APOBEC3 (Kr.22q13.1)A3A, ARP3, PHRBN, bK150C2.1

APOBEC3,  A3A,  

Tämän APOBEC3A:n  kyky muokata vierasta DNA:ta kuten   viruksia ja siten rajoittaa virusten transmissiota, mikä  tekee siitä tietysti  virusten vihollisen ja  evaasioyrityskohteen, joten  on luonnollista,  että tätä  A3A:a tavataan   sellaisissa maligniteeteissa, joissa on taustalla virusvaikutusta ja kroonisita virustulehdusta.  PubMed lähde ottaa esille  mm virukset CMV ja HPV. HPV onkin osallisena 5%:ssa kaikista maligniteeteistä. 

A3A  deaminoi spesifisesti C7mC ja  diskriminoi  ox-mC- muodot , joten ne eivät sanottavasti osallistu demetylaatioon ( niitä ovat  5-OH-metylsytosiini, 5-formylsytosiini, 5-karboksyylisytosiini).
parin viime vuoden aikana on tullut uutta tutkimustulosta . Suomennan seuraavaan artikkeliin  joitain kohtia löydöistä.  Tässä on  taustatietokooste. lähinnä Pubmed lähteestä " Gene ABOBEC3A".

https://www.ncbi.nlm.nih.gov/gene/200315

Also known as

A3A; ARP3; PHRBN; bK150C2.1

Summary

This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. The protein encoded by this gene lacks the zinc binding activity of other family members. The protein plays a role in immunity, by restricting transmission of foreign DNA such as viruses. One mechanism of foreign DNA restriction is deamination of foreign double-stranded DNA cytidines to uridines, which leads to DNA degradation. However, other mechanisms are also thought to be involved, as anti-viral effect is not dependent on deaminase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

Expression

Biased expression in bone marrow (RPKM 38.8), appendix (RPKM 13.8) and 5 other tissues See more

Related articles in PubMed

1. APOBEC3A Is Upregulated by Human Cytomegalovirus (HCMV) in the Maternal-Fetal Interface, Acting as an Innate Anti-HCMV Effector. Weisblum Y, et al. J Virol, 2017 Dec 1. PMID 28956761, Free PMC Article
2. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism. Chen TW, et al. Nat Commun, 2017 Sep 6. PMID 28878238, Free PMC Article
3. Cytosine Deaminase APOBEC3A Sensitizes Leukemia Cells to Inhibition of the DNA Replication Checkpoint. Green AM, et al. Cancer Res, 2017 Sep 1. PMID 28655787,
4. APOBEC3A efficiently deaminates methylated, but not TET-oxidized, cytosine bases in DNA. Schutsky EK, et al. Nucleic Acids Res, 2017 Jul 27. PMID 28472485, Free PMC Article
5. NMR-based method of small changes reveals how DNA mutator APOBEC3A interacts with its single-stranded DNA substrate. Harjes S, et al. Nucleic Acids Res, 2017 May 19. PMID 28369637, Free PMC Article
   

See all (93) citations in PubMed
See citations in PubMed for homologs of this gene provided b

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. direct evidence that both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex formed during HPV infection may regulate A3A protein levels in the cell.
2. review of current understanding of APOBEC3A and APOBEC3B biology in human papillomavirus Infection restriction, evolution, and associated cancer mutagenesis
3. p53 activation alters APOBECA3 gene regulation.Activated p53 binds transcriptional regulatory regions of APOBECA3 gene.
4. These results highlight the fundamental impact of APOBEC3A overexpression on human transcriptome by widespread RNA editing.
5. High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles in Taiwanese oral squamous cell carcinoma patients.
6. Our study demonstrates that 20% of C-->T and C-->G mutations in the TpCpW context-where W denotes A or T, segregating as polymorphisms in human population-or 1.4% of all heritable mutations are attributable to APOBEC3A/B activity.
7. findings reveal the role of A3A as a potent anti-Human cytomegalovirus (HCMV) innate barrier, activated by HCMV infection in the authentic tissues of the maternal-fetal interface. These findings pave the way to new insights into the potential impact of APOBEC proteins on HCMV pathogenesis.
8. APOBEC3A/B and HLA-DQA1 are powerful biomarkers for systemic sclerosis risk evaluation and contribute to the susceptibility to systemic sclerosis.
9. High APOBEC3A expression is associated with acute myelogenous leukemia.
10. Steady-state kinetic analysis reveals that APOBEC3A (A3A) discriminates against all ox-mCs by 3700-fold, arguing that ox-mC deamination does not contribute substantially to demethylation. A3A is, by contrast, highly proficient at C/mC deamination.
    

