Full text data of APOBEC3B
APOBEC3B
[Confidence: low (only semi-automatic identification from reviews)]
DNA dC->dU-editing enzyme APOBEC-3B; A3B; 3.5.4.- (Phorbolin-1-related protein; Phorbolin-2/3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
DNA dC->dU-editing enzyme APOBEC-3B; A3B; 3.5.4.- (Phorbolin-1-related protein; Phorbolin-2/3)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UH17
ID ABC3B_HUMAN Reviewed; 382 AA.
AC Q9UH17; B0QYD2; O95618; Q20WL1; Q5IFJ4; Q7Z2N3; Q7Z6D6; Q9UE74;
read moreDT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=DNA dC->dU-editing enzyme APOBEC-3B;
DE Short=A3B;
DE EC=3.5.4.-;
DE AltName: Full=Phorbolin-1-related protein;
DE AltName: Full=Phorbolin-2/3;
GN Name=APOBEC3B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-146, AND
RP INDUCTION.
RC TISSUE=Keratinocyte;
RX PubMed=10469298; DOI=10.1046/j.1523-1747.1999.00682.x;
RA Madsen P.P., Anant S., Rasmussen H.H., Gromov P., Vorum H.,
RA Dumanski J.P., Tommerup N., Collins J.E., Wright C.L., Dunham I.,
RA Macginnitie A.J., Davidson N.O., Celis J.E.;
RT "Psoriasis upregulated phorbolin-1 shares structural but not
RT functional similarity to the mRNA-editing protein apobec-1.";
RL J. Invest. Dermatol. 113:162-169(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=16060832; DOI=10.1089/aid.2005.21.611;
RA Rose K.M., Marin M., Kozak S.L., Kabat D.;
RT "Regulated production and anti-HIV type 1 activities of cytidine
RT deaminases APOBEC3B, 3F, and 3G.";
RL AIDS Res. Hum. Retroviruses 21:611-619(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS
RP GLU-62 AND LYS-146.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP LYS-146.
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP GENE FAMILY ORGANIZATION, TISSUE SPECIFICITY, RNA-BINDING,
RP ZINC-BINDING, AND INTERACTION WITH APOBEC3G.
RX PubMed=11863358; DOI=10.1006/geno.2002.6718;
RA Jarmuz A., Chester A., Bayliss J., Gisbourne J., Dunham I., Scott J.,
RA Navaratnam N.;
RT "An anthropoid-specific locus of orphan C to U RNA-editing enzymes on
RT chromosome 22.";
RL Genomics 79:285-296(2002).
RN [7]
RP REVIEW ON APOBEC FAMILIES.
RX PubMed=12683974; DOI=10.1016/S0168-9525(03)00054-4;
RA Wedekind J.E., Dance G.S.C., Sowden M.P., Smith H.C.;
RT "Messenger RNA editing in mammals: new members of the APOBEC family
RT seeking roles in the family business.";
RL Trends Genet. 19:207-216(2003).
RN [8]
RP FUNCTION IN HIV-1 INFECTIVITY.
RX PubMed=12859895; DOI=10.1016/S0092-8674(03)00515-4;
RA Mariani R., Chen D., Schroefelbauer B., Navarro F., Koenig R.,
RA Bollman B., Muenk C., Nymark-McMahon H., Landau N.R.;
RT "Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.";
RL Cell 114:21-31(2003).
RN [9]
RP FUNCTION IN SIV RESTRICTION.
RX PubMed=15466872; DOI=10.1074/jbc.M408802200;
RA Yu Q., Chen D., Koenig R., Mariani R., Unutmaz D., Landau N.R.;
RT "APOBEC3B and APOBEC3C are potent inhibitors of simian
RT immunodeficiency virus replication.";
RL J. Biol. Chem. 279:53379-53386(2004).
RN [10]
RP FUNCTION IN RETROTRANSPOSITION.
RX PubMed=16527742; DOI=10.1016/j.cub.2006.01.031;
RA Chen H., Lilley C.E., Yu Q., Lee D.V., Chou J., Narvaiza I.,
RA Landau N.R., Weitzman M.D.;
RT "APOBEC3A is a potent inhibitor of adeno-associated virus and
RT retrotransposons.";
RL Curr. Biol. 16:480-485(2006).
RN [11]
RP DOMAIN CMP/DCMP DEAMINASE ZINC-BINDING.
RX PubMed=17020885; DOI=10.1074/jbc.M604980200;
RA Hakata Y., Landau N.R.;
RT "Reversed functional organization of mouse and human APOBEC3 cytidine
RT deaminase domains.";
RL J. Biol. Chem. 281:36624-36631(2006).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=16699599; DOI=10.1371/journal.ppat.0020041;
RA Wichroski M.J., Robb G.B., Rana T.M.;
RT "Human retroviral host restriction factors APOBEC3G and APOBEC3F
RT localize to mRNA processing bodies.";
RL PLoS Pathog. 2:E41-E41(2006).
RN [13]
RP REVIEW.
RX PubMed=18304004; DOI=10.1146/annurev.immunol.26.021607.090350;
RA Chiu Y.L., Greene W.C.;
RT "The APOBEC3 cytidine deaminases: an innate defensive network opposing
RT exogenous retroviruses and endogenous retroelements.";
RL Annu. Rev. Immunol. 26:317-353(2008).
RN [14]
RP REVIEW ON FUNCTION IN HBV RESTRICTION.
