Coiled-Coil Domain-Containing (CCDC) Proteins: Functional Roles in General and Male Reproductive Physiology

Growth Traits and Sperm Proteomics Analyses of Myostatin Gene-Edited Chinese Yellow Cattle

“…Functional defects for the WDR78 cause complete inability to assemble the axoneme in vertebrates and results in infertility [ 49 ]. Coiled-coil domain-containing proteins play important roles in cilia- and flagella-associated functions, and the proven genes are CCDC9 , CCDC39 , CCDC42 , CCDC63 , CCDC113 , CCDC135 , CCDC147 , CCDC151 , CCDC181 and CCDC189 [ 51 ]. The testis-enriched CCDC42 performs essential functions in connecting the sperm flagella and sperm head.…”

“…The testis-specific serine/threonine kinase (TSSK) has been demonstrated to play essential roles in spermatogenesis, such as TSSK1b , TSSK2 , and TSSK4 encode kinases regulating sperm motility and fertility [ 53 ]. The gene TSSK4 has proven to be essential for maintaining the structural integrity of sperm flagellum, and TSSK4 -KO mice exhibit an impaired sperm structure and reduced sperm motility, which affects fertility [ 51 ], and up-regulated TSSK4 can restore fertility of male mice [ 54 ]. One novel protein kinase A-phosphorylated calcium-binding protein, FSCB, has a temporal appearance during spermatogenesis and is located at the cortex of the fibrous sheath, involved in late steps of fibrous sheath biogenesis [ 55 ].…”

Bi-allelic variants in DNHD1 cause flagellar axoneme defects and asthenoteratozoospermia in humans and mice

“…28 Previous studies have shown that CCDC proteins are implicated in sperm flagellum formation and movement, and several CCDC gene defects result in male infertility due to the abnormalities in flagella assembly. 13,14,29 For example, testis-enriched CFAP58 (also termed CCDC147) plays a vital role in sperm flagellogenesis, and CFAP58 deficiency causes infertility in humans and mice with abnormalities in both axonemes and peri-axonemes. 13 Therefore, DNHD1, which belongs to the CCDC family and is highly expressed in the testis, is thought to be essential for the normal function of flagellar axonemes, and defects in DNHD1 may be responsible for severe asthenoteratozoospermia.…”

The tumour suppressor CCDC6 is involved in ROS tolerance and neoplastic transformation by evading ferroptosis

“…Further, spermatozoa are subjected to enormous oxidative stress during their development, and the role of CCDC6 protein in protecting DNA integrity in these cells is emerging. Nevertheless, functional roles in reproductive physiology and pathology ascribed to the family of proteins containing a coiled-coil domain (CCDC) has been recently reviewed [59].…”