APOBEC3F

Summary

APOBEC3F (apolipoprotein B mRNA editing enzyme catalytic subunit 3F, HGNC:17356) is a protein-coding gene on chromosome 22q13.1, encoding DNA dC->dU-editing enzyme APOBEC-3F (Q8IUX4). DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms.

This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 200316 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total
• Druggable target: yes
• MANE Select transcript: NM_145298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17356
Approved symbol	APOBEC3F
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 3F
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	ARP8, BK150C2.4.MRNA, KA6
Ensembl gene	ENSG00000128394
Ensembl biotype	protein_coding
OMIM	608993
Entrez	200316

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000308521, ENST00000381565, ENST00000476513, ENST00000491387, ENST00000911511

RefSeq mRNA: 2 — MANE Select: NM_145298 NM_001006666, NM_145298

CCDS: CCDS33648, CCDS33649

Canonical transcript exons

ENST00000308521 — 7 exons

Exon	Start	End
ENSE00001378753	39052577	39055972
ENSE00001609243	39045428	39045542
ENSE00001768852	39052074	39052353
ENSE00001791788	39044941	39045220
ENSE00001896979	39040864	39040977
ENSE00003536480	39049425	39049581
ENSE00003633993	39042937	39043090

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 88.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.5056 / max 19.3955, expressed in 1292 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192306	2.5056	1292

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	88.82	gold quality
leukocyte	CL:0000738	81.17	gold quality
monocyte	CL:0000576	80.98	gold quality
mononuclear cell	CL:0000842	80.70	gold quality
spleen	UBERON:0002106	80.47	gold quality
right ovary	UBERON:0002118	79.62	gold quality
left ovary	UBERON:0002119	78.92	gold quality
right uterine tube	UBERON:0001302	78.80	gold quality
lymph node	UBERON:0000029	78.68	gold quality
right adrenal gland	UBERON:0001233	78.54	gold quality
left adrenal gland cortex	UBERON:0035825	78.27	gold quality
left adrenal gland	UBERON:0001234	78.11	gold quality
right adrenal gland cortex	UBERON:0035827	77.54	gold quality
sural nerve	UBERON:0015488	76.98	gold quality
apex of heart	UBERON:0002098	76.84	gold quality
stromal cell of endometrium	CL:0002255	76.79	gold quality
right testis	UBERON:0004534	76.67	gold quality
tendon of biceps brachii	UBERON:0008188	76.56	silver quality
left testis	UBERON:0004533	76.25	gold quality
ovary	UBERON:0000992	76.24	gold quality
vermiform appendix	UBERON:0001154	75.81	gold quality
right atrium auricular region	UBERON:0006631	75.79	gold quality
adrenal gland	UBERON:0002369	75.75	gold quality
adrenal cortex	UBERON:0001235	75.49	gold quality
buccal mucosa cell	CL:0002336	75.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.22	gold quality
body of uterus	UBERON:0009853	75.15	gold quality
endocervix	UBERON:0000458	75.05	gold quality
testis	UBERON:0000473	74.85	gold quality
left uterine tube	UBERON:0001303	74.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.47
E-GEOD-106540	no	120.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting APOBEC3F, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-577	99.78	69.13	2479

Literature-anchored findings (GeneRIF, showing 40)