RX PubMed=18448976; DOI=10.1097/QCO.0b013e3282fe1bb2;
RA Bonvin M., Greeve J.;
RT "Hepatitis B: modern concepts in pathogenesis--APOBEC3 cytidine
RT deaminases as effectors in innate immunity against the hepatitis B
RT virus.";
RL Curr. Opin. Infect. Dis. 21:298-303(2008).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=18667511; DOI=10.1128/JVI.02471-07;
RA Stenglein M.D., Matsuo H., Harris R.S.;
RT "Two regions within the amino-terminal half of APOBEC3G cooperate to
RT determine cytoplasmic localization.";
RL J. Virol. 82:9591-9599(2008).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=20308164; DOI=10.1093/nar/gkq174;
RA Refsland E.W., Stenglein M.D., Shindo K., Albin J.S., Brown W.L.,
RA Harris R.S.;
RT "Quantitative profiling of the full APOBEC3 mRNA repertoire in
RT lymphocytes and tissues: implications for HIV-1 restriction.";
RL Nucleic Acids Res. 38:4274-4284(2010).
RN [17]
RP FUNCTION IN RETROTRANSPOSITION.
RX PubMed=20062055; DOI=10.1038/nsmb.1744;
RA Stenglein M.D., Burns M.B., Li M., Lengyel J., Harris R.S.;
RT "APOBEC3 proteins mediate the clearance of foreign DNA from human
RT cells.";
RL Nat. Struct. Mol. Biol. 17:222-229(2010).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=21835787; DOI=10.1128/JVI.05238-11;
RA Hultquist J.F., Lengyel J.A., Refsland E.W., LaRue R.S., Lackey L.,
RA Brown W.L., Harris R.S.;
RT "Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H
RT demonstrate a conserved capacity to restrict Vif-deficient HIV-1.";
RL J. Virol. 85:11220-11234(2011).
RN [19]
RP REVIEW.
RX PubMed=22912627; DOI=10.3389/fmicb.2012.00275;
RA Arias J.F., Koyama T., Kinomoto M., Tokunaga K.;
RT "Retroelements versus APOBEC3 family members: No great escape from the
RT magnificent seven.";
RL Front. Microbiol. 3:275-275(2012).
RN [20]
RP FUNCTION IN HTLV-1 RESTRICTION.
RX PubMed=22457529; DOI=10.1128/JVI.06570-11;
RA Ooms M., Krikoni A., Kress A.K., Simon V., Muenk C.;
RT "APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-
RT lymphotropic virus type 1.";
RL J. Virol. 86:6097-6108(2012).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=22915799; DOI=10.1128/JVI.00595-12;
RA Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT "HIV-1 replication and APOBEC3 antiviral activity are not regulated by
RT P bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [22]
RP REVIEW.
RX PubMed=22001110; DOI=10.1016/j.semcdb.2011.10.004;
RA Smith H.C., Bennett R.P., Kizilyer A., McDougall W.M., Prohaska K.M.;
RT "Functions and regulation of the APOBEC family of proteins.";
RL Semin. Cell Dev. Biol. 23:258-268(2012).
CC -!- FUNCTION: DNA deaminase (cytidine deaminase) which acts as an
CC inhibitor of retrovirus replication and retrotransposon mobility
CC via deaminase-dependent and -independent mechanisms. After the
CC penetration of retroviral nucleocapsids into target cells of
CC infection and the initiation of reverse transcription, it can
CC induce the conversion of cytosine to uracil in the minus-sense
CC single-strand viral DNA, leading to G-to-A hypermutations in the
CC subsequent plus-strand viral DNA. The resultant detrimental levels
CC of mutations in the proviral genome, along with a deamination-
CC independent mechanism that works prior to the proviral
CC integration, together exert efficient antiretroviral effects in
CC infected target cells. Selectively targets single-stranded DNA and
CC does not deaminate double-stranded DNA or single-or double-
CC stranded RNA. Exhibits antiviral activity against simian
CC immunodeficiency virus (SIV), hepatitis B virus (HBV) and human T-
CC cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility
CC of LTR and non-LTR retrotransposons.
CC -!- CATALYTIC ACTIVITY: Cytidine + H(2)O = uridine + NH(3).
CC -!- COFACTOR: Zinc.
CC -!- SUBUNIT: Homodimer. Interacts with APOBEC3G. Does not interact
CC with APOBEC1.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UH17-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UH17-2; Sequence=VSP_009802;
CC Note=May be due to a competing donor splice site;
CC Name=3;
CC IsoId=Q9UH17-3; Sequence=VSP_044900;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed at high and moderate levels in
CC peripheral blood leukocytes, spleen, testes, heart, thymus,
CC prostate and ovary. Also expressed at low levels in several other
CC tissues.
CC -!- INDUCTION: Phorbol 12-myristate 13-acetate (PMA) induces
CC overexpression in keratinocytes. Up-regulated by IFN-alpha.
CC -!- DOMAIN: The CMP/dCMP deaminase zinc-binding 1 domain mediates RNA
CC binding, RNA-dependent oligomerization and virion incorporation
CC whereas the CMP/dCMP deaminase zinc-binding 2 domain confers
CC deoxycytidine deaminase activity and substrate sequence
CC specificity (PubMed:17020885).
CC -!- MISCELLANEOUS: It is one of seven related genes or pseudogenes
CC found in a cluster, thought to result from gene duplication, on
CC chromosome 22.
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family.
CC -!- SIMILARITY: Contains 2 CMP/dCMP deaminase zinc-binding domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD00089.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAD00090.1; Type=Frameshift; Positions=59, 134; Note=Frameshifts result in two separate ORFs termed phorbolins 2 and 3;
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DR EMBL; U61083; AAD00089.1; ALT_INIT; mRNA.
DR EMBL; U61084; AAD00090.1; ALT_FRAME; mRNA.
DR EMBL; AY743217; AAW31743.1; -; mRNA.
DR EMBL; CT841510; CAJ86440.1; -; mRNA.
DR EMBL; AL022318; CAB45270.1; -; Genomic_DNA.
