Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016020 membrane	IBA GO_REF:0000033	ACCEPT	Summary: PKD-2 is a multi-pass transmembrane protein with 6 transmembrane helices and a pore-forming region (PMID:11553327). Membrane localization is well-established across all PKD2 family members phylogenetically. Reason: PKD-2 is a classic ion channel with multiple transmembrane domains. This IBA annotation is appropriate and supported by extensive experimental evidence including GFP fusion studies showing membrane localization (PMID:11553327). Supporting Evidence: PMID:11553327 Cytoplasmic, nonnuclear staining in cell bodies is punctate, suggesting that one pool of PKD-2 is localized to intracellular membranes while another is found in sensory cilia. file:worm/pkd-2/pkd-2-deep-research-falcon.md model: Edison Scientific Literature
GO:0005262 calcium channel activity	IBA GO_REF:0000033	ACCEPT	Summary: PKD-2 functions as a calcium-permeable cation channel, directly demonstrated by electrophysiological studies in C. elegans (PMID:15862350). This is a core molecular function conserved across the TRPP family. Reason: This is a core molecular function of PKD-2. The IBA annotation is well-supported by direct experimental evidence showing PKD-2 acts as an intracellular Ca2+ release channel that accelerates Ca2+ release from intracellular stores (PMID:15862350). Supporting Evidence: PMID:15862350 we found that polycystin-2 is an intracellular Ca(2+) release channel that is required for the normal pattern of Ca(2+) responses involving IP(3) and ryanodine receptor-mediated Ca(2+) release from intracellular stores.
GO:0050982 detection of mechanical stimulus	IBA GO_REF:0000033	ACCEPT	Summary: PKD-2 functions with LOV-1 as a mechanosensitive receptor-channel complex in sensory cilia (PMID:16481400, PMID:12411744). The polycystins are proposed to act as sensors of the extracellular environment. Reason: This is a well-supported function for the polycystin complex. The LOV-1/PKD-2 complex functions similarly to mammalian PC1/PC2 as mechanosensors. Their localization to sensory cilia and role in detecting hermaphrodite contact supports mechanosensory function (PMID:12411744, PMID:16481400). Supporting Evidence: PMID:12411744 Based on the role of polycystins in C. elegans sensory neuron function and the conservation of PKD pathways we suggest that polycystins act as sensors of the extracellular environment PMID:16481400 In primary cilia of kidney cells, the transient receptor potential polycystin (TRPP) channels polycystin-1 (PC-1) and polycystin-2 (PC-2) act as a mechanosensitive channel
GO:0005509 calcium ion binding	IEA GO_REF:0000002	ACCEPT	Summary: This annotation is based on InterPro domain prediction. PKD-2 belongs to the polycystin family which contains EF-hand-like calcium binding domains. Reason: Reasonable IEA annotation based on domain composition. The PKD2 domain includes calcium-binding capabilities that are important for channel regulation. This is consistent with PKD-2's role as a calcium channel.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 localizes to the ER membrane where it functions as a calcium release channel. This is supported by experimental evidence (PMID:16943275, PMID:15862350). Reason: Appropriate IEA annotation that is validated by experimental data. UniProt annotation and direct studies confirm ER localization (PMID:16943275). PKD-2 accelerates Ca2+ release from intracellular stores in the ER (PMID:15862350). Supporting Evidence: PMID:16943275 PKD-2 is directed to moving dendritic particles by the UNC-101/adaptor protein 1 (AP-1) complex PMID:15862350 Polycystin-2, along with the IP(3) and ryanodine receptors, acts as a major calcium-release channel in the endoplasmic reticulum
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 localizes to the plasma membrane, particularly in the ciliary membrane of sensory neurons (PMID:11553327, PMID:16943275). Reason: IEA annotation supported by extensive experimental evidence showing PKD-2 at the plasma membrane, especially in ciliary membrane compartments (PMID:11553327, PMID:16943275). Supporting Evidence: PMID:11553327 LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies.
GO:0005929 cilium	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 localizes to sensory cilia of male-specific neurons. This is one of the best-characterized aspects of PKD-2 biology. Reason: Core localization well-established by multiple IDA annotations (PMID:11553327, PMID:16943275, PMID:27930654). The IEA appropriately captures this localization.
GO:0006811 monoatomic ion transport	IEA GO_REF:0000043	ACCEPT	Summary: PKD-2 is a cation channel that transports calcium ions. This broad term encompasses its more specific calcium transport function. Reason: Accurate but general annotation. PKD-2 does transport monoatomic ions (calcium). More specific terms (calcium ion transport) are also annotated.
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: PKD-2 is an integral membrane protein with multiple transmembrane domains. This is a basic structural annotation. Reason: Duplicate of IBA annotation above. Both appropriately capture membrane localization based on different evidence sources (InterPro and phylogenetic inference).
GO:0030424 axon	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 is found in axons of male-specific sensory neurons, as shown by GFP localization studies (PMID:11553327, PMID:15563610). Reason: IEA annotation validated by multiple IDA studies showing axonal localization in male sensory neurons.
GO:0030425 dendrite	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 localizes to dendrites of male-specific sensory neurons (PMID:11553327, PMID:18037411). Reason: IEA annotation validated by experimental evidence. The dendritic localization is important for PKD-2 trafficking to cilia.
GO:0034220 monoatomic ion transmembrane transport	IEA GO_REF:0000043	ACCEPT	Summary: PKD-2 mediates transmembrane transport of calcium ions as a TRP channel. Reason: Appropriate IEA annotation based on ion channel keyword. Consistent with PKD-2's established function as a calcium channel (PMID:15862350).
GO:0043204 perikaryon	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 localizes to neuronal cell bodies (perikarya) in addition to cilia and dendrites (PMID:11553327, PMID:18037411). Reason: IEA annotation consistent with experimental data showing cell body localization.
GO:0060170 ciliary membrane	IEA GO_REF:0000044	ACCEPT	Summary: PKD-2 is concentrated in the ciliary membrane of male sensory neurons where it functions in sensory signaling (PMID:16943275). Reason: Key localization for PKD-2 function. Well-supported by experimental evidence showing specific targeting to ciliary membranes (PMID:16943275). Supporting Evidence: PMID:16943275 Ciliary localization of the transient receptor potential polycystin 2 channel (TRPP2/PKD-2) is evolutionarily conserved
GO:0070588 calcium ion transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: Logical inference from calcium channel activity. PKD-2 mediates calcium ion transmembrane transport. Reason: Appropriate inference from calcium channel activity (GO:0005262). Directly supported by experimental evidence (PMID:15862350).
GO:0071683 sensory dendrite	NAS PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2 localizes to sensory dendrites of male-specific neurons in C. elegans. Reason: Appropriate localization annotation. The 2001 paper demonstrates PKD-2::GFP localization in male sensory neurons including their dendritic processes (PMID:11553327). Supporting Evidence: PMID:11553327 LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies.
GO:1902435 regulation of male mating behavior	NAS PMID:10517638 A polycystic kidney-disease gene homologue required for male...	ACCEPT	Summary: PKD-2 is required for male mating behavior in C. elegans (PMID:10517638, PMID:11553327). Reason: Core biological function. The 1999 Nature paper established PKD-2's role in male mating behavior. The NAS evidence is appropriate for the regulatory aspect implied in the term. Supporting Evidence: PMID:10517638 PKD-2, the C. elegans homologue of PKD2, is localized to the same neurons as LOV-1, suggesting that they function in the same pathway.
GO:0005929 cilium	IDA PMID:27930654 Whole-Organism Developmental Expression Profiling Identifies...	ACCEPT	Summary: Direct experimental evidence for ciliary localization of PKD-2 using GFP reporters (PMID:27930654). The study used PKD-2::GFP as a marker for ciliary localization in male sensory neurons. Reason: IDA evidence from developmental expression profiling study that used PKD-2::GFP to examine ciliary localization. Ciliary localization well-established by primary studies (PMID:11553327). Supporting Evidence: PMID:11553327 LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies. PMID:27930654 eCollection 2016 Dec.
GO:0071683 sensory dendrite	IDA PMID:27930654 Whole-Organism Developmental Expression Profiling Identifies...	ACCEPT	Summary: Direct evidence for sensory dendrite localization from GFP studies. Reason: IDA evidence supporting sensory dendrite localization, consistent with other publications. Dendritic localization established by primary papers (PMID:18037411). Supporting Evidence: PMID:18037411 The Caenorhabditis elegans TRPP2 homolog, PKD-2, is restricted to the somatodendritic (cell body and dendrite) and ciliary compartments of male specific sensory neurons. PMID:27930654 eCollection 2016 Dec.
GO:0043025 neuronal cell body	IDA PMID:16481400 Casein kinase II and calcineurin modulate TRPP function and ...	ACCEPT	Summary: PKD-2 localizes to neuronal cell bodies in male-specific sensory neurons, with phosphorylation state affecting its distribution (PMID:16481400). Reason: Strong IDA evidence from study on CK2 and calcineurin regulation of PKD-2. Supporting Evidence: PMID:16481400 CK2 and the calcineurin phosphatase TAX-6 modulate male mating behavior and PKD-2 ciliary localization.
GO:0097730 non-motile cilium	IDA PMID:16481400 Casein kinase II and calcineurin modulate TRPP function and ...	ACCEPT	Summary: PKD-2 localizes to non-motile sensory cilia in male neurons (PMID:16481400). Reason: C. elegans sensory cilia are non-motile (primary) cilia. This is a core localization for PKD-2 function in sensory signaling. Supporting Evidence: PMID:16481400 Feb 15. Casein kinase II and calcineurin modulate TRPP function and ciliary localization.
GO:0023041 neuronal signal transduction	IC PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	ACCEPT	Summary: PKD-2's role in neuronal signal transduction is inferred from its ciliary localization and function in sensory behaviors (PMID:15817158). Reason: Reasonable IC annotation. PKD-2 functions in ciliary sensory signal transduction as a channel component of the sensory machinery (PMID:15817158). Supporting Evidence: PMID:15817158 We propose that NPHP-1 and NPHP-4 proteins play important and redundant roles in facilitating ciliary sensory signal transduction.
GO:0034606 response to hermaphrodite contact	IMP PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	ACCEPT	Summary: pkd-2 mutants show defects in response to hermaphrodite contact, a specific step in male mating behavior (PMID:15817158, PMID:11553327). Reason: Core biological function. This is one of the two main behavioral defects in pkd-2 mutants (PMID:11553327, PMID:15817158). Supporting Evidence: PMID:11553327 Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects. PMID:15817158 Functional characterization of the C.
GO:0034608 vulval location	IMP PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	ACCEPT	Summary: pkd-2 mutants are defective in vulval location, a specific step in male mating behavior (PMID:15817158, PMID:11553327). Reason: Core biological function. This is one of the two main behavioral defects in pkd-2 mutants along with response behavior (PMID:11553327). Supporting Evidence: PMID:11553327 Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects. PMID:15817158 Functional characterization of the C.
GO:0097730 non-motile cilium	IDA PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	ACCEPT	Summary: PKD-2 colocalizes with nephrocystins in non-motile sensory cilia (PMID:15817158). Reason: IDA evidence consistent with other studies showing non-motile cilium localization. Supporting Evidence: PMID:15817158 GFP-tagged NPHP-1 and NPHP-4 proteins localize to ciliated sensory endings of dendrites and colocalize with PKD-2 in male-specific sensory cilia.
GO:0030425 dendrite	IDA PMID:18037411 Distinct protein domains regulate ciliary targeting and func...	ACCEPT	Summary: PKD-2 localizes to dendrites with distinct domains regulating this localization (PMID:18037411). Reason: Strong IDA evidence from structure-function study. Supporting Evidence: PMID:18037411 The Caenorhabditis elegans TRPP2 homolog, PKD-2, is restricted to the somatodendritic (cell body and dendrite) and ciliary compartments of male specific sensory neurons.
GO:0043025 neuronal cell body	IDA PMID:18037411 Distinct protein domains regulate ciliary targeting and func...	ACCEPT	Summary: PKD-2 localizes to neuronal cell bodies with cytoplasmic tails regulating this localization (PMID:18037411). Reason: IDA evidence from domain function analysis. Supporting Evidence: PMID:18037411 the PKD-2 cytosolic termini regulate subcellular distribution and function
GO:0048471 perinuclear region of cytoplasm	IDA PMID:18037411 Distinct protein domains regulate ciliary targeting and func...	ACCEPT	Summary: PKD-2 shows perinuclear localization consistent with ER/Golgi localization during biosynthesis (PMID:18037411). Reason: IDA evidence supporting perinuclear localization, consistent with ER-based synthesis and trafficking. Supporting Evidence: PMID:18037411 Epub 2007 Nov 1. Distinct protein domains regulate ciliary targeting and function of C.
GO:0097730 non-motile cilium	IDA PMID:18037411 Distinct protein domains regulate ciliary targeting and func...	ACCEPT	Summary: PKD-2 localizes to non-motile cilia with transmembrane domains sufficient for this targeting (PMID:18037411). Reason: Key IDA evidence from structure-function study. Supporting Evidence: PMID:18037411 somatodendritic and ciliary targeting requires the transmembrane (TM) region of PKD-2
GO:0034606 response to hermaphrodite contact	IMP PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: pkd-2 mutants are defective in response behavior (PMID:11553327). Reason: Core IMP evidence from the foundational 2001 paper establishing pkd-2 function. Supporting Evidence: PMID:11553327 Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects.
GO:0034606 response to hermaphrodite contact	IMP PMID:12411744 Towards understanding the polycystins.	ACCEPT	Summary: Additional IMP evidence for response behavior defect (PMID:12411744). Reason: Confirms behavioral phenotype from independent study. Supporting Evidence: PMID:12411744 Mutation analysis in C. elegans showed similarly compromised male mating behaviors in all single and double lov-1 and pkd-2 mutants
GO:0034606 response to hermaphrodite contact	IMP PMID:15862350 Polycystin-2 accelerates Ca2+ release from intracellular sto...	ACCEPT	Summary: pkd-2 mutants show response defects linked to calcium signaling abnormalities (PMID:15862350). Reason: IMP evidence connecting behavioral phenotype to calcium channel function. Supporting Evidence: PMID:15862350 A homologue in Caenorhabditis elegans is necessary for male mating behavior.
GO:0034608 vulval location	IMP PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: pkd-2 mutants are defective in vulval location behavior (PMID:11553327). Reason: Core IMP evidence from foundational study. Supporting Evidence: PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
GO:0034608 vulval location	IMP PMID:12411744 Towards understanding the polycystins.	ACCEPT	Summary: Vulval location defect confirmed in independent study (PMID:12411744). Reason: Confirming IMP evidence. Supporting Evidence: PMID:12411744 Towards understanding the polycystins.
GO:0034608 vulval location	IMP PMID:15862350 Polycystin-2 accelerates Ca2+ release from intracellular sto...	ACCEPT	Summary: Vulval location defect in pkd-2 mutants (PMID:15862350). Reason: Additional IMP evidence supporting this behavioral function. Supporting Evidence: PMID:15862350 2005 Apr 14. Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans.
GO:0005262 calcium channel activity	IDA PMID:15862350 Polycystin-2 accelerates Ca2+ release from intracellular sto...	ACCEPT	Summary: Direct electrophysiological evidence that PKD-2 functions as a calcium channel accelerating Ca2+ release from intracellular stores (PMID:15862350). Reason: This is the key IDA evidence for PKD-2's molecular function as a calcium channel. The study compared calcium signaling in wild-type and pkd-2 mutants. Supporting Evidence: PMID:15862350 we found that polycystin-2 is an intracellular Ca(2+) release channel that is required for the normal pattern of Ca(2+) responses involving IP(3) and ryanodine receptor-mediated Ca(2+) release from intracellular stores.
GO:0005783 endoplasmic reticulum	IDA PMID:16943275 General and cell-type specific mechanisms target TRPP2/PKD-2...	ACCEPT	Summary: PKD-2 localizes to the ER during its biosynthesis and trafficking pathway (PMID:16943275, PMID:15862350). Reason: IDA evidence from trafficking study. ER localization supported by functional studies showing PKD-2 acts as a calcium channel in the ER. Supporting Evidence: PMID:15862350 Polycystin-2, along with the IP(3) and ryanodine receptors, acts as a major calcium-release channel in the endoplasmic reticulum in cells where rapid calcium signaling is required PMID:16943275 General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia.
GO:0005886 plasma membrane	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2::GFP localizes to plasma membrane in male sensory neurons (PMID:11553327). Reason: IDA evidence from GFP localization studies. Supporting Evidence: PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
GO:0005929 cilium	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2::GFP concentrates in sensory cilia of male neurons (PMID:11553327). Reason: Foundational IDA evidence for ciliary localization. Supporting Evidence: PMID:11553327 LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies.
GO:0005929 cilium	IDA PMID:16943275 General and cell-type specific mechanisms target TRPP2/PKD-2...	ACCEPT	Summary: Detailed analysis of PKD-2 ciliary targeting mechanisms (PMID:16943275). Reason: Key IDA study on ciliary targeting. Supporting Evidence: PMID:16943275 Ciliary localization of the transient receptor potential polycystin 2 channel (TRPP2/PKD-2) is evolutionarily conserved
GO:0006816 calcium ion transport	IDA PMID:15862350 Polycystin-2 accelerates Ca2+ release from intracellular sto...	ACCEPT	Summary: PKD-2 mediates calcium ion transport as demonstrated by electrophysiology and calcium imaging (PMID:15862350). Reason: Core biological process supported by direct experimental evidence. Supporting Evidence: PMID:15862350 Activity of polycystin-2 creates brief cytosolic Ca(2+) transients with increased amplitude and decreased duration.
GO:0016020 membrane	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2 is a membrane protein as shown by GFP localization (PMID:11553327). Reason: Basic IDA evidence for membrane localization. Supporting Evidence: PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
GO:0043025 neuronal cell body	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2::GFP localizes to neuronal cell bodies (PMID:11553327). Reason: IDA evidence from foundational study. Supporting Evidence: PMID:11553327 LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies.
GO:0043025 neuronal cell body	IDA PMID:12411744 Towards understanding the polycystins.	ACCEPT	Summary: Cell body localization confirmed (PMID:12411744). Reason: Confirming IDA evidence. Supporting Evidence: PMID:12411744 Expression analysis localized LOV-1 and PKD-2 to the ends of sensory neurons in male tails
GO:0043025 neuronal cell body	IDA PMID:16943275 General and cell-type specific mechanisms target TRPP2/PKD-2...	ACCEPT	Summary: Cell body localization in context of trafficking (PMID:16943275). Reason: IDA evidence supporting cell body localization as part of trafficking pathway. Supporting Evidence: PMID:16943275 General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia.
GO:0060170 ciliary membrane	IDA PMID:16943275 General and cell-type specific mechanisms target TRPP2/PKD-2...	ACCEPT	Summary: PKD-2 specifically localizes to the ciliary membrane compartment (PMID:16943275). Reason: Key IDA evidence for ciliary membrane localization. Supporting Evidence: PMID:16943275 PKD-2 stabilization in cilia and cell bodies requires LOV-1, a functional partner and a TRPP1 homolog.
GO:0060179 male mating behavior	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: pkd-2 is required for male mating behavior with mutants showing specific defects in response and vulval location (PMID:11553327). Reason: Core biological function. Evidence code is technically IMP based on mutant phenotype, but the annotation captures the essential function. Supporting Evidence: PMID:11553327 Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects.
GO:0097730 non-motile cilium	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2 localizes to non-motile sensory cilia which remain structurally normal in pkd-2 mutants (PMID:11553327). Reason: IDA evidence establishing that PKD-2 is in non-motile cilia. Supporting Evidence: PMID:11553327 the cilia of lov-1 and pkd-2 single mutants and of lov-1;pkd-2 double mutants are normal as judged by electron microscopy
GO:0097730 non-motile cilium	IDA PMID:15563610 ATP-2 interacts with the PLAT domain of LOV-1 and is involve...	ACCEPT	Summary: PKD-2 colocalizes with ATP-2 in non-motile cilia (PMID:15563610). Reason: IDA evidence from polycystin signaling study. Supporting Evidence: PMID:15563610 ATP-2 and other ATP synthase components colocalize with LOV-1 and PKD-2 in cilia.
GO:0097730 non-motile cilium	IDA PMID:17581863 STAM and Hrs down-regulate ciliary TRP receptors.	ACCEPT	Summary: PKD-2 ciliary localization regulated by STAM-Hrs complex (PMID:17581863). Reason: IDA evidence from study on ciliary receptor regulation. Supporting Evidence: PMID:17581863 overexpression of STAM or Hrs promotes the removal of PKD-2 from cilia
GO:0030425 dendrite	IDA PMID:17581863 STAM and Hrs down-regulate ciliary TRP receptors.	ACCEPT	Summary: PKD-2 in dendrites as part of trafficking pathway (PMID:17581863). Reason: IDA evidence for dendritic localization. Supporting Evidence: PMID:17581863 Jun 20. STAM and Hrs down-regulate ciliary TRP receptors.
GO:0043025 neuronal cell body	IDA PMID:17581863 STAM and Hrs down-regulate ciliary TRP receptors.	ACCEPT	Summary: PKD-2 cell body localization regulated by STAM-Hrs (PMID:17581863). Reason: IDA evidence for cell body localization. Supporting Evidence: PMID:17581863 Jun 20. STAM and Hrs down-regulate ciliary TRP receptors.
GO:0030424 axon	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2::GFP present in axons of male sensory neurons (PMID:11553327). Reason: IDA evidence for axonal localization. Supporting Evidence: PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
GO:0030424 axon	IDA PMID:15563610 ATP-2 interacts with the PLAT domain of LOV-1 and is involve...	ACCEPT	Summary: Axon localization confirmed (PMID:15563610). Reason: Confirming IDA evidence. Supporting Evidence: PMID:15563610 Nov 24. ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling.
GO:0030425 dendrite	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2 in dendrites of male sensory neurons (PMID:11553327). Reason: IDA evidence from foundational study. Supporting Evidence: PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
GO:0030425 dendrite	IDA PMID:15563610 ATP-2 interacts with the PLAT domain of LOV-1 and is involve...	ACCEPT	Summary: Dendritic localization confirmed in polycystin signaling study (PMID:15563610). Reason: Confirming IDA evidence. Supporting Evidence: PMID:15563610 Nov 24. ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling.
GO:0043025 neuronal cell body	IDA PMID:15563610 ATP-2 interacts with the PLAT domain of LOV-1 and is involve...	ACCEPT	Summary: Cell body localization in polycystin complex study (PMID:15563610). Reason: IDA evidence. Supporting Evidence: PMID:15563610 Nov 24. ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling.
GO:0007617 mating behavior	IMP PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: pkd-2 mutants have defective mating behavior (PMID:11553327). Reason: Core biological function. IMP evidence from mutant analysis. Supporting Evidence: PMID:11553327 Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects.
GO:0007617 mating behavior	IGI PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: pkd-2 and lov-1 act in the same pathway for mating behavior (PMID:11553327). Reason: IGI evidence from double mutant analysis showing epistasis. Supporting Evidence: PMID:11553327 pkd-2;lov-1 double mutants are no more severe than either of the single mutants, indicating that lov-1 and pkd-2 act together.
GO:0031090 organelle membrane	IDA PMID:11553327 The Caenorhabditis elegans autosomal dominant polycystic kid...	ACCEPT	Summary: PKD-2 localizes to intracellular organelle membranes (PMID:11553327). Reason: IDA evidence for intracellular membrane localization. Supporting Evidence: PMID:11553327 Cytoplasmic, nonnuclear staining in cell bodies is punctate, suggesting that one pool of PKD-2 is localized to intracellular membranes

