Hexokinase domain-containing protein-1 in metabolic diseases and beyond

Zapater, Joseph L.; Lednovich, Kristen; Khan, Mohsin; Pusec, Carolina M.; Layden, Brian T.

doi:10.1016/j.tem.2021.10.006

Cited by 28 publications

(29 citation statements)

References 60 publications

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“…However, bacterial and lower vertebrate genes code for smaller proteins (about 50 kDa), while mammalian HKs 1-3 and HKDC1 are ≅ 100 kDa in size. HK isoforms possess high sequence similarities (Supplementary Fig 1) at the 'N' and 'C' terminal domains referred to as "Hemi domains" (Fig 1) [4][5][6][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. These hemi domains are thought to have evolved because of a gene duplication event from the bacterial HK enzyme [23,24].…”

Section: Of 17mentioning

confidence: 99%

“…These hemi domains are thought to have evolved because of a gene duplication event from the bacterial HK enzyme [23,24]. Upon subsequent evolutionary divergence, the N-terminal Hemi domain acquired different properties in each isoform (Fig 1) [9][10][11][12][13][14][15][16][17][18][19][20][21][22]25,26]. One characteristic feature of mammalian HKs is allosteric inhibition by G6P, which supports the "gene duplication event theory," suggesting that the duplication event led to the formation of a hemi-domain that evolved into a regulatory binding site [27].…”

Section: Of 17mentioning

confidence: 99%

“…The gene that codes for HKDC1 lies on chromosome 10 in humans near the HK1 gene, and the two share more than 70% sequence similarity [21]. The enzyme has been shown to play a role in modulating glucose tolerance during pregnancy by identifying its genetic variants in a genome-wide association study (GWAS) [14,19]. Like HK1-2, it also contains an 'N' and a 'C' terminal domain, which are the regions predicted to bind glucose and ATP, respectively, and includes amino acid residues, which remain conserved with those of the other HKs (Fig 1).…”

Section: Of 17mentioning

confidence: 99%

“…Not much is known about the kinetic and regulatory properties of HKDC1, and it needs further exploration. However, the genetic locus near HKDC1 is a "hot spot" for various "histone modifications," and it is believed that HKDC1 is subject to different levels of regulation under different physiological and pathophysiological conditions [19,22]. Although HKDC1 has two kinase domains like HK1, there have been contrasting reports on its catalytic potential.…”

Section: Regulation Of Hexokinase Activitymentioning

confidence: 99%

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Aiding Cancer’s “Sweet Tooth”: Role of Hexokinases in Metabolic Reprogramming

Farooq¹,

Ismail²,

Bhat³

et al. 2023

Preprint

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Hexokinases (HKs) convert hexose sugars to hexose-6-phosphate, thus trapping them inside cells to meet the synthetic and energetic demands. HKs participate in various standard and altered physiological processes, including cancer, primarily through the reprogramming of cellular metabolism. Four canonical HKs have been identified with different expression patterns across tissues. HKs 1-3 play a role in glucose utilization, whereas HK 4 (glucokinase, GCK) also acts as a glucose sensor. Recently, a novel 5th HK, hexokinase domain containing 1 (HKDC1), has been identified, which plays a role in whole-body glucose utilization and insulin sensitivity. Beyond the metabolic functions, HKDC1 is differentially expressed in many forms of human cancer. This review focuses on the role of HKs, particularly HKDC1, in metabolic reprogramming and cancer progression.

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Section: Of 17mentioning

confidence: 99%

Section: Of 17mentioning

confidence: 99%

Section: Of 17mentioning

confidence: 99%

Section: Regulation Of Hexokinase Activitymentioning

confidence: 99%

See 2 more Smart Citations

Aiding Cancer’s “Sweet Tooth”: Role of Hexokinases in Metabolic Reprogramming

Farooq¹,

Ismail²,

Bhat³

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Many studies have reported that the abnormal expression of many genes in tumor tissues may increase the risk of cancer [ 6 ]. Therefore, the identification of changes in gene expression levels will provide new insights for studying the pathogenesis of COAD.…”

Section: Introductionmentioning

confidence: 99%

CTHRC1 is a prognosis-related biomarker correlated with immune infiltrates in colon adenocarcinoma

et al. 2022

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Background Colon adenocarcinoma (COAD) is one of the common cancers worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been reported to be involved in cell invasion, angiogenesis, and the promotion of epithelial-mesenchymal transformation by mediating multiple signaling pathways. However, the role of CTHRC1 in COAD has not yet been determined. Methods Differentially expressed genes were evaluated using gene expression data from the Oncomine and TIMER databases. Correlations between CTHRC1 gene expression and clinicopathological factors were analyzed using gene expression data from UALCAN databases. Then, we searched the GEPIA database to evaluate the association of CTHRC1 gene expression with clinical outcomes. The cBioPortal database was used to analyze CTHRC1 genetic alterations. Subsequently, the TIMER website was chosen to assess the correlation of CTHRC1 with the tumor immune cell infiltration level. The TCGA dataset was used for a gene set enrichment analysis (GSEA). Result CTHRC1 was highly expressed in COAD patients, and significantly related to poor prognosis. In addition, elevated expression of CTHRC1 was related to the clinical stage and pathological type of COAD. The GSEA analysis showed that CTHRC1 was enriched in Gα signaling, GCPR ligand binding, neutrophil degranulation, interleukin signaling, and tumor-associated pathways. In addition, CTHRC1 was significantly associated with the expression of multiple immune markers related to specific immune cells. Conclusion This study suggest that CTHRC1 expression is related to the prognosis and immune infiltration of COAD patients. Therefore, CTHRC1 may be a new candidate prognostic biomarker for determining immune infiltration levels and providing COAD prognoses.

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