selenoproteins
Selenoproteins (SEPs), such as GPX6, contain the rare twenty-first amino acid, selenocysteine (sec). These proteins lack common amino acid sequence motifs, but the 3-prime untranslated regions of selenoprotein genes have a common stem-loop structure, the sec insertion sequence (SECIS), that is necessary for the recognition of UGA as a sec codon rather than as a stop signal.
Members (Exemples)
| SEPS1 | SEPX1 | SEPP1 | SEPW1 | SEPN1 | SEP | |
| SELB | SELI | SELO | SELV | SEPN1 | GPXs | SECISBP2 |
Deiodinases (DIOs) are selenoproteins involved in thyroid hormone metabolism. Because SBP2 is epistatic to selenoprotein synthesis, these defects had a generalized effect on selenoproteins. Incomplete loss of SBP2 function probably causes the mild phenotype.
Pathology
abnormal thyroid hormone metabolism (MIM.609698)
- Incorporation of selenocysteine (Sec), through recoding of the UGA stop codon, creates a unique class of proteins.
Animal models
Mice lacking tRNA(Sec) die in utero, but the in vivo role of other components involved in selenoprotein synthesis is unknown, and Sec incorporation defects have not been described in humans.
References
Dumitrescu AM, Liao XH, Abdullah MS, Lado-Abeal J, Majed FA, Moeller LC, Boran G, Schomburg L, Weiss RE, Refetoff S. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat Genet. 2005 Nov;37(11):1247-52. PMID: #16228000#
Curran JE, Jowett JB, Elliott KS, Gao Y, Gluschenko K, Wang J, Abel Azim DM, Cai G, Mahaney MC, Comuzzie AG, Dyer TD, Walder KR, Zimmet P, MacCluer JW, Collier GR, Kissebah AH, Blangero J. Genetic variation in selenoprotein S influences inflammatory response. Nat Genet. 2005 Nov;37(11):1234-41. PMID: #16227999#