DR EMBL; AL022318; CAQ09851.1; -; Genomic_DNA.
DR EMBL; BC053859; AAH53859.1; -; mRNA.
DR RefSeq; NP_001257340.1; NM_001270411.1.
DR RefSeq; NP_004891.4; NM_004900.4.
DR UniGene; Hs.226307; -.
DR UniGene; Hs.658626; -.
DR ProteinModelPortal; Q9UH17; -.
DR SMR; Q9UH17; 4-382.
DR IntAct; Q9UH17; 3.
DR MINT; MINT-4992727; -.
DR STRING; 9606.ENSP00000327459; -.
DR PhosphoSite; Q9UH17; -.
DR DMDM; 12643884; -.
DR PaxDb; Q9UH17; -.
DR PRIDE; Q9UH17; -.
DR DNASU; 9582; -.
DR Ensembl; ENST00000333467; ENSP00000327459; ENSG00000179750.
DR Ensembl; ENST00000335760; ENSP00000338897; ENSG00000179750.
DR Ensembl; ENST00000407298; ENSP00000385068; ENSG00000179750.
DR GeneID; 9582; -.
DR KEGG; hsa:9582; -.
DR UCSC; uc003awp.2; human.
DR CTD; 9582; -.
DR GeneCards; GC22P039378; -.
DR HGNC; HGNC:17352; APOBEC3B.
DR MIM; 607110; gene.
DR neXtProt; NX_Q9UH17; -.
DR PharmGKB; PA24892; -.
DR eggNOG; NOG135704; -.
DR HOGENOM; HOG000033755; -.
DR HOVERGEN; HBG050434; -.
DR KO; K01500; -.
DR OrthoDB; EOG75QR3Z; -.
DR PhylomeDB; Q9UH17; -.
DR GeneWiki; APOBEC3B; -.
DR GenomeRNAi; 9582; -.
DR NextBio; 35465727; -.
DR PRO; PR:Q9UH17; -.
DR ArrayExpress; Q9UH17; -.
DR Bgee; Q9UH17; -.
DR CleanEx; HS_APOBEC3B; -.
DR Genevestigator; Q9UH17; -.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0047844; F:deoxycytidine deaminase activity; IMP:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0010529; P:negative regulation of transposition; IDA:UniProtKB.
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR007904; APOBEC_C.
DR InterPro; IPR013158; APOBEC_N.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR Pfam; PF05240; APOBEC_C; 1.
DR Pfam; PF08210; APOBEC_N; 1.
DR SUPFAM; SSF53927; SSF53927; 2.
DR PROSITE; PS00903; CYT_DCMP_DEAMINASES; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Complete proteome; Hydrolase;
KW Immunity; Innate immunity; Metal-binding; Nucleus; Polymorphism;
KW Reference proteome; Repeat; RNA-binding; Zinc.
FT CHAIN 1 382 DNA dC->dU-editing enzyme APOBEC-3B.
FT /FTId=PRO_0000171753.
FT DOMAIN 66 100 CMP/dCMP deaminase zinc-binding 1.
FT DOMAIN 253 289 CMP/dCMP deaminase zinc-binding 2.
FT ACT_SITE 255 255 Proton donor (Potential).
FT METAL 66 66 Zinc (By similarity).
FT METAL 97 97 Zinc (By similarity).
FT METAL 100 100 Zinc (By similarity).
FT METAL 253 253 Zinc (By similarity).
FT METAL 284 284 Zinc (By similarity).
FT METAL 289 289 Zinc (By similarity).
FT VAR_SEQ 191 382 YLMDPDTFTFNFNNDPLVLRRRQTYLCYEVERLDNGTWVLM
FT DQHMGFLCNEAKNLLCGFYGRHAELRFLDLVPSLQLDPAQI
FT YRVTWFISWSPCFSWGCAGEVRAFLQENTHVRLRIFAARIY
FT DYDPLYKEALQMLRDAGAQVSIMTYDEFEYCWDTFVYRQGC
FT PFQPWDGLEEHSQALSGRLRAILQNQGN -> LRIFSVAFT
FT AAMRSCASWTWFLLCSWTRPRSTGSLGSSPGAPASPGAVPG
FT KCVRSFRRTHT (in isoform 2).
FT /FTId=VSP_009802.
FT VAR_SEQ 242 266 Missing (in isoform 3).
FT /FTId=VSP_044900.
FT VARIANT 62 62 K -> E (in dbSNP:rs2076109).
FT /FTId=VAR_018142.
FT VARIANT 98 98 P -> L (in dbSNP:rs2076110).
FT /FTId=VAR_018143.
FT VARIANT 109 109 S -> A (in dbSNP:rs17000697).
FT /FTId=VAR_033455.
FT VARIANT 146 146 T -> K (in dbSNP:rs5995649).
FT /FTId=VAR_018144.
FT VARIANT 351 351 R -> H (in dbSNP:rs1053813).
FT /FTId=VAR_048722.
FT CONFLICT 103 104 KL -> NV (in Ref. 1; AAD00090).
FT CONFLICT 227 228 TW -> WM (in Ref. 1; AAD00089).
FT CONFLICT 255 256 EL -> DW (in Ref. 1; AAD00089).
FT CONFLICT 306 306 R -> P (in Ref. 1; AAD00089).
FT CONFLICT 356 356 F -> S (in Ref. 2; AAW31743).
