DYNC2LI1 (D2LIC, LIC3) is the light intermediate chain of cytoplasmic dynein-2, the retrograde intraflagellar transport (IFT) motor. It is a ~40 kDa protein with a Ras-like globular core that retains a P-loop nucleotide-binding pocket. It binds the tail of each dynein-2 heavy chain (DYNC2H1) to form the heavy-chain/light-intermediate-chain ("H1") subcomplex, stabilising the heavy-chain tails and the heavy chain itself. DYNC2LI1 is a non-catalytic accessory subunit: it is needed for dynein-2 stability and therefore for retrograde IFT, for clearance of IFT-B proteins from the ciliary tip, for control of primary cilium length, and for Hedgehog pathway regulation (repression of ciliary Smoothened entry, GLI3 processing). The protein is found in the cytoplasm, around centrosomes/basal bodies and the transition zone, and along the axoneme. Biallelic DYNC2LI1 variants cause short-rib thoracic dysplasia 15 with or without polydactyly. An early study also reported colocalisation with DHC2 at the Golgi apparatus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001673 male germ cell nucleus | NAS PMID:36973253 Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 reg... | REMOVE | Summary: NAS annotation to male germ cell nucleus, citing a study of DYNLRB1/DYNLRB2-defined dynein-1 complexes. Reason: The cited full text concerns dynein-1 complexes containing DYNLRB1 or DYNLRB2 in mitosis and male meiosis. It never mentions DYNC2LI1 or dynein-2, and its dynein acts on the cytoplasmic face of the nuclear envelope, not in the nucleus. No evidence places the dynein-2 light intermediate chain in the germ cell nucleus. This is a non-experimental statement unsupported by the cited text. 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:0005515 protein binding | IPI PMID:21252941 BAG3 mediates chaperone-based aggresome-targeting and select... | REMOVE | Summary: Protein binding with SOD1 (P00441) from a study of BAG3-mediated aggresome targeting. Reason: Generic protein binding carries no functional information. The cached paper is about BAG3/HSP70 targeting of mutant SOD1 to aggresomes, and it does not establish a functional DYNC2LI1–SOD1 relationship. Removing the annotation does not mean the reported interaction is false; there is simply no informative MF term to replace it with. |
| GO:0005515 protein binding | IPI PMID:29742051 Interaction of WDR60 intermediate chain with TCTEX1D2 light ... | MODIFY | Summary: Protein binding with DYNC2H1 from VIP-assay mapping of dynein-2 architecture. Reason: The interaction is the defining direct binding of the light intermediate chain to the heavy-chain tail. It is captured more informatively by dynein heavy chain binding, which this paper also supports by IDA. Proposed replacements: dynein heavy chain binding Supporting Evidence: PMID:29742051 For example, the DYNC2H1 tail showed a weak but substantial interaction with DYNC2LI1. |
| GO:0005737 cytoplasm | IDA PMID:26130459 DYNC2LI1 mutations broaden the clinical spectrum of dynein-2... | KEEP AS NON CORE | Summary: Immunofluorescence in ciliated fibroblasts detects DYNC2LI1 in the cytoplasm. Reason: Correct (there is a cytoplasmic pool of the motor), but the functional locations are the cilium, axoneme and ciliary base. Supporting Evidence: PMID:26130459 Using immunofluorescence analysis in ciliated fibroblast cells we confirmed the localization of the DYNC2LI1 protein to the cytoplasm, centrosomes, as well as around the basal body, and the transition zone of the primary cilium |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm, from the UniProt subcellular location mapping. Reason: As for the IDA cytoplasm row. |
| GO:0005794 Golgi apparatus | EXP PMID:11907264 Identification of a novel light intermediate chain (D2LIC) f... | KEEP AS NON CORE | Summary: D2LIC colocalizes with DHC2 at the Golgi apparatus (Grissom et al. 2002). Reason: This is an experimental curator annotation from the paper that identified D2LIC, and it is retained. The Golgi localization reflects the early Golgi-dynein-2 model. Later work established that the subunit's functional location is the cilium and ciliary base, where it acts in retrograde IFT, so Golgi is non-core. Supporting Evidence: PMID:11907264 D2LIC colocalizes with DHC2 at the Golgi apparatus throughout the cell cycle. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Golgi apparatus, from the UniProt subcellular location mapping. Reason: As for the EXP Golgi row. |