• only the C-terminal domain of APOBEC3F and -3G dictates the retroviral minus strand 5’-TC and 5’-CC dinucleotide hypermutation preferences. (PMID:15647250)
• APOBEC3F was less potent than APOBEC3G in inhibitinhg HIV-1; Vif proteins appeared more potent & specific when APOBEC3G is the target rather than APOBEC3F (PMID:16460778)
• The fact that several highly conserved tryphtophan residues in Vif are specifically required for the suppression of APOBEC3F (A3F) but not that of APOBEC3G (A3G) suggests a critical role for A3F in the restriction of HIV-1 in vivo. (PMID:16501124)
• APOBEC3B and APOBEC3F have roles in inhibiting L1 retrotransposition by a DNA deamination-independent mechanism (PMID:16648136)
• novel link between innate immunity against retroviruses and P-bodies suggesting that APOBEC3G and APOBEC3F could function in the context of P-bodies to restrict HIV-1 replication. (PMID:16699599)
• The Chinese population had a higher frequency of small alleles and showed a difference in allelic structure and frequency distribution in apolipoprotein B from European and American in this populations. (PMID:16767679)
• separation of function of the cytidine deaminase domains is maintained in hA3B and hA3F, but roles of the two domains are reversed in mouse A3 (PMID:17020885)
• APOBEC3F and APOBEC3G complexes undergo dynamic conversion during HIV-1 infection (PMID:17142455)
• Findings highlight a role for APOBEC3G/3F in explaining the resistance of most dendritic cells to HIV-1 infection, as well as the susceptibility of a fraction of immature dendritic cells. (PMID:17145955)
• Results reveal two distinct Vif determinants, amino acids Y(40)RHHY(44) and D(14)RMR(17), which are essential for binding to APOBEC3G and APOBEC3F, respectively. (PMID:17522216)
• Vif binding to RNA and DNA offers several non-exclusive ways to counteract APOBEC3G/3F factors, in addition to the well documented Vif-induced degradation by the proteasome and to the Vif-mediated repression of translation of these antiviral factors (PMID:17609216)
• Studies focused mainly on APOBEC3F imply that it occurs associated with mRNA-PABP1 in translationally active polysomes and to a lesser extent in mRNA processing bodies (P-bodies). (PMID:17977970)
• define a number of subtle differences between the ribonucleoprotein complexes associated with APOBEC3F and APOBEC3G and speculate (PMID:18367521)
• results here have indicated that at least two distinct regions in the N-terminal half of HIV-1 Vif are critical for binding and exclusion of APOBEC3G/F (PMID:18603011)
• A VxIPLx(4-5)LxPhix(2)YWxL motif in HIV-1 Vif is identified, which is required for efficient interaction between Vif and APOBEC3G (A3G), Vif-mediated A3G degradation and virion exclusion, and functional suppression of the A3G antiviral activity. (PMID:18619467)
• The APOBEC3F domain that interacts with the Vif DRMR region was located between amino acids 283 and 300 of A3F. (PMID:19036809)
• Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins. (PMID:19088851)
• analysis of genetic editing of HBV DNA by monodomain human APOBEC3G and F cytidine deaminases (PMID:19169351)
• relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors [Review] (PMID:19487726)
• Thus, (21)WxSLVK(26) is a novel functional domain that regulates Vif activity toward both APOBEC3F and APOBEC3G and is a potential drug target to inhibit Vif activity and block HIV-1 replication. (PMID:19535447)
• When recognition loop of 9-11 amino acids is grafted from the donor APOBEC3F or 3G proteins into the acceptor scaffold of AID, the mutational signature of AID changes toward that of the donor proteins. (PMID:19561087)
• APOBEC3G and APOBEC3F gene expression in immune system and hematopoietic system cells (PMID:19587057)
• exosomes secreted by CD4(+)H9 T cells and mature monocyte-derived dendritic cells encapsidate APOBEC3G and APOBEC3F and inhibit L1 and Alu retrotransposition (PMID:20153011)
• The authors observed that both APOBEC3F and APOBEC3G inhibit HIV-1 DNA synthesis and integration, but APOBEC3F is more potent than APOBEC3G in preventing HIV-1 DNA integration. (PMID:20219927)
• hiv1 VIF sequences (81)LGxGxxIxW(89) and (171)EDRW(174) are two novel functional domains that are very critical for Vif function and Vif binding to both A3G and A3F (PMID:20335268)
• These results suggest that APOBEC3F neutralization is dispensable for HIV-1 replication in primary human T-lymphocytes. (PMID:20592068)
• T(Q/D/E)x(5)ADx(2)(I/L) motif of HIV1 Vif protein is a critical motif for interaction with APOBEC3G and APOBEC3F. (PMID:20592083)
• Alternative splicing of A3F mRNA generates truncated antiviral proteins that differ sharply in their sensitivity to Vif. (PMID:20624919)
• Long-term restriction by APOBEC3F selects human immunodeficiency virus type 1 variants with restored Vif function. (PMID:20686027)
• the antiviral activity of endogenous A3F is negligible compared to that of A3G. (PMID:20702622)
• HIV-1 central polypurine tract functions as a second line of defense against APOBEC3G and APOBEC3F. (PMID:20844042)
• G-to-A mutations on V3 HIV peptide caused by APOBEC3F and APOBEC3G facilitate co-receptor switch of HIV from R5 to X4 strains. (PMID:21573951)
• levels of A3G and A3F expression and induced G-to-A hypermutation in a group of children with distinct profiles of disease progression (PMID:21897871)
• Most Vif proteins counteract APOBEC3G and APOBEC3F efficiently but display differences with respect to the inhibition of APOBEC3H. (PMID:22013041)
• APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-alpha/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load. (PMID:22315404)
• Analysis of the A3F (W126A L306A) double mutant revealed that both residues are required for full anti-HIV function (PMID:22451677)
• endogenous levels of APOBEC3D, APOBEC3F, and APOBEC3G combine to restrict Vif-deficient HIV-1 and cause the hallmark dinucleotide hypermutation patterns in in the nonpermissive T cell line CEM2n (PMID:22807680)
• The authors conclude that APOBEC3G exerts a greater restriction effect on HIV-1 than APOBEC3F and APOBEC3DE. (PMID:23097438)
• Data indicate that internal lysines are the dominant ubquuitin (Ub) acceptor sites in both APOBEC3F(A3F) and APOBEC3G (A3G). (PMID:23318957)
• APOBEC3F/G-specific responses in HIV-1-infected patients are CD8+ T cell mediated. (PMID:23536679)

Cross-species orthologs

0 orthologs

Paralogs (9): APOBEC3H (ENSG00000100298), APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC2 (ENSG00000124701), APOBEC3A (ENSG00000128383), APOBEC3B (ENSG00000179750), APOBEC3G (ENSG00000239713), APOBEC3D (ENSG00000243811), APOBEC3C (ENSG00000244509)

Protein

Protein identifiers

DNA dC->dU-editing enzyme APOBEC-3F — Q8IUX4 (reviewed: Q8IUX4)

Alternative names: Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F

All UniProt accessions (1): Q8IUX4

UniProt curated annotations — full annotation on UniProt →

Function. 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 viruse such as HIV-1 or HIV-2. 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.

Subunit / interactions. Homodimer. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with AGO1, AGO2 and AGO3. (Microbial infection) Interacts with HIV-1 Vif, leading to its ubiquitination and degradation by the proteasome. In the absence of Vif protein, specifically packaged into HIV-1 virions.

Subcellular location. Cytoplasm. P-body.

Tissue specificity. Widely expressed. Highly expressed in ovary.

Post-translational modifications. (Microbial infection) Following infection by HIV-1, ubiquitinated by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, leading to its degradation.

Activity regulation. (Microbial infection) 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.

Domain organisation. 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.

Miscellaneous. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. May be due to a competing donor splice site.

Similarity. Belongs to the cytidine and deoxycytidylate deaminase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IUX4-1	1	yes
Q8IUX4-2	2
Q8IUX4-3	3

RefSeq proteins (2): NP_001006667, NP_660341* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002125	CMP_dCMP_dom	Domain
IPR016192	APOBEC/CMP_deaminase_Zn-bd	Binding_site
IPR016193	Cytidine_deaminase-like	Homologous_superfamily
IPR050610	APOBEC_Cyt_Deaminase	Family

Pfam: PF18782

Enzyme classification (BRENDA):

• EC 3.5.4.38 — single-stranded DNA cytosine deaminase (BRENDA: 8 organisms, 58 substrates, 4 inhibitors, 11 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CCCA	0.001–0.073	5
TTCA	0.001–0.019	5

Catalyzed reactions (Rhea), 1 shown:

• a 2’-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2’-deoxyuridine in single-stranded DNA + NH4(+) (RHEA:50948)

UniProt features (72 total): mutagenesis site 30, sequence variant 7, helix 7, cross-link 6, binding site 6, strand 5, splice variant 4, domain 2, turn 2, chain 1, disulfide bond 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
5HX4	X-RAY DIFFRACTION	1.92
5ZVB	X-RAY DIFFRACTION	2
5ZVA	X-RAY DIFFRACTION	2.3
5HX5	X-RAY DIFFRACTION	2.33
3WUS	X-RAY DIFFRACTION	2.54
8VUD	X-RAY DIFFRACTION	2.6
4IOU	X-RAY DIFFRACTION	2.75
4J4J	X-RAY DIFFRACTION	3.1
5W2M	X-RAY DIFFRACTION	3.7
6NIL	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUX4-F1	89.31	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 251 (proton donor)

