May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy. Homodimer or homooligomer. Interacts with DNM2, EPS15, clathrin, the adapter protein complex 2/AP-2 and TFRC. Interacts with the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD; the interaction is most probably direct, preferentially occurs with their inactive GDP-bound form and is negatively regulated by amino acids. (Microbial infection) Interacts with molluscum contagiosum virus protein MC159L; this interaction is important for the suppression of autophagy. Specifically associated with transferrin receptor-containing clathrin-coated pits and clathrin-coated vesicles. May also localize to the nucleus. Expressed in all tissues tested with higher expression in pancreas. Expressed by retinal pigment epithelial cells (at protein level). The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1. Phosphorylated upon EGF stimulation. Phosphorylation prevents interaction with DNM2. Overexpression or depletion of SH3BP4 result in a specific decrease of the transferrin receptor endocytosis that can be rescued by DNM2 overexpression. Dubious isoform produced through aberrant splice sites.