ID   GGH_BOVIN               Reviewed;         318 AA.
AC   A7YWG4;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-2007, sequence version 1.
DT   03-AUG-2022, entry version 84.
DE   RecName: Full=Gamma-glutamyl hydrolase;
DE            EC=3.4.19.9;
DE   AltName: Full=Conjugase;
DE   AltName: Full=GH;
DE   AltName: Full=Gamma-Glu-X carboxypeptidase;
DE   Flags: Precursor;
GN   Name=GGH;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Thalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Hydrolyzes the polyglutamate sidechains of
CC       pteroylpolyglutamates. Progressively removes gamma-glutamyl residues
CC       from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate
CC       (folic acid) and free glutamate. May play an important role in the
CC       bioavailability of dietary pteroylpolyglutamates and in the metabolism
CC       of pteroylpolyglutamates and antifolates. Exhibits either endo- or
CC       exopeptidase activity depending upon the tissue of origin. When
CC       secreted, it acts primarily as an endopeptidase (By similarity).
CC       {ECO:0000250}.
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;
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
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; BC134544; AAI34545.1; -; mRNA.
DR   RefSeq; NP_001098864.1; NM_001105394.1.
DR   AlphaFoldDB; A7YWG4; -.
DR   SMR; A7YWG4; -.
DR   STRING; 9913.ENSBTAP00000009917; -.
DR   MEROPS; C26.001; -.
DR   PaxDb; A7YWG4; -.
DR   PRIDE; A7YWG4; -.
DR   Ensembl; ENSBTAT00000009917; ENSBTAP00000009917; ENSBTAG00000007534.
DR   GeneID; 525303; -.
DR   KEGG; bta:525303; -.
DR   CTD; 8836; -.
DR   VEuPathDB; HostDB:ENSBTAG00000007534; -.
DR   VGNC; VGNC:29340; GGH.
DR   eggNOG; KOG1559; Eukaryota.
DR   GeneTree; ENSGT00490000043388; -.
DR   HOGENOM; CLU_058704_1_1_1; -.
DR   InParanoid; A7YWG4; -.
DR   OMA; APYEWGK; -.
DR   OrthoDB; 877490at2759; -.
DR   TreeFam; TF323437; -.
DR   Reactome; R-BTA-6798695; Neutrophil degranulation.
DR   Proteomes; UP000009136; Chromosome 14.
DR   Bgee; ENSBTAG00000007534; Expressed in thyroid gland and 106 other tissues.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
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   2: Evidence at transcript level;
KW   Glycoprotein; Hydrolase; Lysosome; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..318
FT                   /note="Gamma-glutamyl hydrolase"
FT                   /id="PRO_0000327991"
FT   DOMAIN          25..318
FT                   /note="Gamma-glutamyl hydrolase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00607"
FT   ACT_SITE        134
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00607"
FT   ACT_SITE        244
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00607"
FT   CARBOHYD        116
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        203
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        307
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   318 AA;  35683 MW;  82485B88E5BB8FC0 CRC64;
     MARLGRLLSV LGLVLCGATG LGLSAPPAPT PKKPIIGILM QKCHNKNMRA LGKYYIAASY
     VKFLESAGAR VVPVRLDLKN EEYEKLFKSI NGVLFPGGSV NLMRSGYARV AKMFYNLSIK
     SFGEGDYFPV WGTCLGFEEL IYLVSGESLL TLTDTVGIKL PLNFSRGTLQ SRMFQNFPAD
     LLLSLAVEPL TAHFHKWSLS VMNFTKNEKL KAFFSILTTN TDGNIDFIST MEGYRYPIYG
     VQWHPEKAPY EWGQLRGISH APNAVKAAFY LAEFFVAEAR KSNHHFESDV EETKALIYQY
     RPTYTGNVSS FQQSYIFD