SQ SEQUENCE 382 AA; 45924 MW; DA6EDD23E8856240 CRC64;
MNPQIRNPME RMYRDTFYDN FENEPILYGR SYTWLCYEVK IKRGRSNLLW DTGVFRGQVY
FKPQYHAEMC FLSWFCGNQL PAYKCFQITW FVSWTPCPDC VAKLAEFLSE HPNVTLTISA
ARLYYYWERD YRRALCRLSQ AGARVTIMDY EEFAYCWENF VYNEGQQFMP WYKFDENYAF
LHRTLKEILR YLMDPDTFTF NFNNDPLVLR RRQTYLCYEV ERLDNGTWVL MDQHMGFLCN
EAKNLLCGFY GRHAELRFLD LVPSLQLDPA QIYRVTWFIS WSPCFSWGCA GEVRAFLQEN
THVRLRIFAA RIYDYDPLYK EALQMLRDAG AQVSIMTYDE FEYCWDTFVY RQGCPFQPWD
GLEEHSQALS GRLRAILQNQ GN
//
ID ABC3B_HUMAN Reviewed; 382 AA.
AC Q9UH17; B0QYD2; O95618; Q20WL1; Q5IFJ4; Q7Z2N3; Q7Z6D6; Q9UE74;
read moreDT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=DNA dC->dU-editing enzyme APOBEC-3B;
DE Short=A3B;
DE EC=3.5.4.-;
DE AltName: Full=Phorbolin-1-related protein;
DE AltName: Full=Phorbolin-2/3;
GN Name=APOBEC3B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LYS-146, AND
RP INDUCTION.
RC TISSUE=Keratinocyte;
RX PubMed=10469298; DOI=10.1046/j.1523-1747.1999.00682.x;
RA Madsen P.P., Anant S., Rasmussen H.H., Gromov P., Vorum H.,
RA Dumanski J.P., Tommerup N., Collins J.E., Wright C.L., Dunham I.,
RA Macginnitie A.J., Davidson N.O., Celis J.E.;
RT "Psoriasis upregulated phorbolin-1 shares structural but not
RT functional similarity to the mRNA-editing protein apobec-1.";
RL J. Invest. Dermatol. 113:162-169(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=16060832; DOI=10.1089/aid.2005.21.611;
RA Rose K.M., Marin M., Kozak S.L., Kabat D.;
RT "Regulated production and anti-HIV type 1 activities of cytidine
RT deaminases APOBEC3B, 3F, and 3G.";
RL AIDS Res. Hum. Retroviruses 21:611-619(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS
RP GLU-62 AND LYS-146.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP LYS-146.
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP GENE FAMILY ORGANIZATION, TISSUE SPECIFICITY, RNA-BINDING,
RP ZINC-BINDING, AND INTERACTION WITH APOBEC3G.
RX PubMed=11863358; DOI=10.1006/geno.2002.6718;
RA Jarmuz A., Chester A., Bayliss J., Gisbourne J., Dunham I., Scott J.,
RA Navaratnam N.;
RT "An anthropoid-specific locus of orphan C to U RNA-editing enzymes on
RT chromosome 22.";
RL Genomics 79:285-296(2002).
RN [7]
RP REVIEW ON APOBEC FAMILIES.
RX PubMed=12683974; DOI=10.1016/S0168-9525(03)00054-4;
RA Wedekind J.E., Dance G.S.C., Sowden M.P., Smith H.C.;
RT "Messenger RNA editing in mammals: new members of the APOBEC family
RT seeking roles in the family business.";
RL Trends Genet. 19:207-216(2003).
RN [8]
RP FUNCTION IN HIV-1 INFECTIVITY.
RX PubMed=12859895; DOI=10.1016/S0092-8674(03)00515-4;
RA Mariani R., Chen D., Schroefelbauer B., Navarro F., Koenig R.,
RA Bollman B., Muenk C., Nymark-McMahon H., Landau N.R.;
RT "Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.";
RL Cell 114:21-31(2003).
RN [9]
RP FUNCTION IN SIV RESTRICTION.
RX PubMed=15466872; DOI=10.1074/jbc.M408802200;
RA Yu Q., Chen D., Koenig R., Mariani R., Unutmaz D., Landau N.R.;
RT "APOBEC3B and APOBEC3C are potent inhibitors of simian
RT immunodeficiency virus replication.";
RL J. Biol. Chem. 279:53379-53386(2004).
RN [10]
RP FUNCTION IN RETROTRANSPOSITION.
RX PubMed=16527742; DOI=10.1016/j.cub.2006.01.031;
RA Chen H., Lilley C.E., Yu Q., Lee D.V., Chou J., Narvaiza I.,
RA Landau N.R., Weitzman M.D.;
RT "APOBEC3A is a potent inhibitor of adeno-associated virus and
RT retrotransposons.";
RL Curr. Biol. 16:480-485(2006).
RN [11]
RP DOMAIN CMP/DCMP DEAMINASE ZINC-BINDING.
RX PubMed=17020885; DOI=10.1074/jbc.M604980200;
RA Hakata Y., Landau N.R.;
RT "Reversed functional organization of mouse and human APOBEC3 cytidine
RT deaminase domains.";
RL J. Biol. Chem. 281:36624-36631(2006).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=16699599; DOI=10.1371/journal.ppat.0020041;
RA Wichroski M.J., Robb G.B., Rana T.M.;
RT "Human retroviral host restriction factors APOBEC3G and APOBEC3F
RT localize to mRNA processing bodies.";
RL PLoS Pathog. 2:E41-E41(2006).
RN [13]
RP REVIEW.
RX PubMed=18304004; DOI=10.1146/annurev.immunol.26.021607.090350;
RA Chiu Y.L., Greene W.C.;
RT "The APOBEC3 cytidine deaminases: an innate defensive network opposing
RT exogenous retroviruses and endogenous retroelements.";
RL Annu. Rev. Immunol. 26:317-353(2008).
RN [14]
RP REVIEW ON FUNCTION IN HBV RESTRICTION.