Preferred Names

DNA dC->dU-editing enzyme APOBEC-3A

Names

apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A

phorbolin-1

probable DNA dC->dU-editing enzyme APOBEC-3A

Conserved Domains (3) summary

cd01283
Location:10 → 102

cytidine_deaminase; Cytidine deaminase zinc-binding domain. These enzymes are Zn dependent. The zinc ion in the active site plays a central role in the proposed catalytic mechanism, activating a water molecule to form a hydroxide ion that performs a nucleophilic attack on ...

pfam05240
Location:116 → 161

APOBEC_C; APOBEC-like C-terminal domain

pfam08210
Location:10 → 173

APO

Peptide and history of isoform b

https://www.ncbi.nlm.nih.gov/protein/NP_001257335.1

DNA dC->dU-editing enzyme APOBEC-3A isoform b [Homo sapiens]

NCBI Reference Sequence: NP_001257335.1
Identical Proteins FASTA Graphics

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LOCUS       NP_001257335             181 aa            linear   PRI 23-APR-2018
DEFINITION  DNA dC->dU-editing enzyme APOBEC-3A isoform b [Homo sapiens].
ACCESSION   NP_001257335
VERSION     NP_001257335.1
DBSOURCE    REFSEQ: accession NM_001270406.1
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 181)
  AUTHORS   Westrich JA, Warren CJ, Klausner MJ, Guo K, Liu CW, Santiago ML and
            Pyeon D.
  TITLE     Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by
            Inhibiting Cullin 2-Dependent Protein Degradation
  JOURNAL   J. Virol. 92 (7), e01318-17 (2018)
   PUBMED   29367246
  REMARK    GeneRIF: direct evidence that both A3A and HPV16 E7 interact with
            CUL2, suggesting that the E7-CUL2 complex formed during HPV
            infection may regulate A3A protein levels in the cell.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 181)
  AUTHORS   Weisblum Y, Oiknine-Djian E, Zakay-Rones Z, Vorontsov O,
            Haimov-Kochman R, Nevo Y, Stockheim D, Yagel S, Panet A and Wolf
            DG.
  TITLE     APOBEC3A Is Upregulated by Human Cytomegalovirus (HCMV) in the
            Maternal-Fetal Interface, Acting as an Innate Anti-HCMV Effector
  JOURNAL   J. Virol. 91 (23), e01296-17 (2017)
   PUBMED   28956761
  REMARK    GeneRIF: findings reveal the role of A3A as a potent anti-Human
            cytomegalovirus (HCMV) innate barrier, activated by HCMV infection
            in the authentic tissues of the maternal-fetal interface. These
            findings pave the way to new insights into the potential impact of
            APOBEC proteins on HCMV pathogenesis.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 181)
  AUTHORS   Chen TW, Lee CC, Liu H, Wu CS, Pickering CR, Huang PJ, Wang J,
            Chang IY, Yeh YM, Chen CD, Li HP, Luo JD, Tan BC, Chan TEH, Hsueh
            C, Chu LJ, Chen YT, Zhang B, Yang CY, Wu CC, Hsu CW, See LC, Tang
            P, Yu JS, Liao WC, Chiang WF, Rodriguez H, Myers JN, Chang KP and
            Chang YS.
  TITLE     APOBEC3A is an oral cancer prognostic biomarker in Taiwanese
            carriers of an APOBEC deletion polymorphism
  JOURNAL   Nat Commun 8 (1), 465 (2017)
   PUBMED   28878238
  REMARK    GeneRIF: High-level APOBEC3A expression is associated with better
            overall survival, especially among patients carrying
            APOBEC3B-deletion alleles in Taiwanese oral squamous cell carcinoma
            patients.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 181)
  AUTHORS   Green AM, Budagyan K, Hayer KE, Reed MA, Savani MR, Wertheim GB and
            Weitzman MD.
  TITLE     Cytosine Deaminase APOBEC3A Sensitizes Leukemia Cells to Inhibition
            of the DNA Replication Checkpoint
  JOURNAL   Cancer Res. 77 (17), 4579-4588 (2017)
   PUBMED   28655787
  REMARK    GeneRIF: High APOBEC3A expression is associated with acute
            myelogenous leukemia.
REFERENCE   5  (residues 1 to 181)
  AUTHORS   Warren CJ, Westrich JA, Doorslaer KV and Pyeon D.
  TITLE     Roles of APOBEC3A and APOBEC3B in Human Papillomavirus Infection
            and Disease Progression
  JOURNAL   Viruses 9 (8), E233 (2017)
   PUBMED   28825669
  REMARK    GeneRIF: review of current understanding of APOBEC3A and APOBEC3B
            biology in human papillomavirus Infection restriction, evolution,
            and associated cancer mutagenesis
            Review article
            Publication Status: Online-Only
REFERENCE   6  (residues 1 to 181)
  AUTHORS   Kidd JM, Newman TL, Tuzun E, Kaul R and Eichler EE.
  TITLE     Population stratification of a common APOBEC gene deletion
            polymorphism
  JOURNAL   PLoS Genet. 3 (4), e63 (2007)
   PUBMED   17447845
REFERENCE   7  (residues 1 to 181)
  AUTHORS   Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J and
            Navaratnam N.
  TITLE     An anthropoid-specific locus of orphan C to U RNA-editing enzymes
            on chromosome 22
  JOURNAL   Genomics 79 (3), 285-296 (2002)
   PUBMED   11863358
REFERENCE   8  (residues 1 to 181)
  AUTHORS   Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE,
            Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida
            JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O,
            Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD,
            O'Brien KP et al.
  TITLE     The DNA sequence of human chromosome 22
  JOURNAL   Nature 402 (6761), 489-495 (1999)
   PUBMED   10591208
  REMARK    Erratum:[Nature 2000 Apr 20;404(6780):904]
REFERENCE   9  (residues 1 to 181)
  AUTHORS   Madsen P, Anant S, Rasmussen HH, Gromov P, Vorum H, Dumanski JP,
            Tommerup N, Collins JE, Wright CL, Dunham I, MacGinnitie AJ,
            Davidson NO and Celis JE.
  TITLE     Psoriasis upregulated phorbolin-1 shares structural but not
            functional similarity to the mRNA-editing protein apobec-1
  JOURNAL   J. Invest. Dermatol. 113 (2), 162-169 (1999)
   PUBMED   10469298
REFERENCE   10 (residues 1 to 181)
  AUTHORS   Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE and
            Vandekerckhove J.
  TITLE     Microsequences of 145 proteins recorded in the two-dimensional gel
            protein database of normal human epidermal keratinocytes
  JOURNAL   Electrophoresis 13 (12), 960-969 (1992)
   PUBMED   1286667
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI029063.1, BC144146.1 and
            AL022318.2.
            
