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    GGT5 gamma-glutamyltransferase 5 [ Homo sapiens (human) ]

    Gene ID: 2687, updated on 22-Apr-2024

    Summary

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    Official Symbol
    GGT5provided by HGNC
    Official Full Name
    gamma-glutamyltransferase 5provided by HGNC
    Primary source
    HGNC:HGNC:4260
    See related
    Ensembl:ENSG00000099998 MIM:137168; AllianceGenome:HGNC:4260
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GGL; GGT 5; GGTLA1; GGT-REL
    Summary
    This gene is a member of the gamma-glutamyl transpeptidase gene family, and some reports indicate that it is capable of cleaving the gamma-glutamyl moiety of glutathione. The protein encoded by this gene is synthesized as a single, catalytically-inactive polypeptide, that is processed post-transcriptionally to form a heavy and light subunit, with the catalytic activity contained within the small subunit. The encoded enzyme is able to convert leukotriene C4 to leukotriene D4, but appears to have distinct substrate specificity compared to gamma-glutamyl transpeptidase. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
    Expression
    Ubiquitous expression in fat (RPKM 18.6), kidney (RPKM 15.2) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    22q11.23
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (24219654..24245142, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (24681268..24706753, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (24615622..24641110, complement)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18762 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18763 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24585541-24586182 Neighboring gene sushi domain containing 2 Neighboring gene MPRA-validated peak4472 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18764 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18765 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:24601258-24602226 Neighboring gene uncharacterized LOC124905090 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:24609597-24610123 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18766 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24639831-24640386 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24640387-24640942 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24642055-24642610 Neighboring gene Sharpr-MPRA regulatory region 1554 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24647549-24648049 Neighboring gene gamma-glutamyltransferase light chain 4 pseudogene Neighboring gene POM121 transmembrane nucleoporin like 9, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24651904-24652808 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:24655631-24656248 Neighboring gene BCR pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Cancer-associated fibroblasts-derived gamma-glutamyltransferase 5 promotes tumor growth and drug resistance in lung adenocarcinoma. Wei JR, et al. Aging (Albany NY), 2020 Jul 8. PMID 32640421, Free PMC Article
    2. Evidence for the pro-oxidant effect of gamma-glutamyltranspeptidase-related enzyme. Enoiu M, et al. Free Radic Biol Med, 2000 Nov 1. PMID 11063908
    3. Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Edelmann L, et al. Am J Hum Genet, 1999 Apr. PMID 10090893, Free PMC Article
    4. Localization of a gamma-glutamyl-transferase-related gene family on chromosome 22. Morris C, et al. Hum Genet, 1993 Mar. PMID 8095916
    5. Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: concomitant formation of leukotriene D4 and gamma-glutamyl amino acids. Anderson ME, et al. Proc Natl Acad Sci U S A, 1982 Feb. PMID 6122208, Free PMC Article

    See all (26) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. GGT5 facilitates migration and invasion through the induction of epithelial-mesenchymal transformation in gastric cancer.
      Title: GGT5 facilitates migration and invasion through the induction of epithelial-mesenchymal transformation in gastric cancer.
    2. Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione.
      Title: Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione.
    3. Cancer-associated fibroblasts-derived gamma-glutamyltransferase 5 promotes tumor growth and drug resistance in lung adenocarcinoma.
      Title: Cancer-associated fibroblasts-derived gamma-glutamyltransferase 5 promotes tumor growth and drug resistance in lung adenocarcinoma.
    4. Formation of LTD4 was rapid when catalyzed by gamma-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1beta, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation.
      Title: Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4.
    5. Report different pattern of expression of GGT1 and GGT5 in normal human tissues.
      Title: Immunolabeling of gamma-glutamyl transferase 5 in normal human tissues reveals that expression and localization differ from gamma-glutamyl transferase 1.
    6. There is a significant association of GGT with individual metabolic syndrome components, except HDL and inflammatory parameters (hs-CRP, ferritin).
      Title: Gamma-glutamyl transpeptidase level associated with metabolic syndrome and proinflammatory parameters in the young Roma population in eastern Slovakia: a population-based study.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis.
    EBI GWAS Catalog
    Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of gamma-glutamyltransferase 5 (GGT5) in primary human brain microvascular endothelial cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ92733, DKFZp566O011

