ID ABEC2_HUMAN Reviewed; 224 AA. AC Q9Y235; B2R899; Q53F28; Q5TGU5; Q5TGU6; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 24-JAN-2024, entry version 160. DE RecName: Full=C->U-editing enzyme APOBEC-2; DE EC=3.5.4.36 {ECO:0000269|PubMed:17187054}; DE AltName: Full=mRNA(cytosine(6666)) deaminase 2; GN Name=APOBEC2; 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]. RC TISSUE=Heart; RX PubMed=10403781; DOI=10.1006/bbrc.1999.0925; RA Liao W., Hong S.-H., Chan B.H.-J., Rudolph F.B., Clark S.C., Chan L.; RT "APOBEC-2, a cardiac- and skeletal muscle-specific member of the cytidine RT deaminase supergene family."; RL Biochem. Biophys. Res. Commun. 260:398-404(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skeletal muscle; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-136. RC TISSUE=Pancreas; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=PNS; 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 [7] 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 [8] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 41-224, FUNCTION, CATALYTIC RP ACTIVITY, SUBUNIT, COFACTOR, ACTIVE SITE, AND ZINC-BINDING SITES. RX PubMed=17187054; DOI=10.1038/nature05492; RA Prochnow C., Bransteitter R., Klein M.G., Goodman M.F., Chen X.S.; RT "The APOBEC-2 crystal structure and functional implications for the RT deaminase AID."; RL Nature 445:447-451(2007). CC -!- FUNCTION: Probable C to U editing enzyme whose physiological substrate CC is not yet known. Does not display detectable apoB mRNA editing. Has a CC low intrinsic cytidine deaminase activity. May play a role in the CC epigenetic regulation of gene expression through the process of active CC DNA demethylation. {ECO:0000269|PubMed:17187054, CC ECO:0000269|PubMed:21496894}. CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(6666) in apoB mRNA + H(+) + H2O = NH4(+) + CC uridine(6666) in apoB mRNA; Xref=Rhea:RHEA:21772, Rhea:RHEA- CC COMP:13888, Rhea:RHEA-COMP:13889, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:65315, CC ChEBI:CHEBI:82748; EC=3.5.4.36; CC Evidence={ECO:0000269|PubMed:17187054}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:17187054}; CC Note=Binds 1 Zn(2+) ion per subunit. {ECO:0000269|PubMed:17187054}; CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:17187054}. CC -!- INTERACTION: CC Q9Y235; Q9Y235: APOBEC2; NbExp=2; IntAct=EBI-15616888, EBI-15616888; CC -!- TISSUE SPECIFICITY: Expressed exclusively in heart and skeletal muscle. 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; AF161698; AAD45360.1; -; mRNA. DR EMBL; AK223461; BAD97181.1; -; mRNA. DR EMBL; AK313288; BAG36096.1; -; mRNA. DR EMBL; AL031778; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX04009.1; -; Genomic_DNA. DR EMBL; BC047767; AAH47767.1; -; mRNA. DR EMBL; BC069688; AAH69688.1; -; mRNA. DR EMBL; BC069764; AAH69764.1; -; mRNA. DR CCDS; CCDS4848.1; -. DR RefSeq; NP_006780.1; NM_006789.3. DR PDB; 2NYT; X-ray; 2.50 A; A/B/C/D=41-224. DR PDBsum; 2NYT; -. DR AlphaFoldDB; Q9Y235; -. DR BMRB; Q9Y235; -. DR SMR; Q9Y235; -. DR BioGRID; 116133; 1. DR DIP; DIP-60263N; -. DR STRING; 9606.ENSP00000244669; -. DR iPTMnet; Q9Y235; -. DR PhosphoSitePlus; Q9Y235; -. DR BioMuta; APOBEC2; -. DR DMDM; 23396446; -. DR MassIVE; Q9Y235; -. DR PaxDb; 9606-ENSP00000244669; -. DR PeptideAtlas; Q9Y235; -. DR ProteomicsDB; 85628; -. DR Antibodypedia; 2816; 293 antibodies from 32 providers. DR DNASU; 10930; -. DR Ensembl; ENST00000244669.3; ENSP00000244669.2; ENSG00000124701.6. DR GeneID; 10930; -. DR KEGG; hsa:10930; -. DR MANE-Select; ENST00000244669.3; ENSP00000244669.2; NM_006789.4; NP_006780.1. DR UCSC; uc003opl.4; human. DR