ID   ABEC1_HUMAN             Reviewed;         236 AA.
AC   P41238; Q9UE64; Q9UM71;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 3.
DT   27-MAR-2024, entry version 196.
DE   RecName: Full=C->U-editing enzyme APOBEC-1 {ECO:0000305|PubMed:11727199};
DE            EC=3.5.4.- {ECO:0000269|PubMed:11727199, ECO:0000269|PubMed:30844405};
DE   AltName: Full=Apolipoprotein B mRNA-editing enzyme catalytic subunit 1 {ECO:0000312|HGNC:HGNC:604};
DE            Short=APO1 {ECO:0000303|PubMed:30844405};
DE            Short=APOBEC-1 {ECO:0000303|PubMed:9186903};
DE            Short=Apolipoprotein B mRNA-editing enzyme 1;
DE            EC=3.5.4.36 {ECO:0000269|PubMed:11727199};
DE   AltName: Full=HEPR {ECO:0000303|PubMed:8208612};
DE   AltName: Full=mRNA(cytosine(6666)) deaminase 1 {ECO:0000305|PubMed:11727199};
GN   Name=APOBEC1 {ECO:0000312|HGNC:HGNC:604};
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], AND VARIANT ILE-80.
RC   TISSUE=Intestine;
RX   PubMed=8208612; DOI=10.1093/nar/22.10.1874;
RA   Hadjiagapiou C., Giannoni F., Funahashi T., Skarosi S.F., Davidson N.O.;
RT   "Molecular cloning of a human small intestinal apolipoprotein B mRNA
RT   editing protein.";
RL   Nucleic Acids Res. 22:1874-1879(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, TISSUE SPECIFICITY, AND VARIANT
RP   ILE-80.
RC   TISSUE=Small intestine;
RX   PubMed=8078915; DOI=10.1073/pnas.91.18.8522;
RA   Lau P.P., Zhu H.-J., Baldini A., Charnsangavej C., Chan L.;
RT   "Dimeric structure of a human apolipoprotein B mRNA editing protein and
RT   cloning and chromosomal localization of its gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:8522-8526(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-80.
RC   TISSUE=Osteosarcoma;
RX   PubMed=9186903;
RA   Hirano K., Min J., Funahashi T., Baunoch D.A., Davidson N.O.;
RT   "Characterization of the human apobec-1 gene: expression in
RT   gastrointestinal tissues determined by alternative splicing with production
RT   of a novel truncated peptide.";
RL   J. Lipid Res. 38:847-859(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-80.
RC   TISSUE=Peripheral blood leukocyte;
RX   PubMed=9479499; DOI=10.1006/geno.1997.5110;
RA   Fujino T., Navaratnam N., Scott J.;
RT   "Human apolipoprotein B RNA editing deaminase gene (APOBEC1).";
RL   Genomics 47:266-275(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 16-147.
RA   Hong S.H., Kim J.Q., Lee C.C.;
RT   "A novel mutation in exon 3 of the human apoB editing protein gene.";
RL   Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   INTERACTION WITH HNRPAB.
RX   PubMed=8999813; DOI=10.1074/jbc.272.3.1452;
RA   Lau P.P., Zhu H.J., Nakamuta M., Chan L.;
RT   "Cloning of an Apobec-1-binding protein that also interacts with
RT   apolipoprotein B mRNA and evidence for its involvement in RNA editing.";
RL   J. Biol. Chem. 272:1452-1455(1997).
RN   [7]
RP   INTERACTION WITH SYNCRIP.
RX   PubMed=11352648; DOI=10.1006/bbrc.2001.4679;
RA   Lau P.P., Chang B.-H., Chan L.;
RT   "Two-hybrid cloning identifies an RNA-binding protein, GRY-RBP, as a
RT   component of apobec-1 editosome.";
RL   Biochem. Biophys. Res. Commun. 282:977-983(2001).
RN   [8]
RP   FUNCTION IN NF1 EDITING, AND CATALYTIC ACTIVITY.
