Affinage

DPCD

Protein DPCD · UniProt Q9BVM2

Length
203 aa
Mass
23.2 kDa
Annotated
2026-06-09
28 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DPCD is a CS-domain adaptor protein required for motile cilia function and the determination of left-right asymmetry (PMID:20080492, PMID:38306274). It associates with the R2TP chaperone complex (RUVBL1, RUVBL2, RPAP3, PIH1D1), binding the RUVBL2 DII domain through its highly conserved CS domain to form a stable R2TP-DPCD complex; binding to the RUVBL1/2 AAA-ATPases disrupts the dodecameric R1R2 assembly (PMID:35901867, PMID:38306274). Through this adaptor role DPCD regulates ciliogenesis initiation by modulating Akt kinase phosphorylation rather than Akt stability (PMID:38306274). In motile cilia DPCD localizes to both the cytoplasm and the ciliary compartment of ependymal cells and is required for proper inner dynein arm assembly, with its loss reducing axonemal dynein heavy chain content, producing abnormal ciliary waveforms and reduced cerebrospinal fluid flow (PMID:40719343). Loss of DPCD in mice causes phenotypes characteristic of primary ciliary dyskinesia, including hydrocephalus, situs inversus, sinusitis, and male infertility (PMID:20080492, PMID:21746835).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2003 Medium

    Established DPCD, rather than the adjacent POLL gene, as the ciliogenesis-relevant gene by showing its expression is induced during differentiation of ciliated airway epithelium.

    Evidence Northern analysis during ciliated-cell differentiation of human airway epithelial cells plus sequencing of DPCD in PCD patients

    PMID:14630615

    Open questions at the time
    • No confirmed disease-causing DPCD mutation identified in PCD patients
    • Expression correlation does not define molecular function
  2. 2010 Medium

    Demonstrated that DPCD loss in mice produces the canonical motile-cilia disease spectrum, placing it functionally in the pathway for ciliary motility and laterality.

    Evidence Dpcd/Poll double-knockout mouse phenotyping with laterality, hydrocephalus, sinusitis and fertility readouts

    PMID:20080492

    Open questions at the time
    • Double-knockout design confounds attribution to DPCD alone
    • Molecular basis of the ciliary defect not addressed
  3. 2011 Medium

    Independently confirmed that DPCD-dependent hydrocephalus arises from dysfunctional motile cilia, reinforcing the cilia-centered pathogenesis.

    Evidence Dpcd knockout mouse phenotyping with histopathological analysis

    PMID:21746835

    Open questions at the time
    • Does not identify the molecular target of DPCD within the cilium
    • Mechanism linking cilia dysfunction to hydrocephalus at molecular level unresolved
  4. 2022 High

    Defined DPCD as a direct binding partner of the RUVBL1/RUVBL2 AAA-ATPases and showed it remodels their oligomeric state, providing the first molecular interaction for the protein.

    Evidence Co-IP, in vitro binding, SAXS, structural mass spectrometry, electron microscopy and 3D modeling

    PMID:35901867

    Open questions at the time
    • Functional consequence of R1R2 dodecamer disruption not established
    • Link between RUVBL binding and ciliary phenotype not yet shown
  5. 2024 High

    Integrated DPCD into the R2TP chaperone complex as a CS-domain adaptor and connected it to ciliogenesis initiation via modulation of Akt phosphorylation.

    Evidence Proximity-labeling MS, reciprocal co-IP, in vitro binding, domain mapping, Akt phosphorylation assays and loss-of-function ciliogenesis assays

    PMID:38306274

    Open questions at the time
    • How R2TP-DPCD mechanistically alters Akt phosphorylation is undefined
    • Whether Akt regulation is the same mechanism operating in motile cilia is unclear
  6. 2025 Medium

    Localized DPCD within ependymal cells and tied its loss to defective inner dynein arm assembly, providing a concrete axonemal mechanism for the ciliary motility defect.

