ALK4: Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine- threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C- terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2. ACVRIB is abundantly expressed in systemic sclerosis patient fibroblasts and production of collagen is also induced by activin-A/INHBA. This suggests that the activin/ACRV1B signaling mechanism is involved in systemic sclerosis. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily. 5 isoforms of the human protein are produced by alternative splicing.
Protein type: Protein kinase, TKL; Membrane protein, integral; Kinase, protein; EC 2.7.11.30; Protein kinase, Ser/Thr (receptor); TKL group; STKR family; Type1 subfamily
Chromosomal Location of Human Ortholog: 12q13
Cellular Component: cell surface; integral to plasma membrane; plasma membrane; activin receptor complex; receptor complex
Molecular Function: activin receptor activity; metal ion binding; transmembrane receptor protein serine/threonine kinase activity; transforming growth factor beta receptor activity; protein serine/threonine kinase activity; protein binding; activin receptor activity, type I; ubiquitin protein ligase binding; growth factor binding; activin binding; SMAD binding; ATP binding; receptor signaling protein serine/threonine kinase activity
Biological Process: development of primary female sexual characteristics; central nervous system development; in utero embryonic development; protein amino acid autophosphorylation; positive regulation of erythrocyte differentiation; peptidyl-threonine phosphorylation; activin receptor signaling pathway; signal transduction; protein amino acid phosphorylation; positive regulation of activin receptor signaling pathway; hair follicle development; regulation of transcription, DNA-dependent; transmembrane receptor protein serine/threonine kinase signaling pathway; positive regulation of transcription from RNA polymerase II promoter; negative regulation of cell growth; G1/S transition of mitotic cell cycle
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