ID ABC3A_HUMAN Reviewed; 199 AA. AC P31941; A0AVM1; Q12807; Q5JZ93; Q9UH18; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 3. DT 29-MAY-2024, entry version 195. DE RecName: Full=DNA dC->dU-editing enzyme APOBEC-3A; DE Short=A3A; DE EC=3.5.4.38 {ECO:0000269|PubMed:16527742, ECO:0000269|PubMed:20062055, ECO:0000269|PubMed:20615867, ECO:0000269|PubMed:21123384}; DE AltName: Full=Phorbolin-1; GN Name=APOBEC3A; 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 [MRNA], PROTEIN SEQUENCE OF 19-27; 31-35; 53-60; RP 112-123; 129-137 AND 192-198, AND FUNCTION. 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., Dumanski J.P., RA Tommerup N., Collins J.E., Wright C.L., Dunham I., Macginnitie A.J., RA Davidson N.O., Celis J.E.; RT "Psoriasis upregulated phorbolin-1 shares structural but not functional RT similarity to the mRNA-editing protein apobec-1."; RL J. Invest. Dermatol. 113:162-169(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [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 MRNA]. RC TISSUE=Brain; 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 [5] RP PROTEIN SEQUENCE OF 53-60; 112-121 AND 129-137. RC TISSUE=Keratinocyte; RX PubMed=1286667; DOI=10.1002/elps.11501301199; RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., RA Vandekerckhove J.; RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein RT database of normal human epidermal keratinocytes."; RL Electrophoresis 13:960-969(1992). 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 IN HOST DEFENSE. RX PubMed=12859895; DOI=10.1016/s0092-8674(03)00515-4; RA Mariani R., Chen D., Schroefelbauer B., Navarro F., Koenig R., Bollman B., RA 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 HOST DEFENSE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, RP MUTAGENESIS OF HIS-70; GLU-72 AND CYS-106, AND TISSUE SPECIFICITY. 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 [10] 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 [11] RP FUNCTION IN AAV INHIBITION, AND SUBCELLULAR LOCATION. RX PubMed=19461882; DOI=10.1371/journal.ppat.1000439; RA Narvaiza I., Linfesty D.C., Greener B.N., Hakata Y., Pintel D.J., Logue E., RA Landau N.R., Weitzman M.D.; RT "Deaminase-independent inhibition of parvoviruses by the APOBEC3A cytidine RT deaminase."; RL PLoS Pathog. 5:E1000439-E1000439(2009). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND ALTERNATIVE SPLICING (ISOFORMS RP 1 AND 2). RX PubMed=20615867; DOI=10.1074/jbc.m110.102822; RA Thielen B.K., McNevin J.P., McElrath M.J., Hunt B.V., Klein K.C., RA Lingappa J.R.; RT "Innate immune signaling induces high levels of TC-specific deaminase RT activity in primary monocyte-derived cells through expression of APOBEC3A RT isoforms."; RL J. Biol. Chem. 285:27753-27766(2010). RN [13] RP FUNCTION IN FOREIGN DNA CLEARANCE, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, RP AND INDUCTION. 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 [14] 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 [15] 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 [16] RP FUNCTION. RX PubMed=21460793; DOI=10.1038/embor.2011.46; RA Landry S., Narvaiza I., Linfesty D.C., Weitzman M.D.; RT "APOBEC3A can activate the DNA damage response and cause cell-cycle RT arrest."; RL EMBO Rep. 12:444-450(2011). RN [17] RP FUNCTION IN HOST DEFENSE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF ARG-28; HIS-29; LYS-30; ASN-57; LYS-60; ARG-69; GLU-72; RP TRP-98; ARG-128; TYR-130; ASP-131; ASP-133 AND TYR-136. RX PubMed=21123384; DOI=10.1128/jvi.01651-10; RA Bulliard Y., Narvaiza I., Bertero A., Peddi S., Roehrig U.F., Ortiz M., RA Zoete V., Castro-Diaz N., Turelli P., Telenti A., Michielin O., RA Weitzman M.D., Trono D.; RT "Structure-function analyses point to a polynucleotide-accommodating groove RT essential for APOBEC3A restriction activities."; RL J. Virol. 85:1765-1776(2011). 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 demonstrate a RT conserved capacity to restrict Vif-deficient HIV-1."; RL J. Virol. 85:11220-11234(2011). RN [19] RP FUNCTION. RX PubMed=21368204; DOI=10.1073/pnas.1009687108; RA Suspene R., Aynaud M.M., Guetard D., Henry M., Eckhoff G., Marchio A., RA Pineau P., Dejean A., Vartanian J.P., Wain-Hobson S.; RT "Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 RT cytidine deaminases, a pathway for DNA catabolism."; RL Proc. Natl. Acad. Sci. U.S.A. 108:4858-4863(2011). RN [20] RP REVIEW. RA Love R.; RT "Cytosine deaminases APOBEC3A, APOBEC3C, and APOBEC3H: Current RT understanding of their functional roles."; RL Student Perspec. Contemp. Virol. 0:0-0(2011). RN [21] 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 [22] RP FUNCTION. RX PubMed=22896697; DOI=10.1074/jbc.m112.385161; RA Carpenter M.A., Li M., Rathore A., Lackey L., Law E.K., Land A.M., RA Leonard B., Shandilya S.M., Bohn M.F., Schiffer C.A., Brown W.L., RA Harris R.S.; RT "Methylcytosine and normal cytosine deamination by the foreign DNA RT restriction enzyme APOBEC3A."; RL J. Biol. Chem. 287:34801-34808(2012). RN [23] RP INTERACTION WITH TRIB3, AND SUBCELLULAR LOCATION. RX PubMed=22977230; DOI=10.1074/jbc.m112.372722; RA Aynaud M.M., Suspene R., Vidalain P.O., Mussil B., Guetard D., Tangy F., RA Wain-Hobson S., Vartanian J.P.; RT "Human Tribbles 3 protects nuclear DNA from cytidine deamination by RT APOBEC3A."; RL J. Biol. Chem. 287:39182-39192(2012). RN [24] 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-lymphotropic RT virus type 1."; RL J. Virol. 86:6097-6108(2012). RN [25] RP INTERACTION WITH AGO2. 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 [26] 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) with restriction activity CC against viruses, foreign DNA and mobility of retrotransposons. Exhibits CC antiviral activity against adeno-associated virus (AAV) and human T- CC cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR CC and non-LTR retrotransposons. Selectively targets single-stranded DNA CC and can deaminate both methylcytosine and cytosine in foreign DNA. Can CC induce somatic hypermutation in the nuclear and mitochondrial DNA. May CC also play a role in the epigenetic regulation of gene expression CC through the process of active DNA demethylation. CC {ECO:0000269|PubMed:10469298, ECO:0000269|PubMed:12859895, CC ECO:0000269|PubMed:16527742, ECO:0000269|PubMed:19461882, CC ECO:0000269|PubMed:20062055, ECO:0000269|PubMed:20615867, CC ECO:0000269|PubMed:21123384, ECO:0000269|PubMed:21368204, CC ECO:0000269|PubMed:21460793, ECO:0000269|PubMed:21496894, CC ECO:0000269|PubMed:22457529, ECO:0000269|PubMed:22896697}. 