InterPro domain: IPR045131

Proteins in this family contain the CDGSH-type zinc finger. Interestingly, they do not contain any zinc ions, but rather iron contained in a 2Fe-2S (iron–sulfur) cluster. The conserved sequence C-X-C-X(2)-(S/T)-X(3)-P-X-C-D-G-(S/A/T)-H is a defining feature of this unique family of proteins and is likely involved in iron binding [ 1 ]. They play an important part in the proliferation of breast cancer cells and tumour formation [ 2 ]. CISD1 (also known as mitoNEET) is a mitochondrial protein that plays an important part in mitochondrial bioenergetics. It also plays a part in insulin regulation, inflammation and autophagy [ 3 ]. CISD2 (also known as NAF-1) can be found in endoplasmic reticulum (ER) and mitochondrial outer membrane [ 4 ]. It regulates autophagy [ 5 ].

Mutations of the CISD2 gene cause Wolfram syndrome 2 (WFS2), a rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy [ 6 ].

1. MitoNEET is an iron-containing outer mitochondrial membrane protein that regulates oxidative capacity. Proc. Natl. Acad. Sci. U.S.A. 104, 5318-23
2. NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proc Natl Acad Sci U S A 110, 14676-81
3. mitoNEET as a novel drug target for mitochondrial dysfunction. Drug Discov Today 19, 1601-6
4. Nutrient-deprivation autophagy factor-1 (NAF-1): biochemical properties of a novel cellular target for anti-diabetic drugs. PLoS One 8, e61202
5. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet 81, 673-83