DYNC2H1

UniProt ID: Q8NCM8
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

DYNC2H1 encodes the force-generating heavy chain of cytoplasmic dynein-2, the motor that returns intraflagellar transport trains and cargo from ciliary tips toward the cell body. Its C-terminal motor region couples ATP hydrolysis to movement toward microtubule minus ends, while its N-terminal tail assembles with light intermediate, intermediate and light chains. Dynein-2 activity is controlled by interactions between its two heavy chains and associated subunits. The motor supports the construction and maintenance of sensory and motile cilia. Pathogenic biallelic variants cause skeletal ciliopathies. A short alternative product lacks the AAA motor ring and microtubule-binding stalk.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001673 male germ cell nucleus
NAS
PMID:36973253
Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 reg...
REMOVE
Reason: The cited study concerns cytoplasmic dynein-1 in mouse male germ cells. Its operative Methods identify the DYNC1H1 antibody, and Supplementary Figure 4 identifies DYNC1H1, DYNC1LI2 and p150 at telomere attachment sites on the outside of the nuclear envelope. The separately inspected supplementary workbooks likewise name DYNC1H1, not DYNC2H1. These positive target and compartment identities do not support a DYNC2H1 annotation to the male germ cell nucleus. This is a source-specific miscitation judgment for the NAS assertion, not an inference from the paper title or a general denial of possible nuclear dynein-2 pools.
Supporting Evidence:
PMID:36973253
Dynein accumulates on the cytoplasmic side of the telomere-nuclear envelope attachment sites and drives the movement of the chromosomes
GO:0003774 cytoskeletal motor activity
NAS
PMID:8666668
Mammalian cells express three distinct dynein heavy chains t...
MODIFY
Reason: The broad motor assignment is biologically correct. The 1996 study characterized human DHC2 sequence and antibodies but did not directly determine motor polarity. Independent recombinant human dynein-2 microtubule-gliding measurements in PMID:21723285 establish minus-end direction, providing a specific gene-level refinement. The assay is an ensemble measurement and does not establish the processivity of an individual complex or motor competence of the short alternative product.
Supporting Evidence:
PMID:21723285
In an in vitro MT gliding assay, both dynein-1 and dynein-2 showed minus-end-directed motor activities.
GO:0005515 protein binding
IPI
PMID:29742051
Interaction of WDR60 intermediate chain with TCTEX1D2 light ...
MODIFY
Reason: The named partner Q8TCX1 is DYNC2LI1, a dynein light intermediate chain. PMID:29742051 reports reciprocal association of fluorescently tagged human DYNC2H1 residues 1–1650 and DYNC2LI1 in the HEK293T visible-immunoprecipitation assay; the supplement identifies the human DYNC2H1 cDNA and tail constructs. Thus the literal binding class can be refined to dynein light intermediate chain binding. This does not require purified proteins, but it also does not claim that the co-immunoprecipitation alone resolves a direct interface or every natural isoform. Independent recombinant human complex structure corroborates the subunit relationship.
Supporting Evidence:
PMID:29742051
the H1 subcomplex (the heavy chain DYNC2H1 directly interacting with the light intermediate chain DYNC2LI1)
GO:0005524 ATP binding
IEA
GO_REF:0000002
ACCEPT
Reason: IPR035699 explicitly identifies the hydrolytic ATP-binding dynein motor region and maps to ATP binding. The official DYNC2H1 sequence carries this domain, and recombinant human motor studies independently support ATP-dependent motility. This is an intrinsic component of the heavy-chain motor mechanism, not a separate ATPase assignment to all six AAA modules. The 920-residue alternative product deletes the motor region and is not covered by a full-length motor inference.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR035699 SUPPORTS TRANSFER
Current entry maps its AAA1 hydrolytic ATP-binding domain to GO:0005524; the official full-length target carries it.
GO:0005737 cytoplasm
IEA
GO_REF:0000120
KEEP AS NON CORE
Reason: A cytoplasmic DYNC2H1 pool is positive biology: the original human DHC2 localization study reports cytoplasmic vesicles and Golgi-associated staining, and the soluble fraction can be recovered under its extraction conditions. Retain the broad cytoplasm location as contextual coverage alongside the specialized ciliary motor. The current ARBA00026971 record still outputs cytoplasm, but its exact historical firing condition was not reconstructed from the present target record; that provenance limit does not negate the independently supported location.
Propagation Review
Root cause: NO FAILURE NON CORE
Sources checked:
ARBA:ARBA00026971 UNRESOLVED
Current genuine rule outputs GO:0005737; no complete condition set matched the present official target cross-references and lineage, so historical rule execution remains unresolved.
UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER
The preserved curated cytoplasm mapping agrees with independently read DHC2 localization, without specifying a diffuse soluble cytosolic pool.
GO:0005737 cytoplasm
ISS