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 Evidence={ECO:0000269|PubMed:16527742, ECO:0000269|PubMed:20062055, CC ECO:0000269|PubMed:20615867, ECO:0000269|PubMed:21123384}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC -!- SUBUNIT: Interacts with AGO2. Interacts with TRIB3 (via N-terminus). CC {ECO:0000269|PubMed:22915799, ECO:0000269|PubMed:22977230}. CC -!- INTERACTION: CC P31941; Q16775-2: HAGH; NbExp=3; IntAct=EBI-13050366, EBI-17557678; CC P31941; O95630: STAMBP; NbExp=3; IntAct=EBI-13050366, EBI-396676; CC P31941; Q784Z8: C; Xeno; NbExp=4; IntAct=EBI-13050366, EBI-11666471; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; Synonyms=Phorbolin-1; CC IsoId=P31941-1; Sequence=Displayed; CC Name=2; CC IsoId=P31941-2; Sequence=VSP_041723; CC -!- TISSUE SPECIFICITY: Expressed in peripheral leukocytes with higher CC expression in CD14-positive phagocytic cells. Highly expressed in CC keratinocytes and in periphery blood monocytes. Also detected in non- CC lymphoid tissues including lung and adipose tissues. Found at high CC levels in colorectal adenocarcinoma, Burkitt's lymphoma and chronic CC myelogenous leukemia. {ECO:0000269|PubMed:11863358, CC ECO:0000269|PubMed:16527742, ECO:0000269|PubMed:20062055, CC ECO:0000269|PubMed:20308164}. CC -!- INDUCTION: Up-regulated by interferon and CpG single-stranded DNA (at CC protein level). {ECO:0000269|PubMed:20062055, CC ECO:0000269|PubMed:20615867}. 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 1]: Enzymatically active. CC -!- MISCELLANEOUS: [Isoform 2]: Enzymatically active. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U03891; AAA03706.2; -; mRNA. DR EMBL; CR456393; CAG30279.1; -; mRNA. DR EMBL; AL022318; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC126416; AAI26417.1; -; mRNA. DR CCDS; CCDS13981.1; -. [P31941-1] DR PIR; G01233; G01233. DR RefSeq; NP_001180218.1; NM_001193289.1. [P31941-1] DR RefSeq; NP_663745.1; NM_145699.3. [P31941-1] DR PDB; 2M65; NMR; -; A=1-199. DR PDB; 4XXO; X-ray; 2.84 A; A/B=1-199. DR PDB; 5KEG; X-ray; 2.20 A; A=1-199. DR PDB; 5SWW; X-ray; 3.15 A; A/B/C/D=1-196. DR PDB; 7D3V; NMR; -; A/B=1-199. DR PDB; 7D3W; NMR; -; A=1-199. DR PDB; 7D3X; NMR; -; A=1-199. DR PDB; 8FII; X-ray; 2.94 A; A/B=1-199. DR PDB; 8FIJ; X-ray; 2.80 A; A/B=1-199. DR PDB; 8FIK; X-ray; 1.91 A; A/B=1-199. DR PDB; 8FIL; X-ray; 2.01 A; A/B=1-199. DR PDB; 8FIM; X-ray; 2.22 A; A/B=1-199. DR PDBsum; 2M65; -. DR PDBsum; 4XXO; -. DR PDBsum; 5KEG; -. DR PDBsum; 5SWW; -. DR PDBsum; 7D3V; -. DR PDBsum; 7D3W; -. DR PDBsum; 7D3X; -. DR PDBsum; 8FII; -. DR PDBsum; 8FIJ; -. DR PDBsum; 8FIK; -. DR PDBsum; 8FIL; -. DR PDBsum; 8FIM; -. DR AlphaFoldDB; P31941; -. DR BMRB; P31941; -. DR SMR; P31941; -. DR BioGRID; 128318; 14. DR DIP; DIP-61365N; -. DR IntAct; P31941; 5. DR STRING; 9606.ENSP00000384359; -. DR BindingDB; P31941; -. DR ChEMBL; CHEMBL1741179; -. DR iPTMnet; P31941; -. DR PhosphoSitePlus; P31941; -. DR BioMuta; APOBEC3A; -. DR DMDM; 12644206; -. DR jPOST; P31941; -. DR MassIVE; P31941; -. DR MaxQB; P31941; -. DR PaxDb; 9606-ENSP00000384359; -. DR PeptideAtlas; P31941; -. DR ProteomicsDB; 54806; -. [P31941-1] DR ProteomicsDB; 54807; -. [P31941-2] DR Pumba; P31941; -. DR ABCD; P31941; 1 sequenced antibody. DR Antibodypedia; 26513; 268 antibodies from 33 providers. DR DNASU; 200315; -. DR Ensembl; ENST00000249116.7; ENSP00000249116.2; ENSG00000128383.14. [P31941-1] DR