RX   PubMed=11727199; DOI=10.1086/337952;
RA   Mukhopadhyay D., Anant S., Lee R.M., Kennedy S., Viskochil D.,
RA   Davidson N.O.;
RT   "C-->U editing of neurofibromatosis 1 mRNA occurs in tumors that express
RT   both the type II transcript and apobec-1, the catalytic subunit of the
RT   apolipoprotein B mRNA-editing enzyme.";
RL   Am. J. Hum. Genet. 70:38-50(2002).
RN   [9]
RP   SUBCELLULAR LOCATION.
RX   PubMed=22580899; DOI=10.1161/atvbaha.112.250043;
RA   Sun H., Samarghandi A., Zhang N., Yao Z., Xiong M., Teng B.B.;
RT   "Proprotein convertase subtilisin/kexin type 9 interacts with
RT   apolipoprotein B and prevents its intracellular degradation, irrespective
RT   of the low-density lipoprotein receptor.";
RL   Arterioscler. Thromb. Vasc. Biol. 32:1585-1595(2012).
RN   [10]
RP   FUNCTION, INTERACTION WITH RBM47, AND SUBCELLULAR LOCATION.
RX   PubMed=24916387; DOI=10.15252/embr.201438450;
RA   Fossat N., Tourle K., Radziewic T., Barratt K., Liebhold D., Studdert J.B.,
RA   Power M., Jones V., Loebel D.A., Tam P.P.;
RT   "C to U RNA editing mediated by APOBEC1 requires RNA-binding protein
RT   RBM47.";
RL   EMBO Rep. 15:903-910(2014).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH A1CF AND RBM47.
RX   PubMed=30844405; DOI=10.1016/j.jmb.2019.02.025;
RA   Wolfe A.D., Arnold D.B., Chen X.S.;
RT   "Comparison of RNA Editing Activity of APOBEC1-A1CF and APOBEC1-RBM47
RT   Complexes Reconstituted in HEK293T Cells.";
RL   J. Mol. Biol. 431:1506-1517(2019).
CC   -!- FUNCTION: Cytidine deaminase catalyzing the cytidine to uridine
CC       postranscriptional editing of a variety of mRNAs (PubMed:30844405).
CC       Form complexes with cofactors that confer differential editing activity
CC       and selectivity. Responsible for the postranscriptional editing of a
CC       CAA codon for Gln to a UAA codon for stop in the apolipoprotein B mRNA
CC       (PubMed:24916387). Also involved in CGA (Arg) to UGA (Stop) editing in
CC       the NF1 mRNA (PubMed:11727199). May also play a role in the epigenetic
CC       regulation of gene expression by participating in DNA demethylation (By
CC       similarity). {ECO:0000250|UniProtKB:P51908,
CC       ECO:0000269|PubMed:11727199, ECO:0000269|PubMed:24916387,
CC       ECO:0000269|PubMed:30844405}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a cytidine in mRNA + H(+) + H2O = a uridine in mRNA + NH4(+);
CC         Xref=Rhea:RHEA:74355, Rhea:RHEA-COMP:14658, Rhea:RHEA-COMP:15145,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC         ChEBI:CHEBI:65315, ChEBI:CHEBI:82748;
CC         Evidence={ECO:0000269|PubMed:30844405};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:74356;
CC         Evidence={ECO:0000269|PubMed:30844405};
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:11727199};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21773;
CC         Evidence={ECO:0000269|PubMed:11727199};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q9Y235};
CC       Note=Binds 1 Zn(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9Y235};
CC   -!- SUBUNIT: Homodimer (PubMed:8078915). Interacts with A1CF; form an mRNA
CC       editing complex (PubMed:30844405). Interacts with RBM47; form an mRNA
CC       editing complex (PubMed:24916387, PubMed:30844405). Found in a complex
CC       with CELF2/CUGBP2 and A1CF. Interacts with HNRPAB (PubMed:8999813).
CC       Interacts with SYNCRIP (PubMed:11352648). {ECO:0000269|PubMed:11352648,
CC       ECO:0000269|PubMed:24916387, ECO:0000269|PubMed:30844405,
CC       ECO:0000269|PubMed:8078915, ECO:0000269|PubMed:8999813}.