GO_REF:0000024
KEEP AS NON CORE
Reason: The literal donor Q9JJ79 is rat Dync2h1, not mouse. Its current record retains experimentally grounded cytoplasmic localization, including the tracheal-cell study PMID:8832411 and subsequent D2LIC/DHC2 work. Human DHC2 staining in PMID:8666668 independently supports a cytoplasmic pool. Retain this broad location as non-core without substituting a specific organelle for all original cytoplasmic staining.
Propagation Review
Root cause: NO FAILURE NON CORE
Sources checked:
UniProtKB:Q9JJ79 SUPPORTS TRANSFER
Official Rattus norvegicus Dync2h1 identity and current experimental cytoplasm records were read; the donor is not mislabeled as mouse.
GO:0005794 Golgi apparatus
IDA
PMID:8666668
Mammalian cells express three distinct dynein heavy chains t...
KEEP AS NON CORE
Reason: The independently recovered 1996 original reports DHC2 colocalization with Golgi markers in several cell lines, explicitly including human HeLa cells, as well as rat NRK and monkey COS cells. Preserve this positive experimental localization as a context-specific pool. Later mouse ciliated-tissue imaging emphasizes apical cytoplasm and axonemes and does not show Golgi enrichment in that setting; it does not invalidate the earlier cell-line observation or prove a universal Golgi role.
Supporting Evidence:
PMID:8666668
DHC2 is localized predominantly to the Golgi apparatus.
GO:0005868 cytoplasmic dynein complex
IBA
GO_REF:0000033
ACCEPT
Reason: The literal IBD at PTN002472914 lies on the authenticated DYNC2H1 lineage in the current target-containing PTHR10676 tree; the aligned leaf sequence exactly matches the official 4307-residue target. The node is supported by rat and human experimental complex evidence. The target appearing among those descendant sources is legitimate experimental grounding, not circularity. Human recombinant and endogenous-complex studies directly corroborate membership in cytoplasmic dynein-2.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002472914 SUPPORTS TRANSFER
The literal GO:0005868 IBD and target descent were reconstructed. Human Q8NCM8 is valid descendant evidence; the mismatching modern PTHR46532 lookup was retained as version provenance, not used as this topology.
GO:0005868 cytoplasmic dynein complex
IDA
PMID:21723285
Recombinant human cytoplasmic dynein heavy chain 1 and 2: ob...
ACCEPT
Reason: PMID:21723285 expressed tagged full-length human heavy chains in HEK293 cells and recovered dynein-2 with LIC3. This directly supports cytoplasmic dynein-complex membership. The study did not detect intermediate chains under its purification conditions; this is not evidence that dynein-2 lacks them, as later recombinant human holoenzyme structure establishes the intermediate-chain/light-chain block.
Supporting Evidence:
PMID:21723285
Electron microscopy of the purified molecules revealed a two-headed structure composed of characteristic dynein motor domains.
GO:0005868 cytoplasmic dynein complex
IDA
PMID:25830415
Tctex1d2 associates with short-rib polydactyly syndrome prot...
ACCEPT
Reason: PMID:25830415 includes reciprocal endogenous TCTEX1D2 and WDR60 immunoprecipitations from ciliated human hTERT-RPE cells that recover DYNC2H1, as well as tagged-complex proteomics. The DYNC2H1 and DYNC1H1 antibody identities are distinguished in Methods. This supports DYNC2H1 membership in the dynein-2 complex without transferring a light-chain localization measurement to the heavy chain.
Supporting Evidence:
PMID:25830415
This analysis revealed that Tctex1d2 associated with ciliary Dync2 complex subunits, including Dync2h1, Wdr60, Wdr34, and Dynll1
GO:0005868 cytoplasmic dynein complex
IEA
GO_REF:0000117
ACCEPT
Reason: The current ARBA00088183 rule assigns cytoplasmic dynein complex. Its Primates condition set requires FunFam identifiers 1.20.920.20:FF:000002 and 3.20.180.20:FF:000002, both present in the official human target record. Independent human complex purification and structure corroborate the biological assignment.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
ARBA:ARBA00088183 SUPPORTS TRANSFER
The current Primates/FunFam condition set matches the preserved official target cross-references and predicts GO:0005868. This establishes current consistency, not an undocumented historical rule replay.
GO:0005874 microtubule
IDA
PMID:21525035
PEX14 is required for microtubule-based peroxisome motility ...
ACCEPT
Reason: Retain the experimental microtubule annotation as a core property on independent positive human evidence: PMID:21723285 expressed full-length human dynein-2 heavy chain, recovered a LIC3-containing preparation, and demonstrated ATP-dependent movement of polarity-marked microtubules in a surface-gliding assay. This is direct microtubule engagement, not merely inference from a motor-family name; it does not establish single-complex processivity or a physiological speed limit. The original PMID:21525035 full text remained inaccessible, and the available IntAct PEX14–DYNC2H1 pull-down records do not resolve its precise microtubule endpoint. That source-specific uncertainty is retained without overriding a clearly established gene-level association. The microtubule track and ciliary cellular compartment are compatible descriptions, not mutually exclusive locations.