Ligand- & substrate-binding residues (6): 65; 96; 99; 249; 280; 283

Post-translational modifications (6): 52, 234, 334, 352, 355, 358

Disulfide bonds (1): 280–283

Mutagenesis-validated functional residues (30):

Position	Phenotype
65	reduced but not abolished antiviral activity.
65	nearly abolished antiviral activity; when associated with r-249.
67	decrease in cytidine deaminase and antiviral activity; when associated with a-251.
67	no effect on cytidine deaminase and antiviral activity.
67	reduced but not abolished antiviral activity. nearly abolished antiviral activity; when associated with q-251.
96	reduced but not abolished antiviral activity. nearly abolished antiviral activity; when associated with q-280.
99	reduced but not abolished antiviral activityy. nearly abolished antiviral activity; when associated with s-283.
249	reduced but not abolished antiviral activity.
249	nearly abolished antiviral activity; when associated with r-65.
251	decrease in cytidine deaminase and antiviral activity.
251	decrease in cytidine deaminase and antiviral activity; when associated with a-67.
251	remains able to bind vif.
251	reduced but not abolished antiviral activity. nearly abolished antiviral activity; when associated with q-67.
255	resistant to hiv-1 vif and reduces vif binding but is still efficiently incorporated into the virion.
258	resistant to hiv-1 vif and reduces vif binding but is still efficiently incorporated into the virion.
259	resistant to hiv-1 vif and reduces vif binding but is still efficiently incorporated into the virion.
260–261	does not affect interaction with apobec3g.
262–263	resistant to hiv-1 vif and abolishes vif binding but is still efficiently incorporated into the virion.
264	resistant to hiv-1 vif and reduces vif binding but is still efficiently incorporated into the virion.
265	impaired interaction with hiv-1 vif protein.
269	resistant to hiv-1 vif and reduces vif binding but is still efficiently incorporated into the virion.
280	reduced but not abolished antiviral activity. nearly abolished antiviral activity; when associated with q-96.
283	reduced but not abolished antiviral activity. nearly abolished antiviral activity; when associated with s-99.
289	abolished interaction with hiv-1 vif protein. resistant to hiv-1 vif and reduces vif binding but is still efficiently in
290	resistant to hiv-1 vif and reduces vif binding but is still efficiently incorporated into the virion.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_DNA_MODIFICATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOBP_CHROMATIN_REMODELING

GO Biological Process (15): positive regulation of defense response to virus by host (GO:0002230), transposable element silencing (GO:0010526), base conversion or substitution editing (GO:0016553), cytidine to uridine editing (GO:0016554), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), clearance of foreign intracellular DNA (GO:0044355), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), negative regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045869), negative regulation of viral process (GO:0048525), defense response to virus (GO:0051607), DNA cytosine deamination (GO:0070383), antiviral innate immune response (GO:0140374), immune system process (GO:0002376), negative regulation of macromolecule biosynthetic process (GO:0010558)

GO Molecular Function (8): RNA binding (GO:0003723), cytidine deaminase activity (GO:0004126), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), apolipoprotein B mRNA editing enzyme complex (GO:0030895), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of defense response to virus by host	1
negative regulation of gene expression	1
retrotransposition	1
RNA modification	1
base conversion or substitution editing	1
transcription initiation-coupled chromatin remodeling	1
clearance of foreign intracellular nucleic acids	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of viral genome replication	1
regulation of single stranded viral RNA replication via double stranded DNA intermediate	1
negative regulation of RNA biosynthetic process	1
viral process	1
negative regulation of biological process	1
regulation of viral process	1
defense response	1
response to virus	1
DNA deamination	1
innate immune response	1
defense response to virus	1
biological_process	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule metabolic process	1
nucleic acid binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
transition metal ion binding	1
protein binding	1
molecular_function	1
binding	1
catalytic activity	1
cation binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC3F	CUL5	Q93034	946
APOBEC3F	CDA	P32320	835
APOBEC3F	APOBEC4	Q8WW27	815
APOBEC3F	ELOB	Q15370	783
APOBEC3F	ELOC	Q15369	761
APOBEC3F	APOB	P04114	709
APOBEC3F	TRIM5	Q9C035	676
APOBEC3F	BST2	Q10589	622
APOBEC3F	CBFB	Q13951	612
APOBEC3F	RBX1	P62877	578
APOBEC3F	RNF7	Q9UBF6	573
APOBEC3F	SAMHD1	Q9Y3Z3	571
APOBEC3F	UNG	P13051	570
APOBEC3F	CD2	P06729	535
APOBEC3F	DDX6	P26196	526