RX PubMed=18448976; DOI=10.1097/QCO.0b013e3282fe1bb2;
RA Bonvin M., Greeve J.;
RT "Hepatitis B: modern concepts in pathogenesis--APOBEC3 cytidine
RT deaminases as effectors in innate immunity against the hepatitis B
RT virus.";
RL Curr. Opin. Infect. Dis. 21:298-303(2008).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=18667511; DOI=10.1128/JVI.02471-07;
RA Stenglein M.D., Matsuo H., Harris R.S.;
RT "Two regions within the amino-terminal half of APOBEC3G cooperate to
RT determine cytoplasmic localization.";
RL J. Virol. 82:9591-9599(2008).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=20308164; DOI=10.1093/nar/gkq174;
RA Refsland E.W., Stenglein M.D., Shindo K., Albin J.S., Brown W.L.,
RA Harris R.S.;
RT "Quantitative profiling of the full APOBEC3 mRNA repertoire in
RT lymphocytes and tissues: implications for HIV-1 restriction.";
RL Nucleic Acids Res. 38:4274-4284(2010).
RN [17]
RP FUNCTION IN RETROTRANSPOSITION.
RX PubMed=20062055; DOI=10.1038/nsmb.1744;
RA Stenglein M.D., Burns M.B., Li M., Lengyel J., Harris R.S.;
RT "APOBEC3 proteins mediate the clearance of foreign DNA from human
RT cells.";
RL Nat. Struct. Mol. Biol. 17:222-229(2010).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=21835787; DOI=10.1128/JVI.05238-11;
RA Hultquist J.F., Lengyel J.A., Refsland E.W., LaRue R.S., Lackey L.,
RA Brown W.L., Harris R.S.;
RT "Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H
RT demonstrate a conserved capacity to restrict Vif-deficient HIV-1.";
RL J. Virol. 85:11220-11234(2011).
RN [19]
RP REVIEW.
RX PubMed=22912627; DOI=10.3389/fmicb.2012.00275;
RA Arias J.F., Koyama T., Kinomoto M., Tokunaga K.;
RT "Retroelements versus APOBEC3 family members: No great escape from the
RT magnificent seven.";
RL Front. Microbiol. 3:275-275(2012).
RN [20]
RP FUNCTION IN HTLV-1 RESTRICTION.
RX PubMed=22457529; DOI=10.1128/JVI.06570-11;
RA Ooms M., Krikoni A., Kress A.K., Simon V., Muenk C.;
RT "APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-
RT lymphotropic virus type 1.";
RL J. Virol. 86:6097-6108(2012).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=22915799; DOI=10.1128/JVI.00595-12;
RA Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT "HIV-1 replication and APOBEC3 antiviral activity are not regulated by
RT P bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [22]
RP REVIEW.
RX PubMed=22001110; DOI=10.1016/j.semcdb.2011.10.004;
RA Smith H.C., Bennett R.P., Kizilyer A., McDougall W.M., Prohaska K.M.;
RT "Functions and regulation of the APOBEC family of proteins.";
RL Semin. Cell Dev. Biol. 23:258-268(2012).
CC -!- FUNCTION: DNA deaminase (cytidine deaminase) which acts as an
CC inhibitor of retrovirus replication and retrotransposon mobility
CC via deaminase-dependent and -independent mechanisms. After the
CC penetration of retroviral nucleocapsids into target cells of
CC infection and the initiation of reverse transcription, it can
CC induce the conversion of cytosine to uracil in the minus-sense
CC single-strand viral DNA, leading to G-to-A hypermutations in the
CC subsequent plus-strand viral DNA. The resultant detrimental levels
CC of mutations in the proviral genome, along with a deamination-
CC independent mechanism that works prior to the proviral
CC integration, together exert efficient antiretroviral effects in
CC infected target cells. Selectively targets single-stranded DNA and
CC does not deaminate double-stranded DNA or single-or double-
CC stranded RNA. Exhibits antiviral activity against simian
CC immunodeficiency virus (SIV), hepatitis B virus (HBV) and human T-
CC cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility
CC of LTR and non-LTR retrotransposons.
CC -!- CATALYTIC ACTIVITY: Cytidine + H(2)O = uridine + NH(3).
CC -!- COFACTOR: Zinc.
CC -!- SUBUNIT: Homodimer. Interacts with APOBEC3G. Does not interact
CC with APOBEC1.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UH17-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UH17-2; Sequence=VSP_009802;
CC Note=May be due to a competing donor splice site;
CC Name=3;
CC IsoId=Q9UH17-3; Sequence=VSP_044900;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed at high and moderate levels in
CC peripheral blood leukocytes, spleen, testes, heart, thymus,
CC prostate and ovary. Also expressed at low levels in several other
CC tissues.
CC -!- INDUCTION: Phorbol 12-myristate 13-acetate (PMA) induces
CC overexpression in keratinocytes. Up-regulated by IFN-alpha.
CC -!- DOMAIN: The CMP/dCMP deaminase zinc-binding 1 domain mediates RNA
CC binding, RNA-dependent oligomerization and virion incorporation
CC whereas the CMP/dCMP deaminase zinc-binding 2 domain confers
CC deoxycytidine deaminase activity and substrate sequence
CC specificity (PubMed:17020885).
CC -!- MISCELLANEOUS: It is one of seven related genes or pseudogenes
CC found in a cluster, thought to result from gene duplication, on
CC chromosome 22.
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family.
CC -!- SIMILARITY: Contains 2 CMP/dCMP deaminase zinc-binding domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD00089.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAD00090.1; Type=Frameshift; Positions=59, 134; Note=Frameshifts result in two separate ORFs termed phorbolins 2 and 3;
CC -----------------------------------------------------------------------
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DR EMBL; U61083; AAD00089.1; ALT_INIT; mRNA.
DR EMBL; U61084; AAD00090.1; ALT_FRAME; mRNA.
DR EMBL; AY743217; AAW31743.1; -; mRNA.
DR EMBL; CT841510; CAJ86440.1; -; mRNA.
DR EMBL; AL022318; CAB45270.1; -; Genomic_DNA.
DR EMBL; AL022318; CAQ09851.1; -; Genomic_DNA.
DR EMBL; BC053859; AAH53859.1; -; mRNA.
DR RefSeq; NP_001257340.1; NM_001270411.1.
DR RefSeq; NP_004891.4; NM_004900.4.
DR UniGene; Hs.226307; -.
DR UniGene; Hs.658626; -.
DR ProteinModelPortal; Q9UH17; -.
DR SMR; Q9UH17; 4-382.
DR IntAct; Q9UH17; 3.
DR MINT; MINT-4992727; -.
DR STRING; 9606.ENSP00000327459; -.
DR PhosphoSite; Q9UH17; -.
DR DMDM; 12643884; -.
DR PaxDb; Q9UH17; -.
DR PRIDE; Q9UH17; -.
DR DNASU; 9582; -.
DR Ensembl; ENST00000333467; ENSP00000327459; ENSG00000179750.
DR Ensembl; ENST00000335760; ENSP00000338897; ENSG00000179750.
DR Ensembl; ENST00000407298; ENSP00000385068; ENSG00000179750.
DR GeneID; 9582; -.
DR KEGG; hsa:9582; -.
DR UCSC; uc003awp.2; human.
DR CTD; 9582; -.
DR GeneCards; GC22P039378; -.
DR HGNC; HGNC:17352; APOBEC3B.
DR MIM; 607110; gene.
DR neXtProt; NX_Q9UH17; -.
DR PharmGKB; PA24892; -.
DR eggNOG; NOG135704; -.
DR HOGENOM; HOG000033755; -.
DR HOVERGEN; HBG050434; -.
DR KO; K01500; -.
DR OrthoDB; EOG75QR3Z; -.
DR PhylomeDB; Q9UH17; -.
DR GeneWiki; APOBEC3B; -.
DR GenomeRNAi; 9582; -.
DR NextBio; 35465727; -.
DR PRO; PR:Q9UH17; -.
DR ArrayExpress; Q9UH17; -.
DR Bgee; Q9UH17; -.
DR CleanEx; HS_APOBEC3B; -.
DR Genevestigator; Q9UH17; -.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0047844; F:deoxycytidine deaminase activity; IMP:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0010529; P:negative regulation of transposition; IDA:UniProtKB.
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR007904; APOBEC_C.
DR InterPro; IPR013158; APOBEC_N.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR Pfam; PF05240; APOBEC_C; 1.
DR Pfam; PF08210; APOBEC_N; 1.
DR SUPFAM; SSF53927; SSF53927; 2.
DR PROSITE; PS00903; CYT_DCMP_DEAMINASES; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Complete proteome; Hydrolase;
KW Immunity; Innate immunity; Metal-binding; Nucleus; Polymorphism;
KW Reference proteome; Repeat; RNA-binding; Zinc.
FT CHAIN 1 382 DNA dC->dU-editing enzyme APOBEC-3B.
FT /FTId=PRO_0000171753.
FT DOMAIN 66 100 CMP/dCMP deaminase zinc-binding 1.
FT DOMAIN 253 289 CMP/dCMP deaminase zinc-binding 2.
FT ACT_SITE 255 255 Proton donor (Potential).
FT METAL 66 66 Zinc (By similarity).
FT METAL 97 97 Zinc (By similarity).
FT METAL 100 100 Zinc (By similarity).
FT METAL 253 253 Zinc (By similarity).
FT METAL 284 284 Zinc (By similarity).
FT METAL 289 289 Zinc (By similarity).
FT VAR_SEQ 191 382 YLMDPDTFTFNFNNDPLVLRRRQTYLCYEVERLDNGTWVLM
FT DQHMGFLCNEAKNLLCGFYGRHAELRFLDLVPSLQLDPAQI
FT YRVTWFISWSPCFSWGCAGEVRAFLQENTHVRLRIFAARIY
FT DYDPLYKEALQMLRDAGAQVSIMTYDEFEYCWDTFVYRQGC
FT PFQPWDGLEEHSQALSGRLRAILQNQGN -> LRIFSVAFT
FT AAMRSCASWTWFLLCSWTRPRSTGSLGSSPGAPASPGAVPG
FT KCVRSFRRTHT (in isoform 2).
FT /FTId=VSP_009802.
FT VAR_SEQ 242 266 Missing (in isoform 3).
FT /FTId=VSP_044900.
FT VARIANT 62 62 K -> E (in dbSNP:rs2076109).
FT /FTId=VAR_018142.
FT VARIANT 98 98 P -> L (in dbSNP:rs2076110).
FT /FTId=VAR_018143.
FT VARIANT 109 109 S -> A (in dbSNP:rs17000697).
FT /FTId=VAR_033455.
FT VARIANT 146 146 T -> K (in dbSNP:rs5995649).
FT /FTId=VAR_018144.
FT VARIANT 351 351 R -> H (in dbSNP:rs1053813).
FT /FTId=VAR_048722.
FT CONFLICT 103 104 KL -> NV (in Ref. 1; AAD00090).
FT CONFLICT 227 228 TW -> WM (in Ref. 1; AAD00089).
FT CONFLICT 255 256 EL -> DW (in Ref. 1; AAD00089).
FT CONFLICT 306 306 R -> P (in Ref. 1; AAD00089).
FT CONFLICT 356 356 F -> S (in Ref. 2; AAW31743).
SQ SEQUENCE 382 AA; 45924 MW; DA6EDD23E8856240 CRC64;
MNPQIRNPME RMYRDTFYDN FENEPILYGR SYTWLCYEVK IKRGRSNLLW DTGVFRGQVY
FKPQYHAEMC FLSWFCGNQL PAYKCFQITW FVSWTPCPDC VAKLAEFLSE HPNVTLTISA
ARLYYYWERD YRRALCRLSQ AGARVTIMDY EEFAYCWENF VYNEGQQFMP WYKFDENYAF
LHRTLKEILR YLMDPDTFTF NFNNDPLVLR RRQTYLCYEV ERLDNGTWVL MDQHMGFLCN
EAKNLLCGFY GRHAELRFLD LVPSLQLDPA QIYRVTWFIS WSPCFSWGCA GEVRAFLQEN
THVRLRIFAA RIYDYDPLYK EALQMLRDAG AQVSIMTYDE FEYCWDTFVY RQGCPFQPWD
GLEEHSQALS GRLRAILQNQ GN
//
MIM
607110
*RECORD*
*FIELD* NO
607110
*FIELD* TI
*607110 APOLIPOPROTEIN B mRNA-EDITING ENZYME, CATALYTIC POLYPEPTIDE-LIKE 3B;
APOBEC3B
read more;;PHORBOLIN 1-RELATED PROTEIN
*FIELD* TX
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.
GENE STRUCTURE
Jarmuz et al. (2002) determined that the APOBEC3B gene contains 8 exons.
The 5-prime untranslated region and the 5-prime flanking region contain
repeated sequences. No TATA or CATT box was identified.
MAPPING
Using FISH and cosmid analyses, Madsen et al. (1999) mapped the
phorbolin-1-related gene to chromosome 22q13, close to the phorbolin-1
gene and centromeric to the PDGFB gene (190040).
By FISH and genomic sequence analysis, Jarmuz et al. (2002) mapped the
APOBEC3B gene within a tandem array of 7 APOBEC genes or pseudogenes on
chromosome 22q12-q13.2. All are oriented with a centromeric 5-prime end.
The authors noted that a similar expansion of the APOBEC family is not
present in rodents.
EVOLUTION
Marchetto et al. (2013) described the generation and initial
characterization of induced pluripotent stem (iPS) cells from
chimpanzees and bonobos as tools to explore factors that may have
contributed to great ape evolution. Comparative gene expression analysis
of human and nonhuman primate iPS cells revealed differences in the
regulation of long interspersed element-1 (L1) transposons. A force of
change in mammalian evolution, L1 elements are retrotransposons that
have remained active during primate evolution. Decreased levels of
L1-restricting factors APOBEC3B and PIWIL2 (610312) in nonhuman primate
iPS cells correlated with increased L1 mobility and endogenous L1 mRNA
levels. Moreover, results from the manipulation of APOBEC3B and PIWIL2
levels in iPS cells supported a causal inverse relationship between
levels of these proteins and L1 retrotransposition. Finally, Marchetto
et al. (2013) found increased copy numbers of species-specific L1
elements in the genome of chimpanzees compared to humans, supporting the
idea that increased L1 mobility in nonhuman primates is not limited to
iPS cells in culture and may have also occurred in the germline or
embryonic cells developmentally upstream to germline specification
during primate evolution. Marchetto et al. (2013) proposed that
differences in L1 mobility may have differentially shaped the genomes of
humans and nonhuman primates and could have continuing adaptive
significance.
*FIELD* RF
1. Bogerd, H. P.; Wiegand, H. L.; Hulme, A. E.; Garcia-Perez, J. L.;
O'Shea, K. S.; Moran, J. V.; Cullen, B. R.: Cellular inhibitors of
long interspersed element 1 and Alu retrotransposition. Proc. Nat.
Acad. Sci. 103: 8780-8785, 2006.
2. Burns, M. B.; Lackey, L.; Carpenter, M. A.; Rathore, A.; Land,
A. M.; Leonard, B.; Refsland, E. W.; Kotandeniya, D.; Tretyakova,
N.; Nikas, J. B.; Yee, D.; Temiz, N. A.; Donohue, D. E.; McDougle,
R. M.; Brown, W. L.; Law, E. K.; Harris, R. S.: APOBEC3B is an enzymatic
source of mutation in breast cancer. Nature 494: 366-370, 2013.
Note: Erratum: Nature 502: 580 only, 2013.
3. Jarmuz, A.; Chester, A.; Bayliss, J.; Gisbourne, J.; Dunham, I.;
Scott, J.; Navaratnam, N.: An anthropoid-specific locus of orphan
C to U RNA-editing enzymes on chromosome 22. Genomics 79: 285-296,
2002.
4. Madsen, P.; Anant, S.; Rasmussen, H. H.; Gromov, P.; Vorum, H.;
Dumanski, J. P.; Tommerup, N.; Collins, J. E.; Wright, C. L.; Dunham,
I.; MacGinnitie, A. J.; Davidson, N. O.; Celis, J. E.: Psoriasis
upregulated phorbolin-1 shares structural but not functional similarity
to the mRNA-editing protein apobec-1. J. Invest. Derm. 113: 162-169,
1999.
5. Marchetto, M. C. N.; Narvaiza, I.; Denli, A. M.; Benner, C.; Lazzarini,
T. A.; Nathanson, J. L.; Paquola, A. C. M.; Desai, K. N.; Herai, R.
H.; Weitzman, M. D.; Yeo, G. W.; Muotri, A. R.; Gage, F. H.: Differential
L1 regulation in pluripotent stem cells of humans and apes. Nature 503:
525-529, 2013.