AGR; HGNC:605; -. DR CTD; 10930; -. DR DisGeNET; 10930; -. DR GeneCards; APOBEC2; -. DR HGNC; HGNC:605; APOBEC2. DR HPA; ENSG00000124701; Tissue enhanced (heart muscle, skeletal muscle, tongue). DR MIM; 604797; gene. DR neXtProt; NX_Q9Y235; -. DR OpenTargets; ENSG00000124701; -. DR PharmGKB; PA24890; -. DR VEuPathDB; HostDB:ENSG00000124701; -. DR eggNOG; ENOG502RABR; Eukaryota. DR GeneTree; ENSGT00940000156616; -. DR HOGENOM; CLU_080056_0_0_1; -. DR InParanoid; Q9Y235; -. DR OMA; MAQKEET; -. DR OrthoDB; 4187079at2759; -. DR PhylomeDB; Q9Y235; -. DR TreeFam; TF331356; -. DR PathwayCommons; Q9Y235; -. DR Reactome; R-HSA-72200; mRNA Editing: C to U Conversion. DR Reactome; R-HSA-75094; Formation of the Editosome. DR BioGRID-ORCS; 10930; 11 hits in 1153 CRISPR screens. DR ChiTaRS; APOBEC2; human. DR EvolutionaryTrace; Q9Y235; -. DR GeneWiki; APOBEC2; -. DR GenomeRNAi; 10930; -. DR Pharos; Q9Y235; Tbio. DR PRO; PR:Q9Y235; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9Y235; Protein. DR Bgee; ENSG00000124701; Expressed in skeletal muscle tissue of rectus abdominis and 137 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0004126; F:cytidine deaminase activity; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0016554; P:cytidine to uridine editing; IDA:MGI. DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB. DR GO; GO:0016556; P:mRNA modification; IEA:Ensembl. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1. DR InterPro; IPR002125; CMP_dCMP_dom. DR InterPro; IPR016193; Cytidine_deaminase-like. DR PANTHER; PTHR13857:SF4; C-U-EDITING ENZYME APOBEC-2; 1. DR PANTHER; PTHR13857; MRNA EDITING ENZYME; 1. DR Pfam; PF18772; APOBEC2; 1. DR SUPFAM; SSF53927; Cytidine deaminase-like; 1. DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1. DR Genevisible; Q9Y235; HS. PE 1: Evidence at protein level; KW 3D-structure; Hydrolase; Metal-binding; mRNA processing; KW Reference proteome; Zinc. FT CHAIN 1..224 FT /note="C->U-editing enzyme APOBEC-2" FT /id="PRO_0000171749" FT DOMAIN 64..169 FT /note="CMP/dCMP-type deaminase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 100 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:17187054" FT BINDING 60 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:17187054" FT BINDING 98 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:17187054" FT BINDING 128 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:17187054" FT BINDING 131 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:17187054" FT VARIANT 136 FT /note="I -> T (in dbSNP:rs2076472)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_024406" FT HELIX 48..53 FT /evidence="ECO:0007829|PDB:2NYT" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:2NYT" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:2NYT" FT STRAND 68..77 FT /evidence="ECO:0007829|PDB:2NYT" FT STRAND 83..94 FT /evidence="ECO:0007829|PDB:2NYT" FT HELIX 99..106 FT /evidence="ECO:0007829|PDB:2NYT" FT STRAND 116..125 FT /evidence="ECO:0007829|PDB:2NYT" FT HELIX 129..141 FT /evidence="ECO:0007829|PDB:2NYT" FT STRAND 145..153 FT /evidence="ECO:0007829|PDB:2NYT" FT HELIX 160..171 FT /evidence="ECO:0007829|PDB:2NYT" FT STRAND 175..178 FT /evidence="ECO:0007829|PDB:2NYT" FT HELIX 181..191 FT /evidence="ECO:0007829|PDB:2NYT" FT HELIX 208..223 FT /evidence="ECO:0007829|PDB:2NYT" SQ SEQUENCE 224 AA; 25703 MW; CA0905AFAA8C8FA1 CRC64; MAQKEEAAVA TEAASQNGED LENLDDPEKL KELIELPPFE IVTGERLPAN FFKFQFRNVE YSSGRNKTFL CYVVEAQGKG GQVQASRGYL EDEHAAAHAE EAFFNTILPA FDPALRYNVT WYVSSSPCAA CADRIIKTLS KTKNLRLLIL VGRLFMWEEP EIQAALKKLK EAGCKLRIMK PQDFEYVWQN FVEQEEGESK AFQPWEDIQE NFLYYEEKLA DILK //