APOBEC3G

Summary

APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic subunit 3G, HGNC:17357) is a protein-coding gene on chromosome 22q13.1, encoding DNA dC->dU-editing enzyme APOBEC-3G (Q9HC16). 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. The protein encoded by this gene catalyzes site-specific deamination of both RNA and single-stranded DNA. The encoded protein has been found to be a specific inhibitor of human immunodeficiency virus-1 (HIV-1) infectivity.

Source: NCBI Gene 60489 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 41 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021822

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17357
Approved symbol	APOBEC3G
Name	apolipoprotein B mRNA editing enzyme catalytic subunit 3G
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	CEM15, MDS019, dJ494G10.1, FLJ12740, bK150C2.7
Ensembl gene	ENSG00000239713
Ensembl biotype	protein_coding
OMIM	607113
Entrez	60489

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 retained_intron, 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000407997, ENST00000461827, ENST00000463934, ENST00000480000, ENST00000481958, ENST00000486357, ENST00000494150, ENST00000851527, ENST00000960612

RefSeq mRNA: 3 — MANE Select: NM_021822 NM_001349436, NM_001349437, NM_021822

CCDS: CCDS13984

Canonical transcript exons

ENST00000407997 — 8 exons

Exon	Start	End
ENSE00000880346	39086279	39086567
ENSE00001742329	39087011	39087126
ENSE00001809576	39077275	39077378
ENSE00001868515	39087407	39087743
ENSE00003462837	39080933	39081227
ENSE00003528119	39081471	39081585
ENSE00003564633	39083731	39083884
ENSE00003566101	39078932	39079085

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 98.31.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5736 / max 124.0134, expressed in 722 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192308	2.5353	722
192309	0.0383	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.31	gold quality
epithelium of nasopharynx	UBERON:0001951	95.69	gold quality
olfactory bulb	UBERON:0002264	95.61	gold quality
blood	UBERON:0000178	94.33	gold quality
leukocyte	CL:0000738	93.93	gold quality
lymph node	UBERON:0000029	93.85	gold quality
mononuclear cell	CL:0000842	93.58	gold quality
monocyte	CL:0000576	93.53	gold quality
seminal vesicle	UBERON:0000998	93.02	gold quality
type B pancreatic cell	CL:0000169	92.98	gold quality
palpebral conjunctiva	UBERON:0001812	92.95	gold quality
bone marrow cell	CL:0002092	92.82	gold quality
mucosa of urinary bladder	UBERON:0001259	92.04	gold quality
spleen	UBERON:0002106	91.74	gold quality
bone marrow	UBERON:0002371	90.42	gold quality
vermiform appendix	UBERON:0001154	90.33	gold quality
germinal epithelium of ovary	UBERON:0001304	89.68	gold quality
superficial temporal artery	UBERON:0001614	89.68	gold quality
nasal cavity epithelium	UBERON:0005384	89.47	gold quality
right uterine tube	UBERON:0001302	89.20	gold quality
cervix squamous epithelium	UBERON:0006922	89.05	gold quality
nasal cavity mucosa	UBERON:0001826	88.94	gold quality
right testis	UBERON:0004534	88.79	gold quality
diaphragm	UBERON:0001103	88.60	gold quality
caecum	UBERON:0001153	88.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.55	gold quality
amniotic fluid	UBERON:0000173	87.22	gold quality
left testis	UBERON:0004533	87.17	gold quality
tongue squamous epithelium	UBERON:0006919	86.99	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.98	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	787.71
E-CURD-95	yes	476.27
E-MTAB-9221	yes	362.93
E-MTAB-6701	yes	111.10
E-HCAD-1	yes	81.38
E-CURD-122	yes	41.55
E-MTAB-10287	yes	37.34
E-MTAB-8410	yes	26.99
E-HCAD-8	yes	26.98
E-ANND-3	yes	13.61
E-GEOD-106540	no	1254.42
E-MTAB-6379	no	654.41
E-GEOD-75367	no	233.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF4, NFATC2, SP1, SP3

miRNA regulators (miRDB)

