ARL16

UniProt ID: Q0P5N6
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

ARL16 is a 173-residue Arf-family small GTPase, present since the last eukaryotic common ancestor, with an atypical G-3 motif. In its GTP-bound form it binds the C-terminal domain of the viral RNA sensor RIG-I and blocks RNA binding, restraining RIG-I-mediated interferon signalling. It localizes along the ciliary axoneme, in the cytosol and in mitochondria of RPE1 cells, and in the ciliary region and inner segment of human photoreceptors. In mouse cells it is needed for normal ciliogenesis and for export of IFT140 and INPP5E from the Golgi to cilia.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001917 photoreceptor inner segment
EXP
PMID:35196065
Phylogenetic profiling and cellular analyses of ARL16 reveal...
KEEP AS NON CORE
Summary: Photoreceptor inner segment (EXP). In human retina ARL16 immunostaining labels the photoreceptor ciliary region and inner segment; kept as a non-core tissue-specific location.
Reason: [PMID:35196065 "Prominent ARL16 immunofluorescence labeled the ciliary region (CR) and the inner segment of the photoreceptor layer."]
Supporting Evidence:
PMID:35196065
Prominent ARL16 immunofluorescence labeled the ciliary region (CR) and the inner segment of the photoreceptor layer.
GO:0001917 photoreceptor inner segment
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Photoreceptor inner segment (IEA). In human retina ARL16 immunostaining labels the photoreceptor ciliary region and inner segment; kept as a non-core tissue-specific location.
Reason: [PMID:35196065 "Prominent ARL16 immunofluorescence labeled the ciliary region (CR) and the inner segment of the photoreceptor layer."]
Supporting Evidence:
PMID:35196065
Prominent ARL16 immunofluorescence labeled the ciliary region (CR) and the inner segment of the photoreceptor layer.
GO:0003924 GTPase activity
IEA
GO_REF:0000002
UNDECIDED
Summary: GTPase activity (IEA, InterPro ARF family). ARL16 has an atypical G-3 motif, and no GTP hydrolysis has been measured; left undecided.
Reason: [PMID:38606629 "ARL16 was kept in its wild-type (WT) form as the G-3 motif is atypic"]
Supporting Evidence:
PMID:38606629
ARL16 was kept in its wild-type (WT) form as the G-3 motif is atypic
GO:0005515 protein binding
IPI
PMID:21233210
ARF-like protein 16 (ARL16) inhibits RIG-I by binding with i...
REMOVE
Summary: Protein binding (IPI) with RIG-I. GTP-bound ARL16 binds the RIG-I C-terminal domain and blocks RNA binding, inhibiting RIG-I signalling. The functional consequence is captured by the NEW negative regulation of RIG-I signaling pathway row, and no MF term names this binding more informatively, so the generic row is removed. Removal does not mean the interaction is false.
Reason: [PMID:21233210 "ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA."]
Supporting Evidence:
PMID:21233210
ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: Protein binding (IPI) with PDE6D, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: Protein binding (IPI) with AMPH, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
REMOVE
Summary: Protein binding (IPI) with GOLGA2, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: Protein binding (IPI) with PDE6D, from a yeast two-hybrid study of variant effects. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: Protein binding (IPI) with AMPH, from a yeast two-hybrid study of variant effects. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: Protein binding (IPI) with GOLGA2, from a yeast two-hybrid study of variant effects. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with PDE6D, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with TCF4, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with AMPH, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with REL, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with DEUP1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with GOLGA2, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with GLYR1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding (IPI) with TCF12, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with PMP22, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with PRKN, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with VAPB, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with SOD1, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with APP, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with APP, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with SNCA, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with HTT, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with PSEN2, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with ATXN1, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with TARDBP, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with PEX26, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with APBB2, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ...
REMOVE
Summary: Protein binding (IPI) with OPTN, from a yeast two-hybrid neurodegeneration interactome. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false.
Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own.
GO:0005525 GTP binding
IEA
GO_REF:0000002
ACCEPT
Summary: GTP binding (IEA, InterPro ARF family). In vitro-expressed ARL16 binds radiolabelled GTP, and the T37N mutant does not. Mutants restricted to the GTP-free form fail to bind RIG-I and lose their inhibitory function; accepted as its core molecular property.
Reason: [PMID:21233210 "The results showed that, like ARF1 and ARL1, wild type of ARL16, T61N, and C81L expressed in vitro bound to P 32 -labeled GTP, but T37N did not"] [PMID:21233210 "ARL16 (T37N) and ARL16Ξ”45–54, which were restricted to the GTP-disassociated form, did not interact with RIG-I and also lost the inhibitory function."]
Supporting Evidence:
PMID:21233210
The results showed that, like ARF1 and ARL1, wild type of ARL16, T61N, and C81L expressed in vitro bound to P 32 -labeled GTP, but T37N did not
PMID:21233210
ARL16 (T37N) and ARL16Ξ”45–54, which were restricted to the GTP-disassociated form, did not interact with RIG-I and also lost the inhibitory function.
GO:0005737 cytoplasm
EXP
PMID:35196065
Phylogenetic profiling and cellular analyses of ARL16 reveal...
ACCEPT
Summary: Cytoplasm (EXP). ARL16 shows diffuse cytosolic staining in RPE1 cells, where it can meet the cytosolic RNA sensor RIG-I; accepted.
Reason: [PMID:35196065 "ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A)."]
Supporting Evidence:
PMID:35196065
ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A).
GO:0005737 cytoplasm
IDA
PMID:21233210
ARF-like protein 16 (ARL16) inhibits RIG-I by binding with i...
ACCEPT
Summary: Cytoplasm (IDA). ARL16 shows diffuse cytosolic staining in RPE1 cells, where it can meet the cytosolic RNA sensor RIG-I; accepted.
Reason: [PMID:35196065 "ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A)."]
Supporting Evidence:
PMID:35196065
ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A).
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: Cytoplasm (IEA). ARL16 shows diffuse cytosolic staining in RPE1 cells, where it can meet the cytosolic RNA sensor RIG-I; accepted.