GO:0005886 plasma membrane
IEA
GO_REF:0000044
UNDECIDED
Reason: The curated cell/plasma-membrane assertion is not biologically disproved: GO:0005886 includes associated proteins and does not require an integral membrane protein or a separately established membrane function. However, the traced mouse donor location cites PMID:8666668, whose independently inspected DHC2 Results establish Golgi/cytoplasmic-vesicle association rather than an explicit plasma-membrane measurement. The present source chain does not resolve the claimed plasma-membrane pool. Leave this assertion undecided, without replacing it by cilium solely because that is the principal known compartment.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
UniProtKB-SubCell:SL-0039 UNRESOLVED
The literal curated cell-membrane mapping is preserved; the underlying target-level plasma-membrane observation remains unresolved after bounded source tracing.
GO:0005886 plasma membrane
ISS
GO_REF:0000024
UNDECIDED
Reason: The curated cell/plasma-membrane assertion is not biologically disproved: GO:0005886 includes associated proteins and does not require an integral membrane protein or a separately established membrane function. However, the traced mouse donor location cites PMID:8666668, whose independently inspected DHC2 Results establish Golgi/cytoplasmic-vesicle association rather than an explicit plasma-membrane measurement. The present source chain does not resolve the claimed plasma-membrane pool. Leave this assertion undecided, without replacing it by cilium solely because that is the principal known compartment.
Propagation Review
Root cause: UNRESOLVED
Sources checked:
UniProtKB:Q45VK7 UNRESOLVED
Official mouse Dync2h1 identity is secure and its curated cell-membrane statement is real; the exact primary plasma-membrane evidence behind that statement was not verified.
NAS
PMID:30065109
Emerging mechanisms of dynein transport in the cytoplasm ver...
ACCEPT
Reason: The cited review distinguishes dynein-2 cargo transport within the cilium from axonemal dyneins that drive beating. Its operative dynein-2 sections identify the DYNC2H1-containing motor and its movement along ciliary microtubule doublets. This broad ciliary location is correct and informative; it need not be replaced by a narrower subcompartment that would discard transit through other ciliary regions.
Supporting Evidence:
PMID:30065109
In mammals, the dynein-1 heavy chain is DYNC1H1 and the dynein-2 heavy chain is DYNC2H1
NAS
PMID:32229580
Cytoplasmic dynein-2 at a glance.
ACCEPT
Reason: The authentic abstract of the cited review explicitly describes cytoplasmic dynein-2 driving cargo movement along microtubules within cilia. The normal cache remains abstract-only, but this limited use is directly supported and independently corroborated by the verified human motor/complex evidence. Retain the broad ciliary location without claiming a full-body read of this review.
Supporting Evidence:
PMID:32229580
Cytoplasmic dynein-2 is a motor protein complex that drives the movement of cargoes along microtubules within cilia
TAS
Reactome:R-HSA-5624949
ACCEPT
Reason: The current Reactome record R-HSA-5624949 contains a literal input/output and complex-component path to Q8NCM8 residues 1–4307 in the cilium. The target is modeled as a component of dynein-2 during assembly of the anterograde train. This verifies the target-specific location assertion rather than merely the pathway title. Dynein-2 can be carried as an inactive passenger during anterograde transport; the location row does not assign it an anterograde motor function. Reactome is a curated mechanistic model, not a new direct human localization assay.
TAS
Reactome:R-HSA-5625416
ACCEPT
Reason: The current Reactome record R-HSA-5625416 contains a literal input/output and complex-component path to Q8NCM8 residues 1–4307 in the cilium. The target is modeled as a component of dynein-2 during anterograde transit. This verifies the target-specific location assertion rather than merely the pathway title. Dynein-2 can be carried as an inactive passenger during anterograde transport; the location row does not assign it an anterograde motor function. Reactome is a curated mechanistic model, not a new direct human localization assay.
TAS
Reactome:R-HSA-5625424
ACCEPT
Reason: The current Reactome record R-HSA-5625424 contains a literal input/output and complex-component path to Q8NCM8 residues 1–4307 in the cilium. The target is modeled as a component of dynein-2 during dissociation of the returning retrograde train. This verifies the target-specific location assertion rather than merely the pathway title. Dynein-2 can be carried as an inactive passenger during anterograde transport; the location row does not assign it an anterograde motor function. Reactome is a curated mechanistic model, not a new direct human localization assay.
TAS
Reactome:R-HSA-5625426
ACCEPT
Reason: The current Reactome record R-HSA-5625426 contains a literal input/output and complex-component path to Q8NCM8 residues 1–4307 in the cilium. The target is modeled as a component of dynein-2 during retrograde transit. This verifies the target-specific location assertion rather than merely the pathway title. Dynein-2 can be carried as an inactive passenger during anterograde transport; the location row does not assign it an anterograde motor function. Reactome is a curated mechanistic model, not a new direct human localization assay.