Core Functions

PKD-2 functions as a calcium-permeable TRP channel in ciliary membranes of male sensory neurons, mediating detection of mechanical/chemical stimuli during mating behavior.

Molecular Function:

calcium channel activity

Directly Involved In:

detection of mechanical stimulus response to hermaphrodite contact vulval location

Cellular Locations:

ciliary membrane non-motile cilium

Supporting Evidence:

PMID:15862350
we found that polycystin-2 is an intracellular Ca(2+) release channel that is required for the normal pattern of Ca(2+) responses
PMID:11553327
LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on inter-ontology links

PMID:10517638

A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans.

PKD-2 is the C. elegans homolog of human PKD2

"A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans."
PKD-2 is localized to the same male-specific neurons as LOV-1

"A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans."
PKD-2 functions in sensory neurons of rays, hook, and head

"A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans."

PMID:11553327

The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.

lov-1 and pkd-2 act in the same pathway

"The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway."
Mutations result in identical male sensory behavioral defects

"The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway."
PKD-2::GFP concentrated in cilia and cell bodies

"The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway."
Cilia are structurally normal in pkd-2 mutants

"The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway."

PMID:12411744

Towards understanding the polycystins.

lov-1 and pkd-2 participate in a single genetic pathway

"Towards understanding the polycystins."
LOV-1 and PKD-2 localize to ends of sensory neurons

"Towards understanding the polycystins."
Polycystins act as sensors of the extracellular environment

"Towards understanding the polycystins."

PMID:15563610

ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling.

ATP-2 colocalizes with LOV-1 and PKD-2 in cilia

"ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling."
atp-2, lov-1, and pkd-2 act in the same molecular pathway

"ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling."

PMID:15817158

Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors.

NPHP-1 and NPHP-4 colocalize with PKD-2 in male-specific sensory cilia

"Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors."
Nephrocystins facilitate ciliary sensory signal transduction

"Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors."

PMID:15862350

Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans.

PKD-2 is an intracellular Ca2+ release channel

"Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans."
PKD-2 required for normal Ca2+ response patterns

"Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans."
PKD-2 creates brief cytosolic Ca2+ transients with increased amplitude

"Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans."
PKD-2 works with IP3 and ryanodine receptors in the ER

"Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans."

PMID:16481400

Casein kinase II and calcineurin modulate TRPP function and ciliary localization.

CK2 phosphorylates PKD-2 at Ser-534

"Casein kinase II and calcineurin modulate TRPP function and ciliary localization."
Calcineurin dephosphorylates PKD-2

"Casein kinase II and calcineurin modulate TRPP function and ciliary localization."
Phosphorylation state regulates ciliary localization

"Casein kinase II and calcineurin modulate TRPP function and ciliary localization."
Phospho-defective S534A localizes to cilia

"Casein kinase II and calcineurin modulate TRPP function and ciliary localization."
Phospho-mimetic S534D is absent from cilia

"Casein kinase II and calcineurin modulate TRPP function and ciliary localization."

PMID:16943275

General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia.

PKD-2 moves bidirectionally in dendritic compartment

"General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia."
UNC-101/AP-1 directs PKD-2 to dendritic particles

"General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia."
LOV-1 required for PKD-2 stabilization in cilia

"General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia."
Cell-type specific factors required for dendritic targeting

"General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia."

PMID:17581863

STAM and Hrs down-regulate ciliary TRP receptors.

STAM-1A interacts with LOV-1

"STAM and Hrs down-regulate ciliary TRP receptors."
STAM-Hrs directs LOV-1-PKD-2 for lysosomal degradation

"STAM and Hrs down-regulate ciliary TRP receptors."
Overexpression removes PKD-2 from cilia

"STAM and Hrs down-regulate ciliary TRP receptors."

PMID:18037411

Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2.

Transmembrane region sufficient for ciliary targeting

"Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2."
Cytosolic tails regulate cell body localization

"Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2."
PKD-2 colocalizes with OSM-9 TRPV channel

"Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2."
Human PC-2 partially rescues pkd-2 mutants

"Distinct protein domains regulate ciliary targeting and function of C. elegans PKD-2."

PMID:27930654

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.

PKD-2::GFP used as ciliary marker

"Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport."
Localization to cilia and sensory dendrites

"Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport."

file:worm/pkd-2/pkd-2-deep-research-falcon.md

Deep research report on pkd-2

📚 Additional Documentation

Deep Research Falcon

(pkd-2-deep-research-falcon.md)

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protein_description: 'RecName: Full=Polycystin-2 {ECO:0000303|PubMed:15862350};
Short=CePc2; AltName: Full=Polycystic kidney disease 2 protein homolog {ECO:0000250|UniProtKB:Q13563};'
gene_info: Name=pkd-2 {ECO:0000312|WormBase:Y73F8A.1}; Synonyms=pdk-2 {ECO:0000312|WormBase:Y73F8A.1};
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organism_full: Caenorhabditis elegans.
protein_family: Belongs to the polycystin family. .
protein_domains: PKD1_2_channel. (IPR013122); PKD_2. (IPR003915); Polycystin. (IPR051223);
Polycystin_dom. (IPR046791); PKD_channel (PF08016)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q9U1S7
Protein Description: RecName: Full=Polycystin-2 {ECO:0000303|PubMed:15862350}; Short=CePc2; AltName: Full=Polycystic kidney disease 2 protein homolog {ECO:0000250|UniProtKB:Q13563};
Gene Information: Name=pkd-2 {ECO:0000312|WormBase:Y73F8A.1}; Synonyms=pdk-2 {ECO:0000312|WormBase:Y73F8A.1}; ORFNames=Y73F8A.1 {ECO:0000312|WormBase:Y73F8A.1};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the polycystin family. .
Key Domains: PKD1_2_channel. (IPR013122); PKD_2. (IPR003915); Polycystin. (IPR051223); Polycystin_dom. (IPR046791); PKD_channel (PF08016)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "pkd-2" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'pkd-2' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene pkd-2 (gene ID: pkd-2, UniProt: Q9U1S7) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q9U1S7
Protein Description: RecName: Full=Polycystin-2 {ECO:0000303|PubMed:15862350}; Short=CePc2; AltName: Full=Polycystic kidney disease 2 protein homolog {ECO:0000250|UniProtKB:Q13563};
Gene Information: Name=pkd-2 {ECO:0000312|WormBase:Y73F8A.1}; Synonyms=pdk-2 {ECO:0000312|WormBase:Y73F8A.1}; ORFNames=Y73F8A.1 {ECO:0000312|WormBase:Y73F8A.1};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the polycystin family. .
Key Domains: PKD1_2_channel. (IPR013122); PKD_2. (IPR003915); Polycystin. (IPR051223); Polycystin_dom. (IPR046791); PKD_channel (PF08016)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "pkd-2" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene pkd-2 (gene ID: pkd-2, UniProt: Q9U1S7) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Plan
- Verify identity and organism-specificity; confirm polycystin/TRPP2 family and ciliary channel context. Compile foundational and most recent (2023–2024) primary literature. Extract precise evidence on molecular function, interacting partners, pathways, localization (neurons, subcellular), extracellular vesicle (EV) biology, and quantitative data. Summarize applications and expert perspectives. Provide URLs and publication dates.

Gene/protein verification and core definitions
- Identity and organism. pkd-2 (ORF Y73F8A.1) in Caenorhabditis elegans encodes the nematode polycystin‑2 (TRPP2) homolog, a ciliary membrane protein required for male mating behaviors; this matches UniProt Q9U1S7 and the polycystin family assignment (polycystin/TRPP channel) (Barr and Sternberg, Nature, 1999; Current Biology 2001) (wang2020releaseandtargeting pages 1-2, walsh2022trackingnand pages 2-4).
- Protein family and domains. pkd-2 encodes a TRP polycystin-2–type channel (TRPP family) that forms complexes with the polycystin‑1 homolog LOV-1; live imaging shows PKD‑2 co-traffics and co-releases with the LOV-1 C‑terminal fragment on ciliary EVs, consistent with conserved polycystin complex biology (Walsh et al., PLOS Genetics, 2022; Wang et al., Current Biology, 2021) (walsh2022trackingnand pages 2-4, wang2021sensoryciliaact pages 1-3). Based on TRPP2 family conservation, PKD‑2 is inferred to be a Ca2+-permeable cation channel acting in sensory transduction, although direct single-channel biophysics in C. elegans is not detailed in the retrieved 2021–2024 sources (wang2021sensoryciliaact pages 1-3, walsh2022trackingnand pages 2-4).

Primary function and pathway context
- Function. PKD‑2 acts as a ciliary TRP channel central to male-specific sensory transduction and behavior. It functions with LOV‑1/PKD‑1 in a shared genetic pathway; mutations in lov‑1 or pkd‑2 cause similar defects in male mating behaviors, including response to contact and location of the vulva (Barr and Sternberg, Nature, 1999; Walsh et al., PLOS Genetics, 2022) (wang2020releaseandtargeting pages 1-2, walsh2022trackingnand pages 2-4).
- Polycystin complex and EV signaling. PKD‑2 and LOV‑1 C‑terminus are co-transported from the ER through dendritic vesicles to cilia and co-released on the same environmentally shed EVs, indicating coordinated trafficking and signaling output from cilia (Walsh et al., 2022) (walsh2022trackingnand pages 2-4). Ciliary EVs are a regulated signaling output of sensory neurons; PKD‑2 EVs originate from distinct ciliary microdomains (see below) and can be directionally transferred to mating partners (Wang et al., Current Biology, 2021; Current Biology, 2020) (wang2021sensoryciliaact pages 1-3, wang2020releaseandtargeting pages 1-2, wang2020releaseandtargeting pages 5-6, wang2020releaseandtargeting pages 2-5).

Cellular and subcellular localization
- Neuron classes. pkd‑2 is expressed in male-specific ciliated sensory neurons, including the four CEM head neurons, HOB (hook B-type), and multiple ray B neurons (RnB) in the male tail; expression mapping and EV proteogenomics link these cells to PKD‑2 EV biology (Nikonorova et al., Current Biology, 2022; Nikonorova et al., bioRxiv, 2024) (nikonorova2022isolationprofilingand pages 1-3, nikonorova2024polycystinsrecruitcargo pages 1-3).
- Subcellular compartments and transport. PKD‑2 is transported along dendrites to the ciliary membrane and is enriched at the distal tip and along the shaft; it localizes on cilia-derived EVs released to the environment (Walsh et al., 2022; Wang et al., 2021) (walsh2022trackingnand pages 2-4, wang2021sensoryciliaact pages 1-3).

Extracellular vesicle (EV) biogenesis, sites, and deposition
- Two EV subtypes and release sites. Live Airyscan imaging established two spatially distinct PKD‑2 EV biogenesis sites: (1) distal ciliary tip, generating environmental EVs; and (2) periciliary membrane compartment (PCM) at the ciliary base, producing base EVs that include axonemal/transition-zone markers (Wang et al., Current Biology, 2021; bioRxiv, 2021) (wang2021sensoryciliaact pages 1-3, wang2021sensoryciliaacta pages 1-4). All examined cilia shed base EVs (n=35), while tip EV shedding occurred in 25/35 cilia (wang2021sensoryciliaact pages 1-3).
- Mechanoresponsive release and directional transfer during mating. PKD‑2 EV release is triggered by mechanical stimulation of male ciliary tips: imaging males first under an agarose‑padded coverslip (few EVs) and then under a bare coverslip (abundant EVs) showed significant mechanoresponsiveness (Kruskal–Wallis p<0.01, n=39). EVs were more frequently released from ray cilia tips adjacent to the stimulus; dorsal vs ventral release differences were quantified (n=56 vs 42, two‑proportion Z‑test) (Wang et al., Current Biology, 2020; bioRxiv, 2020) (wang2020releaseandtargeting pages 1-2, wang2020releaseandtargeting pages 5-6, wang2020polycystin2ciliaryextracellular pages 1-4, wang2020polycystin2ciliaryextracellular pages 4-6). During mating, male-derived PKD‑2::GFP EVs are deposited onto the hermaphrodite vulval cuticle, with no EVs detected inside the uterus (Wang et al., Current Biology, 2020) (wang2020releaseandtargeting pages 1-2, wang2020releaseandtargeting pages 5-6, wang2020releaseandtargeting pages 2-5).
- Dynamic sustained release. Time-lapse in vivo imaging shows cilia can sustain PKD‑2 tip EV release for up to approximately two hours without synaptic transmission; sustained release requires ciliary-intrinsic membrane replenishment mechanisms (Wang et al., bioRxiv, 2024) (wang2024ciliaryintrinsicmechanisms pages 3-6).

