ABEC1_HUMAN
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 03-AUG-2022, entry version 188.
DE RecName: Full=C->U-editing enzyme APOBEC-1;
DE EC=3.5.4.36 {ECO:0000269|PubMed:11727199};
DE AltName: Full=Apolipoprotein B mRNA-editing enzyme 1;
DE AltName: Full=HEPR;
DE AltName: Full=mRNA(cytosine(6666)) deaminase 1;
GN Name=APOBEC1;
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], CHARACTERIZATION, AND VARIANT 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).
CC -!- FUNCTION: Catalytic component of the apolipoprotein B mRNA editing
CC enzyme complex which is responsible for the postranscriptional editing
CC of a CAA codon for Gln to a UAA codon for stop in the APOB mRNA. Also
CC involved in CGA (Arg) to UGA (Stop) editing in the NF1 mRNA. May also
CC play a role in the epigenetic regulation of gene expression by
CC participating in DNA demethylation. {ECO:0000269|PubMed:11727199}.
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 -!- 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. Part of the apolipoprotein B mRNA editing complex
CC with A1CF. Found in a complex with CELF2/CUGBP2 and A1CF. Interacts
CC with HNRPAB and SYNCRIP. {ECO:0000269|PubMed:11352648,
CC 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}.
CC -!- TISSUE SPECIFICITY: Expressed exclusively in the small intestine.
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; P41238; -.
DR PRIDE; P41238; -.
DR Antibodypedia; 22955; 169 antibodies from 26 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 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 OMA; MKLYALE; -.
DR OrthoDB; 1246623at2759; -.
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 1068 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 23 other tissues.
DR ExpressionAtlas; P41238; baseline and differential.
DR Genevisible; P41238; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0045293; C:mRNA editing complex; IC:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
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; IBA:GO_Central.
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 assembly; 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; IC: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:0006396; P:RNA processing; TAS:ProtInc.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
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 Pfam; PF18774; APOBEC4_like; 1.
DR SUPFAM; SSF53927; SSF53927; 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; Cytoplasm; Hydrolase; Metal-binding; mRNA processing;
KW 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
