LIMD1

UniProt ID: Q9UGP4
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

LIMD1 encodes a multi-domain LIM zinc-binding adaptor/scaffold protein that assembles regulatory complexes at adherens junctions, P-bodies, cytoplasmic HIF degradation machinery, and the nucleus. Its best-supported functions include mechanosensitive Hippo/LATS-YAP regulation, miRISC-mediated translational repression, PHD2-VHL-dependent HIF-alpha degradation, and pRB/E2F transcriptional corepression.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003714 transcription corepressor activity
IBA
GO_REF:0000033
ACCEPT
Summary: Transcription corepressor activity is supported by pRB/E2F repression and related corepressor interactions.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
GO:0005912 adherens junction
IBA
GO_REF:0000033
ACCEPT
Summary: adherens junction localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: nucleus localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0006355 regulation of DNA-templated transcription
IBA
GO_REF:0000033
MODIFY
Summary: Regulation of DNA-templated transcription is correct but too broad; LIMD1 evidence supports negative transcriptional regulation/corepression.
Reason: Use the directionally specific transcriptional repression term.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
GO:0007010 cytoskeleton organization
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Cytoskeleton organization is a broad downstream description; the mechanistic evidence is more specifically adherens-junction/F-actin tension sensing for Hippo signaling.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
GO:0035331 negative regulation of hippo signaling
IBA
GO_REF:0000033
ACCEPT
Summary: Negative regulation of Hippo signaling is supported by LIMD1-mediated LATS1/2 recruitment/localization at adherens junctions and consequent YAP/TAZ regulation.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
IBA
GO_REF:0000033
ACCEPT
Summary: P-body localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0001666 response to hypoxia
IBA
GO_REF:0000033
ACCEPT
Summary: Response to hypoxia is supported by LIMD1 induction and by LIMD1 scaffolding of PHD2/VHL complexes for HIF-alpha degradation.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a scaffold for the oxygen-sensing degradation machinery by bridging **PHD2** and **VHL** to promote efficient **HIF‑α degradation**, and is itself **HIF-1 inducible**, creating a negative-feedback loop limiting pro-tumorigenic hypoxia signaling.
GO:0005667 transcription regulator complex
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Transcription regulator complex is retained as a non-core complex context for pRB/E2F and SNAI-associated repression, but the more informative annotation is transcription corepressor activity.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
IEA
GO_REF:0000120
ACCEPT
Summary: P-body localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0001666 response to hypoxia
IEA
GO_REF:0000117
ACCEPT
Summary: Response to hypoxia is supported by LIMD1 induction and by LIMD1 scaffolding of PHD2/VHL complexes for HIF-alpha degradation.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a scaffold for the oxygen-sensing degradation machinery by bridging **PHD2** and **VHL** to promote efficient **HIF‑α degradation**, and is itself **HIF-1 inducible**, creating a negative-feedback loop limiting pro-tumorigenic hypoxia signaling.
GO:0005634 nucleus
IEA
GO_REF:0000044
ACCEPT
Summary: nucleus localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: cytoplasm localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005912 adherens junction
IEA
GO_REF:0000044
ACCEPT
Summary: adherens junction localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005925 focal adhesion
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Focal adhesion localization is supported by UniProt/subcellular evidence, but the strongest mechanistic Hippo evidence centers on adherens junctions under tension.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0031047 regulatory ncRNA-mediated gene silencing
IEA
GO_REF:0000043
MODIFY
Summary: Regulatory ncRNA-mediated gene silencing is supported but should be represented more specifically as miRNA-mediated post-transcriptional silencing.
Reason: The evidence is specifically miRISC/miRNA-mediated silencing.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
GO:0035278 miRNA-mediated gene silencing by inhibition of translation
IEA
GO_REF:0000117
ACCEPT
Summary: miRNA-mediated gene silencing by inhibition of translation is supported by LIMD1 function as a miRISC/P-body scaffold linking AGO proteins, GW182/TNRC6, DDX6, and cap-associated translation repression.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
GO:0035331 negative regulation of hippo signaling
IEA
GO_REF:0000117
ACCEPT
Summary: Negative regulation of Hippo signaling is supported by LIMD1-mediated LATS1/2 recruitment/localization at adherens junctions and consequent YAP/TAZ regulation.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
GO:0046872 metal ion binding
IEA
GO_REF:0000043
MODIFY
Summary: The metal-binding evidence is specifically zinc binding by LIM domains, so this broad metal ion binding term should be replaced by zinc ion binding.
Reason: LIM domains are zinc-binding modules; use the specific zinc ion binding term.
Proposed replacements: zinc ion binding
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**LIMD1 is a multi-domain adaptor/scaffold protein**, not an enzyme. Its biological roles derive from assembling protein complexes and controlling where/when those complexes formβ€”particularly at **cell junctions**, **P-bodies**, and in **oxygen-sensing (HIF) degradation complexes**. LIM domains are zinc-binding modules (~55–65 aa) that act as protein-interaction interfaces; LIMD1 contains **three tandem LIM domains** at its C‑terminus.
GO:0005515 protein binding
IPI
PMID:22190034
Global landscape of HIV-human protein complexes.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:22190034
Global landscape of HIV-human protein complexes.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0005515 protein binding
IPI
PMID:28683311
Argonaute Utilization for miRNA Silencing Is Determined by P...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:28683311
Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:33961781
