Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing/stability in malignant human neuroblasts.
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HuD binds exonic and intronic N-MYC RNA and was proposed to regulate nuclear pre-mRNA processing or stability.
"The neuronal-specific RNA-binding Hu proteins are present in cytoplasmic and nuclear fractions of N cells and one of them, HuD, binds specifically to both exonic and intronic N-myc RNA sequences."
RNA-binding analyses of HuC and HuD with the VEGF and c-myc 3'-untranslated regions using a novel ELISA-based assay.
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Recombinant HuD binds VEGF and c-MYC 3-prime UTRs specifically and concentration-dependently.
"With this assay, I demonstrate that HuC and HuD bind to the VEGF 3'-UTR regulatory segment (VRS) and to the c- myc 3'-UTR in a specific and concentration-dependent pattern, with both proteins showing a greater affinity for the VRS."
HuD RNA recognition motifs play distinct roles in the formation of a stable complex with AU-rich RNA.
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Extended AU-rich sequence and cooperative RRM action produce stable nanomolar-affinity HuD-RNA complexes.
"Thus, the three RRMs appear to cooperate not only to increase the affinity of the interaction but also to stabilize the formed complex."
Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-binding protein HuD.
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HuD delays GAP43 mRNA decay and reduces deadenylation in a binding-element- and poly(A)-tail-dependent manner.
"Here we report that overexpression of HuD protein in PC12 cells stabilizes the GAP-43 mRNA by delaying the onset of mRNA degradation and that this process depends on the size of the poly(A) tail."
Post-transcriptional regulation of acetylcholinesterase mRNAs in nerve growth factor-treated PC12 cells by the RNA-binding protein HuD.
A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators.
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Neuronal Hu proteins oppose TIA1/TIAL1 to regulate neuron-specific CALCA pre-mRNA processing in the nucleus.
"We show that in neuron-like cells, Hu proteins block the activity of TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA processing."
The RNA-binding protein HuD binds acetylcholinesterase mRNA in neurons and regulates its expression after axotomy.
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Human HuD binds AChE mRNA in neurons and maintains AChE and GAP43 transcript levels after axotomy.
"Using a herpes simplex virus construct containing the human HuD sequence to infect SCG neurons in vivo, we found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy."
Post-transcriptional regulation of neuro-oncological ventral antigen 1 by the neuronal RNA-binding proteins ELAV.
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HuD/nELAV binding positively controls NOVA1 mRNA stability and translation.
"Gene silencing and overexpression of the nELAV member HuD in motoneuronal NSC34 cells indicate that Nova1 mRNA stability and translation are positively and strongly controlled by the nELAV proteins."
HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects.
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HuD binds SMN, and the interaction recruits HuD and target mRNAs to neuronal granules.
"We further demonstrate that this CARM1-dependent regulatory switch mainly controls the activity of HuD in promoting cell-cycle exit, whereas the interaction between HuD and SMN is required for proper recruitment of HuD and its mRNA targets in neuronal RNA granules."
Structural basis for recognition of AU-rich element RNA by the HuD protein.
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HuD RRM1-RRM2 structures define recognition of pyrimidine-rich AU elements.
"These structures reveal a consensus RNA recognition sequence that suggests a preference for pyrimidine-rich sequences and a requirement for a central uracil residue in the clustered AUUUA repeats found in class II AREs."
Paraneoplastic encephalomyelitis antigens bind to the AU-rich elements of mRNA.
CARM1 regulates proliferation of PC12 cells by methylating HuD.
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CARM1 methylation reduces HuD target-RNA binding and promotes a proliferative cell state.
"Methylation-resistant HuD bound more p21cip1/waf1 mRNA than did the wild type, and its overexpression upregulated p21cip1/waf1 protein expression."
The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons.
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SMN and HuD cotransport in axonal granules, and SMN loss reduces axonal HuD and poly(A) RNA.
"Importantly, SMN knockdown in primary motor neurons resulted in a specific reduction of both HuD protein and poly(A) mRNA levels in the axonal compartment."
RNA-binding protein HuD controls insulin translation.
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In pancreatic beta cells, HuD binds an Ins2 5-prime-UTR element and represses translation.
"Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production."
HuD regulates coding and noncoding RNA to induce APP→Aβ processing.
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In human neuroblastoma cells, HuD increases APP mRNA stability and translation.
"In sum, HuD enhanced both the stability and translation of APP mRNA."
HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.
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Zebrafish HuD is required for motor-axon branches, dendrites, and normal movement.
"Novel mutants reveal that HuD is also necessary for motor axonal branch and dendrite formation."
UniProtKB record for human ELAVL4 (P26378)
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Human HuD is a reviewed 385-amino-acid ELAV-family protein.
"Reviewed; 385 AA."
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The reviewed record assigns three RNA recognition motifs.
"FT DOMAIN 51..129"
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UniProt records cytoplasmic and neuronal-projection localization.
"Cell projection, growth cone"
Manual literature and annotation review notes for human ELAVL4
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All 30 GOA rows were manually adjudicated.
"## Existing annotation decisions"
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The notes distinguish 3-prime-UTR stabilization from target-specific translation effects.
"## Translation is target- and element-dependent"
Manual literature synthesis for human ELAVL4 (P26378)
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The synthesis identifies three linked core RNA-regulatory activities.
"The core annotation model contains three linked activities:"
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The beta-cell translation-repression mechanism is treated as a conserved secondary function.
"The beta-cell 5-prime-UTR/translation-repression mechanism is a strong, conserved secondary function"