| GO:0005813 centrosome | IDA PMID:26130459 DYNC2LI1 mutations broaden the clinical spectrum of dynein-2... | KEEP AS NON CORE | Summary: An anti-DYNC2LI1 antibody labels centrosomes in fibroblasts. Reason: Pericentriolar/centrosomal staining reflects the pool of dynein-2 at the ciliary base. Basal body is the more informative term and is also annotated. Supporting Evidence: PMID:26130459 Our immunocytochemistry using an antibody against DYNC2LI1 supported the localization to the centrosome |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosome, from the UniProt subcellular location mapping. Reason: As for the IDA centrosome row. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Cytosol, from the Human Protein Atlas immunofluorescence (HPA main location Cytosol). Reason: HPA detects a cytosolic pool, consistent with a soluble motor subunit that is recruited to the ciliary base. Correct, but not the functional location. |
| GO:0005868 cytoplasmic dynein complex | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic dynein complex, by phylogenetic inference. Reason: DYNC2LI1 is a bona fide subunit of cytoplasmic dynein-2. GO has no dynein-2-specific complex term, so this is the most specific correct complex term. Supporting Evidence: PMID:31451806 LIC3 binds in a similar way to DHC2-A and -B, stabilizing the portion of the tail distal to the hinge sites |
| GO:0005868 cytoplasmic dynein complex | IDA PMID:21723285 Recombinant human cytoplasmic dynein heavy chain 1 and 2: ob... | ACCEPT | Summary: Cytoplasmic dynein complex, from the recombinant dynein-1/dynein-2 heavy chain expression study. Reason: The cached abstract describes purification of recombinant dynein-2 heavy chains from HEK293 cells. The curator presumably recorded co-purification of DYNC2LI1 from the full text. Membership of the complex is well established independently. |
| GO:0005868 cytoplasmic dynein complex | IDA PMID:31451806 Structure of the dynein-2 complex and its assembly with intr... | ACCEPT | Summary: Cryo-EM structure of the recombinant human dynein-2 complex includes DYNC2LI1 (LIC3) bound to both heavy chains. Reason: Direct structural evidence of complex membership. Supporting Evidence: PMID:31451806 LIC3 binds in a similar way to DHC2-A and -B, stabilizing the portion of the tail distal to the hinge sites |
| GO:0005868 cytoplasmic dynein complex | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoplasmic dynein complex, from InterPro. Reason: Consistent with the experimental data. |
| GO:0005868 cytoplasmic dynein complex | ISS PMID:12802074 A novel dynein light intermediate chain colocalizes with the... | ACCEPT | Summary: By similarity to the Chlamydomonas LIC (D1bLIC), which co-purifies with cDHC1b. Reason: Consistent with direct human evidence. Supporting Evidence: PMID:12802074 indicate that the novel LIC is a component of the cDHC1b/DHC2 retrograde IFT motor in a variety of organisms. |
| GO:0005881 cytoplasmic microtubule | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Colocalizes with cytoplasmic microtubule, transferred by sequence similarity. Reason: Dynein-2 moves on axonemal doublet microtubules inside the cilium. No human data show DYNC2LI1 colocalizing with cytoplasmic (non-axonemal) microtubules. The axoneme annotations already describe the relevant microtubule association. |
| GO:0005929 cilium | IDA GO_REF:0000052 | ACCEPT | Summary: Cilium, from HPA immunofluorescence (HPA primary cilium call, Supported). Reason: Consistent with retrograde IFT motor function and with published immunofluorescence. |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: Cilium, from the UniProt subcellular location mapping. Reason: Correct core location. |
| GO:0005929 cilium | ISS GO_REF:0000024 | ACCEPT | Summary: Cilium, by sequence similarity. Reason: Correct core location. |
| GO:0005929 cilium | NAS PMID:30065109 Emerging mechanisms of dynein transport in the cytoplasm ver... | ACCEPT | Summary: Cilium, stated in a review. Reason: Correct core location. |
| GO:0005929 cilium | NAS PMID:32229580 Cytoplasmic dynein-2 at a glance. | ACCEPT | Summary: Cilium, stated in a review. Reason: Correct core location. Supporting Evidence: PMID:32229580 Cytoplasmic dynein-2 is a motor protein complex that drives the movement of cargoes along microtubules within cilia |
| GO:0005929 cilium | TAS Reactome:R-HSA-5624949 | ACCEPT | Summary: Cilium, Reactome IFT reaction. Reason: Correct core location. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625416 | ACCEPT | Summary: Cilium, Reactome IFT reaction. Reason: Correct core location. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625424 | ACCEPT | Summary: Cilium, Reactome IFT reaction. Reason: Correct core location. |
| GO:0005929 cilium | TAS Reactome:R-HSA-5625426 | ACCEPT | Summary: Cilium, Reactome IFT reaction. Reason: Correct core location. |
| GO:0005930 axoneme | IBA GO_REF:0000033 | ACCEPT | Summary: Axoneme, by phylogenetic inference. Reason: The dynein-2 complex, including its LIC, travels along the axoneme during IFT. Supporting Evidence: PMID:12802074 The mammalian DHC2 and D2LIC also colocalize in the apical cytoplasm and axonemes of ciliated epithelia in the lung, brain, and efferent duct. |
| GO:0005930 axoneme | IEA GO_REF:0000120 | ACCEPT | Summary: Axoneme, from combined automated methods. Reason: Consistent with the IBA row. |
| GO:0005930 axoneme | ISS GO_REF:0000024 | ACCEPT | Summary: Axoneme, by similarity to mouse (Q8K0T2). Reason: Consistent with the IBA row. |
| GO:0030286 dynein complex | NAS PMID:30065109 Emerging mechanisms of dynein transport in the cytoplasm ver... | ACCEPT | Summary: Dynein complex, stated in a review. Reason: Correct, though less specific than cytoplasmic dynein complex. |
| GO:0030286 dynein complex | NAS PMID:32229580 Cytoplasmic dynein-2 at a glance. | ACCEPT | Summary: Dynein complex, stated in a review. Reason: Correct, though less specific than cytoplasmic dynein complex. |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Motile cilium, by Ensembl Compara transfer from mouse. Reason: The mouse protein is found in the axonemes of motile ciliated epithelia, so the location is valid. Dynein-2 acts in all cilia, however, and the primary cilium is where the human protein is best characterized. Supporting Evidence: PMID:12802074 The mammalian DHC2 and D2LIC also colocalize in the apical cytoplasm and axonemes of ciliated epithelia in the lung, brain, and efferent duct. |
| GO:0031514 motile cilium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Motile cilium, by similarity to mouse. Reason: As for the IEA motile cilium row. |
| GO:0035721 intraciliary retrograde transport | IBA GO_REF:0000033 | ACCEPT | Summary: Intraciliary retrograde transport, by phylogenetic inference. Reason: Core process. Loss of human DYNC2LI1 impairs retrograde IFT and causes IFT proteins to accumulate in the cilium. The C. elegans ortholog xbx-1 is also required for retrograde IFT. Supporting Evidence: PMID:26077881 Our results demonstrate that loss of DYNC2LI1 markedly impairs retrograde IFT and leads to the accumulation of IFT proteins within the primary cilium. |
| GO:0035721 intraciliary retrograde transport | IEA GO_REF:0000002 | ACCEPT | Summary: Intraciliary retrograde transport, from InterPro. Reason: Core process. |
| GO:0035721 intraciliary retrograde transport | NAS PMID:31451806 Structure of the dynein-2 complex and its assembly with intr... | ACCEPT | Summary: Intraciliary retrograde transport, stated in the dynein-2 structure paper. Reason: Core process. |
| GO:0035721 intraciliary retrograde transport | NAS PMID:32229580 Cytoplasmic dynein-2 at a glance. | ACCEPT | Summary: Intraciliary retrograde transport, stated in a review. Reason: Core process. |
| GO:0035735 intraciliary transport involved in cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Intraciliary transport involved in cilium assembly, by phylogenetic inference. Reason: As a subunit of the IFT motor, DYNC2LI1 takes part in the intraciliary transport that builds and maintains cilia. |
| GO:0035735 intraciliary transport involved in cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: Intraciliary transport involved in cilium assembly, from InterPro. Reason: Consistent with the IBA and IMP rows. |
| GO:0035735 intraciliary transport involved in cilium assembly | IMP PMID:26077881 Mutations in DYNC2LI1 disrupt cilia function and cause short... | ACCEPT | Summary: DYNC2LI1-mutant SRPS fibroblasts and RPE1 knockdown cells accumulate IFT88 in cilia and show altered cilium length; the phenotype is rescued by wild-type DYNC2LI1. Reason: Experimental support, with rescue, for a role in intraciliary transport during cilium assembly. Supporting Evidence: PMID:26077881 Rescue of mutant fibroblasts with human DYNC2LI1 corrected the cilia phenotype, directly confirming that the changes in cilia length and IFT resulted from the loss of normal DYNC2LI1. |
| GO:0035869 ciliary transition zone | IDA PMID:26130459 DYNC2LI1 mutations broaden the clinical spectrum of dynein-2... | KEEP AS NON CORE | Summary: DYNC2LI1 immunostaining concentrated at the axoneme base and transition-zone region. Reason: Dynein-2 docks onto IFT trains at the ciliary base and passes through the transition zone, so staining there is expected. It is a transit location rather than a site of specific transition-zone function. Supporting Evidence: PMID:26130459 Moreover, we refined the reported localization in the axoneme to be concentrated at its base and at the region of the transition zone |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: Ciliary basal body, by phylogenetic inference. Reason: Dynein-2 accumulates at the ciliary base, where it assembles onto IFT trains. Shown in Chlamydomonas and in human cells. Supporting Evidence: PMID:12802074 Immunocytochemistry reveals that the LIC colocalizes with cDHC1b in the basal body region and along the length of flagella in wild-type cells. |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: Ciliary basal body, from HPA immunofluorescence (Supported). Reason: Consistent with the published localization. |