GO:0005930 axoneme
IBA
GO_REF:0000033
ACCEPT
Reason: The axoneme IBD at the dynein-2 node PTN002472914 is inherited by the exact target sequence. Current mouse donor Q45VK7 retains an IDA assertion from PMID:12802074, whose Methods and Results independently show DHC2 along ciliary axonemes in mouse lung and efferent duct. Human dynein-2 motor structure and its microtubule association are consistent with this conserved ciliary compartment. Axonemal localization does not imply incorporation into the stationary axonemal beating dynein arms.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002472914 SUPPORTS TRANSFER
Literal axoneme IBD, target lineage and mouse experimental donor were recovered. The target resides in the conserved dynein-2 clade.
GO:0005930 axoneme
IEA
GO_REF:0000120
ACCEPT
Reason: The literal mouse Q45VK7/Ensembl and subcellular-location transfer is supported by the current mouse axoneme IDA record and the independently read PMID:12802074 tissue imaging. The study used wild-type mouse tissues, with DHC2 antibody staining along lung and efferent-duct ciliary axonemes. This is conserved compartment support, not proof that every human isoform is axonemal or that DYNC2H1 drives the beating stroke.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:Q45VK7 SUPPORTS TRANSFER
Mouse Dync2h1 has a current axoneme IDA record citing PMID:12802074, corroborated by the original Methods/Results.
ensembl:ENSMUSP00000120007 SUPPORTS TRANSFER
Preserved mouse protein identifier in the same orthology mapping; no substitute clone is introduced.
UniProtKB-SubCell:SL-0304 SUPPORTS TRANSFER
The axoneme location mapping agrees with the independently read mouse target experiment.
GO:0007018 microtubule-based movement
IEA
GO_REF:0000002
ACCEPT
Reason: Both current InterPro entries map the heavy-chain motor to microtubule-based movement. Recombinant human DYNC2H1 drives microtubule gliding, and physiological dynein-2 uses this motor mechanism for retrograde intraflagellar transport. The broader mechanistic process remains useful alongside that specific transport role; it does not imply general dynein-1 cargo transport or ciliary beating.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR004273 SUPPORTS TRANSFER
Current entry explicitly maps to GO:0007018 and is present in the official full-length target record.
InterPro:IPR026983 SUPPORTS TRANSFER
Current entry explicitly maps to GO:0007018 and is present in the official full-length target record.
GO:0007030 Golgi organization
IDA
PMID:8666668
Mammalian cells express three distinct dynein heavy chains t...
KEEP AS NON CORE
Reason: The original functional experiment injected anti-DHC2 antibody into rat NRK cells and observed increased Golgi dispersal compared with preimmune and uninjected controls. Human cDNA-derived antigen and human HeLa Golgi staining are separate parts of the study. Preserve the curated gene-level Golgi-organization annotation as a context-specific role with this organism and perturbation limit. The experiment does not establish a universal Golgi function or a purified transport mechanism, and later ciliated-tissue localization does not erase its positive phenotype.
Supporting Evidence:
PMID:8666668
the Golgi disperses upon microinjection of antibodies to DHC2, suggesting that this motor is involved in establishing proper Golgi organization
GO:0008569 minus-end-directed microtubule motor activity
IDA
PMID:21723285
Recombinant human cytoplasmic dynein heavy chain 1 and 2: ob...
ACCEPT
Reason: Retain the imported contributes_to qualifier. In PMID:21723285, purified complexes containing tagged human DYNC2H1 and LIC3 moved polarity-marked microtubules with the minus end trailing in all 16 reported polarity observations, establishing minus-end-directed dynein-2 motility. This is an ensemble gliding assay with a selected track-length threshold, not a single-complex processivity measurement or an in vivo speed limit. The catalytic heavy chain contributes the motor mechanism within its assembly.
Supporting Evidence:
PMID:21723285
This is the first demonstration of dynein-2 motor activity, which supports the retrograde intraflagellar transport role of dynein-2.
GO:0008569 minus-end-directed microtubule motor activity
IEA
GO_REF:0000002
ACCEPT
Reason: The IPR004273 heavy-chain D6-region entry currently maps to minus-end-directed microtubule motor activity; the whole DYNC2H1 protein, not isolated D6, is the asserted gene product. Independent recombinant human motility establishes the direction. This does not imply every AAA module hydrolyzes ATP, nor does it transfer a complete motor to the 920-residue product that lacks the AAA ring and stalk.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR004273 SUPPORTS TRANSFER
The current family/domain mapping predicts minus-end motor activity and is corroborated by target-specific human motility.
GO:0030286 dynein complex
IEA
GO_REF:0000002
MODIFY