Reason: [PMID:35196065 "ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A)."]
Supporting Evidence:
PMID:35196065
ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A).
GO:0005739 mitochondrion
EXP
PMID:35196065
Phylogenetic profiling and cellular analyses of ARL16 reveal...
KEEP AS NON CORE
Summary: Mitochondrion (EXP). In RPE1 cells ARL16 co-localizes with the mitochondrial protein HSP60. The authors attribute this to a longer ARL16 variant, so it may be isoform-dependent. Kept as non-core, as its known functions are ciliary and RIG-I-related.
Reason: [PMID:35196065 "ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A)."] [PMID:35196065 "Because the endogenous staining of ARL16 in RPE1 cells displays prominent mitochondrial localization, we believe that these cells express at least some of the longer form of ARL16."] Checked for the ORGANELLES project (2026-10-24); a direct row whose assay (endogenous ARL16 co-staining with HSP60, plus the expressed 197-residue long variant) resolves the organelle only, so under rule 2 it stays at the root as non-core.
Supporting Evidence:
PMID:35196065
ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A).
PMID:35196065
Because the endogenous staining of ARL16 in RPE1 cells displays prominent mitochondrial localization, we believe that these cells express at least some of the longer form of ARL16.
GO:0005739 mitochondrion
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Mitochondrion (IEA). In RPE1 cells ARL16 co-localizes with the mitochondrial protein HSP60. The authors attribute this to a longer ARL16 variant, so it may be isoform-dependent. Kept as non-core, as its known functions are ciliary and RIG-I-related.
Reason: [PMID:35196065 "ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A)."] [PMID:35196065 "Because the endogenous staining of ARL16 in RPE1 cells displays prominent mitochondrial localization, we believe that these cells express at least some of the longer form of ARL16."] Examined as a synthesis row (ORGANELLES, 2026-10-24); GO_REF:0000044 maps UniProt SL-0173, which UniProt records for ARL16 with ECO:0000269 from PMID:35196065, so the feature the mapping assumes is present and the organelle claim stands as non-core. Stays at the root, because there is only one weak line for any sub-compartment. ARL16 is a small soluble Arf-family GTPase with no transmembrane segment, and the canonical 173-residue chain has no presequence; the authors attribute the mitochondrial signal to a 197-residue N-terminally extended variant (whether the extension acts as a presequence is untested), which UniProt lists only as an erroneous-initiation sequence caution. No fractionation or protease-protection data exist.
Supporting Evidence:
PMID:35196065
ARL16 also localized to both the cytosol and the mitochondria, as evidenced by its diffuse staining across the cell and colocalization with the mitochondrial protein HSP60, respectively (Supplemental Figure S2A).
PMID:35196065
Because the endogenous staining of ARL16 in RPE1 cells displays prominent mitochondrial localization, we believe that these cells express at least some of the longer form of ARL16.
GO:0005930 axoneme
IEA
GO_REF:0000044
ACCEPT
Summary: Axoneme (IEA). Endogenous ARL16 localizes in puncta along the ciliary axoneme in human RPE1 cells; accepted as its ciliary location.
Reason: [PMID:35196065 "revealed that ARL16 localizes along the ciliary axoneme in a punctate manner (Figure 2A)."]
Supporting Evidence:
PMID:35196065
revealed that ARL16 localizes along the ciliary axoneme in a punctate manner (Figure 2A).
GO:0036064 ciliary basal body
IDA
PMID:35196065
Phylogenetic profiling and cellular analyses of ARL16 reveal...
NEW
Summary: Ciliary basal body (NEW, IDA). In human photoreceptors ARL16 sits in the periciliary region at the base of the connecting cilium, and co-staining with centrin 3 shows it at the basal body next to the daughter centriole. UniProt records this location from the same paper, but GOA has no row for it. This is the site from which its Golgi-to-cilium cargo role would operate.
Reason: [PMID:35196065 "Higher magnification of the ciliary region revealed the localization of ARL16 in the periciliary region at the base of the connecting cilium (stained by anti–centrin 3) in human photoreceptor cells (Figure 2B, bottom panels)."] [PMID:35196065 "The centrin 3 costaining further showed that ARL16 labeled the basal body next to the daughter centriole."]
Supporting Evidence:
PMID:35196065
Higher magnification of the ciliary region revealed the localization of ARL16 in the periciliary region at the base of the connecting cilium (stained by anti–centrin 3) in human photoreceptor cells (Figure 2B, bottom panels).
PMID:35196065
The centrin 3 costaining further showed that ARL16 labeled the basal body next to the daughter centriole.
GO:0039536 negative regulation of RIG-I signaling pathway
IMP
PMID:21233210
ARF-like protein 16 (ARL16) inhibits RIG-I by binding with i...
NEW
Summary: Negative regulation of RIG-I signaling pathway (NEW, IMP). ARL16 overexpression inhibits RIG-I signalling and antiviral activity, its knockdown increases virus-induced IFN-beta, and GTP-bound ARL16 binds the RIG-I CTD to block RNA binding. ARL16 performs the inhibitory step itself.
Reason: [PMID:21233210 "Overexpression of ARL16, but not its homologous proteins ARL1 and ARF1, inhibited RIG-I-mediated downstream signaling and antiviral activity."] [PMID:21233210 "Knockdown of endogenous ARL16 by RNAi potentiated Sendai virus-induced IFN-Ξ² expression and vesicular stomatitis virus replication."] [PMID:21233210 "ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA."]
Supporting Evidence:
PMID:21233210
Overexpression of ARL16, but not its homologous proteins ARL1 and ARF1, inhibited RIG-I-mediated downstream signaling and antiviral activity.
PMID:21233210
Knockdown of endogenous ARL16 by RNAi potentiated Sendai virus-induced IFN-Ξ² expression and vesicular stomatitis virus replication.
PMID:21233210
ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA.
GO:0061512 protein localization to cilium
ISO
PMID:35196065
Phylogenetic profiling and cellular analyses of ARL16 reveal...
NEW
Summary: Protein localization to cilium (NEW, ISO from mouse Arl16). Arl16 knockout fibroblasts lose ciliary IFT140, INPP5E, ARL13B and ARL3, and IFT140 and INPP5E accumulate at the Golgi, indicating a role in Golgi-to-cilium traffic of specific cargo.
Reason: [PMID:35196065 "Instead, both INPP5E and IFT140 accumulate at the Golgi in Arl16 KO lines, while other intraflagellar transport (IFT) proteins do not, suggesting a specific defect in traffic from Golgi to cilia."] [PMID:35196065 "Deletion of ARL16 in mouse embryonic fibroblasts (MEFs) results in decreased ciliogenesis yet increased ciliary length."]
Supporting Evidence:
PMID:35196065
Instead, both INPP5E and IFT140 accumulate at the Golgi in Arl16 KO lines, while other intraflagellar transport (IFT) proteins do not, suggesting a specific defect in traffic from Golgi to cilia.
PMID:35196065
Deletion of ARL16 in mouse embryonic fibroblasts (MEFs) results in decreased ciliogenesis yet increased ciliary length.

