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Protein

DNA dC->dU-editing enzyme APOBEC-3F

Gene

APOBEC3F

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. Exhibits antiviral activity against vif-deficient HIV-1. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity also against hepatitis B virus (HBV), equine infectious anemia virus (EIAV), xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.13 Publications

Catalytic activityi

Cytidine + H2O = uridine + NH3.

Cofactori

Zn2+By similarity

Enzyme regulationi

Antiviral activity is neutralized by the HIV-1 virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi65 – 651ZincBy similarity
Metal bindingi96 – 961ZincBy similarity
Metal bindingi99 – 991ZincBy similarity
Active sitei251 – 2511Proton donorBy similarity

GO - Molecular functioni

  • cytidine deaminase activity Source: HGNC
  • poly(A) RNA binding Source: UniProtKB
  • RNA binding Source: HGNC
  • zinc ion binding Source: HGNC

GO - Biological processi

  • base conversion or substitution editing Source: HGNC
  • defense response to virus Source: UniProtKB
  • DNA cytosine deamination Source: UniProtKB
  • DNA demethylation Source: UniProtKB
  • innate immune response Source: HGNC
  • negative regulation of single stranded viral RNA replication via double stranded DNA intermediate Source: UniProtKB
  • negative regulation of transposition Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • negative regulation of viral process Source: HGNC
  • positive regulation of defense response to virus by host Source: HGNC
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
DNA dC->dU-editing enzyme APOBEC-3F (EC:3.5.4.-)
Alternative name(s):
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F
Short name:
A3F
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:17356. APOBEC3F.

Subcellular locationi

GO - Cellular componenti

  • apolipoprotein B mRNA editing enzyme complex Source: HGNC
  • cytoplasm Source: UniProtKB
  • cytoplasmic mRNA processing body Source: UniProtKB
  • intracellular ribonucleoprotein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi67 – 671E → A: Decrease in cytidine deaminase and antiviral activity; when associated with A-251. 1 Publication
Mutagenesisi67 – 671E → A: No effect on cytidine deaminase and antiviral activity. 1 Publication
Mutagenesisi251 – 2511E → A: Decrease in cytidine deaminase and antiviral activity. 1 Publication
Mutagenesisi251 – 2511E → A: Decrease in cytidine deaminase and antiviral activity; when associated with A-67. 1 Publication

Organism-specific databases

PharmGKBiPA24896.

Chemistry

ChEMBLiCHEMBL2007626.

Polymorphism and mutation databases

BioMutaiAPOBEC3F.
DMDMi161784334.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 373373DNA dC->dU-editing enzyme APOBEC-3FPRO_0000171757Add
BLAST

Proteomic databases

EPDiQ8IUX4.
MaxQBiQ8IUX4.
PaxDbiQ8IUX4.
PeptideAtlasiQ8IUX4.
PRIDEiQ8IUX4.

PTM databases

iPTMnetiQ8IUX4.
PhosphoSiteiQ8IUX4.

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in ovary.3 Publications

Inductioni

Up-regulated by IFN-alpha.

Gene expression databases

BgeeiENSG00000128394.
CleanExiHS_APOBEC3F.
GenevisibleiQ8IUX4. HS.

Interactioni

Subunit structurei

Binds HIV-1 Vif. In the absence of Vif protein, specifically packaged into HIV-1 virions. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with AGO1, AGO2 and AGO3.2 Publications

Protein-protein interaction databases

BioGridi128319. 8 interactions.
DIPiDIP-59966N.
IntActiQ8IUX4. 2 interactions.
MINTiMINT-6631309.
STRINGi9606.ENSP00000309749.

Structurei

Secondary structure

1
373
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi197 – 2037Combined sources
Beta strandi217 – 2259Combined sources
Beta strandi232 – 2398Combined sources
Beta strandi243 – 2453Combined sources
Helixi250 – 26112Combined sources
Beta strandi268 – 27710Combined sources
Helixi281 – 29313Combined sources
Beta strandi297 – 3059Combined sources
Turni307 – 3104Combined sources
Helixi312 – 32312Combined sources
Beta strandi327 – 3304Combined sources
Helixi333 – 34311Combined sources
Helixi357 – 37115Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3WUSX-ray2.54A/B187-373[»]
4IOUX-ray2.75A/B/C/D185-373[»]
4J4JX-ray3.10A/B218-373[»]
5HX4X-ray1.92A/B185-373[»]
5HX5X-ray2.33A/B185-373[»]
ProteinModelPortaliQ8IUX4.
SMRiQ8IUX4. Positions 12-373.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 137109CMP/dCMP-type deaminase 1PROSITE-ProRule annotationAdd
BLAST
Domaini174 – 321148CMP/dCMP-type deaminase 2PROSITE-ProRule annotationAdd
BLAST

Domaini

The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity.1 Publication

Sequence similaritiesi

Contains 2 CMP/dCMP-type deaminase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410JBA1. Eukaryota.
ENOG41119MS. LUCA.
GeneTreeiENSGT00530000062933.
HOGENOMiHOG000142455.
HOVERGENiHBG050434.
KOiK18750.
OMAiNEHIREN.
OrthoDBiEOG091G07EI.
PhylomeDBiQ8IUX4.
TreeFamiTF331356.

