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Protein

Gamma-glutamyl hydrolase

Gene

Ggh

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Biological processi

Complete GO annotation...

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 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1329035. Ggh.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Ensembl
  • extracellular exosome Source: MGI
  • extracellular space Source: UniProtKB-SubCell
  • lysosome Source: MGI
  • melanosome Source: UniProtKB-SubCell
  • nucleus Source: MGI
Complete GO annotation...

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.
GenevisibleiQ9Z0L8. MM.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000095843.

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.
InParanoidiQ9Z0L8.
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. AlignAdd to basket

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

        10         20         30         40         50
MANLGYLLCL LGLLLCGLSS PGMSRPYNHG SERPIIGVVM QECFGKMAKL
60 70 80 90 100
GNYYIAASYV KYIESAGARV VPIRPDLSDA EYEELFRSIN GVLLPGGGAN
110 120 130 140 150
LTDSGYSRVA KIFFSKALES FDNGDHFPVW GTCLGFEELS VLVSGENLLT
160 170 180 190 200
STDTKSKKLP LNFTEGARKS RMFKHFPTEL LDSLALENLT ANFHKWSLSV
210 220 230 240 250
KNFTENEKLK KFFNILTTNT DGKTEFISSM EGFKYPVYAV QWHPEKAAFE
260 270 280 290 300
WKNLGGISHA PNAVKTSFYL AEFLVSEARK NSHHFENVVK ETASLIYKFN
310
PIYTGNISSF QQAYMFD
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000095843.

Protein family/group databases

MEROPSiC26.001.

PTM databases

PhosphoSiteiQ9Z0L8.

Proteomic databases

MaxQBiQ9Z0L8.
PaxDbiQ9Z0L8.
PRIDEiQ9Z0L8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8836.
MGIiMGI:1329035. Ggh.

Phylogenomic databases

eggNOGiNOG251450.
GeneTreeiENSGT00490000043388.
HOGENOMiHOG000006721.
HOVERGENiHBG005833.
InParanoidiQ9Z0L8.
KOiK01307.
OMAiNFTMNEK.
OrthoDBiEOG7BCNC9.
TreeFamiTF323437.

Miscellaneous databases

NextBioi286342.
PROiQ9Z0L8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Z0L8.
CleanExiMM_GGH.
GenevisibleiQ9Z0L8. MM.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 116 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.