Reason: The broad dynein-complex assertion from the two current InterPro mappings is correct. The more informative cytoplasmic dynein complex term includes the DYNC2H1-containing IFT motor and is supported by recombinant human complex purification, endogenous human co-immunoprecipitation and human holoenzyme structure. Refine the complex identity without changing the imported source or asserting membership in axonemal beating dynein arms.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Sources checked:
InterPro:IPR004273 SUPPORTS TRANSFER
The broad dynein-complex mapping is correct; independent target evidence identifies the cytoplasmic dynein-2 subtype.
InterPro:IPR026983 SUPPORTS TRANSFER
The broad dynein-complex mapping is correct; independent target evidence identifies the cytoplasmic dynein-2 subtype.
Proposed replacements: cytoplasmic dynein complex
GO:0030286 dynein complex
NAS
PMID:30065109
Emerging mechanisms of dynein transport in the cytoplasm ver...
MODIFY
Reason: The broad dynein-complex assertion from the directly read dynein-2 sections of PMID:30065109 is correct. The more informative cytoplasmic dynein complex term includes the DYNC2H1-containing IFT motor and is supported by recombinant human complex purification, endogenous human co-immunoprecipitation and human holoenzyme structure. Refine the complex identity without changing the imported source or asserting membership in axonemal beating dynein arms.
Proposed replacements: cytoplasmic dynein complex
Supporting Evidence:
PMID:30065109
In mammals, the dynein-1 heavy chain is DYNC1H1 and the dynein-2 heavy chain is DYNC2H1
GO:0030286 dynein complex
NAS
PMID:32229580
Cytoplasmic dynein-2 at a glance.
MODIFY
Reason: The broad dynein-complex assertion from the authentic abstract of PMID:32229580 is correct. The more informative cytoplasmic dynein complex term includes the DYNC2H1-containing IFT motor and is supported by recombinant human complex purification, endogenous human co-immunoprecipitation and human holoenzyme structure. Refine the complex identity without changing the imported source or asserting membership in axonemal beating dynein arms.
Proposed replacements: cytoplasmic dynein complex
GO:0031514 motile cilium
IEA
GO_REF:0000107
ACCEPT
Reason: Mouse Dync2h1 is directly detected in motile-cilium axonemes in the lung and efferent duct in PMID:12802074. This supports the conserved motile-cilium location in addition to primary cilia. A protein can operate an IFT motor in a motile cilium without generating the beating stroke; lack of a beating-motor assignment is not a reason to demote the compartment assertion.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
UniProtKB:Q45VK7 SUPPORTS TRANSFER
Current mouse motile-cilium IDA record and source tissue imaging are positive.
ensembl:ENSMUSP00000120007 SUPPORTS TRANSFER
Literal mouse orthology identifier is preserved; no human tissue assay or universal isoform localization is inferred.
GO:0035721 intraciliary retrograde transport
IBA
GO_REF:0000033
ACCEPT
Reason: The literal retrograde-IFT IBD lies at the dynein-2 node PTN002472914, and the authenticated target descends from that node. The inference describes a conserved cargo-transport motor, supported by donor experiments and independent human motor/structural evidence. It is not weakened by a short donor list and does not assert that human IFT was directly imaged in the recombinant structural study.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002472914 SUPPORTS TRANSFER
Exact retrograde-IFT IBD and target ancestry are present in the current target-containing tree and preserved IBD release.
GO:0035721 intraciliary retrograde transport
NAS
PMID:31451806
Structure of the dynein-2 complex and its assembly with intr...
ACCEPT
Reason: PMID:31451806 establishes the organization and regulation of a recombinant human dynein-2 holoenzyme made from human genes in Sf9 cells. This supports the known retrograde-IFT motor role. Its placement on an IFT train uses docking to a Chlamydomonas structure, and cooperative loading and tip activation are mechanistic models, not direct measurements of human IFT in that experiment. Preserve the NAS process assertion with these distinct evidence levels.
Supporting Evidence:
PMID:31451806
Dynein-2 assembles with polymeric intraflagellar transport (IFT) trains to form a transport machinery that is crucial for cilia biogenesis and signaling.
GO:0035721 intraciliary retrograde transport
NAS
PMID:32229580
Cytoplasmic dynein-2 at a glance.
ACCEPT
Reason: The authentic PMID:32229580 abstract describes dynein-2 as the motor that drives cargo movement along ciliary microtubules and supports ciliary assembly. The specific retrograde role is independently grounded by the conserved dynein-2 lineage and human minus-end motor evidence. The cache remains abstract-only; no detailed live-cell experiment is attributed to this review.
GO:0045177 apical part of cell
IEA
GO_REF:0000107
KEEP AS NON CORE
Reason: The mouse donor has a positive apical-cell localization record, and PMID:12802074 directly reports DHC2 in apical cytoplasm and ciliary axonemes of mouse ciliated epithelia. Rat tracheal-cell work also reports apical cytoplasmic DHC2. Preserve this tissue-context compartment without treating it as a separate activity or replacing all apical staining with ciliary-tip localization.