Family and domain databases

InterProiIPR016192. APOBEC/CMP_deaminase_Zn-bd.
IPR013158. APOBEC_N.
IPR002125. CMP_dCMP_Zn-bd.
IPR016193. Cytidine_deaminase-like.
[Graphical view]
PfamiPF08210. APOBEC_N. 2 hits.
[Graphical view]
SUPFAMiSSF53927. SSF53927. 2 hits.
PROSITEiPS00903. CYT_DCMP_DEAMINASES_1. 2 hits.
PS51747. CYT_DCMP_DEAMINASES_2. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IUX4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKPHFRNTVE RMYRDTFSYN FYNRPILSRR NTVWLCYEVK TKGPSRPRLD
60 70 80 90 100
AKIFRGQVYS QPEHHAEMCF LSWFCGNQLP AYKCFQITWF VSWTPCPDCV
110 120 130 140 150
AKLAEFLAEH PNVTLTISAA RLYYYWERDY RRALCRLSQA GARVKIMDDE
160 170 180 190 200
EFAYCWENFV YSEGQPFMPW YKFDDNYAFL HRTLKEILRN PMEAMYPHIF
210 220 230 240 250
YFHFKNLRKA YGRNESWLCF TMEVVKHHSP VSWKRGVFRN QVDPETHCHA
260 270 280 290 300
ERCFLSWFCD DILSPNTNYE VTWYTSWSPC PECAGEVAEF LARHSNVNLT
310 320 330 340 350
IFTARLYYFW DTDYQEGLRS LSQEGASVEI MGYKDFKYCW ENFVYNDDEP
360 370
FKPWKGLKYN FLFLDSKLQE ILE
Length:373
Mass (Da):45,020
Last modified:October 23, 2007 - v3
Checksum:iAF1A0E13830695F4
GO
Isoform 2 (identifier: Q8IUX4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     58-79: VYSQPEHHAEMCFLSWFCGNQL → VPPGLQSLCRQELSQLGKQTTH
     80-373: Missing.

Note: May be due to a competing donor splice site. No experimental confirmation available.
Show »
Length:79
Mass (Da):9,445
Checksum:i03ABEACA44AB0748
GO
Isoform 3 (identifier: Q8IUX4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     59-113: YSQPEHHAEM...AEFLAEHPNV → PRSFIRAPFQ...LTAGREQGRP
     114-373: Missing.

Show »
Length:101
Mass (Da):11,823
Checksum:i1659A5E223CB1EFE
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti48 – 481R → P.1 Publication
Corresponds to variant rs35053197 [ dbSNP | Ensembl ].
VAR_038355
Natural varianti61 – 611Q → L.
Corresponds to variant rs2076109 [ dbSNP | Ensembl ].
VAR_018145
Natural varianti97 – 971P → L.
Corresponds to variant rs2076110 [ dbSNP | Ensembl ].
VAR_018146
Natural varianti108 – 1081A → S.1 Publication
Corresponds to variant rs2020390 [ dbSNP | Ensembl ].
VAR_018147
Natural varianti178 – 1781A → T.1 Publication
Corresponds to variant rs34182094 [ dbSNP | Ensembl ].
VAR_025058
Natural varianti231 – 2311V → I.1 Publication
Corresponds to variant rs2076101 [ dbSNP | Ensembl ].
VAR_018148
Natural varianti307 – 3071Y → C.1 Publication
Corresponds to variant rs12157816 [ dbSNP | Ensembl ].
VAR_025059

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei58 – 7922VYSQP…CGNQL → VPPGLQSLCRQELSQLGKQT TH in isoform 2. 1 PublicationVSP_009803Add
BLAST
Alternative sequencei59 – 11355YSQPE…EHPNV → PRSFIRAPFQVLSSPFGQCA PPHGTAQVQWPPQLTAGREQ GRP in isoform 3. 1 PublicationVSP_042754Add
BLAST
Alternative sequencei80 – 373294Missing in isoform 2. 1 PublicationVSP_009804Add
BLAST
Alternative sequencei114 – 373260Missing in isoform 3. 1 PublicationVSP_042755Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR456395 mRNA. Translation: CAG30281.1.
DQ146365 Genomic DNA. Translation: AAZ38720.1.
AL022318 Genomic DNA. Translation: CAQ09853.1.
CH471095 Genomic DNA. Translation: EAW60288.1.
CH471095 Genomic DNA. Translation: EAW60289.1.
BC038808 mRNA. Translation: AAH38808.1.
BC061914 mRNA. Translation: AAH61914.1.
CCDSiCCDS33648.1. [Q8IUX4-1]
CCDS33649.1. [Q8IUX4-3]
RefSeqiNP_001006667.1. NM_001006666.1. [Q8IUX4-3]
NP_660341.2. NM_145298.5. [Q8IUX4-1]
UniGeneiHs.659809.
Hs.660143.