            Summary: This gene is a member of the cytidine deaminase gene
            family. It is one of seven related genes or pseudogenes found in a
            cluster, thought to result from gene duplication, on chromosome 22.
            Members of the cluster encode proteins that are structurally and
            functionally related to the C to U RNA-editing cytidine deaminase
            APOBEC1. The protein encoded by this gene lacks the zinc binding
            activity of other family members. The protein plays a role in
            immunity, by restricting transmission of foreign DNA such as
            viruses. One mechanism of foreign DNA restriction is deamination of
            foreign double-stranded DNA cytidines to uridines, which leads to
            DNA degradation. However, other mechanisms are also thought to be
            involved, as anti-viral effect is not dependent on deaminase
            activity. Two transcript variants encoding different isoforms have
            been found for this gene. [provided by RefSeq, Jul 2012].
            
            Transcript Variant: This variant (3) uses an alternate in-frame
            splice site at the 5' end of a coding exon compared to variant 1.
            The resulting isoform (b) has the same N- and C-termini but is
            shorter compared to isoform a.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC144146.1, KM266647.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2142670, SAMEA2149398
                                           [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..181
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q13.1"
     Protein         1..181
                     /product="DNA dC->dU-editing enzyme APOBEC-3A isoform b"
                     /note="probable DNA dC->dU-editing enzyme APOBEC-3A;
                     phorbolin-1; apolipoprotein B mRNA editing enzyme,
                     catalytic polypeptide-like 3A"
                     /calculated_mol_wt=20829
     Region          10..173
                     /region_name="APOBEC_N"
                     /note="APOBEC-like N-terminal domain; pfam08210"
                     /db_xref="CDD:285428"
     Region          10..102
                     /region_name="cytidine_deaminase"
                     /note="Cytidine deaminase zinc-binding domain. These
                     enzymes are Zn dependent. The zinc ion in the active site
                     plays a central role in the proposed catalytic mechanism,
                     activating a water molecule to form a hydroxide ion that
                     performs a nucleophilic attack on...; cd01283"
                     /db_xref="CDD:238610"
     Site            order(12,14,37,39,52..54,83,88)
                     /site_type="active"
                     /db_xref="CDD:238610"
     Site            order(52..54,82..83,88)
                     /site_type="active"
                     /note="catalytic motif [active]"
                     /db_xref="CDD:238610"
     Site            order(52,54,83,88)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:238610"
     Region          116..161
                     /region_name="APOBEC_C"
                     /note="APOBEC-like C-terminal domain; pfam05240"
                     /db_xref="CDD:283020"
     CDS             1..181
                     /gene="APOBEC3A"
                     /gene_synonym="A3A; ARP3; bK150C2.1; PHRBN"
                     /coded_by="NM_001270406.1:171..716"
                     /note="isoform b is encoded by transcript variant 3"
                     /db_xref="GeneID:200315"
                     /db_xref="HGNC:HGNC:17343"
                     /db_xref="MIM:607109"
ORIGIN      
        1 measpasgpr hktylcyeve rldngtsvkm dqhrgflhnq aknllcgfyg rhaelrfldl
       61 vpslqldpaq iyrvtwfisw spcfswgcag evraflqent hvrlrifaar iydydplyke
      121 alqmlrdaga qvsimtydef khcwdtfvdh qgcpfqpwdg ldehsqalsg rlrailqnqg
      181 n
//