CC   -!- INTERACTION:
CC       P41238; Q00534: CDK6; NbExp=3; IntAct=EBI-12819523, EBI-295663;
CC       P41238; P52597: HNRNPF; NbExp=3; IntAct=EBI-12819523, EBI-352986;
CC       P41238; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-12819523, EBI-7060731;
CC       P41238; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-12819523, EBI-1048945;
CC       P41238; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-12819523, EBI-12111050;
CC       P41238; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-12819523, EBI-11962084;
CC       P41238; A8MTQ0: NOTO; NbExp=3; IntAct=EBI-12819523, EBI-17490746;
CC       P41238; Q9NUQ7: UFSP2; NbExp=3; IntAct=EBI-12819523, EBI-11153325;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22580899}. Nucleus
CC       {ECO:0000269|PubMed:24916387}.
CC   -!- TISSUE SPECIFICITY: Expressed exclusively in the small intestine.
CC       {ECO:0000269|PubMed:8078915}.
CC   -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC       family. {ECO:0000305}.
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DR   EMBL; L25877; AAA86766.1; -; mRNA.
DR   EMBL; L26234; AAA64230.1; -; mRNA.
DR   EMBL; U72891; AAD00185.1; -; mRNA.
DR   EMBL; AB009426; BAA23882.1; -; Genomic_DNA.
DR   EMBL; U78720; AAD10701.1; -; mRNA.
DR   CCDS; CCDS8579.1; -.
DR   PIR; I59323; I59323.
DR   RefSeq; NP_001291495.1; NM_001304566.1.
DR   RefSeq; NP_001635.2; NM_001644.4.
DR   RefSeq; NP_005880.2; NM_005889.3.
DR   PDB; 6X91; X-ray; 3.51 A; A/B/C/D/E/F/G/H=15-236.
DR   PDBsum; 6X91; -.
DR   AlphaFoldDB; P41238; -.
DR   SMR; P41238; -.
DR   BioGRID; 106836; 18.
DR   ComplexPortal; CPX-1097; C-to-U editosome complex.
DR   IntAct; P41238; 8.
DR   STRING; 9606.ENSP00000229304; -.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   iPTMnet; P41238; -.
DR   PhosphoSitePlus; P41238; -.
DR   BioMuta; APOBEC1; -.
DR   DMDM; 152013530; -.
DR   PaxDb; 9606-ENSP00000229304; -.
DR   Antibodypedia; 22955; 177 antibodies from 27 providers.
DR   DNASU; 339; -.
DR   Ensembl; ENST00000229304.5; ENSP00000229304.4; ENSG00000111701.7.
DR   GeneID; 339; -.
DR   KEGG; hsa:339; -.
DR   MANE-Select; ENST00000229304.5; ENSP00000229304.4; NM_001644.5; NP_001635.2.
DR   UCSC; uc001qtb.4; human.
DR   AGR; HGNC:604; -.
DR   CTD; 339; -.
DR   DisGeNET; 339; -.
DR   GeneCards; APOBEC1; -.
DR   HGNC; HGNC:604; APOBEC1.
DR   HPA; ENSG00000111701; Tissue enriched (intestine).
DR   MIM; 600130; gene.
DR   neXtProt; NX_P41238; -.
DR   OpenTargets; ENSG00000111701; -.
DR   PharmGKB; PA24889; -.
DR   VEuPathDB; HostDB:ENSG00000111701; -.
DR   eggNOG; ENOG502SNW2; Eukaryota.
DR   GeneTree; ENSGT00940000161190; -.
DR   HOGENOM; CLU_080056_3_0_1; -.
DR   InParanoid; P41238; -.
DR   OMA; MKLYALE; -.
DR   OrthoDB; 5296257at2759; -.
DR   PhylomeDB; P41238; -.
DR   TreeFam; TF331356; -.
DR   BRENDA; 3.5.4.36; 2681.
DR   BRENDA; 3.5.4.37; 2681.
DR   PathwayCommons; P41238; -.
DR   Reactome; R-HSA-72200; mRNA Editing: C to U Conversion.
DR   Reactome; R-HSA-75094; Formation of the Editosome.
DR   SignaLink; P41238; -.
