2qlu: Difference between revisions
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{{STRUCTURE_2qlu| PDB=2qlu | SCENE= }} | {{STRUCTURE_2qlu| PDB=2qlu | SCENE= }} | ||
===Crystal structure of Activin receptor type II kinase domain from human=== | |||
{{ABSTRACT_PUBMED_17893364}} | |||
=== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/AVR2B_HUMAN AVR2B_HUMAN]] Defects in ACVR2B are the cause of visceral heterotaxy autosomal type 4 (HTX4) [MIM:[http://omim.org/entry/613751 613751]]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy type 4 include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.<ref>PMID:9916847</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/AVR2B_HUMAN AVR2B_HUMAN]] Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating 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, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). 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. 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.<ref>PMID:8622651</ref> | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID:017893364</ref><references group="xtra"/> | <ref group="xtra">PMID:017893364</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Receptor protein serine/threonine kinase]] | [[Category: Receptor protein serine/threonine kinase]] | ||
Revision as of 01:56, 25 March 2013
Crystal structure of Activin receptor type II kinase domain from humanCrystal structure of Activin receptor type II kinase domain from human
Template:ABSTRACT PUBMED 17893364
DiseaseDisease
[AVR2B_HUMAN] Defects in ACVR2B are the cause of visceral heterotaxy autosomal type 4 (HTX4) [MIM:613751]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy type 4 include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.[1]
FunctionFunction
[AVR2B_HUMAN] Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating 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, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). 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. 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.[2]
About this StructureAbout this Structure
2qlu is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Han S, Loulakis P, Griffor M, Xie Z. Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution. Protein Sci. 2007 Oct;16(10):2272-7. PMID:17893364 doi:16/10/2272
- ↑ Kosaki R, Gebbia M, Kosaki K, Lewin M, Bowers P, Towbin JA, Casey B. Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB. Am J Med Genet. 1999 Jan 1;82(1):70-6. PMID:9916847
- ↑ Attisano L, Wrana JL, Montalvo E, Massague J. Activation of signalling by the activin receptor complex. Mol Cell Biol. 1996 Mar;16(3):1066-73. PMID:8622651