16 targeting APOBEC3G, 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-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-7703	97.64	67.00	965
HSA-MIR-526B-5P	97.41	67.99	1074

Literature-anchored findings (GeneRIF, showing 40)

• Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. (PMID:12167863)
• a cytidine deaminase that is able to induce G to A hypermutation in newly synthesized HIV-1 DNA (PMID:12808465)
• APOBEC3G exerts its antiviral effect during reverse transcription to trigger G-to-A hypermutation in the nascent HIV DNA (PMID:12808466)
• mutagenesis analysis on two cytidine deaminase motifs in CEM15/Apobec-3G indicates that the enzymatic activity of this protein is essential but not a sole determinant of the HIV-1 antiviral activity (PMID:12970355)
• Viral infectivity factor prevents virion incorporation of endogenous APOBEC3G by effectively depleting the intracellular levels of this enzyme in HIV-1-infected T cells. (PMID:14527406)
• Vif inhibits packaging of APOBEC3G into virus particles in a dose-dependent manner and reduces its intracellular expression level. (PMID:14557625)
• ability of HIV-1 Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation (PMID:14564014)
• results suggest that Vif functions by targeting APOBEC3G for degradation via the ubiquitin-proteasome pathway and implicate the proteasome as a site of dynamic interplay between microbial and cellular defenses. (PMID:14672928)
• HIV-1 Vif could induce rapid degradation of human APOBEC3G that was blocked by the proteasome inhibitor MG132. The efficiency of Vif-induced downregulation of APOBEC3G expression depended on the level of Vif expression. (PMID:14747572)
• inhibits hepatitis B virus replication; block of HBV DNA accumulation by APOBEC3G seems to result from an inhibition of viral pregenomic RNA packaging (PMID:15031497)
• A single amino acid substitution mutant of human APOBEC3G (D128K) can interact with HIV-1 Vif but is not depleted from cells; thus, it inhibits HIV-1 replication in an HIV-1 Vif-resistant manner. (PMID:15054139)
• APOBEC3G inhibits HIV-1 infection through interference with reverse transcription. (PMID:15156567)
• cytoplasmic apolipoprotein B mRNA editing enzyme(APOBEC3G) becomes membrane-bound in cells expressing HIV-1 Gag, and its incorporation into Gag viral-like particles (VLPs) is proportional to the amount of APOBEC3G expressed in the cell (PMID:15159405)
• APOBEC3G interactions with HIV-1 and nonviral RNAs that are packaged into viral particles are sufficient for APOBEC3G virion incorporation (PMID:15210704)
• APOBEC3G gene has been subject to strong positive selection throughout the history of primate evolution (PMID:15269786)
• observations allow speculation (i) that APOBEC-mediated C-to-U editing may contribute to the sequence variation of viruses that replicate entirely through RNA, and (ii) that additional cellular RNA substrates might exist for the APOBEC enzymes (PMID:15286366)
• expression of the antiviral APOBEC3G editing enzyme is dynamically controlled by the PKCalpha/betaI/MEK/ERK protein kinase cascade in human T lymphocytes (PMID:15297452)
• Results demonstrate that the expression of HIV-1 Gag is sufficient to induce the packaging of human APOBEC3G into Gag particles. (PMID:15358144)
• Depletion of APOBEC3G from Vif expressing cells is not a universal property of Vif and thus is not imperative for the production of infectious virions. (PMID:15373943)
• Depletion of APOBEC3G is not the sole protective mechanism of Vif and additional mechanisms exerted by this protein can be envisioned which counteract APOBEC3G and enhance HIV infectivity. (PMID:15383144)
• cytoplasmic Vif-APOBEC3G interactions are required but are not sufficient for Vif to modulate APOBEC3G and can be monitored by co-localization in vivo (PMID:15537645)
• Vif targets APOBEC3G for degradation by forming an SCF-like E3 ubiquitin ligase containing Cullin 5 and Elongins B and C (Cul5-EloB-EloC) through a novel SOCS-box (PMID:15574592)
• ubiquitination of APOBEC3G by Nedd4-1 favors its targeting to the virus assembly site where APOBEC3G interacts with Gag and is packaged into HIV-1 particles in the absence of Vif (PMID:15581898)
• Induces degradation of APOBEC3G by bringing to relevance that deaminase inhibition can also result from a direct interaction with Vif protein. (PMID:15611076)
• Functional analysis of Vif protein shows less restriction of human immunodeficiency virus type 2 by APOBEC3G. (PMID:15613310)
• only the C-terminal domain of APOBEC3F and -3G dictates the retroviral minus strand 5’-TC and 5’-CC dinucleotide hypermutation preferences. (PMID:15647250)
• APOBEC3G, by editing viral genetic material, provides an ancestral wide cellular defence against endogenous and exogenous invaders (PMID:15674295)
• Using APOBEC3G deletion and point mutants, we mapped the encapsidation determinant to the Zn(2+) coordination residues of the N-terminal catalytic domain (CD1). (PMID:15721369)
• the E3 ubiquitin ligase activity of the Vif-BC-Cul5 complex is essential for Vif function against APOBEC3G (PMID:15781449)
• APOBEC3G potently inhibits replication of the Ty1 LTR retrotransposon in yeast. (PMID:15823539)
• APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 through different mechanisms from that on HIV-1 (PMID:15943885)
• APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. (PMID:16000409)
• APOBEC3G is induced by IFN stimulation in human hepatocytes and thus could be involved in host defense mechanisms directed against hepatitis viruses (PMID:16426578)
• 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)
• Most of the highly conserved tryptophan residues were required for efficient suppression of both APOBEC3G (A3G) and APOBEC3F (A3F), but some of these residues were selectively required for the suppression of A3F but not A3G. (PMID:16501124)
• G –> A mutational gradient generated in viral genomic DNA in vivo could result from an intrinsic processive directional attack by APOBEC3G on single-stranded cDNA (PMID:16622407)
• results provide novel insights into the catalytic function and antiviral property of APOBEC3G (PMID:16641260)
• 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)
• molecular analysis of the deaminase and nucleic acid binding activities of human APOBEC3G (PMID:16731938)
• These findings indicate that APOBEC3G could suppress HBV replication and antigen expression both in vivo and in vitro, promising an advance in treatment of HBV infection. (PMID:16874860)

