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   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.
DR   Genevisible; P36268; HS.
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
FT                   E-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
FT                   C-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
//