ACVR2A

ACVR2A
source
Name	Activin receptor type-2A
Other names	ACTR-IIA
Chromosome	2q22
Organism	Human

ACVR2A is a human gene encoding Activin receptor type-2A, a transmembrane serine/threonine kinase that binds ligands of the transforming growth factor beta superfamily and initiates intracellular signaling. The protein participates in developmental and homeostatic processes conserved across metazoans and is studied in contexts ranging from embryogenesis to cancer biology. ACVR2A research intersects with studies at institutions such as National Institutes of Health, Harvard University, Stanford University, and collaborations visible in consortia like the Human Genome Project and the 1000 Genomes Project.

Structure and Function

The receptor protein comprises an extracellular ligand-binding domain, a transmembrane helix, and an intracellular kinase domain homologous to other type II receptors characterized in structural studies by groups at Max Planck Society and Cold Spring Harbor Laboratory. Crystallography and cryo-EM efforts from teams affiliated with University of Cambridge and Massachusetts Institute of Technology revealed conserved motifs aligning with receptors studied in work from Yale University and University of Oxford. Functional assays developed at Johns Hopkins University and University of California, San Francisco show that the type II receptor phosphorylates type I receptors in complexes described in reviews from Cell Press and Nature Publishing Group. Biochemical mapping by researchers at European Molecular Biology Laboratory and Cold Spring Harbor Laboratory demonstrated ATP-binding pocket conservation similar to kinases characterized by Francis Crick Institute investigators.

Expression and Regulation

Expression analyses using datasets from ENCODE Project and GTEx indicate tissue-specific ACVR2A mRNA profiles in organs studied at centers like Mayo Clinic and Cleveland Clinic. Regulatory mechanisms involving promoter elements were examined in collaborations with University of Pennsylvania and Karolinska Institute, while microRNA targeting and epigenetic modulation were reported in studies from Dana-Farber Cancer Institute and Stanford University School of Medicine. Transcription factor occupancy mapped by laboratories at University of California, Berkeley and Massachusetts General Hospital links receptor expression to developmental regulators characterized in work at Princeton University and University College London.

Signaling Pathways and Interactions

ACVR2A participates in canonical SMAD signaling networks elucidated by foundational labs at University of California, San Diego and University of Michigan; ligand binding leads to recruitment and phosphorylation of type I receptors, propagating signals through receptor-regulated SMADs explored in publications from Rockefeller University and Scripps Research. Non-SMAD pathways intersecting with MAPK and PI3K cascades were investigated by groups at Imperial College London and Northwestern University, and protein–protein interaction maps from BioGRID and STRING Consortium incorporate data from studies at Broad Institute and European Bioinformatics Institute. Ligands such as activins and inhibins studied by researchers at University of Copenhagen and University of Texas MD Anderson Cancer Center show differential affinity influencing downstream effectors characterized by teams at Fred Hutchinson Cancer Research Center.

Role in Development and Physiology

Functional genetics using model organisms investigated at University of Cambridge and Harvard Medical School demonstrate roles in mesoderm formation and reproductive system development referenced alongside classic work from Howard Hughes Medical Institute investigators. Physiological roles in muscle mass regulation and fibrosis were delineated in preclinical studies from University of Edinburgh and Karolinska Institutet, while endocrine effects were evaluated in clinical research at Johns Hopkins Hospital and Mount Sinai Health System. Developmental timing and patterning associated with activin signaling echo findings from developmental biology labs at Stanford University and Columbia University.

Clinical Significance and Disease Associations

Alterations in the receptor pathway have been linked to pathologies investigated at cancer centers including Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center, with associations to colorectal and pancreatic tumors reported in cohort studies from Mayo Clinic and Dana-Farber Cancer Institute. Fibrotic diseases and metabolic disorders with receptor involvement were examined in translational programs at Cleveland Clinic and Vanderbilt University Medical Center. Therapeutic targeting strategies have been pursued in industry-academia partnerships involving companies such as Roche, Novartis, and AstraZeneca and reported in clinical trial registries maintained by World Health Organization and Food and Drug Administration collaborations.

Genetic Variants and Mutations

Population genetics analyses incorporating data from the 1000 Genomes Project, ExAC, and gnomAD catalog variants across cohorts assembled by consortia including UK Biobank and All of Us Research Program. Pathogenic mutations and polymorphisms identified in clinical genetics clinics at Mayo Clinic and research hospitals such as Boston Children's Hospital have been correlated with phenotypes in studies coordinated with American College of Medical Genetics and Genomics guidelines. Functional characterization of missense and truncating variants was performed in laboratories at Cold Spring Harbor Laboratory and Sanger Institute using models and assays developed at Max Planck Institute and Institut Pasteur.

Category:Human genes