| GO:0036064 ciliary basal body | IDA PMID:26130459 DYNC2LI1 mutations broaden the clinical spectrum of dynein-2... | ACCEPT | Summary: DYNC2LI1 detected around the basal body in ciliated fibroblasts. Reason: Experimental support for the basal body pool. Supporting Evidence: PMID:26130459 Using immunofluorescence analysis in ciliated fibroblast cells we confirmed the localization of the DYNC2LI1 protein to the cytoplasm, centrosomes, as well as around the basal body, and the transition zone of the primary cilium |
| GO:0036064 ciliary basal body | ISS PMID:12802074 A novel dynein light intermediate chain colocalizes with the... | ACCEPT | Summary: Colocalizes with basal body, by similarity to the Chlamydomonas LIC. Reason: Consistent with direct human data. |
| GO:0045177 apical part of cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apical part of cell, by Ensembl Compara transfer from mouse. Reason: Reflects the apical cytoplasm staining of mouse D2LIC in ciliated epithelia. Correct, but not informative about function. Supporting Evidence: PMID:12802074 The mammalian DHC2 and D2LIC also colocalize in the apical cytoplasm and axonemes of ciliated epithelia |
| GO:0045177 apical part of cell | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Apical part of cell, by sequence similarity. Reason: As for the IEA apical part of cell row. |
| GO:0045177 apical part of cell | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Apical part of cell, by sequence similarity. Reason: As for the IEA apical part of cell row. |
| GO:0045504 dynein heavy chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dynein heavy chain binding, by phylogenetic inference. Reason: Core molecular function. The LIC binds and stabilises the dynein-2 heavy chain tail, and the heavy chain stays tightly associated with LIC3 even without the intermediate chains. Supporting Evidence: PMID:31451806 DHC2, while maintaining a tight association with LIC3, did not homodimerize in the absence of the bridging IC-LC subunits and was monomeric file:human/DYNC2LI1/DYNC2LI1-deep-research-falcon.md of the ciliary dynein-2 motor, rather than an enzyme with an established substrate or reaction of its own |
| GO:0045504 dynein heavy chain binding | IDA PMID:29742051 Interaction of WDR60 intermediate chain with TCTEX1D2 light ... | ACCEPT | Summary: Direct DYNC2LI1–DYNC2H1 tail interaction in VIP assays (the H1 subcomplex). Reason: Direct experimental evidence for the core binding activity. Supporting Evidence: PMID:29742051 the H1 subcomplex (the heavy chain DYNC2H1 directly interacting with the light intermediate chain DYNC2LI1) |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5624952 | KEEP AS NON CORE | Summary: Ciliary tip, Reactome IFT turnaround reaction. Reason: The ciliary tip is one stage of the dynein-2 cycle, not its only location. |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625416 | KEEP AS NON CORE | Summary: Ciliary tip, Reactome IFT reaction. Reason: As for the other ciliary tip rows. |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625421 | KEEP AS NON CORE | Summary: Ciliary tip, Reactome IFT reaction. Reason: As for the other ciliary tip rows. |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5625426 | KEEP AS NON CORE | Summary: Ciliary tip, Reactome IFT reaction. Reason: As for the other ciliary tip rows. |
| GO:1902017 regulation of cilium assembly | IMP PMID:26077881 Mutations in DYNC2LI1 disrupt cilia function and cause short... | KEEP AS NON CORE | Summary: DYNC2LI1 mutation or knockdown increases cilium length and length variability; rescue restores normal length. Reason: The length phenotype is real and was rescued. It is best read as a downstream consequence of defective retrograde IFT rather than a dedicated regulatory activity, so the annotation is kept as non-core. Supporting Evidence: PMID:26077881 We therefore conclude that DYNC2LI1 and the dynein-2 complex play an important role in the regulation of primary cilia length. |
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Download this section (compressed HTML)Q: Does the conserved P-loop/nucleotide-binding pocket of DYNC2LI1's Ras-like core bind nucleotide, and does nucleotide state regulate dynein-2 activation at the ciliary tip?
Q: Is the Golgi localization reported for D2LIC in 2002 reproducible with validated antibodies and knockout controls, or does it reflect the pericentrosomal ciliary-base pool?
Experiment: Express P-loop mutant DYNC2LI1 in DYNC2LI1-knockout RPE1 cells and test rescue of dynein-2 stability, IFT88 ciliary accumulation and live retrograde IFT velocities.
Hypothesis: Nucleotide binding by the DYNC2LI1 Ras-like domain is required for retrograde IFT.
Type: mutant rescue and live imaging
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