Sperm-associated antigen 4 (SPAG4)

Sperm-associated antigen 4 (SPAG4), also known as SUN4, is a testis-specific structural protein and a member of the SUN domain family, localizing to the nuclear envelope of elongating spermatids, where it is crucial for correct sperm head formation and the anchoring and organization of the manchette, a transient microtubule structure in sperm development[1][3][4]. SPAG4 is a core component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, interfacing with proteins such as Nesprin3 and Odf1 to maintain nuclear envelope integrity and proper sperm head morphology[1][2][3][4]. Deficiency of SPAG4 leads to severe morphological abnormalities in sperm and male infertility[1][3]. Beyond testis, SPAG4 is upregulated in certain cancers, particularly lung and renal carcinomas, where it contributes to tumor cell migration and proliferation via interactions with components of the LINC complex, and may serve as a biomarker of disease presence and progression[2]. There are no known drugs directly targeting SPAG4, and its roles as a drug target or in therapeutic settings are mainly investigational.

Other names

Sad1 and UNC84 domain containing 4SUN4Outer dense fiber-associated protein SPAG4Cancer/testis antigen 127CT127Acrosomal protein ACR55SUN domain-containing protein 4Sperm tail protein SPAG4