DNA dC->dU-editing enzyme APOBEC-3B (APOBEC3B)
The protein contains 382 amino acids for an estimated molecular weight of 45924 Da.
DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. (updated: Dec. 11, 2019)
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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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:rs2076109 | |
| dbSNP:rs2076110 | |
| dbSNP:rs17000697 | |
| dbSNP:rs5995649 | |
| dbSNP:rs1053813 |
No binding partner found
The reference OMIM entry for this protein is 607110
Apolipoprotein b mrna-editing enzyme, catalytic polypeptide-like 3b; apobec3b
Phorbolin 1-related protein
CLONING
Phorbolins-1 and -2 are highly expressed in psoriatic lesions. Treatment of normal keratinocytes with protein kinase C (PRKC; see 176960)-activating phorbol ester leads to the overexpression of both proteins. By comparing the sequence of phorbolin-1 (APOBEC3A; 607109) with other cDNAs isolated from a psoriatic epidermis cDNA expression library, Madsen et al. (1999) obtained a cDNA encoding phorbolin-1-related protein and at least 1 variant that uses an alternative AUG. The deduced 235-amino acid, 28-kD protein is 89% identical to phorbolin-1, with most differences at the N terminus. Like phorbolin-1, phorbolin-1-related protein contains an RNA-editing region but fails to bind apolipoprotein B (APOB; 107730) mRNA. Madsen et al. (1999) concluded that the phorbolin proteins do not manifest any of the functional properties ascribed to APOBEC1 (600130). By Northern blot analysis, Jarmuz et al. (2002) determined that APOBEC3B is expressed primarily in peripheral blood leukocytes, and it was detected in most tumor cell lines examined. Using RT-PCR, Bogerd et al. (2006) found that APOBEC3A was expressed only in peripheral blood leukocytes and spleen, whereas APOBEC3B was expressed at low levels in a wide range of somatic tissues and in undifferentiated human embryonic stem cell lines.GENE FUNCTION
Jarmuz et al. (2002) determined that recombinant APOBEC3B expressed in insect cells bound zinc and dimerized with APOBEC3G (607113), but not with APOBEC1. APOBEC3B did not edit APOB, NF1 (613113), or NAT1 (108345) mRNAs. Bogerd et al. (2006) found that APOBEC3A and APOBEC3B inhibited LINE-1 retrotransposition in HeLa cells. APOBEC3A and APOBEC3B also inhibited Alu mobility, which is mediated by the LINE-1 ORF2 protein. Burns et al. (2013) showed that the DNA cytosine deaminase APOBEC3B is a probable source of somatic C-to-T mutations in breast cancer (114480). APOBEC3B mRNA is upregulated in most primary breast tumors and breast cancer cell lines. Tumors that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53 (191170). Endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell line extracts. Knockdown experiments showed that endogenous APOBEC3B correlates with increased levels of genomic uracil, increased mutation frequencies, and C-to-T transitions. Furthermore, induced APOBEC3B overexpression caused cell cycle deviations, cell death, DNA fragmentation, gamma-H2AX (601772) accumulation, and C-to-T mutations. Burns et al. (2013) concluded that their data suggested a model in which APOBEC3B-catalyzed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explained how some tumors evolve rapidly and manifest heterogeneity. Following up on the report of Burns et al. (2013), which found that APOBEC3B accounts for up to half of the mutational load in breast carcinomas expressing this enzyme, Burns et al. (2013) addressed whether APOBEC3B is broadly responsible for mutagenesis in multiple tumor types. They analyzed gene expression data and mutation patterns, distributions, and loads for 19 different cancer types, with over 4,800 exomes and 1,000,000 somatic mutations. In at least 6 distinct cancers (bladder, cervix, lung adenocarcinoma, lung squamous cell carcinoma, head and neck, and breast), APOBEC3B is upr ... More on the omim web site
Jan. 22, 2020: 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 APOBEC3B
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607110 was added.