Regulators and interacting partners
- Trafficking/EV regulators. Distal tip enrichment of PKD‑2 and tip EV release require the myristoylated coiled‑coil protein CIL‑7 and motor activity from kinesin‑3 KLP‑6 and IFT kinesin‑2; blocking tip shedding increases base shedding (Wang et al., Current Biology, 2021; bioRxiv, 2021) (wang2021sensoryciliaact pages 1-3, wang2021sensoryciliaacta pages 1-4). Under mating‑partner exposure, males alter EV cargo composition, increasing the PKD‑2:CIL‑7 EV ratio (per-animal mean PKD‑2 EVs 28.7 ± 31.4 in virgins vs 47.9 ± 64.4 with partners; CIL‑7 EVs 36.9 ± 33.9 vs 26.6 ± 33.0) (Wang et al., 2021) (wang2021sensoryciliaact pages 6-7).
- Sustained‑release machinery. Extended (but not initial) PKD‑2 tip EV release requires the transition‑zone protein NPHP‑4 and the dihydroceramide desaturase ortholog TTM‑5 (ceramide pathway); ttm‑5 is enriched in EV‑releasing neurons and localizes to cilia (Wang et al., bioRxiv, 2024) (wang2024ciliaryintrinsicmechanisms pages 3-6).
- EV cargo recruitment by polycystins. Using an EV‑TurboID proximity labeling strategy, polycystin complexes were shown to recruit distinct EV cargoes: PACL‑1 (channel‑like), PAML‑1/2 (transmembrane C‑type lectins, with dorsoventral bias), and TRAF‑family adaptors TRF‑1/2. Loading of these components into cilia/EVs relies on LOV‑1, and trf/paml/pacl mutants show impaired response and vulva‑location behaviors (Nikonorova et al., bioRxiv, 2024; Nature Communications, 2025) (nikonorova2024polycystinsrecruitcargo pages 3-5, nikonorova2025polycystinsrecruitcargo pages 13-14).

Behavioral roles and quantitative phenotypes
- Genetic pathway and behavior. pkd‑2 and lov‑1 act in the same pathway controlling male mating behaviors; loss impairs response to contact and vulva location (Barr and Sternberg, Nature, 1999; Barr et al., Current Biology, 2001) (wang2020releaseandtargeting pages 1-2, walsh2022trackingnand pages 2-4). PKD‑2 EV shedding is modulated by partner presence (above); individual detonation-like bursts at the tip can release several to hundreds of EVs (Wang et al., bioRxiv, 2021; Current Biology, 2021) (wang2021sensoryciliaacta pages 1-4, wang2021sensoryciliaact pages 1-3).

Recent developments (2023–2024 priority) and latest research
- Ciliary intrinsic control of sustained EV release (2023/2024). Cilia maintain extended PKD‑2 EV output via transition‑zone and lipid pathway factors (NPHP‑4, TTM‑5), independent of synaptic transmission; authors estimate that a cilium’s membrane area is roughly equivalent to about 60 EVs, highlighting the need for rapid membrane replenishment during sustained release (Wang et al., bioRxiv, posted Nov 3, 2023; updated 2024) (wang2024ciliaryintrinsicmechanisms pages 3-6).
- Polycystin‑guided EV cargo recruitment (2024). A modular EV‑TurboID method mapped PKD‑2/LOV‑1 EV microenvironments and uncovered LOV‑1‑dependent loading of PACL‑1, PAMLs, and TRF‑1/2 to specific EV subtypes, linking polycystin complexes to cargo selection and male‑mating behaviors (bioRxiv Apr 17, 2024; DOI 10.1101/2024.04.17.588758) (nikonorova2024polycystinsrecruitcargo pages 3-5). These findings advanced into peer-reviewed publication (Nature Communications, Apr 2025) consolidating the recruitment model and behavioral impact (nikonorova2025polycystinsrecruitcargo pages 13-14).

Applications and real-world implementations
- C. elegans as a model for polycystin biology and ciliopathies. The worm system provides in vivo access to ciliary trafficking, EV biogenesis, and polycystin complex function, paralleling conserved features with vertebrate cilia and informing ADPKD-related pathways (Wang et al., Current Biology, 2021; Nikonorova et al., Current Biology, 2022; Walsh et al., 2022) (wang2021sensoryciliaact pages 1-3, nikonorova2022isolationprofilingand pages 1-3, walsh2022trackingnand pages 2-4). The MyEVome resource and large-scale EV proteome (2,888 proteins) facilitate cross-tissue and cell-type inference for EV cargo, including ciliary proteins (Nikonorova et al., 2022) (nikonorova2022isolationprofilingand pages 1-3).
- Mechanosensitive EV signaling during mating as a paradigm. The directional deposition of PKD‑2 EVs onto hermaphrodite vulva establishes a tractable model to study inter-animal EV transfer, cargo targeting, and potential antimicrobial or re-mating modulation functions suggested by EV cargo signatures (Wang et al., Current Biology, 2020; 2021) (wang2020releaseandtargeting pages 1-2, wang2020releaseandtargeting pages 2-5, wang2021sensoryciliaact pages 1-3).

Expert perspectives
- Current expert consensus frames ciliary EVs as regulated outputs of sensory cilia, with the polycystin complex acting both as a sensory hub and as a cargo organizer for EV subtype specialization; kinesin motors and ciliary membrane microdomains orchestrate where and when EVs bud (Wang et al., Current Biology, 2021; Akella and Barr, Developmental Neurobiology review, 2021) (wang2021sensoryciliaact pages 1-3, wang2021sensoryciliaacta pages 1-4). The newest work places emphasis on transition zone gating and lipid remodeling in sustaining prolonged EV output, adding physiological depth to earlier trafficking-centric models (Wang et al., bioRxiv, 2024) (wang2024ciliaryintrinsicmechanisms pages 3-6).

Relevant statistics and quantitative data (selected)
- Mechanoresponsive release: padded vs bare coverslip imaging, Kruskal–Wallis p<0.01 (n=39); dorsal vs ventral ray release, two-proportion Z‑test (n=56 dorsal, n=42 ventral) (Wang et al., Current Biology, 2020; bioRxiv, 2020) (wang2020releaseandtargeting pages 5-6, wang2020polycystin2ciliaryextracellular pages 4-6, wang2020polycystin2ciliaryextracellular pages 1-4).
- EV site prevalence: base EVs observed in all cilia examined (n=35); tip EV shedding observed in 25/35 (Wang et al., Current Biology, 2021) (wang2021sensoryciliaact pages 1-3).
- Partner‑dependent EV modulation: mean per‑animal counts show PKD‑2 EVs 28.7 ± 31.4 (virgins) vs 47.9 ± 64.4 (with partners); CIL‑7 EVs 36.9 ± 33.9 vs 26.6 ± 33.0 (Wang et al., Current Biology, 2021) (wang2021sensoryciliaact pages 6-7).
- Sustained release capacity: continuous PKD‑2 tip EV shedding sustained up to ~2 hours; ciliary membrane approximates the area of ~60 EVs, indicating substantial membrane turnover needs (Wang et al., bioRxiv, 2024) (wang2024ciliaryintrinsicmechanisms pages 3-6).

Key concepts and definitions (consolidated)
- PKD‑2: C. elegans polycystin‑2/TRPP2 family ciliary channel localized to male sensory cilia; functions with LOV‑1/PKD‑1 in mating behavior and EV signaling (wang2020releaseandtargeting pages 1-2, walsh2022trackingnand pages 2-4, wang2021sensoryciliaact pages 1-3).
- EV subtypes: tip‑derived environmental EVs vs PCM‑derived base EVs with differing marker content and regulation (wang2021sensoryciliaact pages 1-3, wang2021sensoryciliaacta pages 1-4).
- Regulators: CIL‑7 (myristoylated), KLP‑6 (kinesin‑3), IFT kinesin‑2 for tip sorting/shedding; NPHP‑4 and TTM‑5 (DEGS) for sustained release (wang2021sensoryciliaact pages 1-3, wang2024ciliaryintrinsicmechanisms pages 3-6, wang2021sensoryciliaacta pages 1-4).
- Cargo recruitment: Polycystin complexes recruit defined cargo (PACL‑1, PAML‑1/2, TRF‑1/2) into EVs, often LOV‑1‑dependent; associated mutants exhibit mating behavior deficits (nikonorova2024polycystinsrecruitcargo pages 3-5, nikonorova2025polycystinsrecruitcargo pages 13-14).

Comprehensive summary table
| Category | Key finding (1–2 sentences) | Evidence / source | URL | Publication date |
|---|---|---:|---|---:|
| Identity / organism / family | pkd-2 encodes the C. elegans polycystin-2 (TRPP2) homolog (ORF Y73F8A.1), a member of the polycystin/TRPP family and ciliary protein. | Barr MM, Sternberg PW, Nature, 1999 (identification in C. elegans) (wang2020releaseandtargeting pages 1-2) | https://doi.org/10.1038/43913 | Sep 1999 |
| Molecular function | Functions as a TRP-type polycystin channel involved in sensory transduction and Ca2+-related signaling, and forms functional complexes with LOV-1 (polycystin-1 homolog). | Walsh JD et al., PLOS Genet, 2022; Wang J et al., Curr Biol, 2021 (ciliary TRPP2 channel role and complexing with LOV-1) (walsh2022trackingnand pages 2-4, wang2021sensoryciliaact pages 1-3) | https://doi.org/10.1371/journal.pgen.1010560, https://doi.org/10.1016/j.cub.2021.06.040 | Dec 2022; Jul 2021 |
| Expression (cell/tissue) | Expressed in male-specific ciliated sensory neurons including CEM, RnB (ray B) neurons and HOB (and other EV-releasing neurons). | Nikonorova I. et al., Curr Biol, 2022; Walsh JD et al., PLOS Genet, 2022 (neuronal expression mapping) (nikonorova2022isolationprofilingand pages 1-3, walsh2022trackingnand pages 2-4) | https://doi.org/10.1016/j.cub.2022.03.005, https://doi.org/10.1371/journal.pgen.1010560 | Mar 2022; Dec 2022 |
| Subcellular localization | PKD-2 localizes to the dendrite-to-cilium transport route and ciliary membrane (distal tip and shaft) and is present on environmentally shed ciliary extracellular vesicles (EVs). | Walsh JD et al., PLOS Genet, 2022; Wang J et al., Curr Biol, 2021 (live imaging and co-transport with LOV-1 CTM) (walsh2022trackingnand pages 2-4, wang2021sensoryciliaact pages 1-3) | https://doi.org/10.1371/journal.pgen.1010560, https://doi.org/10.1016/j.cub.2021.06.040 | Dec 2022; Jul 2021 |
| EV biogenesis / release sites | PKD-2 is packaged into two EV subtypes shed from distinct ciliary sites: (1) distal ciliary tip (environmental EVs) and (2) periciliary membrane compartment at the ciliary base (PCM); release is mechanoresponsive and male-derived PKD-2 EVs are deposited onto the hermaphrodite vulva during mating. | Wang J et al., Curr Biol, 2021; Wang J et al., Curr Biol (R), 2020 (mechanosensitive deposition during mating) (wang2021sensoryciliaact pages 1-3, wang2020releaseandtargeting pages 1-2, wang2020releaseandtargeting pages 5-6) | https://doi.org/10.1016/j.cub.2021.06.040, https://doi.org/10.1016/j.cub.2020.05.079 | Jul 2021; Jul 2020 |
| Regulators of PKD-2 trafficking & EV release | Distal tip enrichment and tip-EV shedding require CIL-7 (myristoylated coiled-coil), kinesin-3 KLP-6 and IFT kinesin-2 motors; sustained/extended EV release requires transition-zone protein NPHP-4 and lipid enzyme TTM-5 (DEGS homolog). | Wang J et al., Curr Biol, 2021; Wang J et al., bioRxiv (2023/2024) for sustained-release regulators (wang2021sensoryciliaact pages 1-3, wang2024ciliaryintrinsicmechanisms pages 3-6) | https://doi.org/10.1016/j.cub.2021.06.040, https://doi.org/10.1101/2023.11.01.565151 | Jul 2021; bioRxiv Nov 2023 (posted) |
| EV cargo recruitment (PKD-2–dependent) | PKD-2/LOV-1 complexes recruit specific cargo to distinct EV subtypes, including PACL-1 (channel-like), PAML-1/2 (C-type lectins) and TRAF homologs TRF-1/2; loading of many cargos is LOV-1–dependent. | Nikonorova IA et al., bioRxiv 2024 (EV-TurboID) and Nikonorova et al., Nat Commun 2025 preprint/accepted (cargo ID and LOV-1 dependence) (nikonorova2024polycystinsrecruitcargo pages 3-5, nikonorova2025polycystinsrecruitcargo pages 13-14) | https://doi.org/10.1101/2024.04.17.588758, https://doi.org/10.1038/s41467-025-57512-3 | Apr 2024 (preprint); Apr 2025 (Nat Commun) |
| Quantitative data / examples | Reported per-animal PKD-2 EV counts: mean PKD-2 EVs virgin 28.7 ± 31.4 vs with partners 47.9 ± 64.4; CIL-7 EVs 36.9 ± 33.9 vs 26.6 ± 33.0; mechanoresponse assay n=39, p<0.01; sustained tip release can continue up to ~2 hours and authors estimate ≈60 EVs-worth of membrane equals the ciliary membrane. | Wang J et al., Curr Biol, 2021 (per-animal EV counts/statistics); Wang et al., bioRxiv 2023/2024 (sustained-release & membrane estimate) (wang2021sensoryciliaact pages 6-7, wang2024ciliaryintrinsicmechanisms pages 3-6) | https://doi.org/10.1016/j.cub.2021.06.040, https://doi.org/10.1101/2023.11.01.565151 | Jul 2021; bioRxiv Nov 2023 (posted) |
| Historical genetic pathway & mating phenotypes | lov-1 (PKD1 homolog) and pkd-2 act in the same genetic pathway required for male mating behaviors; pkd-2 or lov-1 mutants show defects in mate response and vulva location. | Barr MM & Sternberg PW, Nature, 1999; Walsh JD et al., PLOS Genet, 2022 (functional/co-transport evidence and behavior links) (wang2020releaseandtargeting pages 1-2, walsh2022trackingnand pages 2-4) | https://doi.org/10.1038/43913, https://doi.org/10.1371/journal.pgen.1010560 | Sep 1999; Dec 2022 |

Table: Compact, evidence-linked summary table of key annotations for C. elegans pkd-2 (Q9U1S7), listing function, localization, regulators, EV biology, quantitative findings, and primary sources (1999–2024) for rapid reference.