    Evidence Dpcd-/- mouse analysis with high-speed video microscopy, dynein heavy chain immunoquantification and subcellular localization imaging

    PMID:40719343

    Open questions at the time
    • Only some IDAs affected; basis of selectivity unknown
    • Mechanistic link between R2TP/Akt activity and IDA assembly not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DPCD's R2TP-adaptor and Akt-modulating activities mechanistically drive inner dynein arm assembly in motile cilia remains unresolved.
  • No unified mechanism connecting R2TP chaperone function to axonemal dynein assembly
  • No human disease-causing mutation confirmed
  • Structural detail of the R2TP-DPCD-dynein assembly pathway lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 1 GO:0005929 cilium 1
Partners
AKT1PIH1D1RPAP3RUVBL1RUVBL2
Complex memberships
R2TP

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 DPCD expression increases during ciliated cell differentiation of human airway epithelial cells, whereas POLL expression decreases, suggesting DPCD (not POLL) is the relevant gene for the PCD phenotype observed in the Poll knockout mouse. No disease-causing mutations in DPCD were confirmed in 51 PCD patients, though one variant could not be excluded. Northern analysis of DPCD and POLL expression during ciliogenesis; sequencing of DPCD coding region in PCD patients American journal of respiratory cell and molecular biology Medium 14630615
2010 Dpcd/Poll double-knockout mice exhibit situs inversus, hydrocephalus, sinusitis, and male infertility—phenotypes consistent with deficient motile cilia function—placing DPCD in the pathway required for ciliary motility and left-right asymmetry determination. Knockout mouse phenotyping (loss-of-function with specific phenotypic readouts including organ laterality, hydrocephalus, sinusitis, infertility) Veterinary pathology Medium 20080492
2011 Dpcd knockout mice develop autosomal recessive congenital hydrocephalus with evidence that dysfunctional motile cilia represent the underlying pathogenetic mechanism. Knockout mouse phenotyping with histopathological analysis Veterinary pathology Medium 21746835
2022 DPCD directly interacts with RUVBL1 (R1) and RUVBL2 (R2) AAA-ATPases both in vitro and in cells. DPCD disrupts the dodecameric state of the R1R2 complex upon binding, and this interaction occurs mainly via the DII domains of R1 and R2. A 3D structural model of DPCD was built, and biophysical characterization showed DPCD's physico-chemical properties in solution. Co-immunoprecipitation (in vivo), direct binding assays (in vitro), small-angle X-ray scattering (SAXS), structural mass spectrometry, electron microscopy, and 3D modeling Journal of molecular biology High 35901867
2024 DPCD functions as an adaptor of the R2TP chaperone complex (RUVBL1, RUVBL2, RPAP3, PIH1D1) and regulates ciliogenesis initiation through interaction with Akt kinase, modulating Akt phosphorylation levels rather than its stability. DPCD is a heart-shaped monomeric protein with two domains; a highly conserved CS (CHORD- and SGT1-containing) domain in DPCD interacts with the RUVBL2 DII domain with high affinity to form a stable R2TP-DPCD complex both in cellulo and in vitro. RUVBL1/2 are proposed to be CS-domain-binding proteins. Proximity-labeling mass spectrometry, co-immunoprecipitation, in vitro binding assays, Akt phosphorylation assays, loss-of-function ciliogenesis assays Cell reports High 38306274
2025 In Dpcd-/- mice, ependymal cilia show decreased amplitude, abnormal waveforms, and low cerebrospinal fluid flow velocity. The amount of dynein axonemal heavy chains in some inner dynein arms (IDAs) is decreased in ependymal cilia of Dpcd-/- mice, indicating that DPCD is required for proper IDA assembly. In wild-type mice, DPCD localizes to both the cytoplasm and cilia of ependymal cells. Knockout mouse analysis, high-speed video microscopy of ciliary motility, immunofluorescence/immunohistochemistry for dynein heavy chain quantification, subcellular localization by imaging Cytoskeleton (Hoboken, N.J.) Medium 40719343

