GGH_RAT
ID GGH_RAT Reviewed; 317 AA.
AC Q62867;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Gamma-glutamyl hydrolase;
DE EC=3.4.19.9 {ECO:0000269|PubMed:8343522, ECO:0000269|PubMed:8621474};
DE AltName: Full=Conjugase;
DE AltName: Full=GH;
DE AltName: Full=Gamma-Glu-X carboxypeptidase;
DE Flags: Precursor;
GN Name=Ggh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-39; 173-182 AND 231-240,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Hepatocyte;
RX PubMed=8621474; DOI=10.1074/jbc.271.15.8525;
RA Yao R., Nimec Z., Ryan T.J., Galivan J.;
RT "Identification, cloning, and sequencing of a cDNA coding for rat gamma-
RT glutamyl hydrolase.";
RL J. Biol. Chem. 271:8525-8528(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Hepatocyte;
RX PubMed=8343522; DOI=10.1016/0167-4838(93)90253-n;
RA Wang Y., Nimec Z., Ryan T.J., Dias J.A., Galivan J.;
RT "The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma
RT cells.";
RL Biochim. Biophys. Acta 1164:227-235(1993).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Hydrolyzes the polyglutamate sidechains of
CC pteroylpolyglutamates (PubMed:8621474, PubMed:8343522). Progressively
CC removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to
CC yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play
CC an important role in the bioavailability of dietary
CC pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates
CC and antifolates. Exhibits either endo- or exopeptidase activity
CC depending upon the tissue of origin. When secreted, it acts primarily
CC as an endopeptidase (By similarity). {ECO:0000250|UniProtKB:Q92820,
CC ECO:0000269|PubMed:8343522, ECO:0000269|PubMed:8621474}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + (n-1) H2O =
CC (6S)-5,6,7,8-tetrahydrofolate + (n-1) L-glutamate;
CC Xref=Rhea:RHEA:56784, Rhea:RHEA-COMP:14738, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:57453, ChEBI:CHEBI:141005;
CC EC=3.4.19.9; Evidence={ECO:0000269|PubMed:8343522,
CC ECO:0000269|PubMed:8621474};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56785;
CC Evidence={ECO:0000305|PubMed:8621474};
CC -!- ACTIVITY REGULATION: Activity is altered by insulin and estrogen.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is from 5 to 7. {ECO:0000269|PubMed:8343522};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q92820}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000250|UniProtKB:Q92820}. Lysosome
CC {ECO:0000250|UniProtKB:Q92820}. Melanosome
CC {ECO:0000250|UniProtKB:Q92820}. Note=While its intracellular location
CC is primarily the lysosome, most of the enzyme activity is secreted.
CC {ECO:0000250|UniProtKB:Q92820}.
CC -!- SIMILARITY: Belongs to the peptidase C26 family. {ECO:0000305}.
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DR EMBL; U38379; AAC52506.1; -; mRNA.
DR EMBL; BC087602; AAH87602.1; -; mRNA.
DR RefSeq; NP_037092.1; NM_012960.2.
DR AlphaFoldDB; Q62867; -.
DR SMR; Q62867; -.
DR STRING; 10116.ENSRNOP00000009758; -.
DR MEROPS; C26.001; -.
DR GlyGen; Q62867; 7 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q62867; -.
DR PhosphoSitePlus; Q62867; -.
DR PaxDb; Q62867; -.
DR PRIDE; Q62867; -.
DR Ensembl; ENSRNOT00000009758; ENSRNOP00000009758; ENSRNOG00000007351.
DR GeneID; 25455; -.
DR KEGG; rno:25455; -.
DR UCSC; RGD:2682; rat.
DR CTD; 8836; -.
DR RGD; 2682; Ggh.
DR eggNOG; KOG1559; Eukaryota.
DR GeneTree; ENSGT00490000043388; -.
DR HOGENOM; CLU_058704_1_1_1; -.
DR InParanoid; Q62867; -.
DR OMA; APYEWGK; -.
DR OrthoDB; 877490at2759; -.
DR PhylomeDB; Q62867; -.
DR TreeFam; TF323437; -.
DR BRENDA; 3.4.19.9; 5301.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:Q62867; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000007351; Expressed in pancreas and 20 other tissues.
DR Genevisible; Q62867; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; IBA:GO_Central.
DR GO; GO:0034722; F:gamma-glutamyl-peptidase activity; IDA:RGD.
DR GO; GO:0070500; P:poly-gamma-glutamate metabolic process; IDA:RGD.
DR GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR GO; GO:0032868; P:response to insulin; IDA:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0010043; P:response to zinc ion; IDA:RGD.
DR GO; GO:0046900; P:tetrahydrofolylpolyglutamate metabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.880; -; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR015527; Pept_C26_g-glut_hydrolase.
DR InterPro; IPR011697; Peptidase_C26.
DR PANTHER; PTHR11315; PTHR11315; 1.
DR Pfam; PF07722; Peptidase_C26; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR PROSITE; PS51275; PEPTIDASE_C26_GGH; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Glycoprotein; Hydrolase; Lysosome;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:8621474"
FT CHAIN 25..317
FT /note="Gamma-glutamyl hydrolase"
FT /id="PRO_0000026541"
FT DOMAIN 25..317
FT /note="Gamma-glutamyl hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00607"
FT ACT_SITE 133
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00607"
FT ACT_SITE 243
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00607"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 317 AA; 35830 MW; CB8D2499374CAEAF CRC64;
MASLGRLLCA WVLLLCGLAS PGLSGSYERG SKRPIIGIIM QECYGNMTKL GRFYIAASYV
KFIESAGARV VPIRLDLNDA QYETLFRSIN GVLLPGGGAN LTHSGYSRVA KIFFTKALES
FDNGDYFPVW GTCLGLEELS VLVSNDNLLT LTNTSSVKLP LNFTRDSKQS RMFRNLPEEL
LNSLASENLT ANFHKWSLSV KNFTENEKLK KFFNILTVNT DGKTEFISSM EGYKYPIYAV
QWHPEKAPFE WKKLRGISHA PNAVKTSFYL AKFFISEALK NDHHFENELE ETESLIYQFC
PVYTGNISSF QQAYMFN
