PCDHGC5

Model summary

A single-pass membrane adhesion receptor that uses tandem cadherin-like extracellular repeats to form calcium-stabilized adhesive assemblies and a cytoplasmic tail to recruit catenin adaptors and the actin cytoskeleton. By organizing junctional complexes at the cell surface, it scaffolds and stabilizes neuronal contacts that shape synapse architecture and promote neuronal survival through adhesion-coupled signaling.

Predicted Gene Ontology terms

1. 01

   I begin by dissecting the InterPro architecture, which is dominated by tandem cadherin-like extracellular modules followed by a cytoplasmic tail specialized for cytoskeletal coupling.

   The N-terminal extracellular region is built from multiple cadherin repeats: IPR015919 (Cadherin-like superfamily) spans residues 29–125, 127–234, 230–351, 345–447, and 443–568, and 558–668, with finer annotation by IPR002126 (Cadherin-like domain) at 27–133, 134–242, 242–350, 359–564, and 579–677. The presence of IPR013164 (Cadherin, N-terminal domain, residues 30–111) establishes the canonical cadherin fold that mediates calcium-stabilized adhesion. Two conserved calcium-binding cadherin motifs are pinpointed by IPR020894 (Cadherin conserved site) at 230–240 and 442–452, with an additional conserved site at 552–562; these motifs rigidify the extracellular repeats and create adhesive interfaces. This extracellular array is followed by IPR032455 (Cadherin, cytoplasmic C-terminal domain, residues 689–791) and IPR031904 (Cadherin, C-terminal catenin-binding domain, residues 823–944), which together define a cytosolic tail that recruits catenins and anchors the complex to the actin cytoskeleton. The ordered layout—extracellular cadherin repeats for adhesion and intracellular catenin-binding modules for cytoskeletal coupling—causes a membrane-anchored adhesion receptor that signals and scaffolds at cell–cell contacts.

2. 02

   From this architecture, the molecular function resolves as multivalent protein binding (GO:0005515).

   The cadherin ectodomains create high-avidity adhesive assemblies, while the cytoplasmic tail binds catenins and other adaptors. This binding capacity is not catalytic but organizational, enabling assembly of junctional complexes.

3. 03

   The biological processes follow directly from adhesion-driven signaling and cytoskeletal anchoring.

   Cadherin-based junctions organize synaptic and other cell–cell contacts; thus the protein drives synapse organization (GO:0050808). By stabilizing neuronal adhesions and coupling to survival pathways via catenin complexes, it suppresses pro-apoptotic signaling in neurons, aligning with negative regulation of neuron apoptotic process (GO:0043524). The extracellular adhesive core and intracellular catenin-binding tail together enforce stable junctions that both pattern synaptic architecture and promote neuronal viability.

4. 04

   Cellular localization is dictated by the single-pass type I topology and adhesion role.

   The cadherin ectodomains and cytosolic catenin-binding tail place the protein at the plasma membrane (GO:0005886), consistent with a membrane-anchored adhesion receptor that concentrates at cell–cell interfaces.

5. 05

   Mechanistically, calcium-stiffened cadherin repeats form trans-adhesive bonds that nucleate junctional assemblies.

   The cytoplasmic C-terminal catenin-binding domain recruits α-, β+, and p120-catenins, which bridge to actin and modulate endocytosis and signaling. I therefore hypothesize interactions with catenin family members and actin-regulatory complexes, enabling dynamic assembly and maintenance of neuronal adhesion sites that coordinate synapse formation and survival pathways.