FTSJ1 is an S-adenosylmethionine-dependent tRNA ribose methyltransferase that modifies the anticodon loop of cytoplasmic tRNAs. THADA supports methylation at position 32, whereas WDR6 supports wobble position 34 methylation. Established catalytic activities include cytidine 32, guanosine 34 and cytidine 34 2-prime-O-methylation, with substrate requirements that differ among tRNAs and assay conditions. Cellular studies also show FTSJ1-dependent uridine 32 methylation in tRNAArg and position 34 ribose methylation in tRNASec; these dependencies extend its substrate scope beyond the separately reconstituted reactions. FTSJ1 acts predominantly in the cytosol, with a smaller nuclear pool. Its modifications prepare tRNAs for decoding and influence codon-specific translation. Loss of FTSJ1 disrupts neuronal function, and pathogenic variants cause X-linked intellectual disability; different variants can affect anticodon-loop positions unequally.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002128 tRNA nucleoside ribose methylation | IEA GO_REF:0000104 | ACCEPT | Summary: Retain tRNA nucleoside ribose methylation as a core activity, process or location. Reason: tRNA nucleoside ribose methylation is a core process spanning independently established positions 32 and 34. Existing wobble-position ribose methylation covers position 34 only; retaining this original process preserves the C32 process context as well as the more specific wobble context. Original UniRule provenance remains exact and is corroborated by human experimental evidence. |
| GO:0002128 tRNA nucleoside ribose methylation | IMP PMID:26310293 Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicat... | ACCEPT | Summary: Retain tRNA nucleoside ribose methylation as a core activity, process or location. Reason: The human patient-LCL original positively establishes ribose methylation at both 32 and 34. This core process retains meaningful C32 coverage beyond the existing wobble-position process. The two process contexts are retained without adding a new redundant annotation or recasting C32 as a wobble site. Supporting Evidence: |
| GO:0002130 wobble position ribose methylation | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited wobble-ribose methylation as core. Reason: The literal wobble-position IBD at AN2/PTN000100323 lies on the actual human lineage with exact donor sets, including legitimate target self-evidence. Independent human experiments establish ribose methylation at tRNA position 34. Preserve the original phylogenetic assertion without relabeling it as a new experimental annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000100323 · PTN000100323 SUPPORTS TRANSFER Literal positive GO:0002130 IBD at PTHR10920 AN2 is on the exact human AN21/PTN002475051 lineage. Original descendant donor set matches; target sequence is the official 329-aa sequence. Biological granularity is adjudicated separately. UniProtKB:Q9UET6 · FTSJ1 SUPPORTS TRANSFER The target is valid experimentally grounded descendant evidence for the ancestral assertion, not circular transfer. |
| GO:0002130 wobble position ribose methylation | IDA PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | ACCEPT | Summary: Human FTSJ1 directly performs wobble-position ribose methylation. Reason: Human FTSJ1-WDR6 reconstitution produces Gm34 on hypomodified tRNA Phe and on Phe transcripts carrying prerequisite m1G37 in the tested assay. FTSJ1 is the catalytic participant in this modification process. The substrate prerequisite is retained as an assay-specific observation, not generalized to every FTSJ1 substrate. Supporting Evidence: |
| GO:0002181 cytoplasmic translation | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: Translation consequences are supported; direct process participation is over-annotated. Reason: GO:0002181 describes ribosome-mediated formation of proteins in the cytoplasm. FTSJ1 catalyses prior tRNA modification rather than a ribosomal translation step. The consequence for translation is directly supported in human cells: PMID:32558197 Figure 7 compares wild-type and FTSJ1-knockout HEK293T cells using normalized dual-luciferase reporters and finds reduced UUU decoding without the corresponding UUC effect. This human result corrects the previous mouse-only evidence summary, but does not by itself establish that FTSJ1 executes the annotated translation process. Mark the process assignment as over-annotated while retaining the supported decoding phenotype and core tRNA-methylation function. The incoming UniRule IEA source remains unchanged; experimental corroboration of a downstream phenotype does not convert this row into a new experimental annotation. |
| GO:0002181 cytoplasmic translation | IMP PMID:32393790 FTSJ1 regulates tRNA 2'-O-methyladenosine modification and s... | MARK AS OVER ANNOTATED | Summary: Translation consequences are supported; direct process participation is over-annotated. Reason: GO:0002181 describes ribosome-mediated formation of proteins in the cytoplasm. FTSJ1 catalyses prior tRNA modification rather than a ribosomal translation step. The consequence for translation is directly supported in human cells: PMID:32558197 Figure 7 compares wild-type and FTSJ1-knockout HEK293T cells using normalized dual-luciferase reporters and finds reduced UUU decoding without the corresponding UUC effect. This human result corrects the previous mouse-only evidence summary, but does not by itself establish that FTSJ1 executes the annotated translation process. Mark the process assignment as over-annotated while retaining the supported decoding phenotype and core tRNA-methylation function. The incoming PMID:32393790 NSCLC study explicitly did not assess protein synthesis. Its bulk tRNA-modification and RNA-expression measurements are retained as that source's actual scope; the human reporter result comes from a separate paper. |
| GO:0002181 cytoplasmic translation | IMP PMID:36720500 The ribose methylation enzyme FTSJ1 has a conserved role in ... | MARK AS OVER ANNOTATED | Summary: Translation consequences are supported; direct process participation is over-annotated. Reason: GO:0002181 describes ribosome-mediated formation of proteins in the cytoplasm. FTSJ1 catalyses prior tRNA modification rather than a ribosomal translation step. The consequence for translation is directly supported in human cells: PMID:32558197 Figure 7 compares wild-type and FTSJ1-knockout HEK293T cells using normalized dual-luciferase reporters and finds reduced UUU decoding without the corresponding UUC effect. This human result corrects the previous mouse-only evidence summary, but does not by itself establish that FTSJ1 executes the annotated translation process. Mark the process assignment as over-annotated while retaining the supported decoding phenotype and core tRNA-methylation function. The incoming PMID:36720500 study measures human tRNA methylation, RNA/miRNA abundance and neuronal morphology rather than protein-synthesis rate. The human reporter and separate mouse-brain ribosome-profiling evidence are not attributed to that paper. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Retain supported protein binding as contextual evidence. Reason: Three source-specific HuRI IntAct records support the exact human FTSJ1–CERT1 isoform 2 pair in yeast two-hybrid screens and validation. The original Q9Y5P4-2 partner is retained. This positive association does not establish a specific catalytic or adaptor role for FTSJ1, purified affinity, or a shared physiological pathway. Retain generic binding as non-core without assigning cohort-level MAPPIT or GPCA assays to this pair. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | KEEP AS NON CORE | Summary: The nuclear fraction is supported but is not the principal characterized setting. Reason: The original human HEK293T tagged-protein imaging and fractionation detect FTSJ1 in the nucleus as well as predominantly in the cytoplasm; fractionation includes compartment controls. This positive observation is retained. It does not establish an endogenous isoform-specific nuclear function or a separate nuclear substrate. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the smaller nuclear pool as contextual localization. Reason: The UniProt nuclear inference agrees with the original human tagged FTSJ1 imaging and nuclear/cytoplasmic fractionation, which detect a smaller nuclear fraction. Retain the positive location without assigning a distinct nuclear catalytic process; the principal demonstrated tRNA-modification setting is cytoplasmic. Supporting Evidence: |
| GO:0005737 cytoplasm | EXP PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | TOO GENERAL | Summary: The original cytoplasmic observation is represented more specifically by cytosol. Reason: The original human study places most tagged FTSJ1 in the cytoplasmic fraction and also supplies the existing cytosol annotation. Cytosol is part_of cytoplasm; this is a specificity decision rather than rejection of the positive experimental localization. The smaller nuclear pool remains separately retained. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | TOO GENERAL | Summary: Cytosol is the more specific established location. Reason: The cytoplasm IBD at AN2/PTN000100323 is on the exact human target lineage, and its target self-donor is valid experimental grounding. Human imaging and fractionation independently support the retained cytosol location, which is part_of cytoplasm. This granularity decision does not challenge the ancestral node or alter original qualifiers. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000100323 · PTN000100323 SUPPORTS TRANSFER Literal positive GO:0005737 IBD at PTHR10920 AN2 is on the exact human AN21/PTN002475051 lineage. Original descendant donor set matches; target sequence is the official 329-aa sequence. Biological granularity is adjudicated separately. UniProtKB:Q9UET6 · FTSJ1 SUPPORTS TRANSFER The target is valid experimentally grounded descendant evidence for the ancestral assertion, not circular transfer. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | TOO GENERAL | Summary: Use the retained cytosol location for greater specificity. Reason: The combined UniProt location/rule cytoplasm mapping is compatible with human imaging, fractionation and the established catalytic context. The retained cytosol term is part_of cytoplasm and provides the narrower location without altering the original rule or subcellular-location provenance. Supporting Evidence: |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Retain cytosol as a core activity, process or location. Reason: The official HPA25 cell-atlas record reports supported cytosolic ICC/IF localization using HPA002718 in A-431, U-251MG and U2OS. This corroborates the established cytoplasmic tRNA-modification setting. The evidence here verifies the recorded assay metadata rather than independently reinterpreting image pixels or establishing exclusive localization. |
| GO:0005829 cytosol | IDA PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | ACCEPT | Summary: Cytosol is a core location of the tRNA-modifying enzyme. Reason: The original human study uses imaging and cytoplasmic/nuclear fractionation with marker controls and shows predominantly cytoplasmic FTSJ1. This agrees with modification of cytoplasmic tRNA substrates. Retain the existing cytosol annotation without inferring that the documented natural alternative isoform has separately demonstrated localization. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9024159 | ACCEPT | Summary: Retain cytosol as a core activity, process or location. Reason: The Reactome C32 reaction and catalyst chain place human FTSJ1 residues 1–329 in cytosol, consistent with independent human HPA and tagged-protein localization. The reaction summation bases its location on yeast homology; retain that source distinction rather than calling Reactome a new human localization experiment. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9024161 | ACCEPT | Summary: Retain cytosol as a core activity, process or location. Reason: The actual Reactome G34 catalyst chain places FTSJ1 in cytosol, independently supported by human localization. Its location inference and older THADA requirement remain explicit model limitations; neither changes the human cytosolic function or overrides the primary WDR6 partner result. |
| GO:0006400 tRNA modification | TAS Reactome:R-HSA-9024159 | TOO GENERAL | Summary: Retain the more specific established scope for tRNA modification. Reason: The actual Reactome C32 reaction identifies human FTSJ1 as catalyst and correctly places its activity in tRNA modification. The retained tRNA nucleoside ribose methylation process is more specific through official is_a ancestry. The modeled cytosolic assignment is attributed to yeast-homology inference and is independently corroborated by human localization data; model provenance is not relabeled as a direct assay. |
| GO:0006400 tRNA modification | TAS Reactome:R-HSA-9024161 | TOO GENERAL | Summary: Retain the more specific established scope for tRNA modification. Reason: The actual Reactome G34 reaction identifies FTSJ1 and supports the broad tRNA-modification context, which is represented more precisely by retained ribose/wobble methylation. Its current THADA requirement is not used to override direct primary FTSJ1-WDR6 G34 biochemistry. Preserve the original reaction and provenance while making this term-granularity judgment. |
| GO:0008033 tRNA processing | IEA GO_REF:0000002 | TOO GENERAL | Summary: Specific tRNA ribose methylation describes the processing function. Reason: The InterPro tRNA-processing inference is compatible with FTSJ1 biology. Existing tRNA nucleoside ribose methylation and wobble-position ribose methylation describe the directly performed steps more precisely; there is no separate evidence here for cleavage, splicing or another processing mechanism. |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: Specific tRNA ribose methyltransferase activities provide the informative scope. Reason: The incoming InterPro methyltransferase inference is biologically sound but broader than the retained position/base-specific tRNA 2-prime-O-methyltransferase activities. Purified human enzyme complexes and cellular tRNA measurements establish those specific functions; no unrelated RNA substrate is inferred from the broad family label. |