Core Functions

GTP-bound ARL16 binds the RIG-I C-terminal domain and blocks its RNA binding, restraining antiviral interferon signalling.

Molecular Function:
GTP binding
Cellular Locations:
Supporting Evidence:
  • PMID:21233210
    ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA.
  • PMID:21233210
    ARL16 (T37N) and ARL16Ξ”45–54, which were restricted to the GTP-disassociated form, did not interact with RIG-I and also lost the inhibitory function.
  • PMID:21233210
    Overexpression of ARL16, but not its homologous proteins ARL1 and ARF1, inhibited RIG-I-mediated downstream signaling and antiviral activity.
  • PMID:21233210
    Knockdown of endogenous ARL16 by RNAi potentiated Sendai virus-induced IFN-Ξ² expression and vesicular stomatitis virus replication.

Ciliary ARF-family GTPase needed for Golgi-to-cilium export of IFT140 and INPP5E.

Molecular Function:
GTP binding
Directly Involved In:
Supporting Evidence:
  • PMID:35196065
    revealed that ARL16 localizes along the ciliary axoneme in a punctate manner (Figure 2A).
  • PMID:35196065
    The centrin 3 costaining further showed that ARL16 labeled the basal body next to the daughter centriole.
  • PMID:35196065
    Instead, both INPP5E and IFT140 accumulate at the Golgi in Arl16 KO lines, while other intraflagellar transport (IFT) proteins do not, suggesting a specific defect in traffic from Golgi to cilia.

References

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Suggested Questions for Experts

Q: Is ARL16's RIG-I inhibition linked to its ciliary role, or are these separate functions in different compartments?

Suggested Experiments

Experiment: Measure GTP hydrolysis by purified ARL16, given its atypical G-3 motif, and identify its GEF and GAP.

Deep Research

Affinage

(ARL16-deep-research-affinage.md)

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πŸ“š Additional Documentation

Notes

(ARL16-notes.md)

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