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables glutathione hydrolase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glutathione hydrolase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables leukotriene C4 gamma-glutamyl transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables leukotriene-C(4) hydrolase IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables leukotriene-C(4) hydrolase IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables peptidyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in amino acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fatty acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in glutathione biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glutathione catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glutathione catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in leukotriene D4 biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in leukotriene D4 biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in leukotriene D4 biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    glutathione hydrolase 5 proenzyme
    Names
    gamma-glutamyl cleaving enzyme
    gamma-glutamyl transpeptidase-related enzyme
    gamma-glutamyl transpeptidase-related protein
    gamma-glutamyltransferase-like activity 1
    gamma-glutamyltranspeptidase 5
    leukotriene-C4 hydrolase
    NP_001093251.1
    NP_001093252.1
    NP_001289393.1
    NP_001289394.1
    NP_004112.2
    XP_005261614.1
    XP_005261615.1
    XP_011528435.1
    XP_011528436.1
    XP_011528437.1
    XP_011528438.1
    XP_011528439.1
    XP_016884257.1
    XP_016884258.1
    XP_047297284.1
    XP_047297285.1
    XP_047297286.1
    XP_047297287.1
    XP_054181502.1
    XP_054181503.1
    XP_054181504.1
    XP_054181505.1
    XP_054181506.1
    XP_054181507.1
    XP_054181508.1
    XP_054181509.1
    XP_054181510.1
    XP_054181511.1
    XP_054181512.1
    XP_054181513.1
    XP_054181514.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001099781.2 → NP_001093251.1  glutathione hydrolase 5 proenzyme isoform 1

      See identical proteins and their annotated locations for NP_001093251.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      BC073999, BU728951, BX403504
      Consensus CDS
      CCDS42990.1
      UniProtKB/TrEMBL
      B4DND4
      Related
      ENSP00000381340.3, ENST00000398292.3
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 582
      G_glu_transpept; Gamma-glutamyltranspeptidase

    2. NM_001099782.2 → NP_001093252.1  glutathione hydrolase 5 proenzyme isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AK225661, BU728951, BX403504
      Consensus CDS
      CCDS42989.1
      UniProtKB/TrEMBL
      B4DEL3
      Related
      ENSP00000263112.7, ENST00000263112.11
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 549
      G_glu_transpept; Gamma-glutamyltranspeptidase

    3. NM_001302464.1 → NP_001289393.1  glutathione hydrolase 5 proenzyme isoform 4

      See identical proteins and their annotated locations for NP_001289393.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has multiple differences in the coding region, one of which results in a translational frameshift, compared to variant 1. The encoded isoform (4) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AK225661, AL117414, BU728951, BX403504
      UniProtKB/Swiss-Prot
      P36269
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 506
      G_glu_transpept; Gamma-glutamyltranspeptidase

    4. NM_001302465.1 → NP_001289394.1  glutathione hydrolase 5 proenzyme isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks two alternate exons and uses an alternate splice site in the 5' coding region, compared to variant 1. The encoded isoform (5) is shorter and contains a distinct internal segment, compared to isoform 1.
      Source sequence(s)
      AK293683, BC073999, BU728951, BX403504
      UniProtKB/TrEMBL
      B4DEL3
      Conserved Domains (1) summary
      cl19223
      Location:123 → 505
      G_glu_transpept; Gamma-glutamyltranspeptidase

    5. NM_004121.5 → NP_004112.2  glutathione hydrolase 5 proenzyme isoform 2

      See identical proteins and their annotated locations for NP_004112.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (2) is one amino acid shorter than isoform 1.
      Source sequence(s)
      AP000353, AP000354
      Consensus CDS
      CCDS13825.1
      UniProtKB/Swiss-Prot
      P36269, Q53XM9, Q6GMP0, Q96FC1, Q9UFM5
      UniProtKB/TrEMBL
      B4DND4
      Related
      ENSP00000330080.4, ENST00000327365.10
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 581
      G_glu_transpept; Gamma-glutamyltranspeptidase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      24219654..24245142 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017028768.3 → XP_016884257.1  glutathione hydrolase 5 proenzyme isoform X6

