MEX3B

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000932 P-body	IEA GO_REF:0000044	ACCEPT	Summary: MEX3B localizes to P-bodies as documented in UniProt based on experimental evidence from PMID:18779327 and PMID:17267406. The deep research confirms MEX3B is "enriched in cytoplasmic processing bodies (P-bodies)" consistent with its role in post-transcriptional mRNA regulation. Reason: P-body localization is well-documented for MEX3B and consistent with its function as an RNA-binding protein involved in mRNA destabilization. This is a core localization for the protein's function. Supporting Evidence: PMID:17267406 hMex-3A and hMex-3B, but not hMex-3C, colocalize with both the hDcp1a decapping factor and Argonaute (Ago) proteins in processing bodies (P bodies) file:human/MEX3B/MEX3B-deep-research-falcon.md MEX-3 family proteins, including MEX3B, are enriched in cytoplasmic processing bodies (P-bodies)
GO:0003676 nucleic acid binding	IEA GO_REF:0000002	MODIFY	Summary: This IEA annotation from InterPro is based on the KH domain (IPR004087). While correct, this term is too general for MEX3B which has well-characterized RNA binding specificity. The protein specifically binds mRNA 3'-UTRs through its tandem KH domains. Reason: MEX3B is specifically an RNA-binding protein, not a general nucleic acid binder. The more specific term GO:0003723 (RNA binding) or even GO:0003730 (mRNA 3'-UTR binding) better captures its function. Proposed replacements: mRNA 3'-UTR binding Supporting Evidence: PMID:17267406 The hMex-3 are phosphoproteins that bind RNA through their KH domains
GO:0003723 RNA binding	IEA GO_REF:0000120	ACCEPT	Summary: This IEA annotation is well-supported by structural and functional data. MEX3B contains two tandem KH domains that mediate sequence-specific RNA recognition. The 2024 structural study defined a high-affinity 12-nt HLA-A 3'UTR motif (CUGAGCUGUAAC) and showed tandem KH1/2 binds approximately 100-fold more strongly than individual KH domains. Reason: RNA binding is a core molecular function of MEX3B, well-established by multiple experimental studies. While mRNA 3'-UTR binding would be more specific, RNA binding is accurate and appropriate. Supporting Evidence: PMID:17267406 The hMex-3 are phosphoproteins that bind RNA through their KH domains file:human/MEX3B/MEX3B-deep-research-falcon.md Tandem KH1/2 of hMEX3B binds an optimized HLA-A 3'UTR 12-nt motif roughly 100-fold more strongly than individual KH domains
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: MEX3B shuttles between cytoplasm and nucleus via the CRM1 export pathway, with predominant cytoplasmic localization. Nuclear localization is documented in UniProt based on experimental evidence from PMID:18779327. Reason: While MEX3B is predominantly cytoplasmic, it does shuttle to the nucleus. This represents a valid, if secondary, localization for the protein. Supporting Evidence: PMID:17267406 The hMex-3 are phosphoproteins that bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: MEX3B is predominantly localized in the cytoplasm where it functions in P-bodies and cytoplasmic RNA granules. This is the primary site of its RNA-binding and post-transcriptional regulatory activities. Reason: Cytoplasmic localization is the primary localization for MEX3B and is essential for its function in mRNA regulation. This is a core annotation. Supporting Evidence: PMID:17267406 The hMex-3 are phosphoproteins that bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway
GO:0008270 zinc ion binding	IEA GO_REF:0000043	ACCEPT	Summary: MEX3B contains a C-terminal RING-type zinc finger domain (C3HC4) that coordinates zinc ions. This domain is essential for its E3 ubiquitin ligase activity. The annotation is derived from UniProtKB keyword mapping. Reason: The RING finger domain (residues 518-558) is a zinc-coordinating domain that is essential for MEX3B's E3 ubiquitin ligase activity. Zinc ion binding is an accurate molecular function annotation. Supporting Evidence: PMID:17267406 encode proteins containing two heterogeneous nuclear ribonucleoprotein K homology (KH) domains and one carboxy-terminal RING finger module
