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    GGCT gamma-glutamylcyclotransferase [ Homo sapiens (human) ]

    Gene ID: 79017, updated on 3-Nov-2024

    Summary

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    Official Symbol
    GGCTprovided by HGNC
    Official Full Name
    gamma-glutamylcyclotransferaseprovided by HGNC
    Primary source
    HGNC:HGNC:21705
    See related
    Ensembl:ENSG00000006625 MIM:137170; AllianceGenome:HGNC:21705
    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
    GGC; GCTG; CRF21; C7orf24
    Summary
    The protein encoded by this gene catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides, the penultimate step in glutathione catabolism, and may play a critical role in glutathione homeostasis. The encoded protein may also play a role in cell proliferation, and the expression of this gene is a potential marker for cancer. Pseudogenes of this gene are located on the long arm of chromosome 5 and the short arm of chromosomes 2 and 20. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]
    Expression
    Ubiquitous expression in skin (RPKM 24.5), colon (RPKM 21.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GGCT in Genome Data Viewer
    Location:
    7p14.3
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (30496621..30504829, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (30634310..30642526, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (30536237..30544445, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:30430683-30431301 Neighboring gene long intergenic non-protein coding RNA 1176 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25811 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30459231-30459834 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25812 Neighboring gene nucleotide binding oligomerization domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18066 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:30489142-30489642 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:30517896-30518640 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30543653-30544532 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:30544533-30545411 Neighboring gene NANOG hESC enhancer GRCh37_chr7:30551764-30552265 Neighboring gene golgin A8 family member A pseudogene Neighboring gene TRPC6 pseudogene 10

    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 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. Widespread expression of γ-glutamyl cyclotransferase suggests it is not a general tumor marker. Amano T, et al. J Histochem Cytochem, 2012 Jan. PMID 22205682, Free PMC Article
    2. Involvement of cancer biomarker C7orf24 in the growth of human osteosarcoma. Uejima D, et al. Anticancer Res, 2011 Apr. PMID 21508379
    3. Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment. Kageyama S, et al. Biomed Res Int, 2015. PMID 26339607, Free PMC Article
    4. γ-Glutamylcyclotransferase Knockdown Inhibits Growth of Lung Cancer Cells Through G0/G1 Phase Arrest. Lin Z, et al. Cancer Biother Radiopharm, 2015 Jun. PMID 25941902
    5. Depletion of gamma-glutamylcyclotransferase inhibits cancer cell growth by activating the AMPK-FOXO3a-p21 axis. Taniguchi K, et al. Biochem Biophys Res Commun, 2019 Sep 17. PMID 31345573

    See all (82) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer.
      Title: Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer.
    2. MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44.
      Title: MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44.
    3. miR-877 inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting gamma-glutamylcyclotransferase.
      Title: miR-877 inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting gamma-glutamylcyclotransferase.
    4. [The expression of GGCT in the bladder urothelial cell carcinoma and its clinical significance].
      Title: [The expression of GGCT in the bladder urothelial cell carcinoma and its clinical significance].
    5. gamma-Glutamyl cyclotransferase contributes to endometrial carcinoma malignant progression and upregulation of PD-L1 expression during activation of epithelial-mesenchymal transition.
      Title: γ-Glutamyl cyclotransferase contributes to endometrial carcinoma malignant progression and upregulation of PD-L1 expression during activation of epithelial-mesenchymal transition.
    6. a role for EP2/EP4 signaling in regulating IGF-1-induced cell proliferation, in which EP2/EP4 signaling represses IGF-1-induced GGCT expression, is reported.
      Title: Inhibition of EP2/EP4 prostanoid receptor-mediated signaling suppresses IGF-1-induced proliferation of pancreatic cancer BxPC-3 cells via upregulating γ-glutamyl cyclotransferase expression.
    7. FOXO3a is identified as a mediator for p21 upregulation by GGCT depletion. AMPK is required for the FOXO3a-mediated p21 upregulation by GGCT depletion. AMPK-FOXO3a-p21 axis plays a role in cancer cell growth inhibition by GGCT depletion.
      Title: Depletion of gamma-glutamylcyclotransferase inhibits cancer cell growth by activating the AMPK-FOXO3a-p21 axis.
    8. GGCT is highly upregulated in HGSC tissues and associated with FIGO stage, lymph node metastasis and ascitic fluid volume. High expression of GGCT is associated with poor survival in HGSC patients.
      Title: γ-Glutamyl cyclotransferase contributes to tumor progression in high grade serous ovarian cancer by regulating epithelial-mesenchymal transition via activating PI3K/AKT/mTOR pathway.
    9. Taken together, the results indicate that PHB2 plays a central role in p21 upregulation following GGCT knockdown and as such may promote deregulated proliferation of cancer cells by suppressing p21.
      Title: Prohibitin-2 is a novel regulator of p21(WAF1/CIP1) induced by depletion of γ-glutamylcyclotransferase.
    10. GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target.
      Title: Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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