Selected source details with URLs and dates
- Barr MM, Sternberg PW. A polycystic kidney‑disease gene homologue required for male mating behaviour in C. elegans. Nature. Sep 1999. https://doi.org/10.1038/43913 (wang2020releaseandtargeting pages 1-2)
- Walsh JD et al. Tracking N‑ and C‑termini of C. elegans polycystin‑1… PLOS Genetics. Dec 2022. https://doi.org/10.1371/journal.pgen.1010560 (walsh2022trackingnand pages 2-4)
- Wang J et al. Sensory cilia act as a specialized venue for regulated extracellular vesicle biogenesis and signaling. Current Biology. Jul 2021. https://doi.org/10.1016/j.cub.2021.06.040 (wang2021sensoryciliaact pages 1-3)
- Nikonorova I et al. Isolation, profiling, and tracking of extracellular vesicle cargo in C. elegans. Current Biology. Mar 2022 (published May 9, 2022 online). https://doi.org/10.1016/j.cub.2022.03.005 (nikonorova2022isolationprofilingand pages 1-3)
- Wang J et al. Release and targeting of polycystin‑2‑carrying ciliary extracellular vesicles. Current Biology (Dispatch). Jul 2020. https://doi.org/10.1016/j.cub.2020.05.079 (wang2020releaseandtargeting pages 1-2, wang2020releaseandtargeting pages 5-6, wang2020releaseandtargeting pages 2-5)
- Wang J et al. Sensory cilia act as a specialized venue for regulated EV biogenesis and signaling. bioRxiv. Feb 2021. https://doi.org/10.1101/2021.02.04.429799 (wang2021sensoryciliaacta pages 1-4)
- Wang J et al. Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release… bioRxiv. Posted Nov 3, 2023 (updated 2024). https://doi.org/10.1101/2023.11.01.565151 (wang2024ciliaryintrinsicmechanisms pages 3-6)
- Nikonorova IA et al. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes. bioRxiv. Apr 17, 2024. https://doi.org/10.1101/2024.04.17.588758 (nikonorova2024polycystinsrecruitcargo pages 3-5)
- Nikonorova IA et al. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans. Nature Communications. Apr 2025. https://doi.org/10.1038/10.1038/s41467-025-57512-3 (nikonorova2025polycystinsrecruitcargo pages 13-14)

Notes on gene symbol ambiguity
- We verified organism specificity (C. elegans) and the polycystin/TRPP2 family identity of pkd‑2 throughout all cited work. If encountering pkd2 literature in other organisms (e.g., human PKD2), do not conflate; all evidence here is worm-specific and cross-validated with conserved polycystin biology (wang2020releaseandtargeting pages 1-2, wang2021sensoryciliaact pages 1-3, walsh2022trackingnand pages 2-4).

References

(wang2020releaseandtargeting pages 1-2): Juan Wang, Inna A. Nikonorova, Amanda Gu, Paul W. Sternberg, and Maureen M. Barr. Release and targeting of polycystin-2-carrying ciliary extracellular vesicles. Current Biology, 30:R755-R756, Jul 2020. URL: https://doi.org/10.1016/j.cub.2020.05.079, doi:10.1016/j.cub.2020.05.079. This article has 43 citations and is from a highest quality peer-reviewed journal.
(walsh2022trackingnand pages 2-4): Jonathon D. Walsh, Juan Wang, Molly DeHart, Inna A. Nikonorova, Jagan Srinivasan, and Maureen M. Barr. Tracking n- and c-termini of c. elegans polycystin-1 reveals their distinct targeting requirements and functions in cilia and extracellular vesicles. PLOS Genetics, 18:e1010560, Dec 2022. URL: https://doi.org/10.1371/journal.pgen.1010560, doi:10.1371/journal.pgen.1010560. This article has 11 citations and is from a domain leading peer-reviewed journal.
(wang2021sensoryciliaact pages 1-3): Juan Wang, Inna Nikonorova, Malan Silva, Jonathon Walsh, Peter Tilton, Amanda Gu, Jothy Akella, and Maureen M. Barr. Sensory cilia act as a specialized venue for regulated extracellular vesicle biogenesis and signaling. Current Biology, 31:3943-3951.e3, Jul 2021. URL: https://doi.org/10.1016/j.cub.2021.06.040, doi:10.1016/j.cub.2021.06.040. This article has 68 citations and is from a highest quality peer-reviewed journal.
(wang2020releaseandtargeting pages 5-6): Juan Wang, Inna A. Nikonorova, Amanda Gu, Paul W. Sternberg, and Maureen M. Barr. Release and targeting of polycystin-2-carrying ciliary extracellular vesicles. Current Biology, 30:R755-R756, Jul 2020. URL: https://doi.org/10.1016/j.cub.2020.05.079, doi:10.1016/j.cub.2020.05.079. This article has 43 citations and is from a highest quality peer-reviewed journal.
(wang2020releaseandtargeting pages 2-5): Juan Wang, Inna A. Nikonorova, Amanda Gu, Paul W. Sternberg, and Maureen M. Barr. Release and targeting of polycystin-2-carrying ciliary extracellular vesicles. Current Biology, 30:R755-R756, Jul 2020. URL: https://doi.org/10.1016/j.cub.2020.05.079, doi:10.1016/j.cub.2020.05.079. This article has 43 citations and is from a highest quality peer-reviewed journal.
(nikonorova2022isolationprofilingand pages 1-3): I. Nikonorova, Juan Wang, Alexander L. Cope, Peter Tilton, Kaiden M. Power, Jonathon D. Walsh, J. S. Akella, Amber R. Krauchunas, Premal Shah, and M. Barr. Isolation, profiling, and tracking of extracellular vesicle cargo in caenorhabditis elegans. Current Biology, 32:1924-1936.e6, Mar 2022. URL: https://doi.org/10.1016/j.cub.2022.03.005, doi:10.1016/j.cub.2022.03.005. This article has 56 citations and is from a highest quality peer-reviewed journal.
(nikonorova2024polycystinsrecruitcargo pages 1-3): Inna A. Nikonorova, Elizabeth desRanleau, Katherine C. Jacobs, Joshua Saul, Jonathon D. Walsh, Juan Wang, and Maureen M. Barr. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.04.17.588758, doi:10.1101/2024.04.17.588758. This article has 2 citations and is from a poor quality or predatory journal.
(wang2021sensoryciliaacta pages 1-4): Juan Wang, Inna A. Nikonorova, Malan Silva, Jonathon D. Walsh, Peter Tilton, Amanda Gu, and Maureen M. Barr. Sensory cilia act as a specialized venue for regulated ev biogenesis and signaling. bioRxiv, Feb 2021. URL: https://doi.org/10.1101/2021.02.04.429799, doi:10.1101/2021.02.04.429799. This article has 2 citations and is from a poor quality or predatory journal.
(wang2020polycystin2ciliaryextracellular pages 1-4): Juan Wang, Inna A. Nikonorova, Amanda Gu, Paul W. Sternberg, and Maureen M. Barr. Polycystin-2 ciliary extracellular vesicle release and targeting. bioRxiv, Apr 2020. URL: https://doi.org/10.1101/2020.04.21.050690, doi:10.1101/2020.04.21.050690. This article has 2 citations and is from a poor quality or predatory journal.
(wang2020polycystin2ciliaryextracellular pages 4-6): Juan Wang, Inna A. Nikonorova, Amanda Gu, Paul W. Sternberg, and Maureen M. Barr. Polycystin-2 ciliary extracellular vesicle release and targeting. bioRxiv, Apr 2020. URL: https://doi.org/10.1101/2020.04.21.050690, doi:10.1101/2020.04.21.050690. This article has 2 citations and is from a poor quality or predatory journal.
(wang2024ciliaryintrinsicmechanisms pages 3-6): Juan Wang, Josh Saul, Inna A. Nikonorova, Carlos Nava Cruz, Kaiden M. Power, Ken C. Nguyen, David H. Hall, and Maureen M. Barr. Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons. bioRxiv, Nov 2024. URL: https://doi.org/10.1101/2023.11.01.565151, doi:10.1101/2023.11.01.565151. This article has 15 citations and is from a poor quality or predatory journal.
(wang2021sensoryciliaact pages 6-7): Juan Wang, Inna Nikonorova, Malan Silva, Jonathon Walsh, Peter Tilton, Amanda Gu, Jothy Akella, and Maureen M. Barr. Sensory cilia act as a specialized venue for regulated extracellular vesicle biogenesis and signaling. Current Biology, 31:3943-3951.e3, Jul 2021. URL: https://doi.org/10.1016/j.cub.2021.06.040, doi:10.1016/j.cub.2021.06.040. This article has 68 citations and is from a highest quality peer-reviewed journal.
(nikonorova2024polycystinsrecruitcargo pages 3-5): Inna A. Nikonorova, Elizabeth desRanleau, Katherine C. Jacobs, Joshua Saul, Jonathon D. Walsh, Juan Wang, and Maureen M. Barr. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.04.17.588758, doi:10.1101/2024.04.17.588758. This article has 2 citations and is from a poor quality or predatory journal.
(nikonorova2025polycystinsrecruitcargo pages 13-14): Inna A. Nikonorova, Elizabeth desRanleau, Katherine C. Jacobs, Josh Saul, Jonathon D. Walsh, Juan Wang, and Maureen M. Barr. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in c. elegans. Nature Communications, Apr 2025. URL: https://doi.org/10.1038/s41467-025-57512-3, doi:10.1038/s41467-025-57512-3. This article has 5 citations and is from a highest quality peer-reviewed journal.

