Function
Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.
Gene References into Functions
- CDGSH iron-sulfur domain-containing protein 2 (CISD2) Wolfram syndrome type 2 (WFS2) primary fibroblast cell lines showed consistent reduction in proliferation. PMID: 29239282
- CISD2 haploinsufficiency disrupts calcium homeostasis, causing ER stress and subsequent nonalcoholic fatty liver disease and nonalcoholic steatohepatitis PMID: 29166610
- CISD2 was increased in glioma samples and was associated with poor prognosis and aggressive tumor behavior. The miR449a/CISD2/beclin1mediated autophagy regulatory network contributed to the proliferation of glioma cells PMID: 28983596
- CISD2 is down-regulated in gastric cancer, and its effects on the inhibition of cellular proliferation, metastatic ability, and increased chemotherapy sensitivity are mediated by antagonism to 5-FU-induced autophagy through the AKT/mTOR pathway. PMID: 28857517
- The c.103 + 1G > A mutation resulted in the loss of functional CISD2 protein in the two Italian Wolfram syndrome type 2 patients. PMID: 29237418
- CISD2 was up-regulated in laryngeal squamous cell carcinoma PMID: 27007153
- CISD2 could be an independent prognostic factor for PC and suggested that the CISD2/Wnt/beta-catenin pathway contributed to the proliferation of PC and EMT PMID: 27983920
- the patient that we describe in this report with the c.215A > G missense CISD2 variant had the classical features of Wolfram syndrome type 1. The c.215A > G (p.Asn72Ser) variant does not induce CISD2 RNA mis-splicing or a reduction in CISD2 protein levels. Thus, we report a novel missense homozygous CISD2 mutation in a patient with clinical features that differ from previously reported Wolfram syndrome 2 case reports. PMID: 28335035
- CISD2 exerts anti-apoptotic and anti-inflammatory effects in neural cells; and (2) curcumin can attenuate the downregulation of CISD2 in SCI and LPS-treated astrocytes. PMID: 26387034
- CISD2 protein may serve as a candidate prognostic marker and a novel therapeutic target for hepatocellular carcinoma (HCC) and play an important role in promoting proliferation and enhanced progression of HCC. PMID: 26722601
- The findings suggested that CISD2 haplotype-tagging single nucleotide polymorphisms are not associated with Alzheimer's disease risk. PMID: 26154755
- NAF-1 is a BCL-2-associated co-factor that targets BCL-2 for antagonism of the autophagy pathway at the endoplasmic reticulum. PMID: 20010695
- NAF-1 as a previously unidentified cell target of anti-diabetes thiazolidinedione drugs. PMID: 23717386
- provides the first structural information, to our knowledge, for future targeting of the NAF-1-Bcl-2 complex in the regulation of apoptosis/autophagy in cancer biology PMID: 24706857
- High CISD2 expression was significantly associated with gastric cancer. PMID: 26565812
- NAF-1 is a major player in the metabolic regulation of breast cancer cells. PMID: 26621032
- A novel CISD2 mutation is associated with wolfram syndrome 2. PMID: 25371195
- Studied the expression pattern and clinicopathological significance of CISD2 in patients with early-stage cervical cancer. PMID: 25134919
- Data show that the protein levels of NAF-1 (CISD2) and mNT (CISD1) are elevated in human epithelial breast cancer cells. PMID: 23959881
- CISD2 has a role in lifespan control and disease [review] PMID: 20649540
- Novel mutation, new phenotypic variant with no diabetes insipidus, presence of peptic ulcer disease, platelet aggregation defect PMID: 14724730
- A single missense mutation was identified in a novel, highly conserved zinc-finger gene, ZCD2, in three consanguineous families of Jordanian descent with Wolfram syndrome (WFS). PMID: 17846994
- The authors show that Miner1 is a homodimer harboring two redox-active 2Fe-2S clusters, indicating for the first time an association of a redox-active FeS protein with Wolfram Syndrome 2. PMID: 19580816
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Involvement in disease
Wolfram syndrome 2 (WFS2)
Subcellular Location
Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion outer membrane; Single-pass membrane protein. Note=According to PubMed:20010695, it mainly localizes to the endoplasmic reticulum. However, experiments in mouse showed that it mainly localizes to the mitochondrion outer membrane.
Protein Families
CISD protein family, CISD2 subfamily
Tissue Specificity
Testis, small intestine, kidney, lung, brain, heart, pancreas and platelets.
