Electronic Gene Ontology annotations created by ARBA machine learning models
Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer.
A proteome-scale map of the human interactome network.
E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
Systematic identification of molecular links between core and candidate genes in breast cancer.
Architecture of the human interactome defines protein communities and disease networks.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
An in vitro vesicle formation assay reveals cargo clients and factors that mediate vesicular trafficking.
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Human LRATD2 associates with vesicle membranes in a GTP-dependent manner and occupies cytoplasmic, juxtanuclear Golgi, and peripheral membrane-associated pools in HEK293T assays.
"Western blot analysis confirmed that FAM84B/LRATD2 was significantly enhanced in the vesicle fraction when the incubation was conducted in the presence of GMPPNP (Fig. 3A, compare lanes 2 and 3). HA-tagged FAM84B/LRATD2 (FAM84B-HA) was partially located at the cytoplasm and partially located at the juxtanuclear Golgi area colocalized with TGN46 (SI Appendix, Fig. S1A)."
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Cross-linked coimmunoprecipitation detected LRATD2 with AP1gamma1 and Sec23A/B, but not Sar1A.
"FAM84B-HA coimmunoprecipitated with AP1γ1 and Sec23A/B, but not Sar1A in the presence of a cross-linker (Fig. 3B)."
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LRATD2 knockdown selectively delayed ER-to-Golgi transport of EGFR and was rescued by siRNA-resistant LRATD2, while ShhN and IGF2 transport was unaffected.
"Knockdown of FAM84B/LRATD2 caused a significant delay of EGFR transport from the ER to the Golgi in the RUSH transport system (Fig. 3C and SI Appendix, Fig. S3 A and B). The defects were rescued by expressing a siRNA-resistant construct of FAM84B-HA (Fig. 3 D and E). In contrast, knockdown of FAM84B/LRATD2 did not cause defects in the ER-to-Golgi transport of SBP-EGFP-ShhN and SBP-EGFP-IGF2-HA (Fig. 3 F–I)."
Binding Affinity Determines Substrate Specificity and Enables Discovery of Substrates for N-Myristoyltransferases.
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Chemical-proteomic labeling identified LRATD2, LRATD1, and ERICH5 as candidate substrates of human NMT1/2.
"However, three proteins LRATD1 (LRAT domain-containing 1, also called FAM84A or neurological sensory protein 1 NSE1), LRATD2 (FAM84B/NSE2), and ERICH5 (glutamate-rich protein 5) demonstrated clear fluorescence signals in the Alk12 treated samples compared to the control without Alk12 treatment, and the signals were hydroxylamine-resistant, suggesting that they are potentially N-myristoylated."
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NMT inhibition and loss of labeling in Gly2-to-Ala mutants confirmed LRATD2 and LRATD1 separately as NMT1/2 substrates.
"Alk12 labeling signals decreased with the treatment of NMT inhibitor in LRATD1, LRATD2, and ERICH5 and were completely removed in G2A mutants, confirming LRATD1, LRATD2, and ERICH5 as substrates of NMT1/2 (Figure 4C)."
FAM84B promotes prostate tumorigenesis through a network alteration.
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Full-length LRATD2, but not a construct deleting the LRAT/HRASLS-homologous region, increased DU145 invasion and anchorage-independent growth.
"FAM84B but not FAM84B (ΔHRASLS) increased DU145 cell invasion and growth in soft agar."
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Tagged full-length and deletion constructs co-precipitated and colocalized, suggesting self-association under overexpression conditions.
"Co-immunoprecipitation and co-localization analyses revealed an interaction between FAM84B and FAM84B (ΔHRASLS), suggesting an intramolecular association among FAM84B molecules."
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The authors inferred from loss of the catalytic cysteine that LRATD2 is unlikely to retain HRASLS phospholipase or O-acyltransferase activity.
"Since the catalytic residue Cys is not conserved (Figure 2), FAM84B is unlikely to have either enzymatic activities, which implies that FAM84B facilitates Ras signaling."
Elevated FAM84B promotes cell proliferation via interacting with NPM1 in esophageal squamous cell carcinoma.
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LRATD2 perturbation altered proliferation and cell-cycle status in ESCC cells, with NPM1 implicated as the mediator.
"Furthermore, we found that the forced expression change of FAM84B can influence ESCC cell proliferation and cell-cycle status, which is probably mediated by NPM1."
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LRATD2 directly interacted with the NPM1 C terminus and increased nuclear NPM1 in the ESCC model.
"A direct interaction between FAM84B and the C-terminal (189-294aa) of NPM1 was identified, which increased the NPM1 nuclear expression."
FAM84B, amplified in pancreatic ductal adenocarcinoma, promotes tumorigenesis through the Wnt/β-catenin pathway.
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LRATD2 knockdown suppressed proliferation, mitochondrial function, and glycolysis in PDAC cell lines, whereas overexpression produced opposite effects.
"FAM84B knockdown also suppressed mitochondrial function and glycolysis of PDAC cells."
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LRATD2 perturbation altered nuclear beta-catenin and downstream readouts, and a Wnt/beta-catenin inhibitor blocked the overexpression phenotypes.
"On the contrary, FAM84B overexpression displayed reversed effects in cell proliferation, apoptosis, mitochondrial function, and glycolysis, which was blocked by the Wnt/β-catenin pathway inhibitor (XAV939)."
Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.
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LRATD2 was recurrently amplified and overexpressed in ESCC and preclinical lesions.
"In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors."
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LRATD2 knockdown reduced growth, migration, and invasion in ESCC cell lines.
"Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion."