ABC3F_HUMAN
ID ABC3F_HUMAN Reviewed; 373 AA.
AC Q8IUX4; B0QYD4; Q45F03; Q6ICH3; Q7Z2N2; Q7Z2N5;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 3.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=DNA dC->dU-editing enzyme APOBEC-3F;
DE EC=3.5.4.38;
DE AltName: Full=Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F;
DE Short=A3F;
GN Name=APOBEC3F;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS THR-178;
RP ILE-231 AND CYS-307.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
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., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., 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., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., 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., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP PRO-48 AND SER-108.
RC TISSUE=Pancreas, Spleen, and 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP GENE FAMILY ORGANIZATION, AND TISSUE SPECIFICITY.
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 seeking
RT roles in the family business.";
RL Trends Genet. 19:207-216(2003).
RN [8]
RP FUNCTION.
RX PubMed=15141007; DOI=10.1128/jvi.78.11.6073-6076.2004;
RA Zheng Y.H., Irwin D., Kurosu T., Tokunaga K., Sata T., Peterlin B.M.;
RT "Human APOBEC3F is another host factor that blocks human immunodeficiency
RT virus type 1 replication.";
RL J. Virol. 78:6073-6076(2004).
RN [9]
RP FUNCTION IN HIV-1 INFECTIVITY, INTERACTION WITH HIV-1 VIF, AND TISSUE
RP SPECIFICITY.
RX PubMed=15152192; DOI=10.1038/sj.emboj.7600246;
RA Wiegand H.L., Doehle B.P., Bogerd H.P., Cullen B.R.;
RT "A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1
RT and HIV-2 Vif proteins.";
RL EMBO J. 23:2451-2458(2004).
RN [10]
RP FUNCTION IN RETROTRANSPOSITION, AND SUBCELLULAR LOCATION.
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., Landau N.R.,
RA 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, AND MUTAGENESIS OF GLU-67 AND GLU-251.
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 FUNCTION IN SFV RESTRICTION.
RX PubMed=16378963; DOI=10.1128/jvi.80.2.605-614.2006;
RA Delebecque F., Suspene R., Calattini S., Casartelli N., Saib A.,
RA Froment A., Wain-Hobson S., Gessain A., Vartanian J.P., Schwartz O.;
RT "Restriction of foamy viruses by APOBEC cytidine deaminases.";
RL J. Virol. 80:605-614(2006).
RN [13]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH APOBEC3G.
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 localize
RT to mRNA processing bodies.";
RL PLoS Pathog. 2:E41-E41(2006).
RN [14]
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 [15]
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 deaminases
RT as effectors in innate immunity against the hepatitis B virus.";
RL Curr. Opin. Infect. Dis. 21:298-303(2008).
RN [16]
RP FUNCTION IN EIAV RESTRICTION.
RX PubMed=19458006; DOI=10.1128/jvi.00015-09;
RA Zielonka J., Bravo I.G., Marino D., Conrad E., Perkovic M., Battenberg M.,
RA Cichutek K., Muenk C.;
RT "Restriction of equine infectious anemia virus by equine APOBEC3 cytidine
RT deaminases.";
RL J. Virol. 83:7547-7559(2009).
RN [17]
RP FUNCTION IN HIV-1 RESTRICTION.
RX PubMed=20219927; DOI=10.1128/jvi.02358-09;
RA Mbisa J.L., Bu W., Pathak V.K.;
RT "APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different
RT mechanisms.";
RL J. Virol. 84:5250-5259(2010).
RN [18]
RP FUNCTION IN XMRV RESTRICTION.
RX PubMed=20335265; DOI=10.1128/jvi.00134-10;
RA Paprotka T., Venkatachari N.J., Chaipan C., Burdick R.,
RA Delviks-Frankenberry K.A., Hu W.S., Pathak V.K.;
RT "Inhibition of xenotropic murine leukemia virus-related virus by APOBEC3
RT proteins and antiviral drugs.";
RL J. Virol. 84:5719-5729(2010).
RN [19]
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 cells.";
RL Nat. Struct. Mol. Biol. 17:222-229(2010).
RN [20]
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 lymphocytes
RT and tissues: implications for HIV-1 restriction.";
RL Nucleic Acids Res. 38:4274-4284(2010).
RN [21]
RP FUNCTION IN DNA DEMETHYLATION.
RX PubMed=21496894; DOI=10.1016/j.cell.2011.03.022;
RA Guo J.U., Su Y., Zhong C., Ming G.L., Song H.;
RT "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA
RT demethylation in the adult brain.";
RL Cell 145:423-434(2011).
RN [22]
RP FUNCTION IN HIV-1 RESTRICTION, SUBCELLULAR LOCATION, AND ACTIVITY
RP REGULATION.
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 demonstrate a
RT conserved capacity to restrict Vif-deficient HIV-1.";
RL J. Virol. 85:11220-11234(2011).
RN [23]
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 [24]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH AGO1; AGO2 AND AGO3.
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 P
RT bodies.";
RL J. Virol. 86:11712-11724(2012).
RN [25]
RP FUNCTION IN HIV-1 INFECTIVITY, INTERACTION WITH HIV-1 VIF, AND MUTAGENESIS
RP OF GLU-251; LEU-255; PHE-258; CYS-259; 262-ILE-LEU-263; SER-264; TYR-269;
RP GLU-289; PHE-290; HIS-294 AND GLU-324.
RX PubMed=23001005; DOI=10.1038/nsmb.2378;
RA Kitamura S., Ode H., Nakashima M., Imahashi M., Naganawa Y., Kurosawa T.,
RA Yokomaku Y., Yamane T., Watanabe N., Suzuki A., Sugiura W., Iwatani Y.;
RT "The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.";
RL Nat. Struct. Mol. Biol. 19:1005-1010(2012).
RN [26]
RP FUNCTION IN HIV-1 RESTRICTION.
RX PubMed=22807680; DOI=10.1371/journal.ppat.1002800;
RA Refsland E.W., Hultquist J.F., Harris R.S.;
RT "Endogenous origins of HIV-1 G-to-A hypermutation and restriction in the
RT nonpermissive T cell line CEM2n.";
RL PLoS Pathog. 8:E1002800-E1002800(2012).
RN [27]
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).
RN [28]
RP FUNCTION IN HIV-1 RESTRICTION.
RX PubMed=23097438; DOI=10.1128/jvi.00676-12;
RA Chaipan C., Smith J.L., Hu W.S., Pathak V.K.;
RT "APOBEC3G restricts HIV-1 to a greater extent than APOBEC3F and APOBEC3DE
RT in human primary CD4+ t cells and macrophages.";
RL J. Virol. 87:444-453(2013).
RN [29]
RP FUNCTION IN HIV-1 RESTRICTION.
RX PubMed=23152537; DOI=10.1128/jvi.02587-12;
RA Gillick K., Pollpeter D., Phalora P., Kim E.Y., Wolinsky S.M., Malim M.H.;
RT "The suppression of HIV-1 infection by APOBEC3 proteins in primary human
RT CD4+ T cells is associated with the inhibition of processive reverse
RT transcription as well as excessive cytidine deamination.";
RL J. Virol. 87:1508-1517(2013).
RN [30]
RP FUNCTION.
RX PubMed=34774569; DOI=10.1016/j.jmb.2021.167355;
RA Meissner M.E., Willkomm N.A., Lucas J., Arndt W.G., Aitken S.F.,
RA Julik E.J., Baliga S., Mansky L.M.;
RT "Differential Activity of APOBEC3F, APOBEC3G, and APOBEC3H in the
RT Restriction of HIV-2.";
RL J. Mol. Biol. 434:167355-167355(2022).
RN [31] {ECO:0007744|PDB:5HX4, ECO:0007744|PDB:5HX5}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 185-373 IN COMPLEX WITH ZINC, AND
RP DISULFIDE BOND.
RX PubMed=27139641; DOI=10.1016/j.jmb.2016.04.026;
RA Shaban N.M., Shi K., Li M., Aihara H., Harris R.S.;
RT "1.92 Angstrom Zinc-Free APOBEC3F Catalytic Domain Crystal Structure.";
RL J. Mol. Biol. 428:2307-2316(2016).
CC -!- FUNCTION: DNA deaminase (cytidine deaminase) which acts as an inhibitor
CC of retrovirus replication and retrotransposon mobility via deaminase-
CC dependent and -independent mechanisms. Exhibits antiviral activity
CC against viruse such as HIV-1 or HIV-2 (PubMed:15141007,
CC PubMed:15152192, PubMed:23001005, PubMed:34774569). After the
CC penetration of retroviral nucleocapsids into target cells of infection
CC and the initiation of reverse transcription, it can induce the
CC conversion of cytosine to uracil in the minus-sense single-strand viral
CC DNA, leading to G-to-A hypermutations in the subsequent plus-strand
CC viral DNA (PubMed:15141007). The resultant detrimental levels of
CC mutations in the proviral genome, along with a deamination-independent
CC mechanism that works prior to the proviral integration, together exert
CC efficient antiretroviral effects in infected target cells. Selectively
CC targets single-stranded DNA and does not deaminate double-stranded DNA
CC or single- or double-stranded RNA. Exhibits antiviral activity also
CC against hepatitis B virus (HBV), equine infectious anemia virus (EIAV),
CC xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV) and
CC may inhibit the mobility of LTR and non-LTR retrotransposons. May also
CC play a role in the epigenetic regulation of gene expression through the
CC process of active DNA demethylation. {ECO:0000269|PubMed:15141007,
CC ECO:0000269|PubMed:15152192, ECO:0000269|PubMed:16378963,
CC ECO:0000269|PubMed:16527742, ECO:0000269|PubMed:19458006,
CC ECO:0000269|PubMed:20062055, ECO:0000269|PubMed:20219927,
CC ECO:0000269|PubMed:20335265, ECO:0000269|PubMed:21496894,
CC ECO:0000269|PubMed:21835787, ECO:0000269|PubMed:22807680,
CC ECO:0000269|PubMed:22915799, ECO:0000269|PubMed:23001005,
CC ECO:0000269|PubMed:23097438, ECO:0000269|PubMed:23152537,
CC ECO:0000269|PubMed:34774569}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in single-stranded DNA + H(+) + H2O = a 2'-
CC deoxyuridine in single-stranded DNA + NH4(+); Xref=Rhea:RHEA:50948,
CC Rhea:RHEA-COMP:12846, Rhea:RHEA-COMP:12847, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:85452,
CC ChEBI:CHEBI:133902; EC=3.5.4.38;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Antiviral activity is neutralized by the HIV-1
CC virion infectivity factor (Vif), that prevents its incorporation into
CC progeny virions by both inhibiting its translation and/or by inducing
CC its ubiquitination and subsequent degradation by the 26S proteasome.
CC {ECO:0000269|PubMed:21835787}.
CC -!- SUBUNIT: Interacts with APOBEC3G in an RNA-dependent manner
CC (PubMed:16699599). Interacts with AGO1, AGO2 and AGO3
CC (PubMed:22915799). {ECO:0000269|PubMed:16699599,
CC ECO:0000269|PubMed:22915799}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Vif
CC (PubMed:15152192, PubMed:23001005). In the absence of Vif protein,
CC specifically packaged into HIV-1 virions (PubMed:15152192).
CC {ECO:0000269|PubMed:15152192, ECO:0000269|PubMed:23001005}.
CC -!- INTERACTION:
CC Q8IUX4; Q8IUX4: APOBEC3F; NbExp=2; IntAct=EBI-11306991, EBI-11306991;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, P-body.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IUX4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IUX4-2; Sequence=VSP_009803, VSP_009804;
CC Name=3;
CC IsoId=Q8IUX4-3; Sequence=VSP_042754, VSP_042755;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in ovary.
CC {ECO:0000269|PubMed:11863358, ECO:0000269|PubMed:15152192,
CC ECO:0000269|PubMed:20308164}.
CC -!- INDUCTION: Up-regulated by IFN-alpha.
CC -!- DOMAIN: The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-
CC dependent oligomerization and virion incorporation whereas the CMP/dCMP
CC deaminase domain 2 confers deoxycytidine deaminase activity and
CC substrate sequence specificity. {ECO:0000269|PubMed:17020885}.
CC -!- MISCELLANEOUS: It is one of seven related genes or pseudogenes found in
CC a cluster, thought to result from gene duplication, on chromosome 22.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing donor splice
CC site. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/apobec3f/";
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DR EMBL; CR456395; CAG30281.1; -; mRNA.
DR EMBL; DQ146365; AAZ38720.1; -; Genomic_DNA.
DR EMBL; AL022318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60288.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW60289.1; -; Genomic_DNA.
DR EMBL; BC038808; AAH38808.1; -; mRNA.
DR EMBL; BC061914; AAH61914.1; -; mRNA.
DR CCDS; CCDS33648.1; -. [Q8IUX4-1]
DR CCDS; CCDS33649.1; -. [Q8IUX4-3]
DR RefSeq; NP_001006667.1; NM_001006666.1. [Q8IUX4-3]
DR RefSeq; NP_660341.2; NM_145298.5. [Q8IUX4-1]
DR RefSeq; XP_016884132.1; XM_017028643.1. [Q8IUX4-3]
DR PDB; 3WUS; X-ray; 2.54 A; A/B=187-373.
DR PDB; 4IOU; X-ray; 2.75 A; A/B/C/D=185-373.
DR PDB; 4J4J; X-ray; 3.10 A; A/B=218-373.
DR PDB; 5HX4; X-ray; 1.92 A; A/B=185-373.
DR PDB; 5HX5; X-ray; 2.33 A; A/B=185-373.
DR PDB; 5W2M; X-ray; 3.70 A; A/B/C/D/J/K/L/M=190-373.
DR PDB; 5ZVA; X-ray; 2.30 A; A/B=220-373.
DR PDB; 5ZVB; X-ray; 2.00 A; A/B=220-373.
DR PDB; 6NIL; EM; 3.90 A; A/D/G/J=185-373.
DR PDBsum; 3WUS; -.
DR PDBsum; 4IOU; -.
DR PDBsum; 4J4J; -.
DR PDBsum; 5HX4; -.
DR PDBsum; 5HX5; -.
DR PDBsum; 5W2M; -.
DR PDBsum; 5ZVA; -.
DR PDBsum; 5ZVB; -.
DR PDBsum; 6NIL; -.
DR AlphaFoldDB; Q8IUX4; -.
DR SMR; Q8IUX4; -.
DR BioGRID; 128319; 146.
DR DIP; DIP-59966N; -.
DR IntAct; Q8IUX4; 13.
DR STRING; 9606.ENSP00000309749; -.
DR ChEMBL; CHEMBL2007626; -.
DR iPTMnet; Q8IUX4; -.
DR PhosphoSitePlus; Q8IUX4; -.
DR BioMuta; APOBEC3F; -.
DR DMDM; 161784334; -.
DR EPD; Q8IUX4; -.
DR jPOST; Q8IUX4; -.
DR MassIVE; Q8IUX4; -.
DR MaxQB; Q8IUX4; -.
DR PaxDb; Q8IUX4; -.
DR PeptideAtlas; Q8IUX4; -.
DR PRIDE; Q8IUX4; -.
DR ProteomicsDB; 70623; -. [Q8IUX4-1]
DR ProteomicsDB; 70624; -. [Q8IUX4-2]
DR ProteomicsDB; 70625; -. [Q8IUX4-3]
DR Antibodypedia; 34783; 201 antibodies from 20 providers.
DR DNASU; 200316; -.
DR Ensembl; ENST00000308521.10; ENSP00000309749.5; ENSG00000128394.17. [Q8IUX4-1]
DR Ensembl; ENST00000381565.2; ENSP00000370977.2; ENSG00000128394.17. [Q8IUX4-3]
DR GeneID; 200316; -.
DR KEGG; hsa:200316; -.
DR MANE-Select; ENST00000308521.10; ENSP00000309749.5; NM_145298.6; NP_660341.2.
DR UCSC; uc003awv.4; human. [Q8IUX4-1]
DR CTD; 200316; -.
DR DisGeNET; 200316; -.
DR GeneCards; APOBEC3F; -.
DR HGNC; HGNC:17356; APOBEC3F.
DR HPA; ENSG00000128394; Low tissue specificity.
DR MIM; 608993; gene.
DR neXtProt; NX_Q8IUX4; -.
DR OpenTargets; ENSG00000128394; -.
DR PharmGKB; PA24896; -.
DR VEuPathDB; HostDB:ENSG00000128394; -.
DR eggNOG; KOG4075; Eukaryota.
DR GeneTree; ENSGT00940000162695; -.
DR HOGENOM; CLU_047918_0_0_1; -.
DR OMA; PWNGLNE; -.
DR PhylomeDB; Q8IUX4; -.
DR TreeFam; TF331356; -.
DR BRENDA; 3.5.4.38; 2681.
DR PathwayCommons; Q8IUX4; -.
DR SignaLink; Q8IUX4; -.
DR SIGNOR; Q8IUX4; -.
DR BioGRID-ORCS; 200316; 13 hits in 1019 CRISPR screens.
DR ChiTaRS; APOBEC3F; human.
DR GeneWiki; APOBEC3F; -.
DR GenomeRNAi; 200316; -.
DR Pharos; Q8IUX4; Tbio.
DR PRO; PR:Q8IUX4; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8IUX4; protein.
DR Bgee; ENSG00000128394; Expressed in granulocyte and 103 other tissues.
DR Genevisible; Q8IUX4; HS.
DR GO; GO:0030895; C:apolipoprotein B mRNA editing enzyme complex; TAS:HGNC-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0004126; F:cytidine deaminase activity; IDA:HGNC-UCL.
DR GO; GO:0047844; F:deoxycytidine deaminase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003723; F:RNA binding; IDA:HGNC-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:HGNC-UCL.
DR GO; GO:0016553; P:base conversion or substitution editing; IDA:HGNC-UCL.
DR GO; GO:0016554; P:cytidine to uridine editing; IBA:GO_Central.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0070383; P:DNA cytosine deamination; IDA:UniProtKB.
DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IDA:HGNC-UCL.
DR GO; GO:0045869; P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; IDA:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0048525; P:negative regulation of viral process; IDA:HGNC-UCL.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:HGNC-UCL.
DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR SUPFAM; SSF53927; SSF53927; 2.
DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 2.
DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiviral defense; Cytoplasm;
KW Disulfide bond; Host-virus interaction; Hydrolase; Immunity;
KW Innate immunity; Metal-binding; Reference proteome; Repeat; Zinc.
FT CHAIN 1..373
FT /note="DNA dC->dU-editing enzyme APOBEC-3F"
FT /id="PRO_0000171757"
FT DOMAIN 29..137
FT /note="CMP/dCMP-type deaminase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT DOMAIN 174..321
FT /note="CMP/dCMP-type deaminase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT ACT_SITE 251
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083,
FT ECO:0000269|PubMed:27139641"
FT BINDING 280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083,
FT ECO:0000269|PubMed:27139641"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083,
FT ECO:0000269|PubMed:27139641"
FT DISULFID 280..283
FT /evidence="ECO:0007744|PDB:5HX4"
FT VAR_SEQ 58..79
FT /note="VYSQPEHHAEMCFLSWFCGNQL -> VPPGLQSLCRQELSQLGKQTTH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009803"
FT VAR_SEQ 59..113
FT /note="YSQPEHHAEMCFLSWFCGNQLPAYKCFQITWFVSWTPCPDCVAKLAEFLAEH
FT PNV -> PRSFIRAPFQVLSSPFGQCAPPHGTAQVQWPPQLTAGREQGRP (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15461802"
FT /id="VSP_042754"
FT VAR_SEQ 80..373
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009804"
FT VAR_SEQ 114..373
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15461802"
FT /id="VSP_042755"
FT VARIANT 48
FT /note="R -> P (in dbSNP:rs35053197)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038355"
FT VARIANT 61
FT /note="Q -> L (in dbSNP:rs2076109)"
FT /id="VAR_018145"
FT VARIANT 97
FT /note="P -> L (in dbSNP:rs201939303)"
FT /id="VAR_018146"
FT VARIANT 108
FT /note="A -> S (in dbSNP:rs2020390)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_018147"
FT VARIANT 178
FT /note="A -> T (in dbSNP:rs34182094)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025058"
FT VARIANT 231
FT /note="V -> I (in dbSNP:rs2076101)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_018148"
FT VARIANT 307
FT /note="Y -> C (in dbSNP:rs12157816)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025059"
FT MUTAGEN 67
FT /note="E->A: Decrease in cytidine deaminase and antiviral
FT activity; when associated with A-251."
FT /evidence="ECO:0000269|PubMed:17020885"
FT MUTAGEN 67
FT /note="E->A: No effect on cytidine deaminase and antiviral
FT activity."
FT /evidence="ECO:0000269|PubMed:17020885"
FT MUTAGEN 251
FT /note="E->A: Decrease in cytidine deaminase and antiviral
FT activity."
FT /evidence="ECO:0000269|PubMed:17020885"
FT MUTAGEN 251
FT /note="E->A: Decrease in cytidine deaminase and antiviral
FT activity; when associated with A-67."
FT /evidence="ECO:0000269|PubMed:17020885"
FT MUTAGEN 251
FT /note="E->Q: Remains able to bind Vif."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 255
FT /note="L->D: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 258
FT /note="F->A: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 259
FT /note="C->K: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 262..263
FT /note="IL->AA: Resistant to HIV-1 Vif and abolishes Vif
FT binding but is still efficiently incorporated into the
FT virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 264
FT /note="S->D: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 269
FT /note="Y->A: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 289
FT /note="E->K: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 290
FT /note="F->K: Resistant to HIV-1 Vif and reduces Vif binding
FT but is still efficiently incorporated into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 294
FT /note="H->D: Resistant to HIV-1 Vif, reduces Vif binding
FT and abolishes incorporation into the virion."
FT /evidence="ECO:0000269|PubMed:23001005"
FT MUTAGEN 324
FT /note="E->K,A: Resistant to HIV-1 Vif and reduces Vif
FT binding."
FT /evidence="ECO:0000269|PubMed:23001005"
FT HELIX 197..204
FT /evidence="ECO:0007829|PDB:5HX4"
FT HELIX 208..212
FT /evidence="ECO:0007829|PDB:5HX4"
FT STRAND 217..226
FT /evidence="ECO:0007829|PDB:5HX4"
FT STRAND 232..239
FT /evidence="ECO:0007829|PDB:5HX4"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:5ZVB"
FT HELIX 250..261
FT /evidence="ECO:0007829|PDB:5HX4"
FT STRAND 267..277
FT /evidence="ECO:0007829|PDB:5HX4"
FT HELIX 281..293
FT /evidence="ECO:0007829|PDB:5HX4"
FT STRAND 297..305
FT /evidence="ECO:0007829|PDB:5HX4"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:5ZVB"
FT HELIX 312..323
FT /evidence="ECO:0007829|PDB:5HX4"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:5HX4"
FT HELIX 333..343
FT /evidence="ECO:0007829|PDB:5HX4"
FT HELIX 357..372
FT /evidence="ECO:0007829|PDB:5HX4"
SQ SEQUENCE 373 AA; 45020 MW; AF1A0E13830695F4 CRC64;
MKPHFRNTVE RMYRDTFSYN FYNRPILSRR NTVWLCYEVK TKGPSRPRLD AKIFRGQVYS
QPEHHAEMCF LSWFCGNQLP AYKCFQITWF VSWTPCPDCV AKLAEFLAEH PNVTLTISAA
RLYYYWERDY RRALCRLSQA GARVKIMDDE EFAYCWENFV YSEGQPFMPW YKFDDNYAFL
HRTLKEILRN PMEAMYPHIF YFHFKNLRKA YGRNESWLCF TMEVVKHHSP VSWKRGVFRN
QVDPETHCHA ERCFLSWFCD DILSPNTNYE VTWYTSWSPC PECAGEVAEF LARHSNVNLT
IFTARLYYFW DTDYQEGLRS LSQEGASVEI MGYKDFKYCW ENFVYNDDEP FKPWKGLKYN
FLFLDSKLQE ILE
