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Q9Z0L8

- GGH_MOUSE

UniProt

Q9Z0L8 - GGH_MOUSE

Protein

Gamma-glutamyl hydrolase

Gene

Ggh

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 110 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      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. Acts as endopeptidase. Lysosomal enzyme is activated by sulfhydryl compounds.

    Catalytic activityi

    Hydrolysis of a gamma-glutamyl bond.

    pH dependencei

    Optimum pH is 4. Active from pH 3 to 5.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei133 – 1331NucleophilePROSITE-ProRule annotation
    Active sitei243 – 2431Proton donorPROSITE-ProRule annotation

    GO - Molecular functioni

    1. gamma-glutamyl-peptidase activity Source: UniProtKB

    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

    Protein family/group databases

    MEROPSiC26.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Gamma-glutamyl hydrolase (EC:3.4.19.9)
    Alternative name(s):
    Conjugase
    FGPH
    Folylpolyglutamate hydrolase
    GH
    Gamma-Glu-x carboxypeptidase
    Gene namesi
    Name:Ggh
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:1329035. Ggh.

    Subcellular locationi

    Secretedextracellular space By similarity. Lysosome By similarity. Melanosome By similarity
    Note: While its intracellular location is primarily the lysosome, most of the enzyme activity is secreted.By similarity

    GO - Cellular componenti

    1. cytosol Source: Ensembl
    2. extracellular space Source: UniProtKB-SubCell
    3. lysosome Source: MGI
    4. melanosome Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Lysosome, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424By similarityAdd
    BLAST
    Chaini25 – 317293Gamma-glutamyl hydrolasePRO_0000026540Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi100 – 1001N-linked (GlcNAc...) (high mannose)1 Publication
    Glycosylationi162 – 1621N-linked (GlcNAc...) (high mannose)1 Publication
    Glycosylationi188 – 1881N-linked (GlcNAc...) (high mannose)1 Publication
    Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi306 – 3061N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ9Z0L8.
    PaxDbiQ9Z0L8.
    PRIDEiQ9Z0L8.

    PTM databases

    PhosphoSiteiQ9Z0L8.

    Expressioni

    Tissue specificityi

    Isoform I (more expressed than isoform II in all tissues) is highly expressed in salivary gland, followed by kidney, liver, lung, stomach and uterus, and weakly expressed in small intestine, brain and fetal liver. Also expressed at a lower level in thymus, spleen and skeletal muscle. Also expressed in tumors.

    Gene expression databases

    BgeeiQ9Z0L8.
    CleanExiMM_GGH.
    GenevestigatoriQ9Z0L8.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Z0L8.
    SMRiQ9Z0L8. Positions 30-317.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 317293Gamma-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.
    GeneTreeiENSGT00490000043388.
    HOGENOMiHOG000006721.
    HOVERGENiHBG005833.
    InParanoidiB1AWC1.
    KOiK01307.
    OMAiNFTMNEK.
    OrthoDBiEOG7BCNC9.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform I (identifier: Q9Z0L8-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MANLGYLLCL LGLLLCGLSS PGMSRPYNHG SERPIIGVVM QECFGKMAKL    50
    GNYYIAASYV KYIESAGARV VPIRPDLSDA EYEELFRSIN GVLLPGGGAN 100
    LTDSGYSRVA KIFFSKALES FDNGDHFPVW GTCLGFEELS VLVSGENLLT 150
    STDTKSKKLP LNFTEGARKS RMFKHFPTEL LDSLALENLT ANFHKWSLSV 200
    KNFTENEKLK KFFNILTTNT DGKTEFISSM EGFKYPVYAV QWHPEKAAFE 250
    WKNLGGISHA PNAVKTSFYL AEFLVSEARK NSHHFENVVK ETASLIYKFN 300
    PIYTGNISSF QQAYMFD 317
    Length:317
    Mass (Da):35,470
    Last modified:July 27, 2011 - v2
    Checksum:i139F56E1EFE6F801
    GO
    Isoform II (identifier: Q9Z0L8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-16: MANLGYLLCLLGLLLC → MVRGWRLLGVLMLS

    Show »
    Length:315
    Mass (Da):35,377
    Checksum:i331F7F9C9D2A9B62
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti125 – 1251D → G in AAC70002. (PubMed:9756990)Curated
    Sequence conflicti125 – 1251D → G in AAC70003. (PubMed:9756990)Curated
    Sequence conflicti125 – 1251D → G in AAD47388. (PubMed:10393243)Curated
    Sequence conflicti170 – 1712SR → NK in AAC70002. (PubMed:9756990)Curated
    Sequence conflicti170 – 1712SR → NK in AAC70003. (PubMed:9756990)Curated
    Sequence conflicti170 – 1712SR → NK in AAD47388. (PubMed:10393243)Curated
    Sequence conflicti248 – 2481A → P in AAC70002. (PubMed:9756990)Curated
    Sequence conflicti248 – 2481A → P in AAC70003. (PubMed:9756990)Curated
    Sequence conflicti248 – 2481A → P in AAD47388. (PubMed:10393243)Curated
    Sequence conflicti299 – 3002FN → VY in AAC70002. (PubMed:9756990)Curated
    Sequence conflicti299 – 3002FN → VY in AAC70003. (PubMed:9756990)Curated
    Sequence conflicti299 – 3002FN → VY in AAD47388. (PubMed:10393243)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1616MANLG…GLLLC → MVRGWRLLGVLMLS in isoform II. CuratedVSP_005447Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF051102 mRNA. Translation: AAC70002.1.
    AF051103 mRNA. Translation: AAC70003.1.
    AF090732
    , AF090725, AF090726, AF090727, AF090728, AF090729, AF090730, AF090731 Genomic DNA. Translation: AAD47388.1.
    AL732527, CR931798 Genomic DNA. Translation: CAM18838.2.
    CR931798, AL732527 Genomic DNA. Translation: CAO78172.1.
    CCDSiCCDS51126.1. [Q9Z0L8-1]
    RefSeqiNP_034411.2. NM_010281.2. [Q9Z0L8-1]
    UniGeneiMm.20461.

    Genome annotation databases

    EnsembliENSMUST00000098242; ENSMUSP00000095843; ENSMUSG00000073987. [Q9Z0L8-1]
    GeneIDi14590.
    KEGGimmu:14590.
    UCSCiuc008sck.1. mouse. [Q9Z0L8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF051102 mRNA. Translation: AAC70002.1 .
    AF051103 mRNA. Translation: AAC70003.1 .
    AF090732
    , AF090725 , AF090726 , AF090727 , AF090728 , AF090729 , AF090730 , AF090731 Genomic DNA. Translation: AAD47388.1 .
    AL732527 , CR931798 Genomic DNA. Translation: CAM18838.2 .
    CR931798 , AL732527 Genomic DNA. Translation: CAO78172.1 .
    CCDSi CCDS51126.1. [Q9Z0L8-1 ]
    RefSeqi NP_034411.2. NM_010281.2. [Q9Z0L8-1 ]
    UniGenei Mm.20461.

    3D structure databases

    ProteinModelPortali Q9Z0L8.
    SMRi Q9Z0L8. Positions 30-317.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    MEROPSi C26.001.

    PTM databases

    PhosphoSitei Q9Z0L8.

    Proteomic databases

    MaxQBi Q9Z0L8.
    PaxDbi Q9Z0L8.
    PRIDEi Q9Z0L8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000098242 ; ENSMUSP00000095843 ; ENSMUSG00000073987 . [Q9Z0L8-1 ]
    GeneIDi 14590.
    KEGGi mmu:14590.
    UCSCi uc008sck.1. mouse. [Q9Z0L8-1 ]

    Organism-specific databases

    CTDi 8836.
    MGIi MGI:1329035. Ggh.

    Phylogenomic databases

    eggNOGi NOG251450.
    GeneTreei ENSGT00490000043388.
    HOGENOMi HOG000006721.
    HOVERGENi HBG005833.
    InParanoidi B1AWC1.
    KOi K01307.
    OMAi NFTMNEK.
    OrthoDBi EOG7BCNC9.
    TreeFami TF323437.

    Miscellaneous databases

    ChiTaRSi GGH. mouse.
    NextBioi 286342.
    PROi Q9Z0L8.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9Z0L8.
    CleanExi MM_GGH.
    Genevestigatori Q9Z0L8.

    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. "Cloning of mouse gamma-glutamyl hydrolase in the form of two cDNA variants with different 5' ends and encoding alternate leader peptide sequences."
      Esaki T., Roy K., Yao R., Galivan J., Sirotnak F.M.
      Gene 219:37-44(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
      Strain: 129/SvJ and BALB/c.
      Tissue: Liver.
    2. "Organization and structure of the mouse gamma-glutamyl hydrolase gene and the functional identification of its promoter."
      Esaki T., Masumoto N., Hayes P., Chen J., Sirotnak F.M.
      Gene 234:93-100(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/SvJ.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    4. "High throughput quantitative glycomics and glycoform-focused proteomics of murine dermis and epidermis."
      Uematsu R., Furukawa J., Nakagawa H., Shinohara Y., Deguchi K., Monde K., Nishimura S.
      Mol. Cell. Proteomics 4:1977-1989(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100; ASN-162 AND ASN-188.
      Tissue: Epidermis.

    Entry informationi

    Entry nameiGGH_MOUSE
    AccessioniPrimary (citable) accession number: Q9Z0L8
    Secondary accession number(s): B1AWC1, Q9Z0L7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 21, 2001
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 110 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3