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 (By similarity). Mediates Notch-induced ubiquitination and degradation of substrates including TCF3/E2A and JAK2 (By similarity). Required during embryonic heart development for complete heart looping (PubMed:32179481). Required for cardiomyocyte differentiation (By similarity). Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA (PubMed:26343497). Also targets DES for proteasomal degradation (PubMed:26343497). Acts as a negative regulator of skeletal muscle mass (PubMed:27182554). Targets filamins FLNA and FLNB for proteasomal degradation (PubMed:23632887). This leads to enhanced adhesion of hematopoietic cells to fibronectin (By similarity). 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 (PubMed:29374072). 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 (PubMed:23632887). Does not promote proteasomal degradation of tyrosine-protein kinases JAK1 or JAK2 in hematopoietic cells (By similarity). Protein modification; protein ubiquitination. Component of a probable ECS E3 ubiquitin-protein ligase complex which contains CUL5, either RBX1 or RNF7/RBX2, Elongin BC complex (ELOB and ELOC) and ASB2. Interacts with SKP2. Through its interaction with SKP2, likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex. Interacts with JAK2; the interaction targets JAK2 for Notch-mediated proteasomal degradation. Interacts with TCF3/E2A; the interaction is mediated by SKP2 and targets TCF3 for Notch-mediated proteasomal degradation. Interacts with DES. Localizes to the Z line in cardiomyocytes. Highest expression in muscle, heart and spleen (PubMed:11111040). Highly expressed in cells of the first and second heart fields in the developing embryonic heart (PubMed:32179481). At 9.5 dpc, robust expression predominantly in the left and right ventricles (RV) and to a lower extent in inflow and outflow tracts (PubMed:32179481). At 10.5 and 11.5 dpc, expression is restricted to the myocardium with no expression observed in the endocardium (PubMed:32179481). Not expressed in immature dendritic cells (PubMed:23632887). Highly expressed in adult skeletal muscle with very low levels in adult bone marrow (PubMed:29374072). Expressed in immature dendritic cells and in primary dendritic cells derived from the spleen (PubMed:23632887). Highly expressed in adult bone marrow with negligible levels in adult skeletal muscle (PubMed:29374072). Expressed at higher levels in T helper type 2 (Th2) cells than in regulatory T (Treg) cells, type 1 helper T (Th1) cells and T helper 17 (Th17) cells (PubMed:31175139). Very low levels found in the developing heart at 9.5 dpc when isoform 2 is the predominant isoform (PubMed:29374072, PubMed:32179481). Expression increases from 11.5 dpc and is the predominant isoform in adult heart (PubMed:29374072, PubMed:32179481). Barely detectable in bone marrow cells but levels progressively increase as cells differentiate into immature dendritic cells and are down-regulated after dendritic cell maturation (PubMed:23632887). Highly expressed in the developing heart at 9.5 dpc when isoform 1 levels are very low (PubMed:29374072). Levels increase up to 11.5 dpc and fall in the adult heart (PubMed:29374072). Repressed by FST in 6-month-old mice but no effect is seen in 24-month-old mice (PubMed:27182554). Expression is increased 4-fold 3 days after denervation, becomes suppressed by approximately 75% 7 days after denervation, and eventually resolves to baseline by 28 days after denervation (PubMed:27182554). The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. Both the N-terminus and ANK repeats 1 to 10 are necessary for interaction with filamins. The UIM domain is required for monoubiquitination. Monoubiquitinated. Not monoubiquitinated. Phosphorylation at Ser-371 is required for association with FLNA and subsequent FLNA degradation. Embryonic lethality with death occurring in utero around 9.5 dpc (PubMed:29374072). Embryos display defects in vascular development and hematopoiesis and increased protein levels of Flna in the heart (PubMed:29374072). Conditional knockout in the whole heart and in the first heart field results in pericardial edema and embryonic lethality (PubMed:32179481). Conditional knockout in the embryonic heart results in impaired heart looping, abnormal expression of Flna expression which is expanded to include the myocardial layer and increased expression of Smad2 (PubMed:32179481). Conditional knockout in hematopoietic stem and progenitor cells results in increased protein levels of Flna and Flnb in immature dendritic cells (PubMed:23632887). Conditional knockout in hematopoietic cells reduces tumor development in a mouse model of colitis-associated tumorigenesis with reduced numbers of T helper type 2 (Th2) cells and regulatory T (Treg) cells and increased numbers of type 1 helper T (Th1) cells and T helper 17 (Th17) cells in the colonic mucosa of tumor-bearing mice (PubMed:31175139). Belongs to the ankyrin SOCS box (ASB) family. Truncated N-terminus.