IntAct

75 interactions, top by confidence:

A	B	Type	Score
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
APOBEC3F	APOBEC3F	psi-mi:“MI:0407”(direct interaction)	0.560
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ZNF71	DKC1	psi-mi:“MI:0914”(association)	0.530
APOBEC3F	APOBEC3G	psi-mi:“MI:0915”(physical association)	0.400
vif	APOBEC3F	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3F	TINF2	psi-mi:“MI:0915”(physical association)	0.370
ACD	APOBEC3F	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ECH1	A2ML1	psi-mi:“MI:0914”(association)	0.350
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
APOBEC3D	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
TRA2A	GAPDHS	psi-mi:“MI:0914”(association)	0.350
PRKD1		psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
PURG	ZNF320	psi-mi:“MI:0914”(association)	0.350
PRR3	ZNF316	psi-mi:“MI:0914”(association)	0.350
HNRNPC	APOBEC3DE	psi-mi:“MI:0914”(association)	0.350
PABPC5	APOBEC3DE	psi-mi:“MI:0914”(association)	0.350
SRSF4		psi-mi:“MI:0914”(association)	0.350
YBX1		psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350

BioGRID (91): APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-Western), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-RNA), APOBEC3F (Affinity Capture-MS), APOBEC3F (Biochemical Activity), APOBEC3F (Biochemical Activity), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS), APOBEC3F (Affinity Capture-MS)

ESM2 similar proteins: A2VDP6, A9QA56, G1SRW8, P0C7P3, P31941, P60704, P60705, Q08AF3, Q19Q52, Q1WBT4, Q2PT36, Q3SYR3, Q4VDN5, Q5RCA5, Q5XI89, Q68D06, Q694B4, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q7Z7L1, Q8IUX4, Q8IXQ6, Q969Y0, Q96AK3, Q99J72, Q9BQQ7, Q9GZX7

Diamond homologs: A9QA56, P31941, P38483, P41238, P47855, P60704, P60705, Q19Q52, Q1WBT4, Q2PT36, Q4VDN5, Q694B3, Q694B5, Q694B6, Q694B7, Q694B8, Q694B9, Q694C0, Q694C1, Q694C2, Q694C4, Q694C5, Q6NTF7, Q75W64, Q7YR23, Q7YR24, Q7YR25, Q8IUX4, Q99J72, Q9EQP0, Q9GZX7, Q9HC16, Q9NRW3, Q9TUI7, Q9UH17, Q9WVE0, Q3SYR3, Q694B4, Q96AK3, Q9WV35

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
APOBEC3F	up-regulates	“Clearance_of_foreign intracellular_DNA”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	6	40.8×	2e-07
RNA Polymerase II Transcription Termination	6	23.5×	4e-06
mRNA 3’-end processing	6	21.1×	7e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	7	19.0×	2e-06
mRNA Splicing	9	17.6×	1e-07
Processing of Capped Intron-Containing Pre-mRNA	12	17.6×	6e-10
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	9	15.7×	2e-07
Eukaryotic Translation Termination	7	15.0×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	8	25.4×	3e-07
mRNA stabilization	5	23.8×	1e-04
cytoplasmic translation	6	14.4×	1e-04
mRNA splicing, via spliceosome	9	10.7×	2e-05
translation	8	10.7×	5e-05
RNA splicing	9	10.3×	2e-05
mRNA processing	7	7.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

