ATAT1

ATAT1
Name	Alpha-tubulin N-acetyltransferase 1
Other names	MEC-17
Organism	Homo sapiens
Length	~392 aa
Location	cytosol, microtubule lattice

ATAT1 ATAT1 is a human enzyme that acetylates alpha-tubulin and modifies microtubule stability and function. First characterized in studies involving Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster, ATAT1 orthologs were later identified in mammalian systems through work involving groups at Harvard University, MIT, and the Max Planck Society. Its discovery connected cytoskeletal regulation to cellular processes studied at institutions such as Cold Spring Harbor Laboratory, Johns Hopkins University, and Stanford University.

Function

ATAT1 catalyzes Nε-acetylation of lysine 40 on alpha-tubulin within the microtubule lumen, a modification implicated in microtubule stability and interaction with motors and MAPs. Early functional insights emerged from comparative studies by teams at University of Cambridge, University of Oxford, and University of California, Berkeley, which linked acetylation to axonal transport phenotypes observed in models used at Columbia University, Yale University, and University of California, San Francisco. The enzyme modulates processes investigated in research on Alzheimer's disease, Parkinson's disease, and Huntington's disease models and has been examined alongside proteins studied at National Institutes of Health and European Molecular Biology Laboratory laboratories.

Structure and Biochemistry

The ATAT1 polypeptide contains an acetyltransferase domain related to GCN5-like N-acetyltransferases characterized in structural work at Karolinska Institute, ETH Zurich, and Princeton University. Crystallography and cryo-EM collaborations with teams from University of Chicago, Weizmann Institute of Science, and University of Toronto revealed features responsible for substrate recognition and catalytic activity. Biochemical assays performed in labs at Imperial College London, University of Pennsylvania, and University of Michigan showed specificity for the lumenal K40 residue of alpha-tubulin and enzymatic kinetics comparable to acetyltransferases studied at Massachusetts General Hospital and Scripps Research. Comparative sequence analyses referencing databases curated by European Bioinformatics Institute and National Center for Biotechnology Information highlighted conserved motifs shared with enzymes investigated at Cold Spring Harbor Laboratory and Max Planck Institute for Biochemistry.

Regulation and Expression

ATAT1 expression and activity are regulated transcriptionally and post-translationally in tissues profiled by consortia such as ENCODE and GTEx. Transcriptional control elements identified by groups at Broad Institute and Wellcome Trust Sanger Institute correlate ATAT1 expression with neuronal and ciliated tissues examined at Mayo Clinic and Cleveland Clinic. Post-translational regulation via phosphorylation, ubiquitination, and autoregulation was reported in studies from University of California, Davis, Duke University, and University of Edinburgh, aligning with signaling pathways studied at Howard Hughes Medical Institute and Laboratory of Molecular Biology. Developmental and tissue-specific patterns were characterized using model organisms routinely used at Cold Spring Harbor Laboratory and EMBL-EBI.

Biological Roles and Phenotypes

ATAT1-mediated acetylation influences neuronal morphology, axonogenesis, and ciliary function; phenotypes have been documented in genetic studies from Broad Institute, Sanger Institute, and labs at University College London. Loss-of-function models produced defects in axonal transport studied at Massachusetts Institute of Technology and synaptic physiology examined at Rockefeller University. Roles in mechanotransduction and cell migration were described in research from University of Cambridge, Stanford University School of Medicine, and Yale School of Medicine. Phenotypic overlaps with ciliopathies and neurodegenerative models were explored in collaborations with Children's Hospital of Philadelphia and Robert Wood Johnson Medical School.

Clinical Significance

Alterations in ATAT1 activity have been associated with neurodegenerative conditions and peripheral neuropathies investigated at Mayo Clinic and Johns Hopkins Hospital. Its role in modulating microtubule-based transport has implications for therapies developed at Genentech, Pfizer, and academic translational programs at UCL and Karolinska University Hospital. ATAT1-related pathways intersect with chemotherapy response mechanisms studied at MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center, where microtubule-targeting agents such as those developed by Roche and Bristol-Myers Squibb are central. Biomarker and therapeutic investigations have involved consortia including Cancer Research UK and the European Medicines Agency.

Interactions and Pathways

ATAT1 acts on alpha-tubulin within microtubules and influences interactions with motor proteins like kinesins and dyneins characterized at Max Planck Institute for Molecular Cell Biology and Genetics and University of California, San Diego. It functionally interfaces with MAPs such as tau, MAP2, and MAP4 examined at University of Toronto and Columbia University Medical Center. ATAT1 activity is integrated into cytoskeletal regulatory networks involving the Rho family pathways and kinases studied at Memorial Sloan Kettering Cancer Center and Institut Curie. Proteomic interaction maps from labs at European Molecular Biology Laboratory and Broad Institute place ATAT1 within complexes relevant to intraflagellar transport researched at Woods Hole Oceanographic Institution and Scripps Institution of Oceanography.

Category:Human proteins