Propagation Review
Root cause: NO FAILURE NON CORE
Sources checked:
UniProtKB:Q45VK7 SUPPORTS TRANSFER
Mouse apical-cell evidence is experimentally grounded in ciliated epithelia.
ensembl:ENSMUSP00000120007 SUPPORTS TRANSFER
The preserved mouse orthology source supports contextual apical localization; it is not a new human localization experiment.
GO:0045505 dynein intermediate chain binding
IBA
GO_REF:0000033
ACCEPT
Reason: The ancestral IBD at PTN000743491 is inherited by the target. Intermediate-chain binding is independently supported in human dynein-2: the 2019 recombinant structure resolves the WDR60/WDR34-associated subunit block against the heavy chains, and earlier human association studies recover this complex. Nondetection of intermediate chains in the 2011 purification does not contradict their membership or binding. This is an assembly-interface contribution, not a claim that every historical pull-down isolated a purified binary interface.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000743491 SUPPORTS TRANSFER
The literal GO:0045505 IBD is experimentally grounded and its root-to-target path is authenticated; independent human complex evidence supports retention.
Supporting Evidence:
PMID:31451806
WDR60 and WDR34 hold the two copies of DHC2TAIL at right angles
GO:0045505 dynein intermediate chain binding
IEA
GO_REF:0000002
ACCEPT
Reason: IPR026983 currently maps dynein heavy chains to intermediate-chain binding. Independent recombinant human dynein-2 structure supports contacts with its WDR34/WDR60-associated intermediate-chain block, consistent with the conserved motor assembly. The short alternative product is not assigned a complete set of these interfaces solely from the full-length result.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR026983 SUPPORTS TRANSFER
Current mapping explicitly includes GO:0045505, and target-specific human holoenzyme evidence corroborates the class.
GO:0051959 dynein light intermediate chain binding
IBA
GO_REF:0000033
ACCEPT
Reason: The literal light-intermediate-chain-binding IBD at PTN000743491 is on the target lineage. Target-specific human DYNC2LI1 association is demonstrated by reciprocal tagged-tail co-immunoprecipitation, and LIC3 copurification and recombinant complex structure independently corroborate it. Thus the ancestral inference remains valid even though its listed descendants include dynein-1 as well as dynein-2; no donor-count or self-grounding objection applies.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000743491 SUPPORTS TRANSFER
Exact GO:0051959 IBD and target descent are present; human DYNC2H1–DYNC2LI1 evidence independently confirms the inherited binding class.
Supporting Evidence:
PMID:31451806
Both copies of DHC2 bind a LIC3 subunit.
GO:0051959 dynein light intermediate chain binding
IEA
GO_REF:0000002
ACCEPT
Reason: The current IPR026983 mapping explicitly includes dynein light intermediate chain binding, which is supported by the independently verified human DYNC2H1–DYNC2LI1 association and holoenzyme structure. The mapping describes the full heavy-chain assembly function, not an activity automatically assigned to every truncated product.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
InterPro:IPR026983 SUPPORTS TRANSFER
The mapped light-intermediate-chain-binding function is directly corroborated for the human target.
GO:0060271 cilium assembly
IBA
GO_REF:0000033
ACCEPT
Reason: The cilium-assembly IBD is placed at the dynein-2 node PTN002472914 and inherited by the authenticated target. DYNC2H1 performs retrograde IFT, recycling ciliary transport machinery and cargo during organelle construction and maintenance, so its contribution is mechanistic rather than disease necessity alone. The imported assertion remains valid without assigning it the polymerization chemistry of the axoneme or assuming motor activity for the short product.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002472914 SUPPORTS TRANSFER
The exact cilium-assembly IBD has rat, mouse and worm descendant experimental grounding; the target is inside that dynein-2 clade.
Supporting Evidence:
PMID:19442771
DYNC2H1 is a component of a cytoplasmic dynein complex and is directly involved in the generation and maintenance of cilia.
GO:0060294 cilium movement involved in cell motility
IBA
GO_REF:0000033
REMOVE
Reason: The literal IBD at the broad dynein root PTN000743491 and the target's descent are verified. PAINT placed an IRD exclusion on the dynein-1 branch PTN000072732 but left the dynein-2 branch unpruned; the review therefore explicitly challenges a real retained ancestral process assertion, not an invalid node or a missing donor. GO:0060294 is_a cilium movement GO:0003341 and denotes movement of the cilium that contributes to cell locomotion. DYNC2H1's characterized specialization is force generation for IFT cargo movement along the axoneme, whereas axonemal beating dyneins generate ciliary bending. The available evidence supports this specialization challenge to the root placement. IFT can power protozoan surface gliding, so the conclusion is not that IFT never contributes to locomotion; movement of an IFT train is distinct from the cilium-movement process defined here. The same root can validly support the separate 9+2 cilium compartment assertion: operating IFT within that organelle does not entail generating its bending stroke. This reasoning preserves the genuine donor experiments and does not apply the sibling IRD to DYNC2H1.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: FUNCTIONAL DIVERGENCE ROLE CONFLATION
