Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
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 Gene Ontology annotation based on Rhea mapping
UniProtKB record for human LMTK1 (Q6ZMQ8)
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The reviewed human Q6ZMQ8 record names LMTK1 a serine/threonine-protein kinase.
"DE RecName: Full=Serine/threonine-protein kinase LMTK1;"
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UniProt records three alternatively spliced human LMTK1 isoforms.
"CC Event=Alternative splicing; Named isoforms=3;"
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UniProt predicts a transmembrane segment at residues 32-52 of the displayed human sequence.
"FT TRANSMEM 32..52"
PANTHER PTHR24417 serine/threonine-protein kinase LMTK family metadata
Epigenetically silenced apoptosis-associated tyrosine kinase (AATK) facilitates a decreased expression of Cyclin D1 and WEE1, phosphorylates TP53 and reduces cell proliferation in a kinase-dependent manner.
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Human AATK/LMTK1 has protein serine/threonine kinase activity, and an immunoprecipitate kinase assay supports TP53 Ser366 as a site-specific substrate.
"Via large-scale kinomic profiling and kinase assays, we demonstrate that AATK acts a Ser/Thr kinase that phosphorylates TP53 at Ser366."
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Wild-type versus kinase-dead AATK experiments link catalytic activity to lower CCND1/WEE1 expression and growth suppression in human cell models.
"The kinase activity of AATK in comparison to the kinase-dead mutant mediates a decreased expression of the key cell cycle regulators Cyclin D1 and WEE1. Moreover, growth suppression through AATK relies on its kinase activity."
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Matched wild-type and kinase-dead human AATK profiling produced heterogeneous phosphotyrosine profiles but a clearly divergent serine/threonine profile.
"The individual basal activity profiles of all three replicates for AATK wt and AATK KD in the PTK assay was very heterogeneous (Fig. S11A). In contrast, the activity profiles from the STK assay comparing the AATK wt and AATK KD expressing clone pools depicted a clearly diverging activity profile (Fig. S11B)."
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Human AATK interactome analysis recovered the previously described STK39 and PPP1CB partners.
"Interactome analysis of AATK (Fig. 3), revealed among others previously described binding partners of AATK such as STK39 and PPP1CB [46, 59]."
Apoptosis-associated tyrosine kinase 1 inhibits growth and migration and promotes apoptosis in melanoma.
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Human AATK perturbation in melanoma cells supports anti-proliferative, anti-migratory, and pro-apoptotic roles.
"Overexpression of AATK inhibited cell proliferation, colony formation, and promoted apoptosis in melanoma cell lines derived from primary and metastatic melanomas."
A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line.
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AATYK expression in human SH-SY5Y cells produced cytoplasmic kinase signal and promoted neuronal differentiation, but the abstract does not identify the AATYK cDNA species.
"Our results demonstrate for the first time that AATYK is an active, non-receptor, cytosolic kinase which induces neuronal differentiation and also promotes differentiation induced by other agents in the SH-SY5Y cells."
Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein.
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A human brain-derived short KIAA0641/AATYK splice fragment binds CDK5R1/p35; human constructs were also tested in HEK293 cells and were phosphorylated by CDK5/p35.
"Both hAATYKs and KIAA0641 bound to and were phosphorylated by Cdk5/p35."
Protein phosphatase 1α interacting proteins in the human brain.
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A high-throughput human-brain yeast-two-hybrid survey identified PP1α interactors; GOA records the AATK-PPP1CA pair from this screen.
"Hence, an in-depth survey was taken to identify specific PP1α PIPs in human brain by a high-throughput Yeast Two-Hybrid approach. Sixty-six proteins were recognized to bind PP1α, 39 being novel PIPs."
Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
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A human DLD-1 kinase-network resource combined perturbation screens with mass-spectrometry interaction mapping and phosphoproteomics; GOA records AATK interactions with PPP1CA/PPP1CC.
"We assembled protein interaction maps using mass spectrometry-based protein interaction analysis and quantitative phosphoproteomics."
A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.
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Human MYTH/MaMTH screens support AATK interactions with PPP1CA/PPP1CC, but interaction does not imply an enzyme-substrate relationship.
"However, it should be noted that these interactions are not equivalent to enzyme-substrate interactions, and therefore do not necessarily suggest that the involved phosphatase directly dephosphorylates a given RTK or, conversely, that the RTK can phosphorylate the phosphatase."
A reference map of the human binary protein interactome.
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HuRI provides systematically retested human binary interactions; GOA records AATK-TEPSIN.