83 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1511 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39043159:A:G	donor_gain	1.0000
22:39043121:C:T	donor_gain	0.9900
22:39043124:GAGC:G	donor_gain	0.9900
22:39043127:C:G	donor_gain	0.9900
22:39052154:CTACG:C	acceptor_gain	0.9900
22:39052320:G:GT	donor_gain	0.9900
22:39052692:G:GG	donor_gain	0.9900
22:39040825:G:GT	donor_gain	0.9800
22:39043141:A:T	donor_gain	0.9800
22:39045177:GC:G	donor_gain	0.9800
22:39052150:C:G	acceptor_gain	0.9800
22:39052321:A:T	donor_gain	0.9800
22:39052350:AAAGG:A	donor_loss	0.9800
22:39052351:AAGG:A	donor_loss	0.9800
22:39052351:AAGGT:A	donor_loss	0.9800
22:39052352:AGG:A	donor_loss	0.9800
22:39052353:GGT:G	donor_loss	0.9800
22:39052354:G:A	donor_loss	0.9800
22:39052354:G:GC	donor_loss	0.9800
22:39052355:T:G	donor_loss	0.9800
22:39052682:A:T	donor_gain	0.9800
22:39052681:G:GT	donor_gain	0.9700
22:39052690:GA:G	donor_gain	0.9700
22:39043158:GA:G	donor_gain	0.9600
22:39043159:A:AG	donor_gain	0.9600
22:39045188:C:T	donor_gain	0.9600
22:39052155:TACG:T	acceptor_gain	0.9600
22:39052156:ACGA:A	acceptor_gain	0.9600
22:39052157:CG:C	acceptor_gain	0.9600
22:39052575:A:AG	acceptor_gain	0.9600

AlphaMissense

2496 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39052182:A:C	S278R	0.989
22:39052184:C:A	S278R	0.989
22:39052184:C:G	S278R	0.989
22:39052218:T:C	F290L	0.980
22:39052220:C:A	F290L	0.980
22:39052220:C:G	F290L	0.980
22:39049516:T:C	F220L	0.978
22:39049518:C:A	F220L	0.978
22:39049518:C:G	F220L	0.978
22:39042968:T:C	F17L	0.977
22:39042970:C:A	F17L	0.977
22:39042970:C:G	F17L	0.977
22:39052167:T:A	W273R	0.976
22:39052167:T:C	W273R	0.976
22:39049468:T:C	F204L	0.975
22:39049470:T:A	F204L	0.975
22:39049470:T:G	F204L	0.975
22:39045430:T:C	F152L	0.974
22:39045432:T:A	F152L	0.974
22:39045432:T:G	F152L	0.974
22:39042980:T:C	F21L	0.972
22:39042982:T:A	F21L	0.972
22:39042982:T:G	F21L	0.972
22:39049456:T:C	F200L	0.972
22:39049458:C:A	F200L	0.972
22:39049458:C:G	F200L	0.972
22:39045037:T:C	F90L	0.971
22:39045039:T:A	F90L	0.971
22:39045039:T:G	F90L	0.971
22:39052179:T:A	W277R	0.971

dbSNP variants (sampled 300 via entrez): RS1000861291 (22:39053489 C>T), RS1001336093 (22:39056122 C>A), RS1001531473 (22:39051699 C>T), RS1001562341 (22:39051473 C>A), RS1001866775 (22:39052489 G>A), RS1002035780 (22:39056317 C>A), RS1002067506 (22:39047949 G>A), RS1002140245 (22:39047043 C>G), RS1002248729 (22:39043460 C>T), RS1002500213 (22:39047731 G>T), RS1002532685 (22:39050700 C>G,T), RS1002565311 (22:39050390 G>C,T), RS1002740053 (22:39046055 C>T), RS1002753533 (22:39050938 A>G), RS1003182434 (22:39045823 C>A,T)

Disease associations

OMIM: gene MIM:608993 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2007626 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
ceric oxide	decreases expression	1
cobalt oxide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Azacitidine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Diuron	decreases expression	1
Doxorubicin	affects expression	1
Hydrogen Peroxide	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Sodium Selenite	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1963966	Functional	PUBCHEM_BIOASSAY: qHTS for Inhibitors of Vif-A3F Interactions: qHTS. (Class of assay: confirmatory)	PubChem BioAssay data set

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.