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GGCT gamma-glutamylcyclotransferase [ Homo sapiens (human) ]

Gene ID: 79017, updated on 7-Apr-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
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Genomic context

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Location:
7p14.3
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (30496621..30504829, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (30634310..30642526, complement)
105.20220307 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
  • 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. [The expression of GGCT in the bladder urothelial cell carcinoma and its clinical significance]. Guo YS, et al. Zhonghua Zhong Liu Za Zhi, 2021 Nov 23. PMID 34794221
  2. 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
  3. γ-Glutamyl cyclotransferase contributes to tumor progression in high grade serous ovarian cancer by regulating epithelial-mesenchymal transition via activating PI3K/AKT/mTOR pathway. Li Y, et al. Gynecol Oncol, 2018 Apr. PMID 29429592
  4. Depletion of γ-glutamylcyclotransferase inhibits breast cancer cell growth via cellular senescence induction mediated by CDK inhibitor upregulation. Matsumura K, et al. BMC Cancer, 2016 Sep 22. PMID 27658708, Free PMC Article
  5. Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling. Shen SH, et al. Biochem Biophys Res Commun, 2016 Mar 18. PMID 26828272

See all (74) 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_2023_10

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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