DR   BioGRID-ORCS; 339; 11 hits in 1147 CRISPR screens.
DR   GeneWiki; APOBEC1; -.
DR   GenomeRNAi; 339; -.
DR   Pharos; P41238; Tbio.
DR   PRO; PR:P41238; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; P41238; Protein.
DR   Bgee; ENSG00000111701; Expressed in jejunal mucosa and 24 other cell types or tissues.
DR   ExpressionAtlas; P41238; baseline and differential.
DR   GO; GO:0030895; C:apolipoprotein B mRNA editing enzyme complex; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0045293; C:mRNA editing complex; NAS:ComplexPortal.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0004126; F:cytidine deaminase activity; IBA:GO_Central.
DR   GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IEA:Ensembl.
DR   GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR   GO; GO:0016554; P:cytidine to uridine editing; IDA:UniProtKB.
DR   GO; GO:0080111; P:DNA demethylation; ISS:UniProtKB.
DR   GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR   GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR   GO; GO:0042158; P:lipoprotein biosynthetic process; IEA:Ensembl.
DR   GO; GO:0042953; P:lipoprotein transport; IEA:Ensembl.
DR   GO; GO:0016556; P:mRNA modification; IDA:ComplexPortal.
DR   GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR   GO; GO:0048255; P:mRNA stabilization; IEA:Ensembl.
DR   GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin formation; ISS:UniProtKB.
DR   GO; GO:2000623; P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:ComplexPortal.
DR   GO; GO:0090209; P:negative regulation of triglyceride metabolic process; IEA:Ensembl.
DR   GO; GO:1901537; P:positive regulation of DNA demethylation; NAS:ComplexPortal.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR   GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
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; IPR041547; APOBEC1.
DR   InterPro; IPR002125; CMP_dCMP_dom.
DR   InterPro; IPR016193; Cytidine_deaminase-like.
DR   PANTHER; PTHR13857:SF26; C-U-EDITING ENZYME APOBEC-1; 1.
DR   PANTHER; PTHR13857; MRNA EDITING ENZYME; 1.
DR   Pfam; PF18774; APOBEC4_like; 1.
DR   SUPFAM; SSF53927; Cytidine deaminase-like; 1.
DR   PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1.
DR   PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1.
DR   Genevisible; P41238; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Hydrolase; Metal-binding; mRNA processing;
KW   Nucleus; Reference proteome; Zinc.
FT   CHAIN           1..236
FT                   /note="C->U-editing enzyme APOBEC-1"
FT                   /id="PRO_0000171742"
FT   DOMAIN          10..134
FT                   /note="CMP/dCMP-type deaminase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01083"
FT   ACT_SITE        63
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y235"
FT   BINDING         61
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y235"
FT   BINDING         93
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y235"
FT   BINDING         96
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y235"
FT   VARIANT         80
FT                   /note="M -> I (in dbSNP:rs2302515)"
FT                   /evidence="ECO:0000269|PubMed:8078915,
FT                   ECO:0000269|PubMed:8208612, ECO:0000269|PubMed:9186903,
FT                   ECO:0000269|PubMed:9479499"
FT                   /id="VAR_013779"
FT   VARIANT         236
FT                   /note="R -> K (in dbSNP:rs12820011)"
FT                   /id="VAR_048720"
FT   CONFLICT        53
FT                   /note="S -> T (in Ref. 5; AAD10701)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        83
FT                   /note="S -> T (in Ref. 5; AAD10701)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   236 AA;  28192 MW;  28466B43F7FD82F7 CRC64;
     MTSEKGPSTG DPTLRRRIEP WEFDVFYDPR ELRKEACLLY EIKWGMSRKI WRSSGKNTTN
     HVEVNFIKKF TSERDFHPSM SCSITWFLSW SPCWECSQAI REFLSRHPGV TLVIYVARLF
     WHMDQQNRQG LRDLVNSGVT IQIMRASEYY HCWRNFVNYP PGDEAHWPQY PPLWMMLYAL
     ELHCIILSLP PCLKISRRWQ NHLTFFRLHL QNCHYQTIPP HILLATGLIH PSVAWR
//