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Q92820

- GGH_HUMAN

UniProt

Q92820 - GGH_HUMAN

Protein

Gamma-glutamyl hydrolase

Gene

GGH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.

    Catalytic activityi

    Hydrolysis of a gamma-glutamyl bond.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei134 – 1341Nucleophile
    Active sitei244 – 2441Proton donor

    GO - Molecular functioni

    1. exopeptidase activity Source: ProtInc
    2. gamma-glutamyl-peptidase activity Source: UniProtKB
    3. omega peptidase activity Source: ProtInc

    GO - Biological processi

    1. glutamine metabolic process Source: InterPro
    2. proteolysis Source: GOC
    3. response to drug Source: Ensembl
    4. response to ethanol Source: Ensembl
    5. response to insulin Source: Ensembl
    6. response to zinc ion Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase

    Enzyme and pathway databases

    BRENDAi3.4.19.9. 2681.

    Protein family/group databases

    MEROPSiC26.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Gamma-glutamyl hydrolase (EC:3.4.19.9)
    Alternative name(s):
    Conjugase
    GH
    Gamma-Glu-X carboxypeptidase
    Gene namesi
    Name:GGH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:4248. GGH.

    Subcellular locationi

    Secretedextracellular space. Lysosome. Melanosome
    Note: While its intracellular location is primarily the lysosome, most of the enzyme activity is secreted. Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. extracellular space Source: UniProtKB-SubCell
    3. extracellular vesicular exosome Source: UniProt
    4. lysosome Source: UniProtKB-SubCell
    5. melanosome Source: UniProtKB-SubCell
    6. nucleus Source: UniProt

    Keywords - Cellular componenti

    Lysosome, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi134 – 1341C → A: Loss of activity. 2 Publications
    Mutagenesisi195 – 1951H → N: Reduces activity 250-fold.
    Mutagenesisi244 – 2441H → A: Loss of activity. 1 Publication
    Mutagenesisi246 – 2461E → A: Slightly reduced catalytic activity. 1 Publication

    Organism-specific databases

    Orphaneti306574. Methotrexate dose selection.
    PharmGKBiPA432.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424By similarityAdd
    BLAST
    Chaini25 – 318294Gamma-glutamyl hydrolasePRO_0000026539Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi116 – 1161N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi163 – 1631N-linked (GlcNAc...)1 Publication
    Glycosylationi203 – 2031N-linked (GlcNAc...)1 Publication
    Glycosylationi307 – 3071N-linked (GlcNAc...); partial1 Publication

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ92820.
    PaxDbiQ92820.
    PeptideAtlasiQ92820.
    PRIDEiQ92820.

    PTM databases

    PhosphoSiteiQ92820.

    Expressioni

    Gene expression databases

    ArrayExpressiQ92820.
    BgeeiQ92820.
    CleanExiHS_GGH.
    GenevestigatoriQ92820.

    Organism-specific databases

    HPAiCAB019296.
    HPA025226.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Protein-protein interaction databases

    BioGridi114363. 11 interactions.
    IntActiQ92820. 2 interactions.
    STRINGi9606.ENSP00000260118.

    Structurei

    Secondary structure

    1
    318
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi35 – 395
    Helixi46 – 494
    Beta strandi53 – 575
    Helixi58 – 669
    Beta strandi70 – 745
    Helixi80 – 8910
    Beta strandi90 – 956
    Turni102 – 1043
    Helixi106 – 12318
    Beta strandi130 – 1334
    Helixi135 – 14511
    Beta strandi151 – 16010
    Turni167 – 1704
    Turni173 – 1764
    Helixi179 – 1879
    Beta strandi191 – 1988
    Helixi201 – 2055
    Helixi208 – 2136
    Beta strandi214 – 22411
    Beta strandi226 – 23611
    Beta strandi238 – 2436
    Helixi247 – 2504
    Helixi262 – 27918
    Helixi289 – 2957
    Helixi297 – 2993
    Turni306 – 3083
    Beta strandi312 – 3176

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1L9XX-ray1.60A/B/C/D25-318[»]
    ProteinModelPortaliQ92820.
    SMRiQ92820. Positions 31-318.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ92820.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 318294Gamma-glutamyl hydrolasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C26 family.Curated
    Contains 1 gamma-glutamyl hydrolase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG251450.
    HOGENOMiHOG000006721.
    HOVERGENiHBG005833.
    InParanoidiQ92820.
    KOiK01307.
    OMAiNFTMNEK.
    OrthoDBiEOG7BCNC9.
    PhylomeDBiQ92820.
    TreeFamiTF323437.

    Family and domain databases

    Gene3Di3.40.50.880. 1 hit.
    InterProiIPR029062. Class_I_gatase-like.
    IPR015527. Pept_C26_g-glut_hydrolase.
    IPR011697. Peptidase_C26.
    [Graphical view]
    PANTHERiPTHR11315. PTHR11315. 1 hit.
    PfamiPF07722. Peptidase_C26. 1 hit.
    [Graphical view]
    SUPFAMiSSF52317. SSF52317. 1 hit.
    PROSITEiPS51275. PEPTIDASE_C26_GGH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q92820-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASPGCLLCV LGLLLCGAAS LELSRPHGDT AKKPIIGILM QKCRNKVMKN    50
    YGRYYIAASY VKYLESAGAR VVPVRLDLTE KDYEILFKSI NGILFPGGSV 100
    DLRRSDYAKV AKIFYNLSIQ SFDDGDYFPV WGTCLGFEEL SLLISGECLL 150
    TATDTVDVAM PLNFTGGQLH SRMFQNFPTE LLLSLAVEPL TANFHKWSLS 200
    VKNFTMNEKL KKFFNVLTTN TDGKIEFIST MEGYKYPVYG VQWHPEKAPY 250
    EWKNLDGISH APNAVKTAFY LAEFFVNEAR KNNHHFKSES EEEKALIYQF 300
    SPIYTGNISS FQQCYIFD 318
    Length:318
    Mass (Da):35,964
    Last modified:August 1, 1998 - v2
    Checksum:iC4069953573B9B24
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti6 – 61C → R.
    Corresponds to variant rs1800909 [ dbSNP | Ensembl ].
    VAR_014697
    Natural varianti31 – 311A → T.
    Corresponds to variant rs11545077 [ dbSNP | Ensembl ].
    VAR_029230
    Natural varianti151 – 1511T → I.
    Corresponds to variant rs11545078 [ dbSNP | Ensembl ].
    VAR_029231

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U55206 mRNA. Translation: AAC05579.1.
    AF147083, AF147081, AF147082 Genomic DNA. Translation: AAF03360.1.
    BC025025 mRNA. Translation: AAH25025.1.
    CCDSiCCDS6177.1.
    PIRiJC6115.
    RefSeqiNP_003869.1. NM_003878.2.
    UniGeneiHs.78619.

    Genome annotation databases

    EnsembliENST00000260118; ENSP00000260118; ENSG00000137563.
    GeneIDi8836.
    KEGGihsa:8836.
    UCSCiuc003xuw.3. human.

    Polymorphism databases

    DMDMi6016127.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U55206 mRNA. Translation: AAC05579.1 .
    AF147083 , AF147081 , AF147082 Genomic DNA. Translation: AAF03360.1 .
    BC025025 mRNA. Translation: AAH25025.1 .
    CCDSi CCDS6177.1.
    PIRi JC6115.
    RefSeqi NP_003869.1. NM_003878.2.
    UniGenei Hs.78619.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1L9X X-ray 1.60 A/B/C/D 25-318 [» ]
    ProteinModelPortali Q92820.
    SMRi Q92820. Positions 31-318.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114363. 11 interactions.
    IntActi Q92820. 2 interactions.
    STRINGi 9606.ENSP00000260118.

    Chemistry

    BindingDBi Q92820.
    ChEMBLi CHEMBL2223.
    DrugBanki DB00158. Folic Acid.
    DB00142. L-Glutamic Acid.

    Protein family/group databases

    MEROPSi C26.001.

    PTM databases

    PhosphoSitei Q92820.

    Polymorphism databases

    DMDMi 6016127.

    Proteomic databases

    MaxQBi Q92820.
    PaxDbi Q92820.
    PeptideAtlasi Q92820.
    PRIDEi Q92820.

    Protocols and materials databases

    DNASUi 8836.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260118 ; ENSP00000260118 ; ENSG00000137563 .
    GeneIDi 8836.
    KEGGi hsa:8836.
    UCSCi uc003xuw.3. human.

    Organism-specific databases

    CTDi 8836.
    GeneCardsi GC08M063977.
    HGNCi HGNC:4248. GGH.
    HPAi CAB019296.
    HPA025226.
    MIMi 601509. gene.
    neXtProti NX_Q92820.
    Orphaneti 306574. Methotrexate dose selection.
    PharmGKBi PA432.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG251450.
    HOGENOMi HOG000006721.
    HOVERGENi HBG005833.
    InParanoidi Q92820.
    KOi K01307.
    OMAi NFTMNEK.
    OrthoDBi EOG7BCNC9.
    PhylomeDBi Q92820.
    TreeFami TF323437.

    Enzyme and pathway databases

    BRENDAi 3.4.19.9. 2681.

    Miscellaneous databases

    EvolutionaryTracei Q92820.
    GeneWikii GGH_(gene).
    GenomeRNAii 8836.
    NextBioi 33164.
    PROi Q92820.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q92820.
    Bgeei Q92820.
    CleanExi HS_GGH.
    Genevestigatori Q92820.

    Family and domain databases

    Gene3Di 3.40.50.880. 1 hit.
    InterProi IPR029062. Class_I_gatase-like.
    IPR015527. Pept_C26_g-glut_hydrolase.
    IPR011697. Peptidase_C26.
    [Graphical view ]
    PANTHERi PTHR11315. PTHR11315. 1 hit.
    Pfami PF07722. Peptidase_C26. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52317. SSF52317. 1 hit.
    PROSITEi PS51275. PEPTIDASE_C26_GGH. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro."
      Yao R., Schneider E., Ryan T.J., Galivan J.
      Proc. Natl. Acad. Sci. U.S.A. 93:10134-10138(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Structural organization of the human gamma-glutamyl hydrolase gene."
      Yin D., Chave K.J., Macaluso C.R., Galivan J., Yao R.
      Gene 238:463-470(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Skin.
    4. "Site-directed mutagenesis establishes cysteine-110 as essential for enzyme activity in human gamma-glutamyl hydrolase."
      Chave K.J., Galivan J., Ryan T.J.
      Biochem. J. 343:551-555(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF CYS-134.
    5. "Molecular modeling and site-directed mutagenesis define the catalytic motif in human gamma -glutamyl hydrolase."
      Chave K.J., Auger I.E., Galivan J., Ryan T.J.
      J. Biol. Chem. 275:40365-40370(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF CYS-134; HIS-244 AND GLU-246, 3D-STRUCTURE MODELING.
    6. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
      Tissue: Melanoma.
    7. "Characterization of human gamma-glutamyl hydrolase in solution demonstrates that the enzyme is a non-dissociating homodimer."
      Eisele L.E., Chave K.J., Lehning A.C., Ryan T.J.
      Biochim. Biophys. Acta 1764:1479-1486(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    8. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
      Tissue: Melanoma.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Three-dimensional structure of human gamma -glutamyl hydrolase. A class I glutamine amidotransferase adapted for a complex substate."
      Li H., Ryan T.J., Chave K.J., Van Roey P.
      J. Biol. Chem. 277:24522-24529(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 25-318, IDENTIFICATION BY MASS SPECTROMETRY, GLYCOSYLATION AT ASN-163; ASN-203 AND ASN-307, SUBUNIT.

    Entry informationi

    Entry nameiGGH_HUMAN
    AccessioniPrimary (citable) accession number: Q92820
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 132 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3