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Q9Z0L8 (GGH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-glutamyl hydrolase

EC=3.4.19.9
Alternative name(s):
Conjugase
FGPH
Folylpolyglutamate hydrolase
GH
Gamma-Glu-x carboxypeptidase
Gene names
Name:Ggh
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length317 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

Hydrolysis of a gamma-glutamyl bond.

Subunit structure

Homodimer By similarity.

Subcellular location

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.

Tissue specificity

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.

Sequence similarities

Belongs to the peptidase C26 family.

Contains 1 gamma-glutamyl hydrolase domain.

Biophysicochemical properties

pH dependence:

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform I (identifier: Q9Z0L8-1)

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.
Isoform II (identifier: Q9Z0L8-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 By similarity
Chain25 – 317293Gamma-glutamyl hydrolase
PRO_0000026540

Regions

Domain25 – 317293Gamma-glutamyl hydrolase

Sites

Active site1331Nucleophile By similarity
Active site2431Proton donor By similarity

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...) (high mannose) Ref.4
Glycosylation1621N-linked (GlcNAc...) (high mannose) Ref.4
Glycosylation1881N-linked (GlcNAc...) (high mannose) Ref.4
Glycosylation2021N-linked (GlcNAc...) Potential
Glycosylation3061N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 1616MANLG…GLLLC → MVRGWRLLGVLMLS in isoform II.
VSP_005447

Experimental info

Sequence conflict1251D → G in AAC70002. Ref.1
Sequence conflict1251D → G in AAC70003. Ref.1
Sequence conflict1251D → G in AAD47388. Ref.2
Sequence conflict170 – 1712SR → NK in AAC70002. Ref.1
Sequence conflict170 – 1712SR → NK in AAC70003. Ref.1
Sequence conflict170 – 1712SR → NK in AAD47388. Ref.2
Sequence conflict2481A → P in AAC70002. Ref.1
Sequence conflict2481A → P in AAC70003. Ref.1
Sequence conflict2481A → P in AAD47388. Ref.2
Sequence conflict299 – 3002FN → VY in AAC70002. Ref.1
Sequence conflict299 – 3002FN → VY in AAC70003. Ref.1
Sequence conflict299 – 3002FN → VY in AAD47388. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform I [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 139F56E1EFE6F801

FASTA31735,470
        10         20         30         40         50         60 
MANLGYLLCL LGLLLCGLSS PGMSRPYNHG SERPIIGVVM QECFGKMAKL GNYYIAASYV 

        70         80         90        100        110        120 
KYIESAGARV VPIRPDLSDA EYEELFRSIN GVLLPGGGAN LTDSGYSRVA KIFFSKALES 

       130        140        150        160        170        180 
FDNGDHFPVW GTCLGFEELS VLVSGENLLT STDTKSKKLP LNFTEGARKS RMFKHFPTEL 

       190        200        210        220        230        240 
LDSLALENLT ANFHKWSLSV KNFTENEKLK KFFNILTTNT DGKTEFISSM EGFKYPVYAV 

       250        260        270        280        290        300 
QWHPEKAAFE WKNLGGISHA PNAVKTSFYL AEFLVSEARK NSHHFENVVK ETASLIYKFN 

       310 
PIYTGNISSF QQAYMFD 

« Hide

Isoform II [UniParc].

Checksum: 331F7F9C9D2A9B62
Show »

FASTA31535,377

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF051102 mRNA. Translation: AAC70002.1.
AF051103 mRNA. Translation: AAC70003.1.
AF090732 expand/collapse EMBL AC list , 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.
CCDSCCDS51126.1. [Q9Z0L8-1]
RefSeqNP_034411.2. NM_010281.2. [Q9Z0L8-1]
UniGeneMm.20461.

3D structure databases

ProteinModelPortalQ9Z0L8.
SMRQ9Z0L8. Positions 30-317.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSC26.001.

PTM databases

PhosphoSiteQ9Z0L8.

Proteomic databases

MaxQBQ9Z0L8.
PaxDbQ9Z0L8.
PRIDEQ9Z0L8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000098242; ENSMUSP00000095843; ENSMUSG00000073987. [Q9Z0L8-1]
GeneID14590.
KEGGmmu:14590.
UCSCuc008sck.1. mouse. [Q9Z0L8-1]

Organism-specific databases

CTD8836.
MGIMGI:1329035. Ggh.

Phylogenomic databases

eggNOGNOG251450.
GeneTreeENSGT00490000043388.
HOGENOMHOG000006721.
HOVERGENHBG005833.
InParanoidB1AWC1.
KOK01307.
OMANFTMNEK.
OrthoDBEOG7BCNC9.
TreeFamTF323437.

Gene expression databases

BgeeQ9Z0L8.
CleanExMM_GGH.
GenevestigatorQ9Z0L8.

Family and domain databases

Gene3D3.40.50.880. 1 hit.
InterProIPR029062. Class_I_gatase-like.
IPR015527. Pept_C26_g-glut_hydrolase.
IPR011697. Peptidase_C26.
[Graphical view]
PANTHERPTHR11315. PTHR11315. 1 hit.
PfamPF07722. Peptidase_C26. 1 hit.
[Graphical view]
SUPFAMSSF52317. SSF52317. 1 hit.
PROSITEPS51275. PEPTIDASE_C26_GGH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGGH. mouse.
NextBio286342.
PROQ9Z0L8.
SOURCESearch...

Entry information

Entry nameGGH_MOUSE
AccessionPrimary (citable) accession number: Q9Z0L8
Secondary accession number(s): B1AWC1, Q9Z0L7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot