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Protein

Gamma-glutamyl hydrolase

Gene

GGH

Organism
Homo sapiens (Human)
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.

Catalytic activityi

Hydrolysis of a gamma-glutamyl bond.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei134Nucleophile1
Active sitei244Proton donor1

GO - Molecular functioni

  • exopeptidase activity Source: ProtInc
  • gamma-glutamyl-peptidase activity Source: UniProtKB
  • omega peptidase activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BioCyciZFISH:HS06361-MONOMER.
BRENDAi3.4.19.9. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:4248. GGH.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Lysosome, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi134C → A: Loss of activity. 2 Publications1
Mutagenesisi195H → N: Reduces activity 250-fold. 1
Mutagenesisi244H → A: Loss of activity. 1 Publication1
Mutagenesisi246E → A: Slightly reduced catalytic activity. 1 Publication1

Organism-specific databases

DisGeNETi8836.
MalaCardsiGGH.
OpenTargetsiENSG00000137563.
Orphaneti306574. Methotrexate dose selection.
PharmGKBiPA432.

Chemistry databases

ChEMBLiCHEMBL2223.
DrugBankiDB00158. Folic Acid.
DB00563. Methotrexate.

Polymorphism and mutation databases

BioMutaiGGH.
DMDMi6016127.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24By similarityAdd BLAST24
ChainiPRO_000002653925 – 318Gamma-glutamyl hydrolaseAdd BLAST294

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi116N-linked (GlcNAc...)Sequence analysis1
Glycosylationi163N-linked (GlcNAc...)1 Publication1
Glycosylationi203N-linked (GlcNAc...)1 Publication1
Glycosylationi307N-linked (GlcNAc...); partial1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ92820.
MaxQBiQ92820.
PaxDbiQ92820.
PeptideAtlasiQ92820.
PRIDEiQ92820.

PTM databases

iPTMnetiQ92820.
PhosphoSitePlusiQ92820.

Expressioni

Gene expression databases

BgeeiENSG00000137563.
CleanExiHS_GGH.
GenevisibleiQ92820. HS.

Organism-specific databases

HPAiCAB019296.
HPA025226.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi114363. 25 interactors.
IntActiQ92820. 2 interactors.
STRINGi9606.ENSP00000260118.

Chemistry databases

BindingDBiQ92820.

Structurei

Secondary structure

1318
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 39Combined sources5
Helixi46 – 49Combined sources4
Beta strandi53 – 57Combined sources5
Helixi58 – 66Combined sources9
Beta strandi70 – 74Combined sources5
Helixi80 – 89Combined sources10
Beta strandi90 – 95Combined sources6
Turni102 – 104Combined sources3
Helixi106 – 123Combined sources18
Beta strandi130 – 133Combined sources4
Helixi135 – 145Combined sources11
Beta strandi151 – 160Combined sources10
Turni167 – 170Combined sources4
Turni173 – 176Combined sources4
Helixi179 – 187Combined sources9
Beta strandi191 – 198Combined sources8
Helixi201 – 205Combined sources5
Helixi208 – 213Combined sources6
Beta strandi214 – 224Combined sources11
Beta strandi226 – 236Combined sources11
Beta strandi238 – 243Combined sources6
Helixi247 – 250Combined sources4
Helixi262 – 279Combined sources18
Helixi289 – 295Combined sources7
Helixi297 – 299Combined sources3
Turni306 – 308Combined sources3
Beta strandi312 – 317Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1L9XX-ray1.60A/B/C/D25-318[»]
ProteinModelPortaliQ92820.
SMRiQ92820.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92820.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 318Gamma-glutamyl hydrolasePROSITE-ProRule annotationAdd BLAST294

Sequence similaritiesi

Belongs to the peptidase C26 family.Curated
Contains 1 gamma-glutamyl hydrolase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1559. Eukaryota.
ENOG410XQKI. LUCA.
GeneTreeiENSGT00490000043388.
HOGENOMiHOG000006721.
HOVERGENiHBG005833.
InParanoidiQ92820.
KOiK01307.
OMAiAPYEWKN.
OrthoDBiEOG091G0E82.
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.

Q92820-1 [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)DescriptionActionsGraphical viewLength
Natural variantiVAR_0146976C → R.Corresponds to variant rs1800909dbSNPEnsembl.1
Natural variantiVAR_02923031A → T.Corresponds to variant rs11545077dbSNPEnsembl.1
Natural variantiVAR_029231151T → I.Corresponds to variant rs11545078dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1L9XX-ray1.60A/B/C/D25-318[»]
ProteinModelPortaliQ92820.
SMRiQ92820.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114363. 25 interactors.
IntActiQ92820. 2 interactors.
STRINGi9606.ENSP00000260118.

Chemistry databases

BindingDBiQ92820.
ChEMBLiCHEMBL2223.
DrugBankiDB00158. Folic Acid.
DB00563. Methotrexate.

Protein family/group databases

MEROPSiC26.001.

PTM databases

iPTMnetiQ92820.
PhosphoSitePlusiQ92820.

Polymorphism and mutation databases

BioMutaiGGH.
DMDMi6016127.

Proteomic databases

EPDiQ92820.
MaxQBiQ92820.
PaxDbiQ92820.
PeptideAtlasiQ92820.
PRIDEiQ92820.

Protocols and materials databases

DNASUi8836.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260118; ENSP00000260118; ENSG00000137563.
GeneIDi8836.
KEGGihsa:8836.
UCSCiuc003xuw.4. human.

Organism-specific databases

CTDi8836.
DisGeNETi8836.
GeneCardsiGGH.
HGNCiHGNC:4248. GGH.
HPAiCAB019296.
HPA025226.
MalaCardsiGGH.
MIMi601509. gene.
neXtProtiNX_Q92820.
OpenTargetsiENSG00000137563.
Orphaneti306574. Methotrexate dose selection.
PharmGKBiPA432.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1559. Eukaryota.
ENOG410XQKI. LUCA.
GeneTreeiENSGT00490000043388.
HOGENOMiHOG000006721.
HOVERGENiHBG005833.
InParanoidiQ92820.
KOiK01307.
OMAiAPYEWKN.
OrthoDBiEOG091G0E82.
PhylomeDBiQ92820.
TreeFamiTF323437.

Enzyme and pathway databases

BioCyciZFISH:HS06361-MONOMER.
BRENDAi3.4.19.9. 2681.
ReactomeiR-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

EvolutionaryTraceiQ92820.
GeneWikiiGGH_(gene).
GenomeRNAii8836.
PROiQ92820.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137563.
CleanExiHS_GGH.
GenevisibleiQ92820. HS.

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...

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: November 30, 2016
This is version 152 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

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 one 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.