ELP3 (human, Q9H9T3) curation notes

Context: RADICAL_SAM project (projects/RADICAL_SAM.md), Phase 1 human. Review created 2026-10-18.

Sources

• Deep research: the falcon provider failed (auth 403). ELP3-deep-research-asta.md is an Asta
  retrieval-only run, and all 20 papers it returned are irrelevant (generic annotation databases,
  network pharmacology, etc.); none concerns ELP3. It was not used as evidence. Literature was
  gathered directly via PubMed and cached with just fetch-pmid.
• UniProt record ELP3-uniprot.txt (Swiss-Prot, entry version 200).

Identity and domains

• 547 aa; radical SAM core domain 82-372 and GNAT N-acetyltransferase domain 396-547
  [file:human/ELP3/ELP3-uniprot.txt "Radical SAM core"; "N-acetyltransferase"].
• Cofactor: [file:human/ELP3/ELP3-uniprot.txt "Binds 1 [4Fe-4S] cluster. The cluster is coordinated
  with 3 cysteines and an exchangeable S-adenosyl-L-methionine."] (by similarity to yeast Q02908).
• Family: NCBIfam TIGR01211 ELP3; PANTHER PTHR11135:SF0; SFLD ELP3-like.

Catalytic function (core)

• Reaction (EC 2.3.1.311, RHEA:61020): uridine(34) in tRNA + acetyl-CoA + SAM + H2O ->
  cm5U34 + 5'-dA + Met + CoA [file:human/ELP3/ELP3-uniprot.txt "acts as a tRNA uridine(34)
  acetyltransferase by mediating formation of carboxymethyluridine in the wobble base at position
  34 in tRNAs"]. Human activity is by similarity to Methanocaldococcus infernus Elp3 (D5VRB9).
• Archaeal Elp3 alone performs the reaction in vitro PMID:25151136; mechanism: radical abstraction from acetyl-CoA PMID:25151136.
  Note: Selvadurai 2014 used the archaeal (M. infernus) enzyme; the D. mccartyi structure is
  Glatt et al. 2016 PMID:27455459.
• Lin et al. 2019 PMID:30733442.
• In yeast, Elongator (all six subunits) is required for an early step of mcm5/ncm5 U34 formation
  and Elp3 co-precipitates substrate tRNA PMID:15769872.
• Human: ELP3 depletion lowers mcm5s2U PMID:29415125.
• cm5U is the first step; the downstream mcm5U/mcm5s2U/ncm5U are made by other enzymes
  (ALKBH8/TRM112 methylation, CTU1/CTU2 thiolation), so ELP3 participates in GO:0002098 and in the
  first step of GO:0002926.

Complex

• Elongator holoenzyme (ELP1-6), ELP1-ELP2-ELP3 core plus ELP4-5-6 ring
  [file:human/ELP3/ELP3-uniprot.txt "Component of the elongator complex which consists of ELP1,
  ELP2, ELP3, ELP4, ELP5 and ELP6."]; ELP5 bridges ELP3 to ELP4 PMID:22854966.
• Purified human holo-Elongator PMID:11714725.

Historic / contested functions

• Histone acetyltransferase / Pol II transcription elongation: purified holo-Elongator acetylates
  H3/H4 and stimulates chromatin transcription in vitro PMID:11818576. In yeast these phenotypes are bypassed by overexpressing
  two tRNAs PMID:17018299.
  UniProt CAUTION: [file:human/ELP3/ELP3-uniprot.txt "it is no longer thought to play a direct role
  in this process and its primary function is thought to be in tRNA modification"].
• Alpha-tubulin acetylation and cortical neuron migration: PMID:19185337; later work in C. elegans indicates indirect regulation
  PMID:27847465. UniProt: "Not a major
  acetyltransferase of tubulin".
• Other protein-acetylation substrates (Drosophila Bruchpilot PMID:22153374, mouse Cx43
  PMID:28507509) rest on reduced acetylation upon Elp3 loss; direct KAT activity on proteins is
  unproven in vivo.
• No GOA row for histone acetyltransferase activity exists for human ELP3 at present; the
  acetyltransferase IDA (PMID:11714725) is to the general GO:0016407.

Localization

• Mainly cytoplasmic/cytosolic (HPA IDA cytosol; several IDA cytoplasm). A minor nuclear pool
  reported PMID:22002106; yeast: PMID:15769872.

Disease / development (pleiotropic, downstream of tRNA modification)

• ALS modifier: PMID:18996918; PMID:29415125.
• Cortical neurogenesis/migration (mouse knockdown/cKO). Melanoma cell migration decreased after
  ELP3 depletion PMID:22854966. These are treated as non-core or over-annotated process terms.

Decisions (summary)

• Generic rows per RADICAL_SAM treatment rule: GO:0003824 -> MODIFY GO:0106261; GO:0051536 ->
  MODIFY GO:0051539. No GO:0051539, GO:0046872 or GO:1904047 row in GOA; GO:1904047 added as NEW
  (radical SAM cosubstrate; cluster coordinated by exchangeable SAM).
• GO:0016407 / GO:0016747 -> MODIFY to GO:0106261.
• Cytoplasm rows -> MODIFY to cytosol (GO:0005829, HPA IDA).
• Protein binding (ELP1 IPI) -> REMOVE (uninformative; captured by elongator holoenzyme complex).