| GO:0008175 tRNA methyltransferase activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: Retain the specific tRNA ribose methyltransferase activities. Reason: The combined rule/domain tRNA methyltransferase mapping agrees with established FTSJ1 function. The retained C32, G34 and C34 ribose activities resolve its substrate and chemistry more specifically; preserve all original rule and domain donors. |
| GO:0008757 S-adenosylmethionine-dependent methyltransferase activity | IEA GO_REF:0000117 | TOO GENERAL | Summary: The SAM-dependent activity is represented by more specific catalytic terms. Reason: Human FTSJ1 directly binds SAM and uses it for tRNA ribose methylation. The broad SAM-dependent methyltransferase assignment is true but redundant with the retained specific catalytic activities. This does not dispute the original ARBA provenance. |
| GO:0016423 tRNA (guanine) methyltransferase activity | IDA PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | TOO GENERAL | Summary: Guanosine 34 ribose methylation is the specific retained activity. Reason: The official tRNA guanine methyltransferase term includes GO:0106340 as an is_a child; its broad name is not evidence of a wrong N-methylation assignment. The original human FTSJ1-WDR6 work directly supports Gm34 production on appropriately modified tRNA substrates. Retain this experimental provenance while preferring the existing specific G34 ribose activity. Supporting Evidence: |
| GO:0022008 neurogenesis | IDA PMID:36720500 The ribose methylation enzyme FTSJ1 has a conserved role in ... | MODIFY | Summary: Refine the developmental phenotype to neuron projection morphogenesis, with pharmacological attribution limits. Reason: In human iPSC-derived developing neuronal cultures, 100 micromolar DAP for 24 hours increased thin neurite protrusions by about 25%. The DCX-positive fraction, used in the paper's neurogenesis quantification, did not change significantly. The positive endpoint therefore supports the more specific GO:0048812 neuron projection morphogenesis rather than retaining the broader process without refinement. The ontology includes this morphology within neurogenesis through GO:0048812 part_of GO:0031175 neuron projection development part_of GO:0048666 neuron development part_of GO:0030182 neuron differentiation part_of GO:0048699 generation of neurons is_a GO:0022008 neurogenesis; the null DCX-fraction result does not contradict every subprocess of the broad term. The human experiment is pharmacological, lacks genetic FTSJ1 rescue and does not establish that every DAP effect is FTSJ1-specific. These attribution limits remain explicit with the narrower annotation. This is a developmental phenotype associated with the inhibition experiment, not an established core role or a direct morphogenetic molecular function. Proposed replacements: neuron projection morphogenesis Supporting Evidence: PMID:36720500 25% increase in the number of interstitial protrusions |
| GO:0030488 tRNA methylation | IEA GO_REF:0000117 | TOO GENERAL | Summary: Retain the more specific established scope for tRNA methylation. Reason: The correct tRNA methylation process is entailed by existing tRNA nucleoside ribose methylation through a direct official is_a edge. No ARBA-specific experimental assay is invented. |
| GO:0030488 tRNA methylation | IGI PMID:25404562 Conservation of an intricate circuit for crucial modificatio... | TOO GENERAL | Summary: Retain the more specific established scope for tRNA methylation. Reason: The original human-FTSJ1 yeast complementation/HPLC directly supports tRNA methylation. Literal donor P38238 is yeast TRM7, verified independently; it is not a guessed human partner. Existing tRNA nucleoside ribose methylation entails this broader process through a direct official is_a edge and retains the original assay’s Cm32-only human result. Supporting Evidence: |
| GO:0030488 tRNA methylation | IMP PMID:36720500 The ribose methylation enzyme FTSJ1 has a conserved role in ... | TOO GENERAL | Summary: Retain the more specific established scope for tRNA methylation. Reason: Human patient-LCL RiboMethSeq establishes FTSJ1-dependent tRNA ribose methylation. The broader tRNA methylation claim is already entailed by the retained tRNA nucleoside ribose methylation process through a direct official is_a edge, without asserting new processes or excluding Nm32 substrates. Supporting Evidence: |
| GO:0106339 tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity | EXP PMID:25404562 Conservation of an intricate circuit for crucial modificatio... | ACCEPT | Summary: Retain tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Human FTSJ1 restores Cm32 on yeast tRNAPhe in complementation/HPLC experiments. The original paper directly tests human THADA coexpressed with human FTSJ1 in S. cerevisiae lacking Trm7 and Trm732, restoring Cm32; it is not solely a sequence-based THADA prediction. Human THADA can substitute for the yeast partner in this host. This establishes a human-protein catalytic capacity measured in yeast, not a native human-cell rescue or an assay-specific natural-product assignment. Supporting Evidence: |
