CUB and Sushi multiple domains 1 (CSMD1)

CSMD1 (CUB and Sushi multiple domains 1) is an unusually large transmembrane protein containing alternating CUB and Sushi (also known as CCP, complement control protein) domains; specifically, it comprises 14 N-terminal CUB domains interspersed with Sushi domains, followed by an additional 15 Sushi domains at the C-terminus[1][2]. CSMD1 is expressed at high levels in the brain and is involved in inhibiting the classical and lectin pathways of complement activation by promoting factor I–mediated degradation of C4b and C3b and blocking the membrane attack complex (MAC) formation[2][4]. CSMD1 has a tumor-suppressor function in several cancers, with loss or reduction promoting cell migration, invasion, and carcinogenesis[1][5]. In the CNS, CSMD1 regulates synaptic pruning and neurodevelopment, and genetic variants are associated with increased risk for schizophrenia, intellectual disability, autism, and other neuropsychiatric diseases[3][4]. CSMD1’s levels in serum and mRNA have shown promise as biomarkers for psychosis and cancer prognosis[3]. Overall, CSMD1 is a multifunctional transmembrane complement regulator with emerging roles in immunology, neurodevelopment, and oncology.

Other names

CSMD1PPP1R24CUB and Sushi domain-containing protein 1

Mechanisms involve inhibition of complement protein deposition and assembly, notably Factor I–mediated degradation of C3b and C4b, and inhibition of membrane attack complex (MAC) formation at C7