EEFSEC encodes eEFSec (also called SelB in prokaryotes; eukaryotic elongation factor, selenocysteine-tRNA-specific), the dedicated translation elongation factor for co-translational incorporation of the 21st amino acid selenocysteine (Sec) at in-frame UGA codons. It is a GTP-binding translational GTPase of the TRAFAC-class, EF-Tu/eEF1A-related SelB subfamily, built from an N-terminal EF-Tu-like GTPase module (domains 1-3) and a distinctive C-terminal domain 4. eEFSec specifically binds selenocysteinyl-tRNA(Sec) with high affinity and GTP, and delivers Sec-tRNA(Sec) to the ribosomal A-site so that an in-frame UGA is decoded as selenocysteine rather than read as a stop codon. Decoding requires the eukaryote-specific factor SECISBP2 (SBP2) bound to the SECIS element in the selenoprotein mRNA 3' UTR: SBP2/SECIS docks onto the 40S and creates a binding site on the stalled 80S ribosome for the eEFSec:GTP:Sec-tRNA(Sec) ternary complex. After GTP hydrolysis (stimulated by the ribosome, with His96 as the catalytic residue), eEFSec releases the tRNA and dissociates, allowing accommodation and peptide-bond formation. eEFSec is therefore essential for synthesis of the entire selenoproteome. It acts in the cytoplasm; a nuclear localization has also been reported. Biallelic loss of EEFSEC function causes an autosomal-recessive early-onset neurodegenerative disorder (global developmental delay, progressive spasticity, ataxia, seizures, cerebellar hypoplasia and progressive atrophy) associated with reduced selenoprotein synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001514 selenocysteine incorporation | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the core, defining biological process of eEFSec: co-translational incorporation of selenocysteine at UGA codons. This is strongly corroborated by direct experimental evidence (IDA, PMID:27708257, PMID:35709277) and by UniProt. Supporting Evidence: PMID:27708257 promotes selenocysteine incorporation into selenoproteins |
| GO:0003746 translation elongation factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation to the core molecular function. eEFSec is a specialized translation elongation factor that delivers aminoacyl (Sec)-tRNA to the ribosomal A-site, functionally analogous to eEF1A/EF-Tu but dedicated to Sec-tRNA(Sec). Well supported by structural/biochemical studies. Supporting Evidence: PMID:27708257 eEFSec is a translational GTPase that binds Sec-tRNASec with high affinity and stringent specificity |
| GO:0001514 selenocysteine incorporation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning (IEA) annotation to the same process supported by the IBA and IDA annotations. Correct but redundant with the experimental annotations to GO:0001514, which are the primary evidence. |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA) annotation to GTPase activity via InterPro/ARBA. Correct - eEFSec is a translational GTPase that hydrolyzes GTP (GTP + H2O = GDP + Pi), and this is directly demonstrated experimentally. Redundant with the IDA GTPase activity annotations. Supporting Evidence: PMID:35709277 GTP is bound to the GTPase pocket in D1 |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based (IEA) annotation to GTP binding. Correct: eEFSec has a canonical G-domain (P-loop, switch 1/2, guanine-binding NKxD motif) and binds GTP/GDP, as shown crystallographically. Supports the GTPase-cycle mechanism but is a molecular capability contributing to the elongation factor function rather than a standalone core function. Supporting Evidence: PMID:35709277 GTP is bound to the GTPase pocket in D1 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation from UniProt SubCell mapping. UniProt lists Nucleus only as an inferred (ECO:0000305) location, consistent with a predicted nuclear localization signal (residues 547-553), but there is no demonstrated nuclear function. eEFSec acts co-translationally at the cytoplasmic 80S ribosome, so nuclear localization is not part of its core function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from UniProt SubCell mapping. Cytoplasm is the functional site of action: eEFSec delivers Sec-tRNA(Sec) to the cytoplasmic 80S ribosome during selenoprotein elongation. Correct, though the term is general (the specific site is the translating ribosome / A-site). |
| GO:0001514 selenocysteine incorporation | IDA PMID:27708257 Crystal structures of the human elongation factor eEFSec sug... | ACCEPT | Summary: Direct experimental evidence for the core process. Structure-guided mutagenesis of the Sec-binding pocket (Asp229, His230, Arg285) and the GTPase site (Thr48, Asp92, His96) abolished eEFSec-mediated UGA read-through and selenoprotein synthesis in vitro, establishing eEFSec as required for selenocysteine incorporation. Supporting Evidence: PMID:27708257 obliterated the ability of eEFSec to promote Sec incorporation |
| GO:0001514 selenocysteine incorporation | IDA PMID:35709277 Structure of the mammalian ribosome as it decodes the seleno... | ACCEPT | Summary: Direct experimental evidence: cryo-EM of the mammalian "selenosome" captured eEFSec:GTP:tRNA(Sec) delivering Sec-tRNA to the A-site in an SBP2/SECIS-dependent manner, and reporter assays showed eEFSec promotes Sec UGA read-through. Confirms the role in selenocysteine incorporation. Supporting Evidence: PMID:35709277 in-frame UGA codons recruit selenocysteinyl-tRNA (Sec-tRNASec) to facilitate the stop-to-Sec recoding |
| GO:0003924 GTPase activity | IDA PMID:27708257 Crystal structures of the human elongation factor eEFSec sug... | ACCEPT | Summary: Direct experimental evidence for GTPase activity. eEFSec binds and hydrolyzes GTP; GTPase-site residues Thr48, Asp92 and His96 are required for hydrolysis, and the GTP-to-GDP transition drives the conformational change underlying Sec-tRNA release. Core catalytic function of this translational GTPase. Supporting Evidence: PMID:27708257 we conclude that Thr48, Asp92 and His96 are important for GTP hydrolysis |
| GO:0003924 GTPase activity | IDA PMID:35709277 Structure of the mammalian ribosome as it decodes the seleno... | ACCEPT | Summary: Direct experimental evidence: the GTPase-defective His96->Ala mutant traps the catalytically incompetent state, confirming His96 is the catalytic residue and that eEFSec is an active GTPase whose hydrolysis drives Sec delivery. Core catalytic function. Supporting Evidence: PMID:35709277 the catalytically incompetent conformation of eEFSec-H96A |
| GO:0000049 tRNA binding | IDA PMID:35709277 Structure of the mammalian ribosome as it decodes the seleno... | NEW | Summary: Proposed annotation (not in GOA seed; supported by the UniProt DR line "GO:0000049 F:tRNA binding" and by direct structural evidence). Cryo-EM shows eEFSec engages selenocysteinyl/seryl-tRNA(Sec) with all four domains (acceptor-TYC arm by D1-D3; variable arm by the D3-D4 linker and D4). A more specific term (aminoacyl-tRNA / Sec-tRNA(Sec) binding) would be ideal, but tRNA binding is the GOA/UniProt-supported term. Core molecular capability underlying Sec delivery. Supporting Evidence: PMID:35709277 Human eEFSec uses all its domains to engage the tRNASec |
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