Citations

walsh2022trackingnand pages 2-4
wang2021sensoryciliaact pages 1-3
wang2024ciliaryintrinsicmechanisms pages 3-6
wang2021sensoryciliaact pages 6-7
nikonorova2024polycystinsrecruitcargo pages 3-5
nikonorova2025polycystinsrecruitcargo pages 13-14
nikonorova2022isolationprofilingand pages 1-3
wang2020releaseandtargeting pages 1-2
wang2021sensoryciliaacta pages 1-4
wang2020releaseandtargeting pages 5-6
wang2020releaseandtargeting pages 2-5
nikonorova2024polycystinsrecruitcargo pages 1-3
https://doi.org/10.1038/43913
https://doi.org/10.1371/journal.pgen.1010560,
https://doi.org/10.1016/j.cub.2021.06.040
https://doi.org/10.1016/j.cub.2022.03.005,
https://doi.org/10.1371/journal.pgen.1010560
https://doi.org/10.1016/j.cub.2021.06.040,
https://doi.org/10.1016/j.cub.2020.05.079
https://doi.org/10.1101/2023.11.01.565151
https://doi.org/10.1101/2024.04.17.588758,
https://doi.org/10.1038/s41467-025-57512-3
https://doi.org/10.1038/43913,
https://doi.org/10.1016/j.cub.2022.03.005
https://doi.org/10.1101/2021.02.04.429799
https://doi.org/10.1101/2024.04.17.588758
https://doi.org/10.1038/10.1038/s41467-025-57512-3
https://doi.org/10.1016/j.cub.2020.05.079,
https://doi.org/10.1101/2021.02.04.429799,
https://doi.org/10.1101/2020.04.21.050690,
https://doi.org/10.1101/2023.11.01.565151,
https://doi.org/10.1038/s41467-025-57512-3,

