C->U-editing enzyme APOBEC-2 (APOBEC2)
The protein contains 224 amino acids for an estimated molecular weight of 25703 Da.
Probable C to U editing enzyme whose physiological substrate is not yet known. Does not display detectable apoB mRNA editing. Has a low intrinsic cytidine deaminase activity. May play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation. (updated: Oct. 25, 2017)
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.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs2076472 |
No binding partner found
The reference OMIM entry for this protein is 604797
Apolipoprotein b mrna-editing enzyme, catalytic polypeptide-like 2; apobec2
Apobec1-like
CLONING
APOBEC1 (600130) is a member of the cytidine deaminase superfamily. By searching an EST database using the mouse Apobec1 amino acid sequence as the query, Liao et al. (1999) identified several human and mouse ESTs encoding polypeptides with sequence similarity to Apobec1, mainly in the region of the cytidine deaminase domain. Using 1 of the mouse ESTs to screen a human heart cDNA library, they isolated a cDNA encoding a protein that they named APOBEC2. The deduced APOBEC2 protein has 224 amino acids. Phylogenetic analysis of the cytidine deaminase superfamily based on the catalytic domains of the proteins indicated that APOBEC2 is evolutionarily closer to APOBEC1 than to the other members. Compared with APOBEC1, APOBEC2 has a longer N-terminal region and a shorter C-terminal region. Northern blot analysis showed that APOBEC2 was expressed exclusively in heart and skeletal muscle. APOBEC2 expression was not detected in brain, lung, liver, pancreas, small intestine, colon, kidney, spleen, thymus, leukocyte, testis, uterus, placenta, or prostate. By Northern, Western, and immunohistochemical analyses of mouse muscle, Sato et al. (2010) found that Apobec2 was expressed predominantly in slow muscle fibers. Apobec2 expression increased during late differentiation in neonatal mouse myoblasts and the C2C12 mouse myoblast cell line. Gel filtration of mouse gastrocnemius muscle revealed that Apobec2 formed a soluble tetramer.GENE FUNCTION
Liao et al. (1999) found that recombinant APOBEC2 had low, but definite, intrinsic cytidine deaminase activity in an in vitro assay. However, unlike APOBEC1, APOBEC2 did not recognize APOB (107730) mRNA as a substrate. Sato et al. (2010) showed that Apobec2 expression increased with denervation of mouse soleus and extensor digitorum longus muscle, which was accompanied by an increase in the proportion of slow muscle fibers. Unlike APOBEC1, Apobec2 did not bind RNA, which is a critical characteristic of RNA-editing enzymes.BIOCHEMICAL FEATURES
- Crystal Structure Prochnow et al. (2007) reported the crystal structure of APOBEC2. APOBEC2 forms a rod-shaped tetramer that differs markedly from the square-shaped tetramer of the free nucleotide cytidine deaminase (AID; 605257), with which APOBEC proteins share considerable sequence homology. In APOBEC2, 2 long alpha-helices of a monomer structure prevent the formation of a square-shaped tetramer and facilitate formation of the rod-shaped tetramer via head-to-head interaction of 2 APOBEC2 dimers. Extensive sequence homology among APOBEC family members allowed Prochnow et al. (2007) to test APOBEC2 structure-based predictions using AID. Prochnow et al. (2007) showed that AID deamination activity is impaired by mutations predicted to interfere with oligomerization and substrate access. The structure suggested how mutations in patients with hyper-IgM-2 syndrome (605258) inactivate AID, resulting in defective antibody maturation.MAPPING
By radiation hybrid mapping, Liao et al. (1999) mapped the human APOBEC2 gene to chromosome 6. Liao et al. (1999) mapped the mouse Apobec2 gene to chromosome 17, where it is located distal to D17Bir7 and proximal to D17Mit85. Based on the homology of synteny between this region of mouse chromosome 17 and human 6p21, Liao et al. (1999) concluded that the human APOBEC2 gene localizes to 6p21.ANIMAL MODEL
Sato et al. (2010) found that Apobec2 -/- mice were viable, appeared norma ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for APOBEC2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604797 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed