GNG5B (G protein subunit gamma 5B; formerly GNG5P2) is an X-linked (Xq23) retrocopy of GNG5. It was reclassified from pseudogene to protein-coding and has a single-exon MANE Select transcript. It encodes a 68-residue heterotrimeric G-protein gamma subunit that is 94% identical to GNG5 (S4F, M10T, R18Q, R25S). It keeps the C-terminal CaaX box (CSFL), whose cysteine is geranylgeranylated and carboxymethylated in G-gamma subunits and anchors the G-beta-gamma dimer to the cytoplasmic face of the plasma membrane. Most of the G-beta-contacting surface is unchanged. Transcripts are detected at low levels (GTEx below 0.3 TPM, mainly pituitary and brain; Bgee reports testis germ-line expression). No peptide-level evidence for the protein and no experimental study of the locus have been reported. By homology it would act as a G-gamma subunit that partners with G-beta in heterotrimeric G proteins downstream of G protein-coupled receptors, but no function has been shown for GNG5B itself.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003925 G protein activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetically inherited G-gamma function. The sequence is consistent with it (the prenylation signal is intact and the G-beta interface is largely conserved), but the protein has not been detected and the function has not been tested for this locus. Reason: GNG5B lies inside the G-gamma5 clade under PTN008551661. Its sequence shows no loss: the CaaX cysteine C65 is retained and 33 of 36 G-beta contact positions are identical (file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md). The node placement is therefore not in question. The open question is whether the product exists. UniProt rates it PE 3, there is no literature, no peptide evidence was found, and transcripts are at about 0.3 TPM or less, with quantification confounded by 94% identity to GNG5. Under the Tier 3 rule for a product that may exist but whose function is untested and only inherited, the row is flagged rather than removed. It should be upgraded to ACCEPT if GNG5B-specific peptides are found. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN008551661 SUPPORTS TRANSFER G-gamma ancestral node; GNG5B is inside the clade with intact CaaX and G-beta interface, so the transfer is structurally sound; only the existence of the target product is unresolved. UniProtKB:P63212 · GNG2 SUPPORTS TRANSFER Bovine GNG2, experimentally characterised G-gamma donor grounding the node. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md All 36 map onto GNG5. **33 of the 36 are identical in GNG5B**. file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md UniProt: PE 3 (Inferred from homology). No peptide-level evidence is cited. |
| GO:0005834 heterotrimeric G-protein complex | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Inherited membership of the heterotrimeric G protein. The G-beta interface is 33/36 conserved relative to GNG5, but complex formation has not been tested and the protein has not been detected. Reason: PTN001013516 is the G-gamma family node, and its donors are experimentally characterised G-gamma subunits (GNG2, GNGT1, GNGT2). GNG5B keeps the structural basis for G-beta pairing. Three N-terminal coiled-coil substitutions (M10T, R18Q, R25S) are at G-beta contact positions mapped from the 1GP2 heterotrimer, and their effect is unknown (file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md). With no evidence that a GNG5B protein exists or assembles with G-beta, the annotation is flagged as inherited and untested, not removed. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001013516 SUPPORTS TRANSFER G-gamma family node for heterotrimer membership; target interface largely retained, existence of the product not established. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md M10T, R18Q and R25S, all in the N-terminal helix that forms the coiled coil with Gbeta's file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md no peptide evidence that we found, and no literature. |
| GO:0005834 heterotrimeric G-protein complex | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO mapping from the G-gamma family (IPR001770). It is consistent with the sequence but untested for this low-expressed retrocopy. Reason: The domain match is genuine and the inference is reasonable for an intact G-gamma, but there is no evidence that this locus's product exists or forms a heterotrimer. The reasoning is the same as for the IBA row. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md structurally plausible but untested on this locus. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: This is a mapping from UniProt's subcellular location line, which is itself by similarity to bovine GNG2. The prenylation signal supports membrane targeting if the protein is made. Reason: The UniProt "Cell membrane" statement carries ECO:0000250 from P63212 (bovine GNG2), so this IEA restates a similarity transfer. The retained CSFL CaaX box makes plasma membrane targeting plausible, but no GNG5B protein has been localised or detected. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md C-terminal CaaX box **CSFL retained**. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: The only row that is not IBA or IEA. It is a UniProt by-similarity transfer from bovine GNG2 (P63212), not an experimental or locus-specific observation, and not even transferred from the parent GNG5. Reason: ECO:0000250 / GO_REF:0000024 marks manual transfer by sequence similarity. The donor is bovine GNG2, a different G-gamma subtype. Nothing was observed for GNG5B, so the row reflects family-level near-identity and not locus-specific evidence. Membrane targeting is plausible given the intact CaaX box, but the product has not been detected (PE 3, no literature). Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P63212 · GNG2 SUPPORTS TRANSFER Bovine GNG2 donor (not GNG5); experimentally membrane-anchored G-gamma. Transfer is structurally plausible; target existence unproven. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md UniProt: PE 3 (Inferred from homology). No peptide-level evidence is cited. |
| GO:0007186 G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Inherited GPCR signalling role. It is plausible for an intact G-gamma, but no receptor, cell type or signalling output has been linked to GNG5B. Reason: The node and its donors (bovine GNG2, Drosophila G-gamma1, mouse and rat G-gamma) are appropriate, and GNG5B's sequence shows no loss. However, the product has not been detected, and its transcript is at a very low level compared with GNG5. Any GPCR signalling contribution of GNG5B is untested. The row is flagged as inherited and unverified. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN008551661 SUPPORTS TRANSFER G-gamma node; target inside clade with no residue loss; existence of the product unresolved. FB:FBgn0004921 SUPPORTS TRANSFER Drosophila G-gamma1 donor. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md Parent GNG5: max median about 275 TPM. |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO process mapping from G-gamma domains. It is untested for this locus. Reason: The same reasoning as for the IBA row. The domain match is genuine, but there is no evidence that a GNG5B product exists or takes part in GPCR signalling. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md UniProt: PE 3 (Inferred from homology). |
| GO:0031681 G-protein beta-subunit binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: G-beta binding mapped from the G-gamma family. 33 of 36 G-beta contact positions match GNG5, but binding has not been tested. Reason: G-beta binding is the most specific and structurally best-supported inference for this sequence, because most of the interface is conserved. The three N-terminal coiled-coil substitutions are unassessed, and there is no evidence that the protein exists. The row is flagged rather than accepted until GNG5B protein is detected and its pairing with G-beta is tested. Supporting Evidence: file:human/GNG5B/GNG5B-bioinformatics/RESULTS.md whether these substitutions change Gbeta affinity or Gbeta-subtype |
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Download this section (compressed HTML)Q: Is GNG5B protein made in any tissue (for example testis or pituitary)? Peptides covering F4/T10 (MSGFSSVAATK) or Q18/S25 (VVQQLQLEAGLNSVK) would tell it apart from GNG5.
Q: Do the N-terminal coiled-coil substitutions R18Q and R25S change G-beta subtype selectivity relative to GNG5?
Q: Should GNG5B be grouped with the G-gamma5 subfamily in PANTHER (it currently has no subfamily assignment in the PTHR13809 entries list)? Should IBA/ISS transfers to PE 3 retrocopies be held until protein evidence exists?
Experiment: Targeted proteomics for GNG5B-unique peptides in testis and pituitary, and co-immunoprecipitation of tagged GNG5B with G-beta1-4 to test heterodimer formation and prenylation-dependent membrane localisation.
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