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måndag 28 maj 2018

APOBEC4 (Kr.1q25.39, C1Orf169 APOBEC, jolla ei ole antiretrovirusominaisuuksia.

APOBEC4  kuuluu AID/APOBEC perheeseen, joka on  polynukleotidi (deoxy)sytidiini deaminaasi entsyymeitä. mRNA.ta editoidessa en muutavat C-sytidiinin  U- uridiiniksi. AID   tarkoittta aktivaatiosta induoituvaa sytidiinideaminaasia. (APOBEC nimi taitaa viitata   ApoB mRNA:n Cytosiinin editoimiseen).
Virallisen nimen suomennosta : " apolipoproteiini  B  mRNA:ta oletettavasti  editoiva entsyymi, joka  muuttaa Cytosiinin Uridiiniksi;  katalyyttinen polypeptidin kaltainen proteiini  4 ".  Tunnetaan myös nimellä C1orf169. 
Muut perheen jäsenet osallistuvat  mRNA-editoimiseen, somaattiseen hypermutaatioon ja immunoglobuliinigeenien rekombinaatioon ja  retrovirusinfektion  luonnolliseen immuunipuolustukseen.  Tätä ABOBEC4 geeniä  esiintyy restriktiivisesti testiksessä.
LÄHDE: 
  • https://www.ncbi.nlm.nih.gov/gene/403314#gene-expression
  • Also known as C1orf169
  • Summary This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy) cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]
  • Expression Restricted expression toward testis (RPKM 6.1) See more

Preferred Names

putative C to U-editing enzyme APOBEC-4
Names
apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 4 (putative)

Peptide sequence and history

https://www.ncbi.nlm.nih.gov/protein/NP_982279.1

Related articles in PubMed

  1. APOBEC4 Enhances the Replication of HIV-1. Marino D, et al. PLoS One, 2016. PMID 27249646 (SUOMENNOSTA:) APOBEC4 kuuluu AID/ABOBEC sytidiinideaminaasi perheeseen. Tutkijat havaitsivat  korkean mRNA pitoisuuden testiksessä, mutta vain hyvin matalan pitoisuuden A4 mRNA:ta   293T:ssa   ym tutkimukseen kuuluneissa soluissa. Ektooppinen A4 (ABOBEC4)  ilmenemä johti proteiinin sytoplasmiseen sijaintiin. He halusivat tietää, olisiko tällä proteiinilla myös antivirusvaikutusta kuten  A3-alaperheellä ja he testasivat HIV-1 viruksen suhteen.  He huomasivat, että  A4 ei pystynyt estämään HIV-1 viruksen replikaatiota, vaan päinvastoin lisäsi HIV-1 virustuotantoa annoksesta riippuvalla tavalla ja näytti  vaikuttavan viruksen LTR- domeeniin. A4 ei myöskään osoittanut havaittavaa sytidiinideaminaasiaktiivisuutta koeputkessa ja reagoi vain  heikosti ssDNA:ta kohtaan.  A4 läsnäolo  lisäsi HIV-1 replikaatiota.  Samalla tavalla A4 pystyi  nopeuttamaan monien promoottorien transkriptiota oli sitten viruksesta tai ihmettäväissolusta kyse. Tutkijat olettavat, että ABOBEC4:n  luonnollinen tehtävä on moduloida  isäntäsolun promoottoreita tai endogeenisia LTR promoottoreita.
    • APOBEC4 (A4) is a member of the AID/APOBEC family of cytidine deaminases. In this study we found a high mRNA expression of A4 in human testis. In contrast, there were only low levels of A4 mRNA detectable in 293T, HeLa, Jurkat or A3.01 cells. Ectopic expression of A4 in HeLa cells resulted in mostly cytoplasmic localization of the protein. To test whether A4 has antiviral activity similar to that of proteins of the APOBEC3 (A3) subfamily, A4 was co-expressed in 293T cells with wild type HIV-1 and HIV-1 luciferase reporter viruses. We found that A4 did not inhibit the replication of HIV-1 but instead enhanced the production of HIV-1 in a dose-dependent manner and seemed to act on the viral LTR. A4 did not show detectable cytidine deamination activity in vitro and weakly interacted with single-stranded DNA. The presence of A4 in virus producer cells enhanced HIV-1 replication by transiently transfected A4 or stably expressed A4 in HIV-susceptible cells. APOBEC4 was capable of similarly enhancing transcription from a broad spectrum of promoters, regardless of whether they were viral or mammalian. We hypothesize that A4 may have a natural role in modulating host promoters or endogenous LTR promoters.
     Free PMC Article
  2. APOBEC deaminases-mutases with defensive roles for immunity. Prochnow C, et al. Sci China C Life Sci, 2009 Oct. PMID 19911124
  3. The DNA sequence and biological annotation of human chromosome 1. Gregory SG, et al. Nature, 2006 May 18. PMID 16710414 (Kommentti: APOBEC4 omaa geeninsä 1-kromosomissa poikkeuksena  muista  APOBEC-perheenjäsensitä. Kuitenkin APOBEC4 ja APOBEC1 joka on kromosomista  12 katsotaan klusteriksi ja toinen  klusteri on APOBEC2 kromosomista  6 ja APOBEC3 kromosomista 22)

