Biomarker: YTHDF2

Histology type: endometrial endometrioid carcinoma

Country: China

Region: Guangzhou

Followed up time :

Conclusion: YTHDF2 expression can accurately assess the depth of myometrial invasion (DMI) in EMAC when EMAC coexists with adenomyosis.

Sample type : tissue

Sample method: qRT-PCR, Western blot, and immunohistochemical (IHC)

Expression pattern : upregulated

Funtion Uniprot: Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:32492408, PubMed:25412658, PubMed:25412661). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31388144, PubMed:31292544, PubMed:32451507, PubMed:31642031). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440).By Similarity21 Publications (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282).1 Publication (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627).

UniProt ID: Q9Y5A9

UniProt Link: https://www.uniprot.org/uniprotkb/Q9Y5A9/entry

Biological function from UniProt: #Cell cycle #Cell division #Differentiation #Host-virus interaction #Immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation.

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Caution: The role of YTHDF2 and N6-methyladenosine (m6A) in virus expression and replication is unclear (PubMed:29109479, PubMed:29447282, PubMed:29659627, PubMed:30559377). According to some reports, YTHDF2 promotes viral gene expression and replication of polyomavirus SV40 and herpesvirus (KSHV) by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282, PubMed:29659627). Another report however suggests that YTHDF2 regulates virus expression and replication indirectly, via its ability to inhibit the type I interferon response, thereby promoting virus expression (PubMed:30559377). Indirect regulation via inhibition of type I interferon response might explain why contradictory results have been reported for its role in KSHV virus replication (PubMed:29109479, PubMed:29659627).4 Publications Previous studies suggested the 3 different paralogs (YTHDF1, YTHDF2 and YTHDF3) have unique functions with limited redundancy (PubMed:26046440). However, later studies showed that YTHDF1, YTHDF2 and YTHDF3 paralogs have redundant functions to a profound extent and directly promote degradation of m6A-containing mRNAs (PubMed:32492408).2 Publications

Recommended name: YTH domain-containing family protein 2

Gene name from HGNC: YTHDF2 (CAHL, HGRG8, NY-REN-2)

HPA class: Plasma proteins

AlphaFold DB: Q9Y5A9

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q9Y5A9

Induction: Following heat shock stress.

HPA link: https://www.proteinatlas.org/ENSG00000198492-YTHDF2

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Nuclear expression in most tissues with variable levels.

Single cell type specificity Cell type enhanced (Syncytiotrophoblasts)

Immune cell specificity: Non-specific - Gene expression (mainly)

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

Pathology link: https://www.proteinatlas.org/ENSG00000198492-YTHDF2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000198492-YTHDF2/pathology/endometrial+cancer

OMIM: 610640

OMIM link2: https://www.omim.org/entry/610640

HGNC ID: HGNC:31675

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:31675