    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

    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

    • MGC3077, FLJ11717

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables gamma-glutamylcyclotransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables gamma-glutamylcyclotransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in release of cytochrome c from mitochondria IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 

    General protein information

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    Preferred Names
    gamma-glutamylcyclotransferase
    Names
    cytochrome c-releasing factor 21
    gamma -glutamyl cyclotransferase
    NP_001186744.1
    NP_001186745.1
    NP_001186746.1
    NP_076956.1

    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_001199815.2 → NP_001186744.1  gamma-glutamylcyclotransferase isoform 2

      See identical proteins and their annotated locations for NP_001186744.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has multiple differences in the coding region, compared to variant 1, one of which results in a translational frameshift. The resulting protein (isoform 2) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC005154, BC019243, BE407390
      Consensus CDS
      CCDS56476.1
      UniProtKB/Swiss-Prot
      O75223
      Related
      ENSP00000387235.1, ENST00000409390.5
      Conserved Domains (1) summary
      cd06661
      Location:19 → 97
      GGCT_like; GGCT-like domains, also called AIG2-like family. Gamma-glutamyl cyclotransferase (GGCT) catalyzes the formation of pyroglutamic acid (5-oxoproline) from dipeptides containing gamma-glutamyl, and is a dimeric protein. In Homo sapiens, the protein is ...

    2. NM_001199816.2 → NP_001186745.1  gamma-glutamylcyclotransferase isoform 3

      See identical proteins and their annotated locations for NP_001186745.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC005154, BC005356, BC019243
      Consensus CDS
      CCDS56475.1
      UniProtKB/Swiss-Prot
      O75223
      Related
      ENSP00000005374.6, ENST00000005374.10
      Conserved Domains (1) summary
      cd06661
      Location:19 → 97
      GGCT_like; GGCT-like domains, also called AIG2-like family. Gamma-glutamyl cyclotransferase (GGCT) catalyzes the formation of pyroglutamic acid (5-oxoproline) from dipeptides containing gamma-glutamyl, and is a dimeric protein. In Homo sapiens, the protein is ...

    3. NM_001199817.2 → NP_001186746.1  gamma-glutamylcyclotransferase isoform 4

      See identical proteins and their annotated locations for NP_001186746.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks multiple exons in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 4, which is shorter than isoform 1.
      Source sequence(s)
      AC005154, BC019243, BE885397
      Consensus CDS
      CCDS56474.1
      UniProtKB/Swiss-Prot
      O75223
      Related
      ENSP00000386610.1, ENST00000409144.5
      Conserved Domains (2) summary
      cd06661
      Location:19 → 47
      GGCT_like; GGCT-like domains, also called AIG2-like family. Gamma-glutamyl cyclotransferase (GGCT) catalyzes the formation of pyroglutamic acid (5-oxoproline) from dipeptides containing gamma-glutamyl, and is a dimeric protein. In Homo sapiens, the protein is ...
      cl22886
      Location:35 → 66
      GGCT_like; GGCT-like domains, also called AIG2-like family. Gamma-glutamyl cyclotransferase (GGCT) catalyzes the formation of pyroglutamic acid (5-oxoproline) from dipeptides containing gamma-glutamyl, and is a dimeric protein. In Homo sapiens, the protein is ...

    4. NM_024051.4 → NP_076956.1  gamma-glutamylcyclotransferase isoform 1

      See identical proteins and their annotated locations for NP_076956.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC005154, BC000625, BC019243
      Consensus CDS
      CCDS5428.1
      UniProtKB/Swiss-Prot
      B2RDN0, B8ZZN4, B8ZZR8, O75223, Q9BS37
      UniProtKB/TrEMBL
      A0A090N7V5
      Related
      ENSP00000275428.4, ENST00000275428.9
      Conserved Domains (1) summary
      pfam13772
      Location:78 → 160
      AIG2_2; AIG2-like family

    RNA

    1. NR_037669.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks an exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC005154, BC019243, BG527593
      Related
      ENST00000440082.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      30496621..30504829 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      30634310..30642526 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O75223.1 GenPept UniProtKB/Swiss-Prot:O75223

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