    The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
See all (8) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. APOBEC4 is expressed primarily in testis which suggests the possibility that it is an editing enzyme for mRNAs involved in spermatogenesis 
  2.  
  3. Abstract ( SUOMENNOSTA. Varsinainen APOBEC4  geenin normaali funktio) . APOBEC4- proteiinin sinkkipitoinen  koordinoiva  motiivi osallistuu katalyysiin ja sekundääristruktuurit ovat  aktiivia polynukleotidi(deoxy)sytosiinideaminaaseja.  Fylogeneettisesti APOBEC4 on selvästi eri ryhmä:  APOBEC4 ja APOBEC1 muodostavat  oman klusterinsa, joka eroaa AID, APOBEC2 ja APOBEC3 alaryhmistä. Imettäväisissä APOBEC4 ilmenee primääristi testiksessä, mikä viittaa siihen amhdollisuuteen, että se on spermatogeneesiin osallistuva mRN:.ta editoiva entsyymi.  (Kommenttini:  Tavallaan HIV-1 virus voi ilmeisesti  kaapata tämän  virusreplikaation eduksi evaasiostrategioissaan).
    • Using iterative database searches, we identified a new subfamily of the AID/APOBEC family of RNA/DNA editing cytidine deaminases. The new subfamily, which is represented by readily identifiable orthologs in mammals, chicken, and frog, but not fishes, was designated APOBEC4. The zinc-coordinating motifs involved in catalysis and the secondary structure of the APOBEC4 deaminase domain are evolutionarily conserved, suggesting that APOBEC4 proteins are active polynucleotide (deoxy)cytidine deaminases. In reconstructed maximum likelihood phylogenetic trees, APOBEC4 forms a distinct clade with a high statistical support. APOBEC4 and APOBEC1 are joined in a moderately supported cluster clearly separated from AID, APOBEC2 and APOBEC3 subfamilies. In mammals, APOBEC4 is expressed primarily in testis which suggests the possibility that it is an editing enzyme for mRNAs involved in spermatogenesis.