Sources checked:
PANTHER:PTN000743491 SUPPORTS SOURCE BUT NOT TARGET
The literal IBD and target descent are verified, but the broad root placement crosses the demonstrated functional specialization between IFT cargo motors and axonemal beating motors. Donor source experiments are not alleged to be false.
Supporting Evidence:
file:human/DYNC2H1/DYNC2H1-bioinformatics/RESULTS.md
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Reason: Preserve the contextual human urinary-exosome detection. The original-linked NHLBI identification table reports DYNC2H1, two peptides and RefSeq NP_001073932, assigned to PMID:19056867. The current official UniProt cross-reference maps NP_001073932.1 to Q8NCM8-2, rather than the canonical product. The study purified a low-density urinary membrane fraction consisting chiefly of exosomes from healthy volunteers and used peptide identification and gene-level ambiguity controls. Its Methods explicitly allow peptides shared by splice variants of one gene to count as an unambiguous gene identification, so this table does not establish isoform-discriminating peptides or exclusive localization of Q8NCM8-2. The positive fraction-level observation supports non-core retention without establishing vesicle topology, active secretion, an exosome-specific function, or target-specific orthogonal localization. Neither the protein's size nor its soluble motor role establishes contamination.
Supporting Evidence:
file:human/DYNC2H1/DYNC2H1-bioinformatics/RESULTS.md
GO:0097542 ciliary tip
TAS
Reactome:R-HSA-5624952
ACCEPT
Reason: Reactome R-HSA-5624952 has an explicit component path to Q8NCM8 residues 1–4307 in the ciliary-tip physical entity during retrograde-train assembly. The path is independently reconstructed from saved current records. This supports the curated tip location within the IFT cycle, without treating modeled activation at that location as a directly measured human switch or a separate catalytic function.
Supporting Evidence:
Reactome:R-HSA-5624952
Retrograde transport is driven by the multi-subunit dynein-2 motor in an ATP-dependent fashion
GO:0097542 ciliary tip
TAS
Reactome:R-HSA-5625416
ACCEPT
Reason: Reactome R-HSA-5625416 has an explicit component path to Q8NCM8 residues 1–4307 in the ciliary-tip physical entity during arrival of the anterograde train. The path is independently reconstructed from saved current records. This supports the curated tip location within the IFT cycle, without treating modeled activation at that location as a directly measured human switch or a separate catalytic function.
GO:0097542 ciliary tip
TAS
Reactome:R-HSA-5625421
ACCEPT
Reason: Reactome R-HSA-5625421 has an explicit component path to Q8NCM8 residues 1–4307 in the ciliary-tip physical entity during anterograde-train disassembly. The path is independently reconstructed from saved current records. This supports the curated tip location within the IFT cycle, without treating modeled activation at that location as a directly measured human switch or a separate catalytic function.
GO:0097542 ciliary tip
TAS
Reactome:R-HSA-5625426
ACCEPT
Reason: Reactome R-HSA-5625426 has an explicit component path to Q8NCM8 residues 1–4307 in the ciliary-tip physical entity during departure of the retrograde train. The path is independently reconstructed from saved current records. This supports the curated tip location within the IFT cycle, without treating modeled activation at that location as a directly measured human switch or a separate catalytic function.
GO:0097729 9+2 motile cilium
IBA
GO_REF:0000033
ACCEPT
Reason: Retain the genuine PAINT compartment assertion: the target leaf PTN002472916 descends from the literal GO:0097729 IBD at PTN000743491, and the sibling dynein-1 IRD at PTN000072732 is not on its path. Independent mouse DHC2 immunofluorescence in PMID:12802074 identifies the protein along lung and efferent-duct motile-cilium axonemes, corroborating the conserved compartment rather than serving as a newly inferred human tissue assay. The IBA provides the phylogenetic judgment; the mouse imaging does not by itself demonstrate every aspect of activity or every human isoform. There is no established target-specific loss of IFT in motile cilia that warrants rejecting this inherited location. A 9+2 organelle can contain an IFT motor without that motor driving its bending stroke, which explains the different decision for GO:0060294. Preserve the imported is_active_in qualifier and do not use an ordinary source qualifier or the composition of the donor list as an additional rejection criterion.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000743491 SUPPORTS TRANSFER
Literal IBD and target ancestry are real, and independent mouse DHC2 motile-cilium localization supports the conserved compartment despite mechanistic divergence from beating dyneins.
Supporting Evidence:
file:human/DYNC2H1/DYNC2H1-bioinformatics/RESULTS.md