| GO:0106339 tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity | EXP PMID:26310293 Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicat... | ACCEPT | Summary: Retain tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Human patient-LCL purified tRNAPhe HPLC shows loss of Cm with FTSJ1 deletion/splice variants; the independent human-FTSJ1 yeast experiment supports the enzymatic interpretation. Preserve this EXP source context without treating it as a purified binary reaction. |
| GO:0106339 tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity | IDA PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | ACCEPT | Summary: Retain tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Human FTSJ1 Cm32 activity is established by yeast complementation and patient-cell tRNA measurements. The original 2020 study supports cellular FTSJ1-dependent Cm32, whereas its isolated FTSJ1-WDR6 binary reaction produces Gm34 and not Cm32. Retain the gene-level C32 activity without mislabeling that binary reaction; the later human FTSJ1-THADA structure and activity study independently supports the C32 partner context. |
| GO:0106339 tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity | IMP PMID:26310293 Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicat... | ACCEPT | Summary: Retain tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: The original human FTSJ1 perturbation data support the same core Cm32 capacity: independent splice variants and deletion reduce tRNAPhe Cm. A26P selective Gm loss does not negate normal FTSJ1 Cm32 activity. Supporting Evidence: |
| GO:0106339 tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity | IMP PMID:36720500 The ribose methylation enzyme FTSJ1 has a conserved role in ... | ACCEPT | Summary: Retain tRNA (cytidine(32)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Human patient-LCL RiboMethSeq supports FTSJ1-dependent Cm32. For Phe, the original requires raw cleavage-profile inspection because MethScore is confounded by adjacent Nm and reverse-transcription arrest. These limitations do not remove the independently corroborated core chemistry. |
| GO:0106340 tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity | EXP PMID:25404562 Conservation of an intricate circuit for crucial modificatio... | ACCEPT | Summary: Retain tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Human FTSJ1 Gm34 activity is independently established by patient-LCL HPLC, RiboMethSeq and human FTSJ1-WDR6 reconstitution. The original 2015 yeast complementation paper, retained as the incoming citation, reports no detectable Gm in its human-FTSJ1 yeast assay and inconclusive WDR6 complementation. Accept the gene-level activity without claiming that this original experiment positively measured human Gm34 formation. |
| GO:0106340 tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity | EXP PMID:26310293 Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicat... | ACCEPT | Summary: Retain tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Purified tRNAPhe from human patient LCLs lacks Gm after FTSJ1 deletion/splice disruption; A26P selectively loses Gm while retaining Cm. This supports the core Gm34 capacity without equating patient perturbation with purified-enzyme kinetics. Supporting Evidence: |
| GO:0106340 tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited G34 ribose methyltransferase activity as core. Reason: The literal Gm34 IBD at PTHR10920 AN2/PTN000100323 lies on the actual human AN21/PTN002475051 lineage, with matching donor sets and exact target sequence. Human target self-evidence is legitimate grounding. Independent human purified FTSJ1-WDR6 and patient-cell studies support this chemistry; no target loss or divergence is established. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000100323 · PTN000100323 SUPPORTS TRANSFER Literal positive GO:0106340 IBD at PTHR10920 AN2 is on the exact human AN21/PTN002475051 lineage. Original descendant donor set matches; target sequence is the official 329-aa sequence. Biological granularity is adjudicated separately. UniProtKB:Q9UET6 · FTSJ1 SUPPORTS TRANSFER The target is valid experimentally grounded descendant evidence for the ancestral assertion, not circular transfer. |
| GO:0106340 tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity | IMP PMID:26310293 Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicat... | ACCEPT | Summary: Retain tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: The original human FTSJ1 mutant LCL measurements establish Gm dependence. The detailed mechanistic yeast Trm7 mutant/partner experiments corroborate conservation but must remain identified as yeast assays. Supporting Evidence: |