Ensembl; ENST00000402255.5; ENSP00000384359.1; ENSG00000128383.14. [P31941-1] DR Ensembl; ENST00000570508.3; ENSP00000461288.1; ENSG00000262156.6. [P31941-1] DR Ensembl; ENST00000623492.3; ENSP00000485234.1; ENSG00000262156.6. [P31941-1] DR GeneID; 100913187; -. DR GeneID; 200315; -. DR KEGG; hsa:100913187; -. DR KEGG; hsa:200315; -. DR MANE-Select; ENST00000249116.7; ENSP00000249116.2; NM_145699.4; NP_663745.1. DR MANE-Select; ENST00000570508.3; ENSP00000461288.1; NM_001193289.2; NP_001180218.1. DR UCSC; uc003awn.2; human. [P31941-1] DR AGR; HGNC:17343; -. DR AGR; HGNC:44196; -. DR CTD; 100913187; -. DR CTD; 200315; -. DR DisGeNET; 100913187; -. DR DisGeNET; 200315; -. DR GeneCards; APOBEC3A; -. DR HGNC; HGNC:17343; APOBEC3A. DR HPA; ENSG00000128383; Group enriched (bone marrow, lymphoid tissue, urinary bladder). DR MIM; 607109; gene. DR neXtProt; NX_P31941; -. DR OpenTargets; ENSG00000128383; -. DR PharmGKB; PA24891; -. DR VEuPathDB; HostDB:ENSG00000128383; -. DR eggNOG; KOG4075; Eukaryota. DR GeneTree; ENSGT00940000164701; -. DR HOGENOM; CLU_080056_2_0_1; -. DR InParanoid; P31941; -. DR OMA; GNRWMIL; -. DR OrthoDB; 5355962at2759; -. DR PhylomeDB; P31941; -. DR TreeFam; TF331356; -. DR BRENDA; 3.5.4.38; 2681. DR PathwayCommons; P31941; -. DR Reactome; R-HSA-72200; mRNA Editing: C to U Conversion. DR Reactome; R-HSA-75094; Formation of the Editosome. DR SignaLink; P31941; -. DR SIGNOR; P31941; -. DR BioGRID-ORCS; 100913187; 2 hits in 89 CRISPR screens. DR BioGRID-ORCS; 200315; 13 hits in 1139 CRISPR screens. DR ChiTaRS; APOBEC3A; human. DR Pharos; P31941; Tchem. DR PRO; PR:P31941; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P31941; Protein. DR Bgee; ENSG00000128383; Expressed in monocyte and 136 other cell types or tissues. DR ExpressionAtlas; P31941; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000932; C:P-body; IBA:GO_Central. DR GO; GO:0004126; F:cytidine deaminase activity; IDA:UniProtKB. DR GO; GO:0047844; F:deoxycytidine deaminase activity; IMP:UniProtKB. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0044355; P:clearance of foreign intracellular DNA; IDA:UniProtKB. 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; IBA:GO_Central. DR GO; GO:0080111; P:DNA demethylation; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0045869; P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; IBA:GO_Central. DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB. DR GO; GO:0044029; P:positive regulation of gene expression via CpG island demethylation; IDA:UniProtKB. DR GO; GO:0010526; P:retrotransposon silencing; IDA:UniProtKB. DR CDD; cd01283; cytidine_deaminase; 1. DR Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1. DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd. DR InterPro; IPR002125; CMP_dCMP_dom. DR InterPro; IPR016193; Cytidine_deaminase-like. DR PANTHER; PTHR13857:SF39; DNA DC-DU-EDITING ENZYME APOBEC-3A-RELATED; 1. DR PANTHER; PTHR13857; MRNA EDITING ENZYME; 1. DR Pfam; PF18782; NAD2; 1. DR SUPFAM; SSF53927; Cytidine deaminase-like; 1. DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1. DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Antiviral defense; Cytoplasm; KW Direct protein sequencing; Hydrolase; Immunity; Innate immunity; KW Metal-binding; Nucleus; Reference proteome; Zinc. FT CHAIN 