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Q92820

- GGH_HUMAN

UniProt

Q92820 - GGH_HUMAN

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Protein

Gamma-glutamyl hydrolase

Gene

GGH

Organism
Homo sapiens (Human)
Status
Reviewed - 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.

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
Complete GO annotation...

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: Ensembl
  3. extracellular vesicular exosome Source: UniProtKB
  4. lysosome Source: UniProtKB-KW
  5. nucleus Source: UniProt
Complete GO annotation...

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

BgeeiQ92820.
CleanExiHS_GGH.
GenevestigatoriQ92820.

Organism-specific databases

HPAiCAB019296.
HPA025226.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi114363. 23 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.
GeneTreeiENSGT00490000043388.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MASPGCLLCV LGLLLCGAAS LELSRPHGDT AKKPIIGILM QKCRNKVMKN
60 70 80 90 100
YGRYYIAASY VKYLESAGAR VVPVRLDLTE KDYEILFKSI NGILFPGGSV
110 120 130 140 150
DLRRSDYAKV AKIFYNLSIQ SFDDGDYFPV WGTCLGFEEL SLLISGECLL
160 170 180 190 200
TATDTVDVAM PLNFTGGQLH SRMFQNFPTE LLLSLAVEPL TANFHKWSLS
210 220 230 240 250
VKNFTMNEKL KKFFNVLTTN TDGKIEFIST MEGYKYPVYG VQWHPEKAPY
260 270 280 290 300
EWKNLDGISH APNAVKTAFY LAEFFVNEAR KNNHHFKSES EEEKALIYQF
310
SPIYTGNISS FQQCYIFD
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. 23 interactions.
IntActi Q92820. 2 interactions.
STRINGi 9606.ENSP00000260118.

Chemistry

BindingDBi Q92820.
ChEMBLi CHEMBL2223.
DrugBanki DB00158. Folic Acid.
DB00563. Methotrexate.

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 GC08M063928.
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.
GeneTreei ENSGT00490000043388.
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

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

« Hide 'large scale' publications
  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 29, 2014
This is version 133 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