| GO:0106340 tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity | IMP PMID:36720500 The ribose methylation enzyme FTSJ1 has a conserved role in ... | ACCEPT | Summary: Retain tRNA (guanosine(34)-2'-O-ribose)-methyltransferase activity as a core activity, process or location. Reason: Human patient-LCL RiboMethSeq detects FTSJ1-dependent Phe Gm34 and corroborates the earlier human HPLC result. This is core tRNA anticodon-ribose chemistry, not evidence of every potential tRNA substrate. |
| GO:0141098 tRNA (cytidine(34)-2'-O-ribose)-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain C34 ribose methyltransferase activity as core. Reason: The literal Cm34 IBD at AN2/PTN000100323 lies on the exact human target path. Its single Drosophila experimental donor is not a weakness by itself. Independently, the original human patient tRNA study and Supplementary Figure S3 directly show FTSJ1-WDR6 methylating C34 of tRNA Trp(CCA). The earlier 2020 negative Trp assay remains an assay-specific observation rather than a universal substrate exclusion. PMID:32558197 also reports C34 methylation of tRNALeu(CAA) as an established substrate with the f5Cm34 modification, citing earlier Leu work; Leu was explicitly excluded from its new 16-transcript reconstitution screen. That context supports inclusion of Leu in the substrate synthesis without misdescribing a new Leu reconstitution in the 2020 paper. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000100323 · PTN000100323 SUPPORTS TRANSFER Literal positive GO:0141098 IBD at PTHR10920 AN2 is on the exact human AN21/PTN002475051 lineage. Original descendant donor set matches; target sequence is the official 329-aa sequence. Biological granularity is adjudicated separately. |
| GO:1904047 S-adenosyl-L-methionine binding | IDA PMID:32558197 Intellectual disability-associated gene ftsj1 is responsible... | ACCEPT | Summary: SAM binding is an integral cofactor interaction of the methyltransferase. Reason: The original human FTSJ1 study measures SAM binding by isothermal titration calorimetry at approximately four micromolar affinity. This specific methyl-donor interaction is integral to the established catalytic function. It is not inferred solely from a generic protein-binding screen. Supporting Evidence: |
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Download this section (compressed HTML)Q: How does the documented two-residue alternative product differ in partner recruitment, substrate selectivity or localization? Sequence identity is established, but none of the selected assays directly compares the 219–220 deletion product with the longer product.
Q: Which substrate features and assay conditions determine FTSJ1-WDR6 activity on different tRNAs? Human Trp results differ between tested 2020 and 2021 contexts, and a Phe reconstitution required prior m1G37 modification.
Q: Which tRNA-modification changes causally connect FTSJ1 loss to neuronal morphology and decoding? Human UUU reporter and patient-cell modification results, mouse brain ribosome profiling and human DAP-treated neuronal morphology address different endpoints. The human neuronal differentiation fraction was unchanged, and genetic perturbation/rescue is needed to distinguish FTSJ1-dependent morphology from other DAP effects.
Q: Which partner and substrate modifications are required for direct uridine 32 and tRNASec position 34 ribose methylation by human FTSJ1? Cellular knockout/patient data establish dependence; isolated, site-resolved reactions are needed before assigning those specific catalytic capacities.
Q: How do the composition and substrate occupancy of cytosolic FTSJ1-THADA and FTSJ1-WDR6 complexes change across tRNA maturation states? Both partner contexts are experimentally supported, but a generic tRNA methyltransferase complex term would not resolve their distinct composition or stoichiometry.
Experiment: Compare sequence-verified 329-aa and 327-aa FTSJ1 proteins with THADA or WDR6 using matched substrates, site-resolved mass spectrometry and controlled protein abundance.
Experiment: Compare purified and cell-derived Phe and Trp tRNAs with defined pre-existing modifications across matched FTSJ1-WDR6 reactions, including catalytically inactive and partner-omission controls.
Experiment: Combine genetic FTSJ1 perturbation and rescue in human neuronal cells with site-resolved tRNA analysis, codon-sensitive translation measurements and separate differentiation-rate and neurite-morphology endpoints.
Experiment: Reconstitute candidate U32 and Sec34 reactions with sequence-verified human FTSJ1, defined partner proteins and appropriately modified substrates; use site-resolved mass spectrometry and catalytically inactive, partner-omission and substrate controls.
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