Source of the InterPro2GO rows on this protein (IPR005821 Ion_trans_dom, IPR001696 Na_channel_asu, IPR010526 Na_trans_assoc_dom, IPR043203 VGCC_Ca_Na). The domain matches are correct; the mapped terms are simply pitched at the level the shared signatures can support.

Source of the three PANTHER/TreeGrafter process annotations (neuronal action potential, sodium ion transmembrane transport, membrane depolarization during action potential), all via node PTN000004433.

Source of the voltage-gated sodium channel activity, voltage-gated sodium channel complex and plasma membrane rows, combining InterPro, PANTHER and UniRule.

The primary paper. Reports that naked mole-rat nociceptors are inhibited rather than excited by acid, and attributes this to a species-specific NaV1.7 variant that is potently blocked by protons. UniProt cites this paper as the sole literature reference for G9DCX3, and the EMBL entry JF912494 that defines this accession was submitted by its authors.

Independent confirmation that acid insensitivity in the naked mole-rat is conferred by a functional motif of NaV1.7, and evidence that the same functional convergence arose at least six times independently in hibernating mammals.

Screen of eight African rodent species related to the naked mole-rat, tracing sequence variants in transduction channels including NaV1.7 that accompany insensitivity to capsaicin, acid and AITC.

Full-text review by the authors of the primary work. States the mechanism (variants that enhance proton block of NaV1.7), names the motif as a charge inversion of a trio of residues in domain IV from KKV to EKD or EKE, and records that the EKE variant specifically has been shown experimentally to increase proton block.

Also notes that NaV1.7 matters far more for somatic than visceral pain, which is the key to reconciling the cutaneous acid insensitivity with the residual acid responses of colonic afferents reported in PMID:31992138.

Independent group restating the mechanism: a variation in naked mole-rat NaV1.7 renders the channel hypersensitive to proton-mediated block and prevents acid-driven action potential initiation from the skin.

Reports that naked mole-rat colonic afferents still respond to acid, and explains this by the known redundancy of NaV1.7 in visceral afferents. This is about visceral, not cutaneous, afferents and must not be read as qualifying the cutaneous acid-insensitivity phenotype.

Corrects the popular over-claim that naked mole-rats feel no pain, emphasising that the original finding was of selective insensitivity and that normal nocifensive responses to noxious heat and mechanical stimuli were reported. This is why the review accepts neuronal action potential and does not treat the NaV1.7 variant as a loss of channel function.

Restates the mechanism as a gene variant that renders NaV1.7 more susceptible to inhibition by acid, shutting down action potential firing in nociceptor fibres, and notes the same variant in the Cape mole-rat.

Names NaV1.7, alongside the NGF receptor TrkA, as one of the two proteins whose accumulated mutations underlie this species' selective analgesia.

Loss-of-function SCN9A mutations abolish pain perception in humans, establishing NaV1.7 as an essential and non-redundant requirement for nociception. Used as the orthologous grounding for the proposed sensory perception of pain annotation.

Cryo-EM structures of human NaV1.7 with beta subunits, supporting the voltage-gated sodium channel complex cellular component for the orthologous alpha subunit.

Human data on NaV1.7 subcellular distribution, including localisation to nodes of Ranvier. Noted here as the reason the review does NOT project axon, nerve terminal or node of Ranvier onto the naked mole-rat: those localisations are established only in human and mouse.

The only study that tested the naked mole-rat motif experimentally. Patch-clamp recordings show that inserting the naked mole-rat EKE motif into human NaV1.7 increases proton-evoked tonic inhibition, confirming the causal role of the motif, but also reduce channel function in the chimera.

It also qualifies the mechanism. A homology model places the EKE residues outside the pore lumen and too far from the pore mouth for direct steric obstruction, and across NaV1.2 to NaV1.8 motif charge does not correlate with proton sensitivity. The motif is therefore the sequence correlate of enhanced proton block rather than an established pore-block site, and the review's wording follows that distinction.

Independently locates the motif in the domain IV P-loop, which agrees with the position determined here by direct sequence comparison.

Naked-mole-rat-specific deep research report (Edison Scientific Literature, 15 citations) generated during this review. It reaches the same conclusions arrived at independently here: NaV1.7 identity, a plasma-membrane electrogenic sodium-selective threshold channel, enhanced proton inhibition as the species-specific specialization, and the fragment caveat on G9DCX3.

Its one genuinely new contribution was surfacing Harms et al. 2017 (PMID:28939386), which was not in the publication cache and which neither the affinage human record nor the cached naked-mole-rat corpus contained. That paper changed how the mechanism is worded in this review.

It also independently confirms the localisation gap recorded here: no dedicated naked-mole-rat immunolocalisation or spatial-transcriptomic study maps this protein, which is why the cellular component annotation stops at plasma membrane. Its suggested process term "regulation of membrane potential" was not adopted, because GO:0086010 is already annotated and is more precise for a channel that carries the depolarizing current itself.

G9DCX3 is a 1884-residue TrEMBL fragment (Flags Fragment, NON_TER at both ends) derived from EMBL JF912494, the mRNA submitted by the authors of PMID:22174253. It carries four Pfam PF00520 ion-transport domains, 20 transmembrane helices, the PF11933 cytoplasmic domain, the PF06512 sodium-ion-transport-associated domain and a C-terminal IQ motif, and is assigned to PANTHER PTHR10037:SF221 and the sodium channel (TC 1.A.1.10) family.

Reproducible comparison of the domain IV S5-pore linker triplet across seven mammalian NaV1.7 sequences, anchored on invariant flanking residues. The naked mole-rat protein carries EKE at fragment positions 1698-1700 where human, mouse, rat, rabbit and thirteen-lined ground squirrel carry KKV and guinea pig carries HKV. This reproduces the published motif directly in the sequence under review instead of relying on residue numbers recalled from memory, and places it in the distal half of the domain IV extracellular P-loop (S5 ends at 1641, S6 begins at 1717 in this entry). The file records the location only; it explicitly defers to PMID:28939386 on mechanism.

The fragment spans approximately human residues 23-1901, missing 22 N-terminal and 87 C-terminal residues, at 92.1% identity within matched blocks. All four homologous repeats, all voltage sensors and all four pore loops are present, so the truncation does not undercut the molecular function or cellular component annotations.

Machine-fetched Affinage record for the HUMAN ortholog SCN9A (Q15858), retrieved deliberately as a conserved-mechanism baseline because Affinage covers human genes only. It is a useful account of human NaV1.7 as a threshold-setting nociceptor channel, of its channelopathies, and of its CRMP2/Nedd4-2 trafficking control.

It contains nothing about the naked mole-rat and nothing about proton block. None of PMID:22174253, PMID:24352952, PMID:31147513 or PMID:32206859 appears among its 42 citation-anchored findings, and the strings mole-rat, glaber and proton do not occur in the file. The entire evidence base for this gene's species-specific function had to be found independently.

Its own GO grounding collapses to uninformative parents: mechanism_profile gives molecular_activity as GO:0005215 transporter activity for a protein whose defining activity is GO:0005248 voltage-gated sodium channel activity. No identifier from it was imported; every term here was re-grounded from GOA, QuickGO and the literature.