Core Functions

The DYNC2H1 heavy chain supplies ATP-driven minus-end-directed movement to the dynein-2 complex during intraciliary retrograde transport. Human recombinant motor measurements establish polarity, and the human holoenzyme structure shows how its heavy-chain tails and accessory subunits organize an inhibited assembly. Conserved retrograde IFT returns transport machinery and cargo during cilium assembly and maintenance; this is a transport contribution, not axonemal polymerization. The 920-residue alternative product lacks the six AAA regions and stalk and is not assigned a complete motor function.

Supporting Evidence:

The N-terminal DYNC2H1 tail binds DYNC2LI1/LIC3 within the dynein-2 motor assembly. The recombinant human holoenzyme structure resolves the light-intermediate-chain interface; reciprocal co-immunoprecipitation of human DYNC2H1 residues 1–1650 with DYNC2LI1 independently supports this association. The heavy-chain tails also contact the WDR34/WDR60-associated intermediate-chain block. These complementary subunit interfaces organize the asymmetric assembly of the same motor complex. Full-length and engineered-tail experiments do not establish binding competence of every natural product.

Supporting Evidence:

References

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Suggested Questions for Experts

Q: Is the Golgi localization of DHC2 reported in 1996 reproducible with modern tagged alleles, and does dynein-2 have any non-ciliary role in Golgi organization?

Q: What triggers release of dynein-2 autoinhibition at the ciliary tip?

Q: Which original experiments underlie the mouse Q45VK7 cell-membrane annotation, and do they distinguish a membrane-associated motor pool from an intrinsic membrane component?

Suggested Experiments

Experiment: Endogenous tagging of DYNC2H1 in RPE1 cells with live imaging and expansion microscopy to quantify Golgi versus ciliary pools.

Experiment: Single-molecule motility assays of dynein-2 carrying SRTD3/Jeune patient mutations to relate motor defects to disease severity.

Deep Research

Falcon

(DYNC2H1-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(DYNC2H1-notes.md)

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Bioinformatics Results

(RESULTS.md)

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Source Guide

(DYNC2H1-source-guide.md)

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πŸ“„ View Raw YAML

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