Biomarker: G9a

Histology type: endometrial carcinoma

Country: Taiwan

Region: New Taipei

Study type: retrospective study

Followed up time :

Subgroup 1 name : EC

Subgroup 1 number: 94

Subgroup 2 name: normal tissues

Subgroup 2 number: 28

Conclusion: This study provides the first clear evidence that G9a contributes to endometrial cancer progression. Mechanistic investigations suggest that E-cadherin repression mediates the effects of G9a. Targeting G9a-mediated epigenetic pathway dysregulation may be a therapeutic strategy for endometrial cancers.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : high expression(>cutoff, staining index (SI: values 0–6, the distribution plots and the number of cases and events were considered in determining the final cutoff between low and high expression (2 categories).).

Expression elevation: To assess G9a expression, a staining index (SI) was calculated as the product of the intensity (0–2) and the positive tumor cell area (\10, 10–50, [50 %). The expression categories were initially based on the quartiles of the resulting staining index (SI: values 0–6). The distribution plots and the number of cases and events were considered in determining the final cutoff between low and high expression (2 categories).

Funtion description: Cell invasiveness was inhibited by an RNAi-mediated knockdown of G9a in invasive endometrial cancer cells in vitro and in vivo. An important mediator of G9a-induced tumor invasion is the epigenetic silencing of E-cadherin. Knockdown of G9a restored E-cadherin expression by reducing H3K9me2 levels and decreasing CDH1 promoter DNA methyltransferase recruitment. Knockdown of RNAi-mediated E-cadherin substantially relieved the invasion suppression imposed by G9a suppression.

Funtion Uniprot: Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.

UniProt ID: Q96KQ7

UniProt Link: https://www.uniprot.org/uniprotkb/Q96KQ7/entry

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow.

Subcellular UniProt: #Chromosome #Nucleus

Alternative name from UniProt:

Caution: While NG36 and G9a were originally thought to derive from 2 separate genes, all G9A transcripts also contain the in frame coding sequence of NG36. It is uncertain whether Met-1 or Met-21 is the initiator methionine.

Catalytic activity: N6-methyl-L-lysyl9-[histone H3] + S-adenosyl-L-methionine = H+ + N6,N6-dimethyl-L-lysyl9-[histone H3] + S-adenosyl-L-homocysteine;L-lysyl9-[histone H3] + S-adenosyl-L-methionine = H+ + N6-methyl-L-lysyl9-[histone H3] + S-adenosyl-L-homocysteine;

Recommended name: Histone-lysine N-methyltransferase EHMT2

Gene name from HGNC: EHMT2 (BAT8, C6orf30, Em:AF134726.3, G9A, KMT1C, NG36/G9a)

HPA class: Metabolic proteins Plasma proteins

AlphaFold DB: Q96KQ7

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q96KQ7

HPA link: https://www.proteinatlas.org/ENSG00000204371-EHMT2

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Nuclear expression in several tissues.

Single cell type specificity Low cell type specificity

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Nuclear speckles

Cancer prognostic summary HPA Prognostic marker in liver cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000204371-EHMT2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000204371-EHMT2/pathology/endometrial+cancer

OMIM: 604599

OMIM link2: https://www.omim.org/entry/604599

HGNC ID: HGNC:14129

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14129