin in the
CC endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P36268-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P36268-2; Sequence=VSP_033757;
CC Name=3;
CC IsoId=P36268-3; Sequence=VSP_053716;
CC -!- TISSUE SPECIFICITY: Highly expressed in fetal and adult kidney and
CC liver.
CC -!- PTM: Not cleaved by autocatalysis into a large and a small subunit
CC resulting in loss of cell membrane localization and catalytic activity.
CC {ECO:0000269|PubMed:23682772}.
CC -!- SIMILARITY: Belongs to the gamma-glutamyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AP000550; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BG743316; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AA632626; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M30479; AAA52765.1; -; Genomic_DNA.
DR EMBL; M30475; AAA52765.1; JOINED; Genomic_DNA.
DR EMBL; M30476; AAA52765.1; JOINED; Genomic_DNA.
DR EMBL; M30477; AAA52765.1; JOINED; Genomic_DNA.
DR EMBL; M30478; AAA52765.1; JOINED; Genomic_DNA.
DR EMBL; M30474; AAA52548.1; -; mRNA.
DR PIR; A36742; A36742.
DR AlphaFoldDB; P36268; -.
DR SMR; P36268; -.
DR STRING; 9606.ENSP00000385721; -.
DR MEROPS; T03.015; -.
DR GlyConnect; 1396; 4 N-Linked glycans (2 sites).
DR GlyCosmos; P36268; 4 sites, 5 glycans.
DR GlyGen; P36268; 4 sites, 5 N-linked glycans (3 sites).
DR iPTMnet; P36268; -.
DR PhosphoSitePlus; P36268; -.
DR BioMuta; GGT2; -.
DR DMDM; 189047137; -.
DR jPOST; P36268; -.
DR MassIVE; P36268; -.
DR MaxQB; P36268; -.
DR PaxDb; 9606-ENSP00000385721; -.
DR PeptideAtlas; P36268; -.
DR Pumba; P36268; -.
DR Antibodypedia; 23460; 85 antibodies from 14 providers.
DR UCSC; uc062byb.1; human. [P36268-1]
DR AGR; HGNC:4251; -.
DR GeneCards; GGT2P; -.
DR HGNC; HGNC:4251; GGT2P.
DR MIM; 137181; gene.
DR neXtProt; NX_P36268; -.
DR VEuPathDB; HostDB:ENSG00000133475; -.
DR eggNOG; KOG2410; Eukaryota.
DR HOGENOM; CLU_014813_4_1_1; -.
DR InParanoid; P36268; -.
DR PhylomeDB; P36268; -.
DR TreeFam; TF313608; -.
DR PathwayCommons; P36268; -.
DR SignaLink; P36268; -.
DR ChiTaRS; GGT2; human.
DR Pharos; P36268; Tbio.
DR PRO; PR:P36268; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P36268; Protein.
DR Bgee; ENSG00000133475; Expressed in primordial germ cell in gonad and 53 other cell types or tissues.
DR ExpressionAtlas; P36268; baseline and differential.
DR Genevisible; P36268; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0006751; P:glutathione catabolic process; IBA:GO_Central.
DR GO; GO:1901750; P:leukotriene D4 biosynthetic process; ISS:UniProtKB.
DR GO; GO:0031179; P:peptide modification; IBA:GO_Central.
DR GO; GO:0002682; P:regulation of immune system process; IBA:GO_Central.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR Gene3D; 1.10.246.130; -; 1.
DR Gene3D; 3.60.20.40; -; 1.
DR InterPro; IPR043138; GGT_lsub_C.
DR InterPro; IPR000101; GGT_peptidase.
DR InterPro; IPR043137; GGT_ssub.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR PANTHER; PTHR11686; GAMMA GLUTAMYL TRANSPEPTIDASE; 1.
DR PANTHER; PTHR11686:SF56; GLUTATHIONE HYDROLASE 1 PROENZYME-RELATED; 1.
DR Pfam; PF01019; G_glu_transpept; 1.
DR PRINTS; PR01210; GGTRANSPTASE.
DR SUPFAM; SSF56235; N-terminal nucleophile aminohydrolases (Ntn hydrolases); 1.
DR PROSITE; PS00462; G_GLU_TRANSPEPTIDASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Endoplasmic reticulum; Glycoprotein;
KW Reference proteome; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..569
FT /note="Inactive glutathione hydrolase 2"
FT /id="PRO_0000425541"
FT ACT_SITE 381
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 107
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 399
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT BINDING 451..452
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 511
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 192..193
FT /note="WY -> CPLCPGE (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053716"
FT VAR_SEQ 404..413
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2573352"
FT /id="VSP_033757"
FT MUTAGEN 192
FT /note="W->C: No effect on the absence of autocatalytic
FT cleavage and catalytic activity; when associated with E-
FT 193."
FT /evidence="ECO:0000269|PubMed:23682772"
FT MUTAGEN 193
FT /note="Y->E: No effect on the absence of autocatalytic
FT cleavage and catalytic activity; when associated with C-
FT 192."
FT /evidence="ECO:0000269|PubMed:23682772"
SQ SEQUENCE 569 AA; 61771 MW; 96458403C83B9FFF CRC64;
MKKKLVVLGL LAVVLVLVIV GLCLWLPSAS KEPDNHVYTR AAMAADAKQC LEIGRDTLRD
GGSAVDAAIA ALLCVGLMNA HSMGIGVGLF LTIYNSTTGK AEVINAREVA PRLAFASMFN
SSEQSQKGGL SVAVPGEIRG YELAHQRHGR LPWARLFQPS IQLARQGFPV GKGLAAVLEN
KRTVIEQQPV LWYVFCRDRK VLREGERLTL PRLADTYEML AIEGAQAFYN GSLMAQIVKD
IQAAGGIVTA EDLNNYRAEL IEHPLNISLG DAVLYMPSAR LSGPVLALIL NILKGYNFSR
ESVETPEQKG LTYHRIVEAF RFAYAKRTLL GDPKFVDVTE VVRNMTSEFF AAQLRSQISD
HTTHPISYYK PEFYTPDDGG TAHLSVVAED GSAVSATSTI NLYFGSKVCS PVSGILFNNE
WTTSALPAFT NEFGAPPSPA NFIQPGKQPL LSMCLTIMVG QDGQVRMVVG AAGGTQITTD
TALAIIYNLW FGYDVKRAVE EPRLHNKLLP NVTTVERNID QAVTAALETR HHHTQIASTF
IAVVQAIVRT AGGWAAALDS RKGGEPAGY
//