📄 View Raw YAML

id: Q9U1S7
gene_symbol: pkd-2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: PKD-2 (Polycystin-2) is a calcium-permeable TRP (transient receptor
  potential) cation channel that is the C. elegans ortholog of human PKD2/TRPP2.
  It functions together with LOV-1 (the PKD1 ortholog) in male-specific sensory 
  neurons (ray neurons, hook neurons, and CEM neurons) where it localizes to 
  sensory cilia and is required for male mating behaviors including response to 
  hermaphrodite contact and vulva location. PKD-2 acts as an intracellular 
  calcium release channel that accelerates Ca2+ release from intracellular 
  stores, working alongside IP3 and ryanodine receptors. Its ciliary 
  localization is regulated by phosphorylation at Ser-534 by CK2 and 
  dephosphorylation by calcineurin. The LOV-1/PKD-2 complex represents an 
  evolutionarily conserved mechanosensory receptor-channel system.
existing_annotations:
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PKD-2 is a multi-pass transmembrane protein with 6 transmembrane 
      helices and a pore-forming region (PMID:11553327). Membrane localization 
      is well-established across all PKD2 family members phylogenetically.
    action: ACCEPT
    reason: PKD-2 is a classic ion channel with multiple transmembrane domains. 
      This IBA annotation is appropriate and supported by extensive experimental
      evidence including GFP fusion studies showing membrane localization 
      (PMID:11553327).
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Cytoplasmic, nonnuclear staining in cell bodies is 
        punctate, suggesting that one pool of PKD-2 is localized to 
        intracellular membranes while another is found in sensory cilia.
    - reference_id: file:worm/pkd-2/pkd-2-deep-research-falcon.md
      supporting_text: 'model: Edison Scientific Literature'
- term:
    id: GO:0005262
    label: calcium channel activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PKD-2 functions as a calcium-permeable cation channel, directly 
      demonstrated by electrophysiological studies in C. elegans 
      (PMID:15862350). This is a core molecular function conserved across the 
      TRPP family.
    action: ACCEPT
    reason: This is a core molecular function of PKD-2. The IBA annotation is 
      well-supported by direct experimental evidence showing PKD-2 acts as an 
      intracellular Ca2+ release channel that accelerates Ca2+ release from 
      intracellular stores (PMID:15862350).
    supported_by:
    - reference_id: PMID:15862350
      supporting_text: we found that polycystin-2 is an intracellular Ca(2+) 
        release channel that is required for the normal pattern of Ca(2+) 
        responses involving IP(3) and ryanodine receptor-mediated Ca(2+) release
        from intracellular stores.
- term:
    id: GO:0050982
    label: detection of mechanical stimulus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: PKD-2 functions with LOV-1 as a mechanosensitive receptor-channel 
      complex in sensory cilia (PMID:16481400, PMID:12411744). The polycystins 
      are proposed to act as sensors of the extracellular environment.
    action: ACCEPT
    reason: This is a well-supported function for the polycystin complex. The 
      LOV-1/PKD-2 complex functions similarly to mammalian PC1/PC2 as 
      mechanosensors. Their localization to sensory cilia and role in detecting 
      hermaphrodite contact supports mechanosensory function (PMID:12411744, 
      PMID:16481400).
    supported_by:
    - reference_id: PMID:12411744
      supporting_text: Based on the role of polycystins in C. elegans sensory 
        neuron function and the conservation of PKD pathways we suggest that 
        polycystins act as sensors of the extracellular environment
    - reference_id: PMID:16481400
      supporting_text: In primary cilia of kidney cells, the transient receptor 
        potential polycystin (TRPP) channels polycystin-1 (PC-1) and 
        polycystin-2 (PC-2) act as a mechanosensitive channel
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This annotation is based on InterPro domain prediction. PKD-2 
      belongs to the polycystin family which contains EF-hand-like calcium 
      binding domains.
    action: ACCEPT
    reason: Reasonable IEA annotation based on domain composition. The PKD2 
      domain includes calcium-binding capabilities that are important for 
      channel regulation. This is consistent with PKD-2's role as a calcium 
      channel.
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 localizes to the ER membrane where it functions as a calcium 
      release channel. This is supported by experimental evidence 
      (PMID:16943275, PMID:15862350).
    action: ACCEPT
    reason: Appropriate IEA annotation that is validated by experimental data. 
      UniProt annotation and direct studies confirm ER localization 
      (PMID:16943275). PKD-2 accelerates Ca2+ release from intracellular stores 
      in the ER (PMID:15862350).
    supported_by:
    - reference_id: PMID:16943275
      supporting_text: PKD-2 is directed to moving dendritic particles by the 
        UNC-101/adaptor protein 1 (AP-1) complex
    - reference_id: PMID:15862350
      supporting_text: Polycystin-2, along with the IP(3) and ryanodine 
        receptors, acts as a major calcium-release channel in the endoplasmic 
        reticulum
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 localizes to the plasma membrane, particularly in the ciliary
      membrane of sensory neurons (PMID:11553327, PMID:16943275).
    action: ACCEPT
    reason: IEA annotation supported by extensive experimental evidence showing 
      PKD-2 at the plasma membrane, especially in ciliary membrane compartments 
      (PMID:11553327, PMID:16943275).
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: LOV-1::GFP and PKD-2::GFP are expressed in the same 
        male-specific sensory neurons and are concentrated in cilia and cell 
        bodies.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 localizes to sensory cilia of male-specific neurons. This is 
      one of the best-characterized aspects of PKD-2 biology.
    action: ACCEPT
    reason: Core localization well-established by multiple IDA annotations 
      (PMID:11553327, PMID:16943275, PMID:27930654). The IEA appropriately 
      captures this localization.
- term:
    id: GO:0006811
    label: monoatomic ion transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PKD-2 is a cation channel that transports calcium ions. This broad 
      term encompasses its more specific calcium transport function.
    action: ACCEPT
    reason: Accurate but general annotation. PKD-2 does transport monoatomic 
      ions (calcium). More specific terms (calcium ion transport) are also 
      annotated.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: PKD-2 is an integral membrane protein with multiple transmembrane 
      domains. This is a basic structural annotation.
    action: ACCEPT
    reason: Duplicate of IBA annotation above. Both appropriately capture 
      membrane localization based on different evidence sources (InterPro and 
      phylogenetic inference).
- term:
    id: GO:0030424
    label: axon
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 is found in axons of male-specific sensory neurons, as shown 
      by GFP localization studies (PMID:11553327, PMID:15563610).
    action: ACCEPT
    reason: IEA annotation validated by multiple IDA studies showing axonal 
      localization in male sensory neurons.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 localizes to dendrites of male-specific sensory neurons 
      (PMID:11553327, PMID:18037411).
    action: ACCEPT
    reason: IEA annotation validated by experimental evidence. The dendritic 
      localization is important for PKD-2 trafficking to cilia.
- term:
    id: GO:0034220
    label: monoatomic ion transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: PKD-2 mediates transmembrane transport of calcium ions as a TRP 
      channel.
    action: ACCEPT
    reason: Appropriate IEA annotation based on ion channel keyword. Consistent 
      with PKD-2's established function as a calcium channel (PMID:15862350).
- term:
    id: GO:0043204
    label: perikaryon
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 localizes to neuronal cell bodies (perikarya) in addition to 
      cilia and dendrites (PMID:11553327, PMID:18037411).
    action: ACCEPT
    reason: IEA annotation consistent with experimental data showing cell body 
      localization.
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: PKD-2 is concentrated in the ciliary membrane of male sensory 
      neurons where it functions in sensory signaling (PMID:16943275).
    action: ACCEPT
    reason: Key localization for PKD-2 function. Well-supported by experimental 
      evidence showing specific targeting to ciliary membranes (PMID:16943275).
    supported_by:
    - reference_id: PMID:16943275
      supporting_text: Ciliary localization of the transient receptor potential 
        polycystin 2 channel (TRPP2/PKD-2) is evolutionarily conserved
- term:
    id: GO:0070588
    label: calcium ion transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: Logical inference from calcium channel activity. PKD-2 mediates 
      calcium ion transmembrane transport.
    action: ACCEPT
    reason: Appropriate inference from calcium channel activity (GO:0005262). 
      Directly supported by experimental evidence (PMID:15862350).
- term:
    id: GO:0071683
    label: sensory dendrite
  evidence_type: NAS
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2 localizes to sensory dendrites of male-specific neurons in C.
      elegans.
    action: ACCEPT
    reason: Appropriate localization annotation. The 2001 paper demonstrates 
      PKD-2::GFP localization in male sensory neurons including their dendritic 
      processes (PMID:11553327).
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: LOV-1::GFP and PKD-2::GFP are expressed in the same 
        male-specific sensory neurons and are concentrated in cilia and cell 
        bodies.
- term:
    id: GO:1902435
    label: regulation of male mating behavior
  evidence_type: NAS
  original_reference_id: PMID:10517638
  review:
    summary: PKD-2 is required for male mating behavior in C. elegans 
      (PMID:10517638, PMID:11553327).
    action: ACCEPT
    reason: Core biological function. The 1999 Nature paper established PKD-2's 
      role in male mating behavior. The NAS evidence is appropriate for the 
      regulatory aspect implied in the term.
    supported_by:
    - reference_id: PMID:10517638
      supporting_text: PKD-2, the C. elegans homologue of PKD2, is localized to 
        the same neurons as LOV-1, suggesting that they function in the same 
        pathway.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: PMID:27930654
  review:
    summary: Direct experimental evidence for ciliary localization of PKD-2 
      using GFP reporters (PMID:27930654). The study used PKD-2::GFP as a marker
      for ciliary localization in male sensory neurons.
    action: ACCEPT
    reason: IDA evidence from developmental expression profiling study that used
      PKD-2::GFP to examine ciliary localization. Ciliary localization 
      well-established by primary studies (PMID:11553327).
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: LOV-1::GFP and PKD-2::GFP are expressed in the same 
        male-specific sensory neurons and are concentrated in cilia and cell 
        bodies.
    - reference_id: PMID:27930654
      supporting_text: eCollection 2016 Dec.
- term:
    id: GO:0071683
    label: sensory dendrite
  evidence_type: IDA
  original_reference_id: PMID:27930654
  review:
    summary: Direct evidence for sensory dendrite localization from GFP studies.
    action: ACCEPT
    reason: IDA evidence supporting sensory dendrite localization, consistent 
      with other publications. Dendritic localization established by primary 
      papers (PMID:18037411).
    supported_by:
    - reference_id: PMID:18037411
      supporting_text: The Caenorhabditis elegans TRPP2 homolog, PKD-2, is 
        restricted to the somatodendritic (cell body and dendrite) and ciliary 
        compartments of male specific sensory neurons.
    - reference_id: PMID:27930654
      supporting_text: eCollection 2016 Dec.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:16481400
  review:
    summary: PKD-2 localizes to neuronal cell bodies in male-specific sensory 
      neurons, with phosphorylation state affecting its distribution 
      (PMID:16481400).
    action: ACCEPT
    reason: Strong IDA evidence from study on CK2 and calcineurin regulation of 
      PKD-2.
    supported_by:
    - reference_id: PMID:16481400
      supporting_text: CK2 and the calcineurin phosphatase TAX-6 modulate male 
        mating behavior and PKD-2 ciliary localization.
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:16481400
  review:
    summary: PKD-2 localizes to non-motile sensory cilia in male neurons 
      (PMID:16481400).
    action: ACCEPT
    reason: C. elegans sensory cilia are non-motile (primary) cilia. This is a 
      core localization for PKD-2 function in sensory signaling.
    supported_by:
    - reference_id: PMID:16481400
      supporting_text: Feb 15. Casein kinase II and calcineurin modulate TRPP 
        function and ciliary localization.
- term:
    id: GO:0023041
    label: neuronal signal transduction
  evidence_type: IC
  original_reference_id: PMID:15817158
  review:
    summary: PKD-2's role in neuronal signal transduction is inferred from its 
      ciliary localization and function in sensory behaviors (PMID:15817158).
    action: ACCEPT
    reason: Reasonable IC annotation. PKD-2 functions in ciliary sensory signal 
