Sushi domain-containing protein 4 (SUSD4)

Sushi domain-containing protein 4 (SUSD4) is a cell surface transmembrane protein with four Sushi domains, encoded on human chromosome 1q41. SUSD4 is predominantly expressed in the central nervous system, particularly in the brain (oligodendrocytes, axons), spinal cord, eyes (photoreceptors), and testis[1][4]. It acts as a complement regulatory protein, modulating the alternative pathway by interacting with complement component C3b, influencing immune response and innate defense mechanisms[1][2]. In neurons, SUSD4 regulates the trafficking and degradation of GluA2-containing AMPA receptors, thereby controlling synaptic plasticity and learning[4]. SUSD4 has also been implicated as a tumor suppressor in cancer, partly through its ability to inhibit EGFR function (not phosphorylation-dependent), enhance autophagy via LKB1/AMPKα1 axis, and influence cancer cell proliferation[3]. Genetic loss or reduced expression of SUSD4 is associated with neurological disorders such as autism and Fryns syndrome, as well as poor prognosis in certain cancers[1][2][4]. No available drugs target SUSD4 directly as of now, but its expression may serve as a biomarker for patient prognosis in cancer[2][3].

Other names

SUSD4Sushi domain-containing protein 4UNQ196/PRO222FLJ10052PRO222YHGM196testicular secretory protein Li 55

Drugs (experimental) that modulate Sushi domain proteins may: Regulate complement activation at the C3 convertase step Influence autophagic flux and AMPKα1 pathway activation Inhibit EGFR function through direct interaction without affecting phosphorylation