Gprc5c (mouse, Q8K3J9) review notes

Deep research via just deep-research-falcon was not available in this session
(authentication failure), so literature research was done directly from PubMed
(39 hits for Gprc5c/GPRC5C/RAIG3, 2026-10-19) and the cached publications below.
Context: RAR_MISANNOTATION, re-examining
the GO:0005118 sevenless binding flag from Wei et al. 2020
PMID:32470107.

Identity and family

• Gprc5c (RAIG-3) is a retinoic-acid-inducible class C (family 3) orphan GPCR
  with a short N-terminus, unlike other class C receptors
  PMID:10945465.
  Epitope-tagged human RAIG-3 reached the cell surface in HEK293T cells and is
  induced by all-trans retinoic acid
  PMID:10945465.
• UniProt Q8K3J9: 440 aa, signal peptide 1-22, extracellular N-terminus 23-49,
  7TM (TM1 50-70 ... TM6 241-261); "Belongs to the G protein-coupled receptor 3 family".
• GPRC5 receptors are chordate-specific; invertebrate "GPRC5-like" sequences,
  including Drosophila BOSS, are only distantly related and have long N-termini
  PMID:21827690
  PMID:21827690
  PMID:21827690.

The sevenless-binding question (IPR002956)

• IPR002956 = "Bride of sevenless protein" family, built from a single PRINTS
  fingerprint (PR01223 BRIDEOF7LESS). Its InterPro2GO mappings are
  GO:0005118 sevenless binding, GO:0007601 visual perception, GO:0016020 membrane
  [file:mouse/Gprc5c/Gprc5c-bioinformatics/RESULTS.md "InterPro2GO terms: GO:0005118 sevenless binding; GO:0007601 visual perception; GO:0016020 membrane"].
• Among Swiss-Prot entries, only the two Drosophila BOSS proteins and mouse Gprc5c
  match it; human GPRC5C, mouse/human GPRC5A/B and human GPRC5D do not
  [file:mouse/Gprc5c/Gprc5c-bioinformatics/RESULTS.md "Q9NQ84 human GPRC5C: IPR002956 match = no"].
  The match on mouse Gprc5c is two fingerprint segments (48-73, 241-265),
  essentially TM1 and TM6, i.e. generic 7TM sequence, not the BOSS ectodomain.
• BOSS binds Sevenless through its large extracellular region; the binding
  epitope is a C-terminal peptide of the BOSS ECR
  PMID:39827240
  PMID:39827240.
  Gprc5c has a 27-residue extracellular N-terminus and therefore lacks the
  structure that does the binding.
• BOSS orthologs are recognisable outside Diptera only by the 7TM domain; the ECR
  co-evolves fast with Sevenless, and vertebrate c-Ros ligands were unknown
  PMID:18392882
  PMID:18392882.
• The mammalian ROS1 ligand turned out to be NELL2, a secreted EGF-like protein,
  not a GPCR PMID:32499443.
• PubMed search "(ROS1 OR c-ros) AND (GPRC5C OR GPRC5B OR GPRC5A OR bride of sevenless OR RAIG)"
  returned only Drosophila Sevenless/BOSS papers and an unrelated rat colon study:
  no evidence links any GPRC5 receptor to ROS1.
• Verdict: the Wei et al. flag holds, but for the reason the project page
  anticipated: it is the InterPro2GO mapping on a weak, species-idiosyncratic
  PRINTS hit, not the taxon. GO:0005118 and GO:0007601 on Q8K3J9 should be
  removed; the IPR002956 hit on Q8K3J9 is a false-positive family assignment
  (the human ortholog does not get it).

Experimental biology (mostly mouse)

• HSC dormancy: GPRC5C marks dormant human HSCs; loss/gain of function; hyaluronic
  acid acts through GPRC5C
  PMID:35725769.
  Gprc5c-KO HSCs divide faster
  PMID:35725769;
  HA/NAG effects on HSCs need Gprc5c
  PMID:35725769.
  HA and NAG raise Ca2+ in GPRC5C-overexpressing cells
  PMID:35725769.
  Ligand evidence is docking + Ca2+ + PLA proximity, not direct binding.
  Earlier: a Gprc5c-controlled reporter mouse was used to track dormant HSCs
  PMID:28479188.
• AML: Gprc5c drives NF-kB/BCAA metabolism in leukemia
  PMID:37639313.
• Vascular smooth muscle: GPRC5C dimerizes with AT1 and facilitates Ang II binding
  and signaling; SMC-specific KO mice have reduced Ang II hypertension
  PMID:38597112.
  GPRC5C, like GPRC5B, also dimerizes with EP2 and IP
  PMID:42544579.
• Olfactory cilia: GPRC5C at the ciliary transition zone of olfactory sensory neurons
  PMID:38110903;
  KO alters cilia composition.
• Kidney: apical membrane of proximal tubule; KO alters acid-base balance;
  alkaline pH triggers internalization; increases NHE3 activity
  PMID:29196502.
• Pancreatic islets: knockdown lowers GSIS and cAMP
  PMID:28228611 (abstract only).
• Saccharide 'off' response in heterologous cells
  PMID:37418589 (abstract only).
• Osteoblasts: knockdown reduces BMP2/GSK126-induced mineralization
  PMID:37558192.
• Gprc5c-deficient mice are viable with no behavioral phenotype
  PMID:21840300.

Other annotations

• Mitochondrion HDA (PMID:14651853, Mootha 2003 proteome, abstract only): no
  supporting biology; Gprc5c is a plasma-membrane/cilium GPCR. Likely contaminant.
• Signaling receptor complex (ISO/IBA from human GPRC5C IDA, PMID:23382219 PX-FERM
  cargo screen): the cached text does not show GPRC5C data. GPCR heterodimers with
  AT1/EP2/IP would independently fit "signaling receptor complex".
• Protein kinase activator activity (IBA, donor GPRC5B Q9NZH0): GPRC5B activates Fyn;
  no GPRC5C data.
• Centriolar satellite (ISO from human Q9NQ84): the human annotation no longer
  appears in QuickGO (2026-10-19); source not traceable.