ASB2
Domain
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes.
Isoform 2
Both the N-terminus and ANK repeats 1 to 10 are necessary for interaction with filamins.
Isoform 1
The UIM domain is required for monoubiquitination.
Function
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 (PubMed:15590664, PubMed:16325183). Mediates Notch-induced ubiquitination and degradation of substrates including TCF3/E2A and JAK2 (PubMed:21119685). Required during embryonic heart development for complete heart looping (By similarity). Required for cardiomyocyte differentiation (PubMed:32179481).
Isoform 1
Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA (PubMed:19300455). 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 (PubMed:21737450, PubMed:22916308, PubMed:24044920, PubMed:24052262). This leads to enhanced adhesion of hematopoietic cells to fibronectin (PubMed:21737450). 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 (PubMed:22916308).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Isoform 1
Monoubiquitinated.
Isoform 2
Not monoubiquitinated.
Isoform 2
Phosphorylation at Ser-371 is required for association with FLNA and subsequent FLNA degradation.
Sequence Similarities
Belongs to the ankyrin SOCS box (ASB) family.
Tissue Specificity
Isoform 1
Expressed in muscle cells.
Isoform 2
Expressed in hematopoietic cells.
Cellular localization
- Cytoplasm
- Cytoskeleton
- Stress fiber
- Isoform 1
- Cytoplasm
- Myofibril
- Sarcomere
- Z line
- Localizes to the Z line in cardiomyocytes.
Alternative names
Ankyrin repeat and SOCS box protein 2, ASB-2, ASB2