      transduction as a channel component of the sensory machinery 
      (PMID:15817158).
    supported_by:
    - reference_id: PMID:15817158
      supporting_text: We propose that NPHP-1 and NPHP-4 proteins play important
        and redundant roles in facilitating ciliary sensory signal transduction.
- term:
    id: GO:0034606
    label: response to hermaphrodite contact
  evidence_type: IMP
  original_reference_id: PMID:15817158
  review:
    summary: pkd-2 mutants show defects in response to hermaphrodite contact, a 
      specific step in male mating behavior (PMID:15817158, PMID:11553327).
    action: ACCEPT
    reason: Core biological function. This is one of the two main behavioral 
      defects in pkd-2 mutants (PMID:11553327, PMID:15817158).
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Mutations in either lov-1 or pkd-2 result in identical 
        male sensory behavioral defects.
    - reference_id: PMID:15817158
      supporting_text: Functional characterization of the C.
- term:
    id: GO:0034608
    label: vulval location
  evidence_type: IMP
  original_reference_id: PMID:15817158
  review:
    summary: pkd-2 mutants are defective in vulval location, a specific step in 
      male mating behavior (PMID:15817158, PMID:11553327).
    action: ACCEPT
    reason: Core biological function. This is one of the two main behavioral 
      defects in pkd-2 mutants along with response behavior (PMID:11553327).
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Mutations in either lov-1 or pkd-2 result in identical 
        male sensory behavioral defects.
    - reference_id: PMID:15817158
      supporting_text: Functional characterization of the C.
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:15817158
  review:
    summary: PKD-2 colocalizes with nephrocystins in non-motile sensory cilia 
      (PMID:15817158).
    action: ACCEPT
    reason: IDA evidence consistent with other studies showing non-motile cilium
      localization.
    supported_by:
    - reference_id: PMID:15817158
      supporting_text: GFP-tagged NPHP-1 and NPHP-4 proteins localize to 
        ciliated sensory endings of dendrites and colocalize with PKD-2 in 
        male-specific sensory cilia.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IDA
  original_reference_id: PMID:18037411
  review:
    summary: PKD-2 localizes to dendrites with distinct domains regulating this 
      localization (PMID:18037411).
    action: ACCEPT
    reason: Strong IDA evidence from structure-function study.
    supported_by:
    - reference_id: PMID:18037411
      supporting_text: The Caenorhabditis elegans TRPP2 homolog, PKD-2, is 
        restricted to the somatodendritic (cell body and dendrite) and ciliary 
        compartments of male specific sensory neurons.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:18037411
  review:
    summary: PKD-2 localizes to neuronal cell bodies with cytoplasmic tails 
      regulating this localization (PMID:18037411).
    action: ACCEPT
    reason: IDA evidence from domain function analysis.
    supported_by:
    - reference_id: PMID:18037411
      supporting_text: the PKD-2 cytosolic termini regulate subcellular 
        distribution and function
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:18037411
  review:
    summary: PKD-2 shows perinuclear localization consistent with ER/Golgi 
      localization during biosynthesis (PMID:18037411).
    action: ACCEPT
    reason: IDA evidence supporting perinuclear localization, consistent with 
      ER-based synthesis and trafficking.
    supported_by:
    - reference_id: PMID:18037411
      supporting_text: Epub 2007 Nov 1. Distinct protein domains regulate 
        ciliary targeting and function of C.
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:18037411
  review:
    summary: PKD-2 localizes to non-motile cilia with transmembrane domains 
      sufficient for this targeting (PMID:18037411).
    action: ACCEPT
    reason: Key IDA evidence from structure-function study.
    supported_by:
    - reference_id: PMID:18037411
      supporting_text: somatodendritic and ciliary targeting requires the 
        transmembrane (TM) region of PKD-2
- term:
    id: GO:0034606
    label: response to hermaphrodite contact
  evidence_type: IMP
  original_reference_id: PMID:11553327
  review:
    summary: pkd-2 mutants are defective in response behavior (PMID:11553327).
    action: ACCEPT
    reason: Core IMP evidence from the foundational 2001 paper establishing 
      pkd-2 function.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Mutations in either lov-1 or pkd-2 result in identical 
        male sensory behavioral defects.
- term:
    id: GO:0034606
    label: response to hermaphrodite contact
  evidence_type: IMP
  original_reference_id: PMID:12411744
  review:
    summary: Additional IMP evidence for response behavior defect 
      (PMID:12411744).
    action: ACCEPT
    reason: Confirms behavioral phenotype from independent study.
    supported_by:
    - reference_id: PMID:12411744
      supporting_text: Mutation analysis in C. elegans showed similarly 
        compromised male mating behaviors in all single and double lov-1 and 
        pkd-2 mutants
- term:
    id: GO:0034606
    label: response to hermaphrodite contact
  evidence_type: IMP
  original_reference_id: PMID:15862350
  review:
    summary: pkd-2 mutants show response defects linked to calcium signaling 
      abnormalities (PMID:15862350).
    action: ACCEPT
    reason: IMP evidence connecting behavioral phenotype to calcium channel 
      function.
    supported_by:
    - reference_id: PMID:15862350
      supporting_text: A homologue in Caenorhabditis elegans is necessary for 
        male mating behavior.
- term:
    id: GO:0034608
    label: vulval location
  evidence_type: IMP
  original_reference_id: PMID:11553327
  review:
    summary: pkd-2 mutants are defective in vulval location behavior 
      (PMID:11553327).
    action: ACCEPT
    reason: Core IMP evidence from foundational study.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
        kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
- term:
    id: GO:0034608
    label: vulval location
  evidence_type: IMP
  original_reference_id: PMID:12411744
  review:
    summary: Vulval location defect confirmed in independent study 
      (PMID:12411744).
    action: ACCEPT
    reason: Confirming IMP evidence.
    supported_by:
    - reference_id: PMID:12411744
      supporting_text: Towards understanding the polycystins.
- term:
    id: GO:0034608
    label: vulval location
  evidence_type: IMP
  original_reference_id: PMID:15862350
  review:
    summary: Vulval location defect in pkd-2 mutants (PMID:15862350).
    action: ACCEPT
    reason: Additional IMP evidence supporting this behavioral function.
    supported_by:
    - reference_id: PMID:15862350
      supporting_text: 2005 Apr 14. Polycystin-2 accelerates Ca2+ release from 
        intracellular stores in Caenorhabditis elegans.
- term:
    id: GO:0005262
    label: calcium channel activity
  evidence_type: IDA
  original_reference_id: PMID:15862350
  review:
    summary: Direct electrophysiological evidence that PKD-2 functions as a 
      calcium channel accelerating Ca2+ release from intracellular stores 
      (PMID:15862350).
    action: ACCEPT
    reason: This is the key IDA evidence for PKD-2's molecular function as a 
      calcium channel. The study compared calcium signaling in wild-type and 
      pkd-2 mutants.
    supported_by:
    - reference_id: PMID:15862350
      supporting_text: we found that polycystin-2 is an intracellular Ca(2+) 
        release channel that is required for the normal pattern of Ca(2+) 
        responses involving IP(3) and ryanodine receptor-mediated Ca(2+) release
        from intracellular stores.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:16943275
  review:
    summary: PKD-2 localizes to the ER during its biosynthesis and trafficking 
      pathway (PMID:16943275, PMID:15862350).
    action: ACCEPT
    reason: IDA evidence from trafficking study. ER localization supported by 
      functional studies showing PKD-2 acts as a calcium channel in the ER.
    supported_by:
    - reference_id: PMID:15862350
      supporting_text: Polycystin-2, along with the IP(3) and ryanodine 
        receptors, acts as a major calcium-release channel in the endoplasmic 
        reticulum in cells where rapid calcium signaling is required
    - reference_id: PMID:16943275
      supporting_text: General and cell-type specific mechanisms target 
        TRPP2/PKD-2 to cilia.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2::GFP localizes to plasma membrane in male sensory neurons 
      (PMID:11553327).
    action: ACCEPT
    reason: IDA evidence from GFP localization studies.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
        kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2::GFP concentrates in sensory cilia of male neurons 
      (PMID:11553327).
    action: ACCEPT
    reason: Foundational IDA evidence for ciliary localization.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: LOV-1::GFP and PKD-2::GFP are expressed in the same 
        male-specific sensory neurons and are concentrated in cilia and cell 
        bodies.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: PMID:16943275
  review:
    summary: Detailed analysis of PKD-2 ciliary targeting mechanisms 
      (PMID:16943275).
    action: ACCEPT
    reason: Key IDA study on ciliary targeting.
    supported_by:
    - reference_id: PMID:16943275
      supporting_text: Ciliary localization of the transient receptor potential 
        polycystin 2 channel (TRPP2/PKD-2) is evolutionarily conserved
- term:
    id: GO:0006816
    label: calcium ion transport
  evidence_type: IDA
  original_reference_id: PMID:15862350
  review:
    summary: PKD-2 mediates calcium ion transport as demonstrated by 
      electrophysiology and calcium imaging (PMID:15862350).
    action: ACCEPT
    reason: Core biological process supported by direct experimental evidence.
    supported_by:
    - reference_id: PMID:15862350
      supporting_text: Activity of polycystin-2 creates brief cytosolic Ca(2+) 
        transients with increased amplitude and decreased duration.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2 is a membrane protein as shown by GFP localization 
      (PMID:11553327).
    action: ACCEPT
    reason: Basic IDA evidence for membrane localization.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
        kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2::GFP localizes to neuronal cell bodies (PMID:11553327).
    action: ACCEPT
    reason: IDA evidence from foundational study.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: LOV-1::GFP and PKD-2::GFP are expressed in the same 
        male-specific sensory neurons and are concentrated in cilia and cell 
        bodies.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:12411744
  review:
    summary: Cell body localization confirmed (PMID:12411744).
    action: ACCEPT
    reason: Confirming IDA evidence.
    supported_by:
    - reference_id: PMID:12411744
      supporting_text: Expression analysis localized LOV-1 and PKD-2 to the ends
        of sensory neurons in male tails
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:16943275
  review:
    summary: Cell body localization in context of trafficking (PMID:16943275).
    action: ACCEPT
    reason: IDA evidence supporting cell body localization as part of 
      trafficking pathway.
    supported_by:
    - reference_id: PMID:16943275
      supporting_text: General and cell-type specific mechanisms target 
        TRPP2/PKD-2 to cilia.
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IDA
  original_reference_id: PMID:16943275
  review:
    summary: PKD-2 specifically localizes to the ciliary membrane compartment 
      (PMID:16943275).
    action: ACCEPT
    reason: Key IDA evidence for ciliary membrane localization.
    supported_by:
    - reference_id: PMID:16943275
      supporting_text: PKD-2 stabilization in cilia and cell bodies requires 
        LOV-1, a functional partner and a TRPP1 homolog.
- term:
    id: GO:0060179
    label: male mating behavior
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: pkd-2 is required for male mating behavior with mutants showing 
      specific defects in response and vulval location (PMID:11553327).
    action: ACCEPT
    reason: Core biological function. Evidence code is technically IMP based on 
      mutant phenotype, but the annotation captures the essential function.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Mutations in either lov-1 or pkd-2 result in identical 
        male sensory behavioral defects.
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2 localizes to non-motile sensory cilia which remain 
      structurally normal in pkd-2 mutants (PMID:11553327).
    action: ACCEPT
    reason: IDA evidence establishing that PKD-2 is in non-motile cilia.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: the cilia of lov-1 and pkd-2 single mutants and of 
        lov-1;pkd-2 double mutants are normal as judged by electron microscopy
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:15563610
  review:
    summary: PKD-2 colocalizes with ATP-2 in non-motile cilia (PMID:15563610).
    action: ACCEPT
    reason: IDA evidence from polycystin signaling study.
    supported_by:
    - reference_id: PMID:15563610
      supporting_text: ATP-2 and other ATP synthase components colocalize with 
        LOV-1 and PKD-2 in cilia.
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:17581863
  review:
    summary: PKD-2 ciliary localization regulated by STAM-Hrs complex 
      (PMID:17581863).