Peptidesequence

GenPept
putative C->U-editing enzyme APOBEC-4 [Homo sapiens]
NCBI Reference Sequence: NP_982279.1
Identical Proteins FASTA Graphics
LOCUS       NP_982279                367 aa            linear   PRI 10-MAY-2018
DEFINITION  putative C-to U-editing enzyme APOBEC-4 [Homo sapiens].
ACCESSION   NP_982279
VERSION     NP_982279.1
DBSOURCE    REFSEQ: accession NM_203454.2
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 367)
  AUTHORS   Marino D, Perkovic M, Hain A, Jaguva Vasudevan AA, Hofmann H,
            Hanschmann KM, Muhlebach MD, Schumann GG, Konig R, Cichutek K,
            Haussinger D and Munk C.
  TITLE     APOBEC4 Enhances the Replication of HIV-1
  JOURNAL   PLoS ONE 11 (6), e0155422 (2016)
   PUBMED   27249646
  REMARK    GeneRIF: APOBEC4 was capable of similarly enhancing transcription
            from a broad spectrum of promoters, regardless of whether they were
            viral or mammalian
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 367)
  AUTHORS   Yang W, Tang H, Zhang Y, Tang X, Zhang J, Sun L, Yang J, Cui Y,
            Zhang L, Hirankarn N, Cheng H, Pan HF, Gao J, Lee TL, Sheng Y, Lau
            CS, Li Y, Chan TM, Yin X, Ying D, Lu Q, Leung AM, Zuo X, Chen X,
            Tong KL, Zhou F, Diao Q, Tse NK, Xie H, Mok CC, Hao F, Wong SN, Shi
            B, Lee KW, Hui Y, Ho MH, Liang B, Lee PP, Cui H, Guo Q, Chung BH,
            Pu X, Liu Q, Zhang X, Zhang C, Chong CY, Fang H, Wong RW, Sun Y,
            Mok MY, Li XP, Avihingsanon Y, Zhai Z, Rianthavorn P, Deekajorndej
            T, Suphapeetiporn K, Gao F, Shotelersuk V, Kang X, Ying SK, Zhang
            L, Wong WH, Zhu D, Fung SK, Zeng F, Lai WM, Wong CM, Ng IO,
            Garcia-Barcelo MM, Cherny SS, Shen N, Tam PK, Sham PC, Ye DQ, Yang
            S, Zhang X and Lau YL.
  TITLE     Meta-analysis followed by replication identifies loci in or near
            CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic
            lupus erythematosus in Asians
  JOURNAL   Am. J. Hum. Genet. 92 (1), 41-51 (2013)
   PUBMED   23273568
REFERENCE   3  (residues 1 to 367)
  AUTHORS   Prochnow C, Bransteitter R and Chen XS.
  TITLE     APOBEC deaminases-mutases with defensive roles for immunity
  JOURNAL   Sci. China, C, Life Sci. 52 (10), 893-902 (2009)
   PUBMED   19911124
  REMARK    GeneRIF: Studies indicate the APOBEC family consists of 11 members:
            APOBEC-1 (Apo1), APOBEC-2 (Apo2), activation induced cytidine
            deaminase (AID), APOBEC- 3A, -3B, -3C, -3DE, -3F, -3H (Apo3A-H) and
            APOBEC- 4 (Apo4).
            Review article
REFERENCE   4  (residues 1 to 367)
  AUTHORS   Rogozin IB, Basu MK, Jordan IK, Pavlov YI and Koonin EV.
  TITLE     APOBEC4, a new member of the AID/APOBEC family of polynucleotide
            (deoxy)cytidine deaminases predicted by computational analysis
  JOURNAL   Cell Cycle 4 (9), 1281-1285 (2005)
   PUBMED   16082223
  REMARK    GeneRIF: APOBEC4 is expressed primarily in testis which suggests
            the possibility that it is an editing enzyme for mRNAs involved in
            spermatogenesis
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC021711.2 and AI961390.1.
            
            Summary: This gene encodes a member of the AID/APOBEC family of
            polynucleotide (deoxy)cytidine deaminases, which convert cytidine
            to uridine. Other AID/APOBEC family members are involved in mRNA
            editing, somatic hypermutation and recombination of immunoglobulin
            genes, and innate immunity to retroviral infection. [provided by
            RefSeq, Jul 2008].
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC021711.2, AK098557.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968968, SAMEA2144333
                                           [ECO:0000348]
            ##Evidence-Data-END##
FEATURES             Location/Qualifiers
     source          1..367
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q25.3"
     Protein         1..367
                     /product="putative C->U-editing enzyme APOBEC-4"
                     /note="apolipoprotein B mRNA editing enzyme, catalytic
                     polypeptide-like 4 (putative)"
                     /calculated_mol_wt=41450
     Region          47..213
                     /region_name="APOBEC_N"
                     /note="APOBEC-like N-terminal domain; pfam08210"
                     /db_xref="CDD:285428"
     CDS             1..367
                     /gene="APOBEC4"
                     /gene_synonym="C1orf169"
                     /coded_by="NM_203454.2:273..1376"
                     /db_xref="CCDS:CCDS1358.1"
                     /db_xref="GeneID:403314"
                     /db_xref="HGNC:HGNC:32152"
                     /db_xref="MIM:609908"
ORIGIN      
        1 mepiyeeyla nhgtivkpyy wlsfsldcsn cpyhirtgee arvsltefcq ifgfpygttf
       61 pqtkhltfye lktssgslvq kghassctgn yihpesmlfe mngyldsaiy nndsirhiil
      121 ysnnspcnea nhcciskmyn flitypgitl siyfsqlyht emdfpasawn realrslasl
      181 wprvvlspis ggiwhsvlhs fisgvsgshv fqpiltgral adrhnayein aitgvkpyft
      241 dvllqtkrnp ntkaqeales yplnnafpgq ffqmpsgqlq pnlppdlrap vvfvlvplrd
      301 lppmhmgqnp nkprnivrhl nmpqmsfqet kdlgrlptgr sveiveiteq fasskeadek
      361 kkkkgkk
//
Päivitys. Suomennosta muutamiin artikkeleihin 9.6. 2018 ,08:36.
Päivitys 26.11. 2019 . Löytyi maininta CLR5- pohjaisesta  E3-ubikitiiniligasikompleksista, joka  voi säätää APOBEC  antiretroviraalista proteiinia ja miten retrovirus voi  suorittaa evaasion APOBEC- proteiinista.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812663/

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