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Q92820 (GGH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-glutamyl hydrolase

EC=3.4.19.9
Alternative name(s):
Conjugase
GH
Gamma-Glu-X carboxypeptidase
Gene names
Name:GGH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length318 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.

Catalytic activity

Hydrolysis of a gamma-glutamyl bond.

Subunit structure

Homodimer. Ref.7 Ref.10

Subcellular location

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. Ref.6 Ref.8

Sequence similarities

Belongs to the peptidase C26 family.

Contains 1 gamma-glutamyl hydrolase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 By similarity
Chain25 – 318294Gamma-glutamyl hydrolase
PRO_0000026539

Regions

Domain25 – 318294Gamma-glutamyl hydrolase

Sites

Active site1341Nucleophile
Active site2441Proton donor

Amino acid modifications

Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1631N-linked (GlcNAc...) Ref.10
Glycosylation2031N-linked (GlcNAc...) Ref.10
Glycosylation3071N-linked (GlcNAc...); partial Ref.10

Natural variations

Natural variant61C → R.
Corresponds to variant rs1800909 [ dbSNP | Ensembl ].
VAR_014697
Natural variant311A → T.
Corresponds to variant rs11545077 [ dbSNP | Ensembl ].
VAR_029230
Natural variant1511T → I.
Corresponds to variant rs11545078 [ dbSNP | Ensembl ].
VAR_029231

Experimental info

Mutagenesis1341C → A: Loss of activity. Ref.4 Ref.5
Mutagenesis1951H → N: Reduces activity 250-fold.
Mutagenesis2441H → A: Loss of activity. Ref.5
Mutagenesis2461E → A: Slightly reduced catalytic activity. Ref.5

Secondary structure

.................................................... 318
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q92820 [UniParc].

Last modified August 1, 1998. Version 2.
Checksum: C4069953573B9B24

FASTA31835,964
        10         20         30         40         50         60 
MASPGCLLCV LGLLLCGAAS LELSRPHGDT AKKPIIGILM QKCRNKVMKN YGRYYIAASY 

        70         80         90        100        110        120 
VKYLESAGAR VVPVRLDLTE KDYEILFKSI NGILFPGGSV DLRRSDYAKV AKIFYNLSIQ 

       130        140        150        160        170        180 
SFDDGDYFPV WGTCLGFEEL SLLISGECLL TATDTVDVAM PLNFTGGQLH SRMFQNFPTE 

       190        200        210        220        230        240 
LLLSLAVEPL TANFHKWSLS VKNFTMNEKL KKFFNVLTTN TDGKIEFIST MEGYKYPVYG 

       250        260        270        280        290        300 
VQWHPEKAPY EWKNLDGISH APNAVKTAFY LAEFFVNEAR KNNHHFKSES EEEKALIYQF 

       310 
SPIYTGNISS FQQCYIFD 

« Hide

References

« Hide 'large scale' references
[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]"Proteomic analysis of early melanosomes: identification of novel melanosomal proteins."
Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E.
J. Proteome Res. 2:69-79(2003) [PubMed] [Europe PMC] [Abstract]
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]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Tissue: Melanoma.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U55206 mRNA. Translation: AAC05579.1.
AF147083, AF147081, AF147082 Genomic DNA. Translation: AAF03360.1.
BC025025 mRNA. Translation: AAH25025.1.
PIRJC6115.
RefSeqNP_003869.1. NM_003878.2.
UniGeneHs.78619.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1L9XX-ray1.60A/B/C/D25-318[»]
ProteinModelPortalQ92820.
SMRQ92820. Positions 31-318.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114363. 11 interactions.
IntActQ92820. 2 interactions.
STRING9606.ENSP00000260118.

Chemistry

BindingDBQ92820.
ChEMBLCHEMBL2223.
DrugBankDB00158. Folic Acid.
DB00142. L-Glutamic Acid.

Protein family/group databases

MEROPSC26.001.

PTM databases

PhosphoSiteQ92820.

Polymorphism databases

DMDM6016127.

Proteomic databases

PaxDbQ92820.
PeptideAtlasQ92820.
PRIDEQ92820.

Protocols and materials databases

DNASU8836.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260118; ENSP00000260118; ENSG00000137563.
GeneID8836.
KEGGhsa:8836.
UCSCuc003xuw.3. human.

Organism-specific databases

CTD8836.
GeneCardsGC08M063977.
HGNCHGNC:4248. GGH.
HPACAB019296.
HPA025226.
MIM601509. gene.
neXtProtNX_Q92820.
Orphanet306574. Methotrexate dose selection.
PharmGKBPA432.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG251450.
HOGENOMHOG000006721.
HOVERGENHBG005833.
InParanoidQ92820.
KOK01307.
OMANFTMNEK.
OrthoDBEOG7BCNC9.
PhylomeDBQ92820.
TreeFamTF323437.

Enzyme and pathway databases

BRENDA3.4.19.9. 2681.

Gene expression databases

ArrayExpressQ92820.
BgeeQ92820.
CleanExHS_GGH.
GenevestigatorQ92820.

Family and domain databases

InterProIPR015527. Pept_C26_g-glut_hydrolase.
IPR011697. Peptidase_C26.
[Graphical view]
PANTHERPTHR11315. PTHR11315. 1 hit.
PfamPF07722. Peptidase_C26. 1 hit.
[Graphical view]
PROSITEPS51275. PEPTIDASE_C26_GGH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ92820.
GeneWikiGGH_(gene).
GenomeRNAi8836.
NextBio33164.
PROQ92820.
SOURCESearch...

Entry information

Entry nameGGH_HUMAN
AccessionPrimary (citable) accession number: Q92820
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 1, 1998
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM