Ankyrin repeat and SOCS box protein 2

Definition:

Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Mediates Notch-induced ubiquitination and degradation of substrates including TCF3/E2A and JAK2. Required during embryonic heart development for complete heart looping (By similarity). Required for cardiomyocyte differentiation.; [Isoform 1]: Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA. Also targets DES for proteasomal degradation (By similarity). Acts as a negative regulator of skeletal muscle mass (By similarity).; [Isoform 2]: Targets filamins FLNA and FLNB for proteasomal degradation. This leads to enhanced adhesion of hematopoietic cells to fibronectin. Required for FLNA degradation in immature cardiomyocytes which is necessary for actin cytoskeleton remodeling, leading to proper organization of myofibrils and function of mature cardiomyocytes (By similarity). Required for degradation of FLNA and FLNB in immature dendritic cells (DC) which enhances immature DC migration by promoting DC podosome formation and DC-mediated degradation of the extracellular matrix (By similarity). Does not promote proteasomal degradation of tyrosine-protein kinases JAK1 or JAK2 in hematopoietic cells.

References:

[1]. Junya Kohroki, et al. ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes. FEBS Lett. 2005 Dec 19;579(30):6796-802. [Content Brief]

[2]. Rim Zakaria, et al. Phosphorylation of serine 323 of ASB2α is pivotal for the targeting of filamin A to degradation. Cell Signal. 2013 Dec;25(12):2823-30. [Content Brief]

[3]. Lei Nie, et al. Notch-induced Asb2 expression promotes protein ubiquitination by forming non-canonical E3 ligase complexes. Cell Res. 2011 May;21(5):754-69. [Content Brief]

[4]. Abir Yamak, et al. Loss of Asb2 Impairs Cardiomyocyte Differentiation and Leads to Congenital Double Outlet Right Ventricle. iScience. 2020 Mar 27;23(3):100959. [Content Brief]

[5]. Isabelle Lamsoul, et al. Filamins but not Janus kinases are substrates of the ASB2α cullin-ring E3 ubiquitin ligase in hematopoietic cells. PLoS One. 2012;7(8):e43798. [Content Brief]

[6]. Isabelle Lamsoul, et al. Functional and structural insights into ASB2alpha, a novel regulator of integrin-dependent adhesion of hematopoietic cells. J Biol Chem. 2011 Sep 2;286(35):30571-30581. [Content Brief]

[7]. Mélina L Heuzé, et al. ASB2 is an Elongin BC-interacting protein that can assemble with Cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex. J Biol Chem. 2005 Feb 18;280(7):5468-74. [Content Brief]

[8]. N F Bello, et al. The E3 ubiquitin ligase specificity subunit ASB2beta is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death Differ. 2009 Jun;16(6):921-32. [Content Brief]

[9]. Ziba Razinia, et al. ASB2α, an E3 ubiquitin ligase specificity subunit, regulates cell spreading and triggers proteasomal degradation of filamins by targeting the filamin calponin homology 1 domain. J Biol Chem. 2013 Nov 1;288(44):32093-105. [Content Brief]

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