CDGSH iron-sulfur domain-containing protein 2 (CISD2)
The protein contains 135 amino acids for an estimated molecular weight of 15278 Da.
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. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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The reference OMIM entry for this protein is 604928
Wolfram syndrome 2; wfs2
A number sign (#) is used with this entry because Wolfram syndrome-2 (WFS2) is caused by homozygous mutation in the CISD2 gene (611507) on chromosome 4q24.
DESCRIPTION
Wolfram syndrome-2 is an autosomal recessive neurodegenerative disorder characterized by diabetes mellitus, high frequency sensorineural hearing loss, optic atrophy or neuropathy, and defective platelet aggregation resulting in peptic ulcer bleeding (summary by Mozzillo et al., 2014). For a discussion of genetic heterogeneity of Wolfram syndrome, see WFS1 (222300).CLINICAL FEATURES
El-Shanti et al. (2000) reported 16 individuals from 4 consanguineous Jordanian families with a phenotype consistent with Wolfram syndrome. The patients developed diabetes mellitus in the first or second decade, followed by visual loss due to optic atrophy in all patients, and high frequency sensorineural hearing loss in all except 2 patients. Eight patients had urinary tract dilatation. Several patients had profound upper gastrointestinal ulceration and bleeding. None of the patients developed diabetes insipidus. In a follow-up of 3 of the families reported by El-Shanti et al. (2000), Amr et al. (2007) noted that 1 of the patients had depression resulting in suicide and that several additional patients had developed symptomatic hearing loss. Mozzillo et al. (2014) reported a 17-year-old Caucasian girl, born of unrelated Italian parents, with WFS2. She presented with recurrent bleeding upper intestinal ulcers at age 5 years. At age 16, she had reduced visual acuity associated with optic neuropathy, but not optic atrophy. At age 17, she developed diabetes mellitus, and was also found to have bilateral sensorineural hearing loss affecting high frequencies. Laboratory studies showed defective platelet aggregation in response to ADP. Mozzillo et al. (2014) suggested that the patients reported by El-Shanti et al. (2000) may have had optic neuropathy rather than optic atrophy.INHERITANCE
The transmission pattern in the families with WFS2 reported by El-Shanti et al. (2000) was consistent with autosomal recessive inheritance.MAPPING
With the use of 3 microsatellite markers reported to be linked to the 4p16.1 locus, El-Shanti et al. (2000) excluded linkage in 3 of the 4 families. Two affected individuals in 1 family showed homozygosity for all 3 markers from the region of linkage on 4p16.1. For the other 3 families, genetic heterogeneity for Wolfram syndrome was verified with demonstration of linkage to 4q22-q24.MOLECULAR GENETICS
In affected members of 3 consanguineous families of Jordanian descent with Wolfram syndrome studied by El-Shanti et al. (2000), Amr et al. (2007) identified a homozygous truncating mutation in the CISD2 gene (611507.0001). The CISD2-encoded protein, ERIS (endoplasmic reticulum intermembrane small protein), localizes to the endoplasmic reticulum. In a 17-year-old Caucasian girl, born of unrelated Italian parents, with WFS2, Mozzillo et al. (2014) identified a homozygous intragenic deletion in the CISD2 gene (611507.0002).ANIMAL MODEL
Chen et al. (2009) provided evidence that the Cisd2 gene is involved in mammalian life span control. In mice, Cisd2 was primarily localized to the mitochondria and associated with the outer mitochondrial membrane. Cisd2-null mice showed early senescence and shortened life span compared to wildtype mice. Features included prominent eyes, protruding ears, corneal opacities and de ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604928 was added.
Sept. 16, 2015: Protein entry updated
Automatic update: model status changed