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Congenital hydrocephalus in genetically engineered mice. Veterinary pathology 115 21746835
2010 Situs inversus in Dpcd/Poll-/-, Nme7-/- , and Pkd1l1-/- mice. Veterinary pathology 73 20080492
2017 Changes in the myosin secondary structure and shrimp surimi gel strength induced by dense phase carbon dioxide. Food chemistry 56 28274425
2019 Plant proteases during developmental programmed cell death. Journal of experimental botany 54 30793182
2003 Investigation of the possible role of a novel gene, DPCD, in primary ciliary dyskinesia. American journal of respiratory cell and molecular biology 51 14630615
2021 Insights into Plant Programmed Cell Death Induced by Heavy Metals-Discovering a Terra Incognita. Cells 48 33406697
2016 Plant programmed cell death from a chromatin point of view. Journal of experimental botany 30 27639093
2020 The regulatory framework of developmentally programmed cell death in floral organs: A review. Plant physiology and biochemistry : PPB 29 33307422
2018 Autophagy counteracts instantaneous cell death during seasonal senescence of the fine roots and leaves in Populus trichocarpa. BMC plant biology 27 30373512
2005 Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation. Human genetics 21 16235095
2021 Transcriptional Regulation and Signaling of Developmental Programmed Cell Death in Plants. Frontiers in plant science 18 34394156
2013 Discontinuous microduplications at chromosome 10q24.31 identified in a Chinese family with split hand and foot malformation. BMC medical genetics 10 23596994
2020 Calcium phosphate enriched synthetic tyrosine-derived polycarbonate - dicalcium phosphate dihydrate polymer scaffolds for enhanced bone regeneration. Materialia 8 32968719
2022 Deciphering cellular and molecular determinants of human DPCD protein in complex with RUVBL1/RUVBL2 AAA-ATPases. Journal of molecular biology 7 35901867
2024 DPCD is a regulator of R2TP in ciliogenesis initiation through Akt signaling. Cell reports 6 38306274
2025 Fertilization-induced synergid cell death by RALF12-triggered ROS production and ethylene signaling. Nature communications 5 40155397
2025 Effect of dense phase carbon dioxide on the digestive properties of shrimp surimi gels: Insight from digestive kinetic. Food research international (Ottawa, Ont.) 4 40022380
2022 Quark Cheese Processed by Dense-Phase Carbon Dioxide: Shelf-Life Evaluation and Physiochemical, Rheological, Microstructural and Volatile Properties Assessment. Foods (Basel, Switzerland) 4 35954106
2024 Spatiotemporal regulation of anther's tapetum degeneration paved the way for a reversible male sterility system in cotton. Plant biotechnology journal 2 39607303
2023 Hormonal Signaling during dPCD: Cytokinin as the Determinant of RNase-Based Self-Incompatibility in Solanaceae. Biomolecules 2 37509069
2020 [Genetic analysis of a pedigree affected with congenital split-hand/foot malformation]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 32219839
2017 Molecular Genetic Characterization of a Chinese Family with Severe Split Hand/Foot Malformation. Genetic testing and molecular biomarkers 2 28422522
2024 Inactivation effect and kinetics of cathepsin L from white shrimp (Litopenaeus vannamei) by dense phase carbon dioxide. Current research in food science 1 39435452
2018 The effect of dense phase carbon dioxide on the conformation of hemoglobin. Food research international (Ottawa, Ont.) 1 29580000
2018 [Identification of pathogenic mutation in a Chinese pedigree affected with split hand/split foot malformation]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 30512151
2026 Programmed cell death during plant development. Development (Cambridge, England) 0 41757576
2025 Dpcd Induces Hydrocephalus Because of Partial Defects in the Inner Dynein Arms, With Abnormal Ciliary Motility. Cytoskeleton (Hoboken, N.J.) 0 40719343
2025 Reducing allergenicity of Trachinotus ovatus parvalbumin: Insights into digestibility and IgE-binding ability after dense phase CO₂ treatment. International journal of biological macromolecules 0 40930353

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