      UniProtKB/TrEMBL
      B4DND4

    2. XM_017028769.3 → XP_016884258.1  glutathione hydrolase 5 proenzyme isoform X10

      UniProtKB/TrEMBL
      B4DEL3

    3. XM_011530135.3 → XP_011528437.1  glutathione hydrolase 5 proenzyme isoform X5

      Conserved Domains (1) summary
      pfam01019
      Location:60 → 586
      G_glu_transpept; Gamma-glutamyltranspeptidase

    4. XM_005261558.4 → XP_005261615.1  glutathione hydrolase 5 proenzyme isoform X3

      UniProtKB/TrEMBL
      B4DND4
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 612
      G_glu_transpept; Gamma-glutamyltranspeptidase

    5. XM_005261557.4 → XP_005261614.1  glutathione hydrolase 5 proenzyme isoform X2

      UniProtKB/TrEMBL
      B4DND4
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 613
      G_glu_transpept; Gamma-glutamyltranspeptidase

    6. XM_011530134.3 → XP_011528436.1  glutathione hydrolase 5 proenzyme isoform X4

      UniProtKB/TrEMBL
      B4DND4
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 587
      G_glu_transpept; Gamma-glutamyltranspeptidase

    7. XM_011530133.3 → XP_011528435.1  glutathione hydrolase 5 proenzyme isoform X1

      UniProtKB/TrEMBL
      B4DND4
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 618
      G_glu_transpept; Gamma-glutamyltranspeptidase

    8. XM_011530136.3 → XP_011528438.1  glutathione hydrolase 5 proenzyme isoform X8

      Conserved Domains (1) summary
      pfam01019
      Location:60 → 544
      G_glu_transpept; Gamma-glutamyltranspeptidase

    9. XM_047441331.1 → XP_047297287.1  glutathione hydrolase 5 proenzyme isoform X13

    10. XM_047441330.1 → XP_047297286.1  glutathione hydrolase 5 proenzyme isoform X12

    11. XM_047441328.1 → XP_047297284.1  glutathione hydrolase 5 proenzyme isoform X7

    12. XM_047441329.1 → XP_047297285.1  glutathione hydrolase 5 proenzyme isoform X9

    13. XM_011530137.4 → XP_011528439.1  glutathione hydrolase 5 proenzyme isoform X11

      UniProtKB/TrEMBL
      B4DND4
      Conserved Domains (1) summary
      pfam01019
      Location:60 → 544
      G_glu_transpept; Gamma-glutamyltranspeptidase

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      24681268..24706753 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054325532.1 → XP_054181507.1  glutathione hydrolase 5 proenzyme isoform X6

    2. XM_054325536.1 → XP_054181511.1  glutathione hydrolase 5 proenzyme isoform X10

    3. XM_054325531.1 → XP_054181506.1  glutathione hydrolase 5 proenzyme isoform X5

    4. XM_054325529.1 → XP_054181504.1  glutathione hydrolase 5 proenzyme isoform X3

    5. XM_054325528.1 → XP_054181503.1  glutathione hydrolase 5 proenzyme isoform X2

    6. XM_054325530.1 → XP_054181505.1  glutathione hydrolase 5 proenzyme isoform X4

    7. XM_054325527.1 → XP_054181502.1  glutathione hydrolase 5 proenzyme isoform X1

    8. XM_054325534.1 → XP_054181509.1  glutathione hydrolase 5 proenzyme isoform X8

    9. XM_054325539.1 → XP_054181514.1  glutathione hydrolase 5 proenzyme isoform X13

    10. XM_054325538.1 → XP_054181513.1  glutathione hydrolase 5 proenzyme isoform X12

    11. XM_054325533.1 → XP_054181508.1  glutathione hydrolase 5 proenzyme isoform X7

    12. XM_054325535.1 → XP_054181510.1  glutathione hydrolase 5 proenzyme isoform X9

    13. XM_054325537.1 → XP_054181512.1  glutathione hydrolase 5 proenzyme isoform X11

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P36269.2 GenPept UniProtKB/Swiss-Prot:P36269

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