ABEC2_HUMAN
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 03-AUG-2022, entry version 153.
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}.
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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; Q9Y235; -.
DR PeptideAtlas; Q9Y235; -.
DR PRIDE; Q9Y235; -.
DR ProteomicsDB; 85628; -.
DR Antibodypedia; 2816; 279 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 CTD; 10930; -.
DR DisGeNET; 10930; -.
DR GeneCards; APOBEC2; -.
DR HGNC; HGNC:605; APOBEC2.
DR HPA; ENSG00000124701; Group enriched (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 OMA; MAQKEET; -.
DR OrthoDB; 1380685at2759; -.
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; 10 hits in 1074 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 136 other tissues.
DR Genevisible; Q9Y235; HS.
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 InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR SUPFAM; SSF53927; SSF53927; 1.
DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1.
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
