GGCT gamma-glutamylcyclotransferase [Homo sapiens (human)] - Gene

Summary

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

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
[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].
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:314949 (e-PCR)
- UniSTS:156503

RH48212 (e-PCR)
- UniSTS:30566

D7S2241 (e-PCR)
- UniSTS:29610

D7S2404 (e-PCR)
- UniSTS:154284

RH69806 (e-PCR)
- UniSTS:65737

G44750 (e-PCR)
- UniSTS:95209

G49180 (e-PCR)
- UniSTS:96234

D11S3316 (e-PCR)
- UniSTS:152558

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 more info	PubMed

General protein information

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Preferred Names: gamma-glutamylcyclotransferase

Names: cytochrome c-releasing factor 21; gamma -glutamyl cyclotransferase

NP_001186744.1

EC 4.3.2.9

NP_001186745.1

EC 4.3.2.9

NP_001186746.1

EC 4.3.2.9

NP_076956.1

EC 4.3.2.9

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)

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 ...
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 ...
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 ...
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

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