*FIELD* CN
Ada Hamosh - updated: 01/09/2014
Ada Hamosh - updated: 3/21/2013
Patricia A. Hartz - updated: 7/12/2006
Patricia A. Hartz - updated: 5/19/2003
*FIELD* CD
Paul J. Converse: 7/23/2002
*FIELD* ED
alopez: 01/09/2014
alopez: 12/4/2013
alopez: 4/2/2013
terry: 3/21/2013
joanna: 11/23/2009
mgross: 7/12/2006
mgross: 5/19/2003
mgross: 5/5/2003
mgross: 8/23/2002
mgross: 7/23/2002
*RECORD*
*FIELD* NO
607110
*FIELD* TI
*607110 APOLIPOPROTEIN B mRNA-EDITING ENZYME, CATALYTIC POLYPEPTIDE-LIKE 3B;
APOBEC3B
read more;;PHORBOLIN 1-RELATED PROTEIN
*FIELD* TX
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.
GENE STRUCTURE
Jarmuz et al. (2002) determined that the APOBEC3B gene contains 8 exons.
The 5-prime untranslated region and the 5-prime flanking region contain
repeated sequences. No TATA or CATT box was identified.
MAPPING
Using FISH and cosmid analyses, Madsen et al. (1999) mapped the
phorbolin-1-related gene to chromosome 22q13, close to the phorbolin-1
gene and centromeric to the PDGFB gene (190040).
By FISH and genomic sequence analysis, Jarmuz et al. (2002) mapped the
APOBEC3B gene within a tandem array of 7 APOBEC genes or pseudogenes on
chromosome 22q12-q13.2. All are oriented with a centromeric 5-prime end.
The authors noted that a similar expansion of the APOBEC family is not
present in rodents.
EVOLUTION
Marchetto et al. (2013) described the generation and initial
characterization of induced pluripotent stem (iPS) cells from
chimpanzees and bonobos as tools to explore factors that may have
contributed to great ape evolution. Comparative gene expression analysis
of human and nonhuman primate iPS cells revealed differences in the
regulation of long interspersed element-1 (L1) transposons. A force of
change in mammalian evolution, L1 elements are retrotransposons that
have remained active during primate evolution. Decreased levels of
L1-restricting factors APOBEC3B and PIWIL2 (610312) in nonhuman primate
iPS cells correlated with increased L1 mobility and endogenous L1 mRNA
levels. Moreover, results from the manipulation of APOBEC3B and PIWIL2
levels in iPS cells supported a causal inverse relationship between
levels of these proteins and L1 retrotransposition. Finally, Marchetto
et al. (2013) found increased copy numbers of species-specific L1
elements in the genome of chimpanzees compared to humans, supporting the
idea that increased L1 mobility in nonhuman primates is not limited to
iPS cells in culture and may have also occurred in the germline or
embryonic cells developmentally upstream to germline specification
during primate evolution. Marchetto et al. (2013) proposed that
differences in L1 mobility may have differentially shaped the genomes of
humans and nonhuman primates and could have continuing adaptive
significance.
*FIELD* RF
1. Bogerd, H. P.; Wiegand, H. L.; Hulme, A. E.; Garcia-Perez, J. L.;
O'Shea, K. S.; Moran, J. V.; Cullen, B. R.: Cellular inhibitors of
long interspersed element 1 and Alu retrotransposition. Proc. Nat.
Acad. Sci. 103: 8780-8785, 2006.
2. Burns, M. B.; Lackey, L.; Carpenter, M. A.; Rathore, A.; Land,
A. M.; Leonard, B.; Refsland, E. W.; Kotandeniya, D.; Tretyakova,
N.; Nikas, J. B.; Yee, D.; Temiz, N. A.; Donohue, D. E.; McDougle,
R. M.; Brown, W. L.; Law, E. K.; Harris, R. S.: APOBEC3B is an enzymatic
source of mutation in breast cancer. Nature 494: 366-370, 2013.
Note: Erratum: Nature 502: 580 only, 2013.
3. Jarmuz, A.; Chester, A.; Bayliss, J.; Gisbourne, J.; Dunham, I.;
Scott, J.; Navaratnam, N.: An anthropoid-specific locus of orphan
C to U RNA-editing enzymes on chromosome 22. Genomics 79: 285-296,
2002.
4. Madsen, P.; Anant, S.; Rasmussen, H. H.; Gromov, P.; Vorum, H.;
Dumanski, J. P.; Tommerup, N.; Collins, J. E.; Wright, C. L.; Dunham,
I.; MacGinnitie, A. J.; Davidson, N. O.; Celis, J. E.: Psoriasis
upregulated phorbolin-1 shares structural but not functional similarity
to the mRNA-editing protein apobec-1. J. Invest. Derm. 113: 162-169,
1999.
5. Marchetto, M. C. N.; Narvaiza, I.; Denli, A. M.; Benner, C.; Lazzarini,
T. A.; Nathanson, J. L.; Paquola, A. C. M.; Desai, K. N.; Herai, R.
H.; Weitzman, M. D.; Yeo, G. W.; Muotri, A. R.; Gage, F. H.: Differential
L1 regulation in pluripotent stem cells of humans and apes. Nature 503:
525-529, 2013.
*FIELD* CN
Ada Hamosh - updated: 01/09/2014
Ada Hamosh - updated: 3/21/2013
Patricia A. Hartz - updated: 7/12/2006
Patricia A. Hartz - updated: 5/19/2003
*FIELD* CD
Paul J. Converse: 7/23/2002
*FIELD* ED
alopez: 01/09/2014
alopez: 12/4/2013
alopez: 4/2/2013
terry: 3/21/2013
joanna: 11/23/2009
mgross: 7/12/2006
mgross: 5/19/2003
mgross: 5/5/2003
mgross: 8/23/2002
mgross: 7/23/2002