"To map the reference interactome, we performed nine screens of Space III, followed by pairwise verification by quadruplicate retesting and sequence confirmation."
Physical and functional interactome atlas of human receptor tyrosine kinases.
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A human kinase-interactome atlas used complementary stable-interaction, proximity, and substrate assays; GOA records the AATK-PPP1CC pair.
"We use affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates."
Apoptosis-associated tyrosine kinase scaffolding of protein phosphatase 1 and SPAK reveals a novel pathway for Na-K-2C1 cotransporter regulation.
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AATYK1 expressed in Xenopus oocytes uses PP1- and SPAK-binding motifs for a kinase-independent scaffold effect on NKCC1; the abstract does not state the construct species.
"Taken together, our data are consistent with AATYK1 indirectly inhibiting the SPAK/WNK4 activation of the cotransporter by scaffolding an inhibitory phosphatase in proximity to a stimulatory kinase."
Characterization of the apoptosis-associated tyrosine kinase (AATYK) expressed in the CNS.
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Mouse AATYK expressed in 293 cells showed reported tyrosine kinase/autophosphorylation, and wild-type versus kinase-deficient mouse AATYK altered apoptosis of mouse cerebellar neurons.
"We isolated three related cDNA clones from a mouse cerebellar library; the type I cDNA was identical to the gene encoding the apoptosis-associated tyrosine kinase (AATYK), whose expression in myeloid precursor cells is increased during growth arrest or apoptosis."
Palmitoylation-dependent endosomal localization of AATYK1A and its interaction with Src.
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Transmembrane-domain-free AATYK1A was palmitoylated and localized to recycling endosomes in cortical neurons/COS-7 cells; Src/Fyn phosphorylated AATYK1A Tyr25/Tyr46.
"AATYK1A, an isoform without a transmembrane domain, is highly expressed in neurons. We identified palmitoylation of AATYK1A at three N-terminal cysteine residues in cortical cultured neurons and COS-7 cells and found that palmitoylation determined localization of AATYK1A to the transferrin receptor-positive recycling endosomes."
Phosphorylation of AATYK1 by Cdk5 suppresses its tyrosine phosphorylation.
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CDK5/p35 binds and phosphorylates rodent AATYK1A at Ser34 in mixed cultured-cell, rat-neuron, and mouse-brain systems, suppressing Src-family-dependent tyrosine phosphorylation.
"AATYK1A was phosphorylated at Ser34 by Cdk5/p35 in vitro, in cultured neurons and in mouse brain."
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The paper classifies AATYK1 as a serine/threonine kinase.
"Apoptosis-associated tyrosine kinase 1 (AATYK1), a novel serine/threonine kinase that is highly expressed in the brain, is involved in neurite extension and apoptosis of cerebellar granule neurons; however, its precise function remains unknown."
AATYK1A phosphorylation by Cdk5 regulates the recycling endosome pathway.
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In CHO-K1 cells, AATYK1A and its CDK5-site phosphomutants regulate the Rab11A-positive pericentrosomal recycling-endosome compartment without detectable direct AATYK1A-Rab11A binding.
"Although no direct interaction between AATYK1A and Rab11A could be detected, the exchange of guanine nucleotides bound to Rab11A was significantly reduced in the presence of the phosphorylation-mimic AATYK1A-S34D."
LMTK1/AATYK1 is a novel regulator of axonal outgrowth that acts via Rab11 in a Cdk5-dependent manner.
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Mouse cortical-neuron knockdown/knockout and rescue experiments show that LMTK1 restrains axon elongation by regulating Rab11A-positive endosome dynamics downstream of CDK5.
"Thus, LMTK1 can negatively control axonal outgrowth by regulating Rab11A activity in a Cdk5-dependent manner, and Cdk5-LMTK1-Rab11 is a novel signaling pathway involved in axonal outgrowth."
LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.
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Mouse cortical-neuron and in-vivo knockout experiments show that LMTK1 restrains dendrite growth and branching by modulating Rab11A-positive endosome movement downstream of CDK5.
"Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth."
The LMTK1-TBC1D9B-Rab11A Cascade Regulates Dendritic Spine Formation via Endosome Trafficking.
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Mouse neuron and brain perturbations place TBC1D9B between LMTK1 and Rab11A in a pathway that restrains dendritic-spine formation, maturation, and density.
"Depletion of LMTK1 increases spine formation, maturation, and density in primary cultured neurons and in mouse brain of either sex."