2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0002076 osteoblast development
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: osteoblast development is retained as a non-core osteoblast/Wnt-related role supported by UniProt-curated literature, but it is peripheral to the main LIMD1 scaffold functions synthesized here.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts.
GO:0003714 transcription corepressor activity
IEA
GO_REF:0000107
ACCEPT
Summary: Transcription corepressor activity is supported by pRB/E2F repression and related corepressor interactions.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
GO:0045668 negative regulation of osteoblast differentiation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: negative regulation of osteoblast differentiation is retained as a non-core osteoblast/Wnt-related role supported by UniProt-curated literature, but it is peripheral to the main LIMD1 scaffold functions synthesized here.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts.
GO:0090090 negative regulation of canonical Wnt signaling pathway
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: negative regulation of canonical Wnt signaling pathway is retained as a non-core osteoblast/Wnt-related role supported by UniProt-curated literature, but it is peripheral to the main LIMD1 scaffold functions synthesized here.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
ACCEPT
Summary: nucleoplasm localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005925 focal adhesion
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: Focal adhesion localization is supported by UniProt/subcellular evidence, but the strongest mechanistic Hippo evidence centers on adherens junctions under tension.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0035278 miRNA-mediated gene silencing by inhibition of translation
IMP
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
ACCEPT
Summary: miRNA-mediated gene silencing by inhibition of translation is supported by LIMD1 function as a miRISC/P-body scaffold linking AGO proteins, GW182/TNRC6, DDX6, and cap-associated translation repression.
Supporting Evidence:
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234159
ACCEPT
Summary: cytosol localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234163
ACCEPT
Summary: cytosol localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234173
ACCEPT
Summary: cytosol localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234177
ACCEPT
Summary: cytosol localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234183
ACCEPT
Summary: cytosol localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0003714 transcription corepressor activity
ISS
GO_REF:0000024
ACCEPT
Summary: Transcription corepressor activity is supported by pRB/E2F repression and related corepressor interactions.
Supporting Evidence:
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
GO:0002076 osteoblast development
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: osteoblast development is retained as a non-core osteoblast/Wnt-related role supported by UniProt-curated literature, but it is peripheral to the main LIMD1 scaffold functions synthesized here.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts.
GO:0045668 negative regulation of osteoblast differentiation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: negative regulation of osteoblast differentiation is retained as a non-core osteoblast/Wnt-related role supported by UniProt-curated literature, but it is peripheral to the main LIMD1 scaffold functions synthesized here.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts.
GO:0090090 negative regulation of canonical Wnt signaling pathway
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: negative regulation of canonical Wnt signaling pathway is retained as a non-core osteoblast/Wnt-related role supported by UniProt-curated literature, but it is peripheral to the main LIMD1 scaffold functions synthesized here.
Supporting Evidence:
file:human/LIMD1/LIMD1-uniprot.txt
Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts.
GO:0001666 response to hypoxia
IDA
PMID:22286099
The LIMD1 protein bridges an association between the prolyl ...
ACCEPT
Summary: Response to hypoxia is supported by LIMD1 induction and by LIMD1 scaffolding of PHD2/VHL complexes for HIF-alpha degradation.
Supporting Evidence:
PMID:22286099
The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a scaffold for the oxygen-sensing degradation machinery by bridging **PHD2** and **VHL** to promote efficient **HIF‑α degradation**, and is itself **HIF-1 inducible**, creating a negative-feedback loop limiting pro-tumorigenic hypoxia signaling.
GO:0005515 protein binding
IPI
PMID:18331720
Ajuba LIM proteins are snail/slug corepressors required for ...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:18331720
Ajuba LIM proteins are snail/slug corepressors required for neural crest development in Xenopus.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0005515 protein binding
IPI
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0005515 protein binding
IPI
PMID:22286099
The LIMD1 protein bridges an association between the prolyl ...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:22286099
The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0045892 negative regulation of DNA-templated transcription
IMP
PMID:22286099
The LIMD1 protein bridges an association between the prolyl ...
ACCEPT
Summary: Negative regulation of DNA-templated transcription is supported by both pRB/E2F repression and HIF pathway repression through enhanced HIF-alpha degradation.
Supporting Evidence:
PMID:22286099
The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a scaffold for the oxygen-sensing degradation machinery by bridging **PHD2** and **VHL** to promote efficient **HIF‑α degradation**, and is itself **HIF-1 inducible**, creating a negative-feedback loop limiting pro-tumorigenic hypoxia signaling.
GO:0005515 protein binding
IPI
PMID:20303269
Ajuba LIM proteins are negative regulators of the Hippo sign...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:20303269
Mar 18. Ajuba LIM proteins are negative regulators of the Hippo signaling pathway.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0005634 nucleus
IDA
PMID:18439753
Cell cycle regulated phosphorylation of LIMD1 in cell lines ...