Genome annotation databases

EnsembliENST00000308521; ENSP00000309749; ENSG00000128394. [Q8IUX4-1]
ENST00000381565; ENSP00000370977; ENSG00000128394. [Q8IUX4-3]
GeneIDi200316.
KEGGihsa:200316.
UCSCiuc003awv.4. human. [Q8IUX4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR456395 mRNA. Translation: CAG30281.1.
DQ146365 Genomic DNA. Translation: AAZ38720.1.
AL022318 Genomic DNA. Translation: CAQ09853.1.
CH471095 Genomic DNA. Translation: EAW60288.1.
CH471095 Genomic DNA. Translation: EAW60289.1.
BC038808 mRNA. Translation: AAH38808.1.
BC061914 mRNA. Translation: AAH61914.1.
CCDSiCCDS33648.1. [Q8IUX4-1]
CCDS33649.1. [Q8IUX4-3]
RefSeqiNP_001006667.1. NM_001006666.1. [Q8IUX4-3]
NP_660341.2. NM_145298.5. [Q8IUX4-1]
UniGeneiHs.659809.
Hs.660143.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3WUSX-ray2.54A/B187-373[»]
4IOUX-ray2.75A/B/C/D185-373[»]
4J4JX-ray3.10A/B218-373[»]
5HX4X-ray1.92A/B185-373[»]
5HX5X-ray2.33A/B185-373[»]
ProteinModelPortaliQ8IUX4.
SMRiQ8IUX4. Positions 12-373.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128319. 8 interactions.
DIPiDIP-59966N.
IntActiQ8IUX4. 2 interactions.
MINTiMINT-6631309.
STRINGi9606.ENSP00000309749.

Chemistry

ChEMBLiCHEMBL2007626.

PTM databases

iPTMnetiQ8IUX4.
PhosphoSiteiQ8IUX4.

Polymorphism and mutation databases

BioMutaiAPOBEC3F.
DMDMi161784334.

Proteomic databases

EPDiQ8IUX4.
MaxQBiQ8IUX4.
PaxDbiQ8IUX4.
PeptideAtlasiQ8IUX4.
PRIDEiQ8IUX4.

Protocols and materials databases

DNASUi200316.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308521; ENSP00000309749; ENSG00000128394. [Q8IUX4-1]
ENST00000381565; ENSP00000370977; ENSG00000128394. [Q8IUX4-3]
GeneIDi200316.
KEGGihsa:200316.
UCSCiuc003awv.4. human. [Q8IUX4-1]

Organism-specific databases

CTDi200316.
GeneCardsiAPOBEC3F.
H-InvDBHIX0213264.
HGNCiHGNC:17356. APOBEC3F.
MIMi608993. gene.
neXtProtiNX_Q8IUX4.
PharmGKBiPA24896.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBA1. Eukaryota.
ENOG41119MS. LUCA.
GeneTreeiENSGT00530000062933.
HOGENOMiHOG000142455.
HOVERGENiHBG050434.
KOiK18750.
OMAiNEHIREN.
OrthoDBiEOG091G07EI.
PhylomeDBiQ8IUX4.
TreeFamiTF331356.

Miscellaneous databases

ChiTaRSiAPOBEC3F. human.
GeneWikiiAPOBEC3F.
GenomeRNAii200316.
PROiQ8IUX4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128394.
CleanExiHS_APOBEC3F.
GenevisibleiQ8IUX4. HS.

Family and domain databases

InterProiIPR016192. APOBEC/CMP_deaminase_Zn-bd.
IPR013158. APOBEC_N.
IPR002125. CMP_dCMP_Zn-bd.
IPR016193. Cytidine_deaminase-like.
[Graphical view]
PfamiPF08210. APOBEC_N. 2 hits.
[Graphical view]
SUPFAMiSSF53927. SSF53927. 2 hits.
PROSITEiPS00903. CYT_DCMP_DEAMINASES_1. 2 hits.
PS51747. CYT_DCMP_DEAMINASES_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiABC3F_HUMAN
AccessioniPrimary (citable) accession number: Q8IUX4
Secondary accession number(s): B0QYD4
, Q45F03, Q6ICH3, Q7Z2N2, Q7Z2N5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: October 23, 2007
Last modified: September 7, 2016
This is version 130 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.