GNB1 (human, P62873) review notes

Process log

2026-10-23: just fetch-gene human GNB1 had already been run (uniprot, goa, stub
review with 150 PENDING rows).
Deep research: just deep-research-falcon human GNB1 --fallback perplexity-lite was run
twice and FAILED both times (falcon: "Exception: Failed to authenticate" from the Edison
API; fallback perplexity-lite: "Provider 'perplexity' not available"). No
-deep-research-*.md file exists; this review is based on UniProt, the cached
publications and the notes below.
just fetch-gene-pmids human GNB1: 31/31 publications cached. Additional papers fetched
with just fetch-pmid: 18403039, 1606965, 31300275, 27108799, 25485910, 8521505
(8538741 was fetched by mistake; it is an unrelated plant paper and is not cited).

GNB1 encodes Gbeta1, the WD40 beta subunit shared by heterotrimeric G proteins. Human
liver Gs/Gi beta is identical to the rod transducin beta subunit
PMID:3095147.
Seven-bladed WD40 propeller, obligate dimer with Ggamma, two contact regions with
Galpha [PMID:8521505 "Repeated WD motifs in beta form a circularized sevenfold beta
propeller."; "an extended interface between beta and nearly all of gamma"].
Gbeta has no nucleotide-binding domain. Nucleotide exchange and GTP hydrolysis take place
on Galpha PMID:31300275. The GOA "GTPase activity" rows on GNB1 (IDA
PMID:1543505, TAS PMID:3095147) attribute a Galpha activity to Gbeta. The cached abstract
of PMID:1543505 is a cDNA cloning study of mouse Gbeta4 and says only that
"The beta and gamma subunits are thought to have a more passive role in G protein function".

Heterotrimer assembly / receptor coupling. Gbeta1gamma2 is the standard Gbetagamma
used in reconstituted and cryo-EM GPCR-G protein complexes (5-HT1B-mini-Go
PMID:29925951; D2-Gi PMID:32528175; CTR-Gs PMID:28437792; GPR88-Gi1 PMID:35501348;
muOR-Gi PMID:42870023). Gbeta contacts receptor ICL1/helix 8 in the GCGR-Gs structure
PMID:32371397. In a
coIP screen, Gbeta1 formed heterotrimers with Galphai1/Galphas and essentially every
Ggamma PMID:25733868. PAINT represents this with
"signaling receptor complex adaptor activity" (GO:0030159, IBA).
Effector activation by free Gbetagamma.
GIRK channels: purified Gbeta1gamma2 activates reconstituted GIRK2
PMID:23739333.
Supports GO:0099104 potassium channel activator activity (IDA).
Phospholipase C-beta: PMID:1606965. Transducin betagamma is
Gbeta1gamma1, so this is direct evidence for Gbeta1 (GO:0016004 phospholipase activator
activity).
Ras-GRF: PMID:8717044. This is indirect (phosphorylation
dependent), so it supports GPCR signaling and not a direct Ras pathway role.
Other interactors. p67phox binding is indirect, through Galphai2
PMID:16782902. Rhes (RASD2) binds
Gbeta1 by Y2H PMID:19255495. Radil/Rap1 complexes co-purify Gbetagamma PMID:23209302.
Chaperone (PFDN5) and huntingtin/neurodegeneration screen interactions are
high-throughput and functionally uninformative.

Gbetagamma is anchored to the cytoplasmic face of the plasma membrane through Ggamma
prenylation (the muOR study purified "prenylated Gβγ" from membranes, PMID:42870023).
Reactome places Gbetagamma in the "cytosol" compartment for 79 reactions; this captures
the cytoplasmic side but not the membrane anchoring. Kept as non-core.
In rods GNB1 is the transducin beta subunit (photoreceptor outer segment / disc membrane).
Exosome, extracellular vesicle and lysosomal-membrane rows come from proteomics (HDA).

smFRET of the Galphai alpha-helical domain (AHD) in muOR-Gi complexes. The Gbetagamma
was human Gbeta1 with Ggamma2 PMID:42870023, and the WT heterotrimer was Galphai1 beta1
gamma2 PMID:42870023.
The paper explains why the dwell times in the open AHD state do not depend on the ligand:
PMID:42870023. This agrees with rhodopsin-transducin structures in which the
GalphaT helical domain contacts Gbetagamma PMID:31300275.
This suggests Gbeta1 may do more than anchor Galpha during receptor-catalysed exchange:
it may also hold the open AHD in place. The paper does not test this directly, so it is
kept as a suggested question and not added as an annotation.

De novo GNB1 missense variants cause neurodevelopmental disorder with hypotonia and
seizures (MRD42) PMID:27108799.
Somatic GNB1 mutations (K57, I80) in myeloid/B-cell neoplasms
PMID:25485910.

GTPase activity: REMOVE. Gbeta has no catalytic site, and the activity belongs to Galpha.
protein binding: MODIFY to G-protein alpha-subunit binding (GO:0001965) where the partner
is GNAI1/GNAI2, and to G-protein gamma-subunit binding (GO:0031682) where the partner is
GNG2/GNG5. REMOVE the other partners (indirect or uninformative).
signal transduction: MODIFY to GPCR signaling pathway (GO:0007186).
membrane (ISS): MODIFY to plasma membrane.
Ras protein signal transduction: MARK_AS_OVER_ANNOTATED, because Gbetagamma acts upstream
of Ras-GRF and not within the Ras cascade.
Reactome cytosol (79 rows): KEEP_AS_NON_CORE.