1..199 FT /note="DNA dC->dU-editing enzyme APOBEC-3A" FT /id="PRO_0000171752" FT DOMAIN 27..143 FT /note="CMP/dCMP-type deaminase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083" FT ACT_SITE 72 FT /note="Proton donor" FT /evidence="ECO:0000250" FT BINDING 70 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 101 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT BINDING 106 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250" FT VAR_SEQ 1..12 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_041723" FT VARIANT 19 FT /note="T -> A (in dbSNP:rs17000556)" FT /id="VAR_048721" FT MUTAGEN 28 FT /note="R->E: No effect on deaminase activity despite an FT altered restriction activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 29 FT /note="H->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 30 FT /note="K->F: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 57 FT /note="N->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 60 FT /note="K->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 69 FT /note="R->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 70 FT /note="H->R: Altered deaminase activity." FT /evidence="ECO:0000269|PubMed:16527742" FT MUTAGEN 72 FT /note="E->Q: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:16527742, FT ECO:0000269|PubMed:21123384" FT MUTAGEN 98 FT /note="W->L: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 106 FT /note="C->S: Altered deaminase activity." FT /evidence="ECO:0000269|PubMed:16527742" FT MUTAGEN 128 FT /note="R->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 130 FT /note="Y->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 131 FT /note="D->N: No effect on deaminase activity despite an FT altered restriction activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 133 FT /note="D->N: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT MUTAGEN 136 FT /note="Y->A: Altered deaminase activity and restriction FT activity towards genetic invaders." FT /evidence="ECO:0000269|PubMed:21123384" FT STRAND 6..8 FT /evidence="ECO:0007829|PDB:7D3W" FT HELIX 15..21 FT /evidence="ECO:0007829|PDB:5KEG" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:4XXO" FT STRAND 27..29 FT /evidence="ECO:0007829|PDB:2M65" FT STRAND 32..41 FT /evidence="ECO:0007829|PDB:5KEG" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:5KEG" FT HELIX 49..51 FT /evidence="ECO:0007829|PDB:5KEG" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:5KEG" FT TURN 62..65 FT /evidence="ECO:0007829|PDB:5KEG" FT HELIX 71..82 FT /evidence="ECO:0007829|PDB:5KEG" FT STRAND 88..98 FT /evidence="ECO:0007829|PDB:5KEG" FT TURN 103..105 FT /evidence="ECO:0007829|PDB:2M65" FT HELIX 106..116 FT /evidence="ECO:0007829|PDB:5KEG" FT STRAND 120..128 FT /evidence="ECO:0007829|PDB:5KEG" FT HELIX 136..145 FT /evidence="ECO:0007829|PDB:5KEG" FT STRAND 149..152 FT /evidence="ECO:0007829|PDB:5KEG" FT HELIX 155..165 FT /evidence="ECO:0007829|PDB:5KEG" FT HELIX 179..195 FT /evidence="ECO:0007829|PDB:5KEG" FT TURN 196..198 FT /evidence="ECO:0007829|PDB:7D3V" SQ SEQUENCE 199 AA; 23012 MW; 42E99E0D7DF7AA14 CRC64; MEASPASGPR HLMDPHIFTS NFNNGIGRHK TYLCYEVERL DNGTSVKMDQ HRGFLHNQAK NLLCGFYGRH AELRFLDLVP SLQLDPAQIY RVTWFISWSP CFSWGCAGEV RAFLQENTHV RLRIFAARIY DYDPLYKEAL QMLRDAGAQV SIMTYDEFKH CWDTFVDHQG CPFQPWDGLD EHSQALSGRL RAILQNQGN //