ACCEPT
Summary: nucleus localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
PMID:18439753
2008 Apr 24. Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005737 cytoplasm
IDA
PMID:18439753
Cell cycle regulated phosphorylation of LIMD1 in cell lines ...
ACCEPT
Summary: cytoplasm localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
PMID:18439753
2008 Apr 24. Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005912 adherens junction
IDA
PMID:20303269
Ajuba LIM proteins are negative regulators of the Hippo sign...
ACCEPT
Summary: adherens junction localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
PMID:20303269
Mar 18. Ajuba LIM proteins are negative regulators of the Hippo signaling pathway.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005925 focal adhesion
IDA
PMID:18439753
Cell cycle regulated phosphorylation of LIMD1 in cell lines ...
KEEP AS NON CORE
Summary: Focal adhesion localization is supported by UniProt/subcellular evidence, but the strongest mechanistic Hippo evidence centers on adherens junctions under tension.
Supporting Evidence:
PMID:18439753
2008 Apr 24. Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0016310 phosphorylation
IDA
PMID:18439753
Cell cycle regulated phosphorylation of LIMD1 in cell lines ...
REMOVE
Summary: LIMD1 is a scaffold protein and not a kinase; the cited paper concerns phosphorylation of LIMD1 rather than LIMD1 catalyzing phosphorylation.
Reason: Substrate-as-enzyme misannotation.
Supporting Evidence:
PMID:18439753
2008 Apr 24. Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers.
GO:0035331 negative regulation of hippo signaling
IDA
PMID:20303269
Ajuba LIM proteins are negative regulators of the Hippo sign...
ACCEPT
Summary: Negative regulation of Hippo signaling is supported by LIMD1-mediated LATS1/2 recruitment/localization at adherens junctions and consequent YAP/TAZ regulation.
Supporting Evidence:
PMID:20303269
Mar 18. Ajuba LIM proteins are negative regulators of the Hippo signaling pathway.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
IDA
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
ACCEPT
Summary: P-body localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0016442 RISC complex
IDA
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
ACCEPT
Summary: RISC complex is supported by LIMD1 function as a miRISC/P-body scaffold linking AGO proteins, GW182/TNRC6, DDX6, and cap-associated translation repression.
Supporting Evidence:
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
GO:0033962 P-body assembly
IMP
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
ACCEPT
Summary: P-body assembly is supported by LIMD1 function as a miRISC/P-body scaffold linking AGO proteins, GW182/TNRC6, DDX6, and cap-associated translation repression.
Supporting Evidence:
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
GO:0035195 miRNA-mediated post-transcriptional gene silencing
IMP
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
ACCEPT
Summary: miRNA-mediated post-transcriptional gene silencing is supported by LIMD1 function as a miRISC/P-body scaffold linking AGO proteins, GW182/TNRC6, DDX6, and cap-associated translation repression.
Supporting Evidence:
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
GO:0005515 protein binding
IPI
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is over-broad for LIMD1. Specific adaptor/scaffold roles with AGO/TNRC6/DDX6, LATS1/2, PHD/VHL, and pRB are more informative.
Reason: Avoid generic protein binding when specific complex/adaptor mechanisms are known.
Supporting Evidence:
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription.
file:human/LIMD1/LIMD1-deep-research-falcon.md
LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.
GO:0005634 nucleus
IDA
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor...
ACCEPT
Summary: nucleus localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0005737 cytoplasm
IDA
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor...
ACCEPT
Summary: cytoplasm localization is supported for LIMD1 scaffold function across junctional, cytoplasmic/P-body, and nuclear compartments.
Supporting Evidence:
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.
file:human/LIMD1/LIMD1-uniprot.txt
Cytoplasm. Nucleus. Cytoplasm, P-body. Cell junction, adherens junction. Cell junction, focal adhesion.
GO:0045892 negative regulation of DNA-templated transcription
IDA
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor...
ACCEPT
Summary: Negative regulation of DNA-templated transcription is supported by both pRB/E2F repression and HIF pathway repression through enhanced HIF-alpha degradation.
Supporting Evidence:
PMID:15542589
LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**Primary function:** LIMD1 acts as a scaffold for the oxygen-sensing degradation machinery by bridging **PHD2** and **VHL** to promote efficient **HIF‑α degradation**, and is itself **HIF-1 inducible**, creating a negative-feedback loop limiting pro-tumorigenic hypoxia signaling.
GO:0060090 molecular adaptor activity
IDA
PMID:20616046
LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for...
NEW
Summary: LIMD1 molecular adaptor activity is directly supported by PMID:20616046, which shows LIMD1/Ajuba/WTIP linking Ago1/2, eIF4E-cap complexes, and miRNA-mediated silencing machinery; this captures the broader scaffold/adaptor role synthesized across LIMD1 pathways.
Reason: The existing GOA annotations capture downstream processes but lack the core molecular adaptor/scaffold activity demonstrated by primary mechanistic literature.
Supporting Evidence:
PMID:20616046
these LIM-domain proteins facilitate miRNA-mediated gene silencing by acting as an essential molecular link between the translationally inhibited eIF4E-m(7)GTP-5(')cap and Ago1/2 within the miRISC complex attached to the 3'-UTR of mRNA, creating an inhibitory closed-loop complex.
file:human/LIMD1/LIMD1-deep-research-falcon.md
**LIMD1 is a multi-domain adaptor/scaffold protein**, not an enzyme. Its biological roles derive from assembling protein complexes and controlling where/when those complexes formβ€”particularly at **cell junctions**, **P-bodies**, and in **oxygen-sensing (HIF) degradation complexes**. LIM domains are zinc-binding modules (~55–65 aa) that act as protein-interaction interfaces; LIMD1 contains **three tandem LIM domains** at its C‑terminus.

Core Functions

Mechanosensitive adaptor activity at adherens junctions that recruits/localizes LATS1/2 and negatively regulates Hippo signaling output.

Supporting Evidence:
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    **Primary function:** LIMD1 acts as a **mechanosensitive scaffold** controlling the **subcellular localization** (and functional availability) of **LATS1/2** kinases at adherens junctions, thereby influencing YAP/TAZ phosphorylation state and nuclear localization.
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    **LIMD1 is a multi-domain adaptor/scaffold protein**, not an enzyme. Its biological roles derive from assembling protein complexes and controlling where/when those complexes formβ€”particularly at **cell junctions**, **P-bodies**, and in **oxygen-sensing (HIF) degradation complexes**. LIM domains are zinc-binding modules (~55–65 aa) that act as protein-interaction interfaces; LIMD1 contains **three tandem LIM domains** at its C‑terminus.

miRISC/P-body adaptor activity that promotes miRNA-mediated translational repression by coupling Argonaute, TNRC6/GW182, DDX6, and cap-associated machinery.

Supporting Evidence:
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    **Primary function:** LIMD1 is a **miRISC adaptor/scaffold** that promotes productive AGO-dependent silencing by coupling Argonaute to GW182/TNRC6 and downstream effector complexes, and by linking silencing to translation initiation control at the 5β€² cap.
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    **Localization:** LIMD1 colocalizes with GW182/TNRC6 and other miRISC components in **P-bodies**.

Adaptor activity in hypoxia signaling that bridges PHD2/VHL machinery to promote HIF-alpha degradation and limit hypoxic transcriptional responses.

Supporting Evidence:
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    **Primary function:** LIMD1 acts as a scaffold for the oxygen-sensing degradation machinery by bridging **PHD2** and **VHL** to promote efficient **HIF‑α degradation**, and is itself **HIF-1 inducible**, creating a negative-feedback loop limiting pro-tumorigenic hypoxia signaling.
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    LIMD1 (Q9UGP4) is best understood as a **multi-compartment scaffold** that (i) couples **mechanical tension** at adherens junctions to **Hippo pathway kinase (LATS) localization**, (ii) enables efficient **miRNA-mediated translational repression** by scaffolding Argonaute and GW182/TNRC6 and engaging the cap complex, (iii) promotes **HIF‑α degradation** by scaffolding PHD2–VHL complexes and participating in a HIF-driven negative feedback loop, and (iv) exerts tumor suppressor functions via **pRB/E2F repression** and via maintaining homeostatic control over hypoxia and mechanotransduction outputs.

Nuclear transcription corepressor activity through pRB/E2F repression.

Supporting Evidence:
  • file:human/LIMD1/LIMD1-deep-research-falcon.md
    **Primary function:** LIMD1 binds **pRB** and represses **E2F-driven transcription**, coupling LIMD1 to cell-cycle control.

References

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Deep Research

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(LIMD1-deep-research-falcon.md)

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