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: This annotation is a parent term of zinc ion binding (GO:0008270). While technically correct, it is redundant given the more specific zinc ion binding annotation. Reason: While redundant with zinc ion binding, this IEA annotation from keyword mapping is accurate. The RING finger domain does bind metal ions (specifically zinc). Keeping as acceptable IEA annotation. Supporting Evidence: PMID:17267406 encode proteins containing two heterogeneous nuclear ribonucleoprotein K homology (KH) domains and one carboxy-terminal RING finger module
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	MODIFY	Summary: This annotation is from a large-scale study on 14-3-3 protein interactions. MEX3B interacts with YWHAE (14-3-3 epsilon) as documented in IntAct. The interaction is functionally relevant as 14-3-3 binding at phospho-Ser-462 regulates MEX3B localization to P-bodies and its RNA-binding activity. Reason: While the protein-protein interaction is valid, "protein binding" (GO:0005515) is too vague and uninformative. The specific interaction with 14-3-3 proteins is functionally significant and should be annotated with a more specific term. 14-3-3 protein binding (GO:0071889) would be more appropriate. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:18779327 14-3-3 bind to hMex-3B but not to the three other hMex-3 family members. Serine 462, when phosphorylated, is the major 14-3-3 docking site on hMex-3B
GO:0000932 P-body	IDA PMID:23408853 CDX2 regulation by the RNA-binding protein MEX3A: impact on ...	ACCEPT	Summary: Note: PMID:23408853 is primarily about MEX3A, not MEX3B. However, the paper discusses MEX3 family proteins and P-body localization. P-body localization for MEX3B is well-documented from other sources (PMID:18779327, PMID:17267406). Reason: While the specific reference may be about MEX3A, P-body localization for MEX3B is well-established from other experimental studies. This is a core localization for MEX3B function in post-transcriptional mRNA regulation. Supporting Evidence: PMID:17267406 hMex-3A and hMex-3B, but not hMex-3C, colocalize with both the hDcp1a decapping factor and Argonaute (Ago) proteins in processing bodies (P bodies)
GO:0003723 RNA binding	IDA PMID:23408853 CDX2 regulation by the RNA-binding protein MEX3A: impact on ...	ACCEPT	Summary: Note: PMID:23408853 is primarily about MEX3A, not MEX3B. The paper demonstrates RNA binding for MEX3A through its KH domains. However, MEX3B RNA binding is well-established from other sources including the 2024 structural study showing specific binding to HLA-A 3'UTR. Reason: While the specific reference is about MEX3A, RNA binding for MEX3B is extensively documented. The two KH domains mediate sequence-specific RNA recognition with high affinity for specific 3'UTR sequences. Supporting Evidence: PMID:17267406 The hMex-3 are phosphoproteins that bind RNA through their KH domains
GO:0003723 RNA binding	HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ...	ACCEPT	Summary: PMID:22681889 is a high-throughput study that identified the mRNA-bound proteome using photoreactive nucleotide-enhanced UV crosslinking. MEX3B was identified among approximately 800 proteins in the mRNA-bound proteome of HEK293 cells. Reason: This HDA (high-throughput direct assay) evidence supports MEX3B as an mRNA-binding protein. While less specific than targeted studies, it provides independent validation of MEX3B's RNA-binding activity. Supporting Evidence: PMID:22681889 Application to a human embryonic kidney cell line identified close to 800 proteins
GO:0005509 calcium ion binding	ISS GO_REF:0000024	REMOVE	Summary: This ISS annotation was transferred from MEX3C (Q96RR4). There is no evidence that MEX3B binds calcium ions. MEX3B has KH domains (RNA binding) and a RING finger (zinc binding), neither of which are calcium-binding domains. This appears to be an erroneous annotation transfer. Reason: MEX3B contains no recognizable calcium-binding domains. Its domain architecture consists of two KH domains and a RING finger domain. The RING domain binds zinc, not calcium. There is no functional or structural basis for calcium ion binding by MEX3B. Supporting Evidence: PMID:17267406 encode proteins containing two heterogeneous nuclear ribonucleoprotein K homology (KH) domains and one carboxy-terminal RING finger module
GO:0006468 protein phosphorylation	ISS GO_REF:0000024	REMOVE	Summary: MISANNOTATION: MEX3B is an RNA-binding protein with KH domains and a RING finger domain (E3 ubiquitin ligase), NOT a kinase. ISS transfer from MEX3C (Q96RR4) is erroneous. UniProt documents that MEX3B is PHOSPHORYLATED at Ser-4, Ser-288, Ser-462 - it is a phosphorylation SUBSTRATE, not an enzyme that phosphorylates other proteins. Reason: MEX3B has no kinase domain and no evidence of kinase activity. It is itself phosphorylated by other kinases. The RING finger domain has E3 ubiquitin ligase activity, not kinase activity. This is a clear misannotation. Supporting Evidence: PMID:18779327 Serine 462, when phosphorylated, is the major 14-3-3 docking site on hMex-3B
GO:0046777 protein autophosphorylation	ISS GO_REF:0000024	REMOVE	Summary: MISANNOTATION: MEX3B is an RNA-binding E3 ubiquitin ligase, NOT a kinase. Autophosphorylation requires kinase activity which MEX3B does not possess. The ISS transfer from MEX3C is erroneous - MEX3 proteins are RNA-binding proteins, not kinases. Reason: MEX3B cannot autophosphorylate because it lacks any kinase domain or activity. Its domain architecture (KH domains + RING finger) provides RNA-binding and E3 ubiquitin ligase activities, not kinase activity. This annotation is biologically impossible. Supporting Evidence: PMID:17267406 encode proteins containing two heterogeneous nuclear ribonucleoprotein K homology (KH) domains and one carboxy-terminal RING finger module
GO:0003730 mRNA 3'-UTR binding	IDA file:human/MEX3B/MEX3B-deep-research-falcon.md	NEW	Summary: NEW ANNOTATION: The 2024 structural/biophysical study definitively demonstrated that MEX3B binds specifically to the HLA-A 3'-UTR through a defined 12-nt motif (CUGAGCUGUAAC). NMR/SAXS and mutagenesis revealed the molecular mechanism of this interaction. Reason: This is a core molecular function of MEX3B with high-quality experimental evidence. The term mRNA 3'-UTR binding (GO:0003730) is more specific than RNA binding and accurately captures MEX3B's demonstrated activity. Supporting Evidence: file:human/MEX3B/MEX3B-deep-research-falcon.md Defined the sequence-specific HLA-A 3'UTR binding by hMEX3B. Mapped a high-affinity 12-nt motif (CUGAGCUGUAAC)
GO:0061158 3'-UTR-mediated mRNA destabilization	IDA file:human/MEX3B/MEX3B-deep-research-falcon.md	NEW	Summary: NEW ANNOTATION: MEX3B binding to the HLA-A 3'-UTR promotes mRNA degradation and reduces HLA-A surface expression. This is a core biological process function with direct evidence from the 2024 study. Reason: This biological process annotation captures MEX3B's primary post-transcriptional regulatory function - destabilizing mRNAs by binding to their 3'-UTRs. This is well-documented for HLA-A and likely applies to other targets. Supporting Evidence: file:human/MEX3B/MEX3B-deep-research-falcon.md MEX3B binding promotes degradation of substrate mRNAs and reduces HLA-A surface expression
GO:0004842 ubiquitin-protein transferase activity	IDA file:human/MEX3B/MEX3B-deep-research-falcon.md	NEW	Summary: NEW ANNOTATION: MEX3B functions as an E3 ubiquitin ligase via its C-terminal RING finger domain. Validated ubiquitination substrates include SNUPN (Snurportin-1), RUNX3, and SUZ12, often in complexes scaffolded by the lncRNA HOTAIR. Reason: E3 ubiquitin ligase activity is a core molecular function of MEX3B mediated by its RING finger domain. This dual function (RNA binding + E3 ligase) is characteristic of MEX3 family proteins. Supporting Evidence: file:human/MEX3B/MEX3B-deep-research-falcon.md MEX3B is reported to ubiquitinate and promote degradation of specific proteins, including SNUPN (Snurportin-1), SUZ12, and RUNX3
GO:0002590 negative regulation of antigen processing and presentation of peptide antigen via MHC class I	IDA file:human/MEX3B/MEX3B-deep-research-falcon.md	NEW	Summary: NEW ANNOTATION: MEX3B negatively regulates MHC class I antigen presentation by destabilizing HLA-A mRNA through 3'-UTR binding. This reduces HLA-A surface expression and contributes to tumor immune evasion and resistance to anti-PD-1 immunotherapy. Reason: This biological process annotation captures the functional consequence of MEX3B's mRNA-destabilizing activity on HLA-A. This is directly relevant to tumor immunity and has been extensively validated. Supporting Evidence: file:human/MEX3B/MEX3B-deep-research-falcon.md MEX3B directly represses HLA-A expression at the mRNA level via 3'UTR binding, yielding reduced MHC-I surface expression and antigen display