    action: ACCEPT
    reason: IDA evidence from study on ciliary receptor regulation.
    supported_by:
    - reference_id: PMID:17581863
      supporting_text: overexpression of STAM or Hrs promotes the removal of 
        PKD-2 from cilia
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IDA
  original_reference_id: PMID:17581863
  review:
    summary: PKD-2 in dendrites as part of trafficking pathway (PMID:17581863).
    action: ACCEPT
    reason: IDA evidence for dendritic localization.
    supported_by:
    - reference_id: PMID:17581863
      supporting_text: Jun 20. STAM and Hrs down-regulate ciliary TRP receptors.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:17581863
  review:
    summary: PKD-2 cell body localization regulated by STAM-Hrs (PMID:17581863).
    action: ACCEPT
    reason: IDA evidence for cell body localization.
    supported_by:
    - reference_id: PMID:17581863
      supporting_text: Jun 20. STAM and Hrs down-regulate ciliary TRP receptors.
- term:
    id: GO:0030424
    label: axon
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2::GFP present in axons of male sensory neurons 
      (PMID:11553327).
    action: ACCEPT
    reason: IDA evidence for axonal localization.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
        kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
- term:
    id: GO:0030424
    label: axon
  evidence_type: IDA
  original_reference_id: PMID:15563610
  review:
    summary: Axon localization confirmed (PMID:15563610).
    action: ACCEPT
    reason: Confirming IDA evidence.
    supported_by:
    - reference_id: PMID:15563610
      supporting_text: Nov 24. ATP-2 interacts with the PLAT domain of LOV-1 and
        is involved in Caenorhabditis elegans polycystin signaling.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2 in dendrites of male sensory neurons (PMID:11553327).
    action: ACCEPT
    reason: IDA evidence from foundational study.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
        kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IDA
  original_reference_id: PMID:15563610
  review:
    summary: Dendritic localization confirmed in polycystin signaling study 
      (PMID:15563610).
    action: ACCEPT
    reason: Confirming IDA evidence.
    supported_by:
    - reference_id: PMID:15563610
      supporting_text: Nov 24. ATP-2 interacts with the PLAT domain of LOV-1 and
        is involved in Caenorhabditis elegans polycystin signaling.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:15563610
  review:
    summary: Cell body localization in polycystin complex study (PMID:15563610).
    action: ACCEPT
    reason: IDA evidence.
    supported_by:
    - reference_id: PMID:15563610
      supporting_text: Nov 24. ATP-2 interacts with the PLAT domain of LOV-1 and
        is involved in Caenorhabditis elegans polycystin signaling.
- term:
    id: GO:0007617
    label: mating behavior
  evidence_type: IMP
  original_reference_id: PMID:11553327
  review:
    summary: pkd-2 mutants have defective mating behavior (PMID:11553327).
    action: ACCEPT
    reason: Core biological function. IMP evidence from mutant analysis.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Mutations in either lov-1 or pkd-2 result in identical 
        male sensory behavioral defects.
- term:
    id: GO:0007617
    label: mating behavior
  evidence_type: IGI
  original_reference_id: PMID:11553327
  review:
    summary: pkd-2 and lov-1 act in the same pathway for mating behavior 
      (PMID:11553327).
    action: ACCEPT
    reason: IGI evidence from double mutant analysis showing epistasis.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: pkd-2;lov-1 double mutants are no more severe than either
        of the single mutants, indicating that lov-1 and pkd-2 act together.
- term:
    id: GO:0031090
    label: organelle membrane
  evidence_type: IDA
  original_reference_id: PMID:11553327
  review:
    summary: PKD-2 localizes to intracellular organelle membranes 
      (PMID:11553327).
    action: ACCEPT
    reason: IDA evidence for intracellular membrane localization.
    supported_by:
    - reference_id: PMID:11553327
      supporting_text: Cytoplasmic, nonnuclear staining in cell bodies is 
        punctate, suggesting that one pool of PKD-2 is localized to 
        intracellular membranes
core_functions:
- description: PKD-2 functions as a calcium-permeable TRP channel in ciliary 
    membranes of male sensory neurons, mediating detection of 
    mechanical/chemical stimuli during mating behavior.
  molecular_function:
    id: GO:0005262
    label: calcium channel activity
  directly_involved_in:
  - id: GO:0050982
    label: detection of mechanical stimulus
  - id: GO:0034606
    label: response to hermaphrodite contact
  - id: GO:0034608
    label: vulval location
  locations:
  - id: GO:0060170
    label: ciliary membrane
  - id: GO:0097730
    label: non-motile cilium
  supported_by:
  - reference_id: PMID:15862350
    supporting_text: we found that polycystin-2 is an intracellular Ca(2+) 
      release channel that is required for the normal pattern of Ca(2+) 
      responses
  - reference_id: PMID:11553327
    supporting_text: LOV-1::GFP and PKD-2::GFP are expressed in the same 
      male-specific sensory neurons and are concentrated in cilia and cell 
      bodies.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on 
    inter-ontology links
  findings: []
- id: PMID:10517638
  title: A polycystic kidney-disease gene homologue required for male mating 
    behaviour in C. elegans.
  findings:
  - statement: PKD-2 is the C. elegans homolog of human PKD2
    supporting_text: A polycystic kidney-disease gene homologue required for 
      male mating behaviour in C. elegans.
  - statement: PKD-2 is localized to the same male-specific neurons as LOV-1
    supporting_text: A polycystic kidney-disease gene homologue required for 
      male mating behaviour in C. elegans.
  - statement: PKD-2 functions in sensory neurons of rays, hook, and head
    supporting_text: A polycystic kidney-disease gene homologue required for 
      male mating behaviour in C. elegans.
- id: PMID:11553327
  title: The Caenorhabditis elegans autosomal dominant polycystic kidney disease
    gene homologs lov-1 and pkd-2 act in the same pathway.
  findings:
  - statement: lov-1 and pkd-2 act in the same pathway
    supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
      kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
  - statement: Mutations result in identical male sensory behavioral defects
    supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
      kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
  - statement: PKD-2::GFP concentrated in cilia and cell bodies
    supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
      kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
  - statement: Cilia are structurally normal in pkd-2 mutants
    supporting_text: The Caenorhabditis elegans autosomal dominant polycystic 
      kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
- id: PMID:12411744
  title: Towards understanding the polycystins.
  findings:
  - statement: lov-1 and pkd-2 participate in a single genetic pathway
    supporting_text: Towards understanding the polycystins.
  - statement: LOV-1 and PKD-2 localize to ends of sensory neurons
    supporting_text: Towards understanding the polycystins.
  - statement: Polycystins act as sensors of the extracellular environment
    supporting_text: Towards understanding the polycystins.
- id: PMID:15563610
  title: ATP-2 interacts with the PLAT domain of LOV-1 and is involved in 
    Caenorhabditis elegans polycystin signaling.
  findings:
  - statement: ATP-2 colocalizes with LOV-1 and PKD-2 in cilia
    supporting_text: ATP-2 interacts with the PLAT domain of LOV-1 and is 
      involved in Caenorhabditis elegans polycystin signaling.
  - statement: atp-2, lov-1, and pkd-2 act in the same molecular pathway
    supporting_text: ATP-2 interacts with the PLAT domain of LOV-1 and is 
      involved in Caenorhabditis elegans polycystin signaling.
- id: PMID:15817158
  title: Functional characterization of the C. elegans nephrocystins NPHP-1 and 
    NPHP-4 and their role in cilia and male sensory behaviors.
  findings:
  - statement: NPHP-1 and NPHP-4 colocalize with PKD-2 in male-specific sensory 
      cilia
    supporting_text: Functional characterization of the C. elegans nephrocystins
      NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors.
  - statement: Nephrocystins facilitate ciliary sensory signal transduction
    supporting_text: Functional characterization of the C. elegans nephrocystins
      NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors.
- id: PMID:15862350
  title: Polycystin-2 accelerates Ca2+ release from intracellular stores in 
    Caenorhabditis elegans.
  findings:
  - statement: PKD-2 is an intracellular Ca2+ release channel
    supporting_text: Polycystin-2 accelerates Ca2+ release from intracellular 
      stores in Caenorhabditis elegans.
  - statement: PKD-2 required for normal Ca2+ response patterns
    supporting_text: Polycystin-2 accelerates Ca2+ release from intracellular 
      stores in Caenorhabditis elegans.
  - statement: PKD-2 creates brief cytosolic Ca2+ transients with increased 
      amplitude
    supporting_text: Polycystin-2 accelerates Ca2+ release from intracellular 
      stores in Caenorhabditis elegans.
  - statement: PKD-2 works with IP3 and ryanodine receptors in the ER
    supporting_text: Polycystin-2 accelerates Ca2+ release from intracellular 
      stores in Caenorhabditis elegans.
- id: PMID:16481400
  title: Casein kinase II and calcineurin modulate TRPP function and ciliary 
    localization.
  findings:
  - statement: CK2 phosphorylates PKD-2 at Ser-534
    supporting_text: Casein kinase II and calcineurin modulate TRPP function and
      ciliary localization.
  - statement: Calcineurin dephosphorylates PKD-2
    supporting_text: Casein kinase II and calcineurin modulate TRPP function and
      ciliary localization.
  - statement: Phosphorylation state regulates ciliary localization
    supporting_text: Casein kinase II and calcineurin modulate TRPP function and
      ciliary localization.
  - statement: Phospho-defective S534A localizes to cilia
    supporting_text: Casein kinase II and calcineurin modulate TRPP function and
      ciliary localization.
  - statement: Phospho-mimetic S534D is absent from cilia
    supporting_text: Casein kinase II and calcineurin modulate TRPP function and
      ciliary localization.
- id: PMID:16943275
  title: General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia.
  findings:
  - statement: PKD-2 moves bidirectionally in dendritic compartment
    supporting_text: General and cell-type specific mechanisms target 
      TRPP2/PKD-2 to cilia.
  - statement: UNC-101/AP-1 directs PKD-2 to dendritic particles
    supporting_text: General and cell-type specific mechanisms target 
      TRPP2/PKD-2 to cilia.
  - statement: LOV-1 required for PKD-2 stabilization in cilia
    supporting_text: General and cell-type specific mechanisms target 
      TRPP2/PKD-2 to cilia.
  - statement: Cell-type specific factors required for dendritic targeting
    supporting_text: General and cell-type specific mechanisms target 
      TRPP2/PKD-2 to cilia.
- id: PMID:17581863
  title: STAM and Hrs down-regulate ciliary TRP receptors.
  findings:
  - statement: STAM-1A interacts with LOV-1
    supporting_text: STAM and Hrs down-regulate ciliary TRP receptors.
  - statement: STAM-Hrs directs LOV-1-PKD-2 for lysosomal degradation
    supporting_text: STAM and Hrs down-regulate ciliary TRP receptors.
  - statement: Overexpression removes PKD-2 from cilia
    supporting_text: STAM and Hrs down-regulate ciliary TRP receptors.
- id: PMID:18037411
  title: Distinct protein domains regulate ciliary targeting and function of C. 
    elegans PKD-2.
  findings:
  - statement: Transmembrane region sufficient for ciliary targeting
    supporting_text: Distinct protein domains regulate ciliary targeting and 
      function of C. elegans PKD-2.
  - statement: Cytosolic tails regulate cell body localization
    supporting_text: Distinct protein domains regulate ciliary targeting and 
      function of C. elegans PKD-2.
  - statement: PKD-2 colocalizes with OSM-9 TRPV channel
    supporting_text: Distinct protein domains regulate ciliary targeting and 
      function of C. elegans PKD-2.
  - statement: Human PC-2 partially rescues pkd-2 mutants
    supporting_text: Distinct protein domains regulate ciliary targeting and 
      function of C. elegans PKD-2.
- id: PMID:27930654
  title: Whole-Organism Developmental Expression Profiling Identifies RAB-28 as 
    a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar 
    Transport.
  findings:
  - statement: PKD-2::GFP used as ciliary marker
    supporting_text: Whole-Organism Developmental Expression Profiling 
      Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and
      Intraflagellar Transport.
  - statement: Localization to cilia and sensory dendrites
    supporting_text: Whole-Organism Developmental Expression Profiling 
      Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and
      Intraflagellar Transport.
- id: file:worm/pkd-2/pkd-2-deep-research-falcon.md
  title: Deep research report on pkd-2
  findings: []
tags:
- caeel-ciliopathy

pkd-2

Gene Description

Existing Annotations Review

Core Functions

PKD-2 functions as a calcium-permeable TRP channel in ciliary membranes of male sensory neurons, mediating detection of mechanical/chemical stimuli during mating behavior.

References

Tags

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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