Cross-species orthologs

0 orthologs

Paralogs (9): APOBEC3H (ENSG00000100298), APOBEC1 (ENSG00000111701), AICDA (ENSG00000111732), APOBEC2 (ENSG00000124701), APOBEC3A (ENSG00000128383), APOBEC3F (ENSG00000128394), APOBEC3B (ENSG00000179750), APOBEC3D (ENSG00000243811), APOBEC3C (ENSG00000244509)

Protein

Protein identifiers

DNA dC->dU-editing enzyme APOBEC-3G — Q9HC16 (reviewed: Q9HC16)

Alternative names: APOBEC-related cytidine deaminase, APOBEC-related protein 9, CEM-15, Deoxycytidine deaminase

All UniProt accessions (1): Q9HC16

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 potent 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 simian immunodeficiency viruses (SIVs), hepatitis B virus (HBV), equine infectious anemia virus (EIAV), xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV). May inhibit the mobility of LTR and non-LTR retrotransposons.

Subunit / interactions. Homodimer. Homooligomer. Can bind RNA to form ribonucleoprotein complexes of high-molecular-mass (HMM) or low-molecular-mass (LMM). HMM is inactive and heterogeneous in protein composition because of binding nonselectively to cellular RNAs, which in turn are associated with variety of cellular proteins. The LMM form which is enzymatically active has few or no RNAs associated. Its ability to form homooligomer is distinct from its ability to assemble into HMM. Interacts with APOBEC3B, APOBEC3F, MOV10, AGO2, EIF4E, EIF4ENIF1, DCP2 and DDX6 in an RNA-dependent manner. Interacts with AGO1, AGO3 and PKA/PRKACA. (Microbial infection) Interacts with HIV-1 Vif; promoting its ubiquitination by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif. (Microbial infection) Interacts with HIV-1 reverse transcriptase/ribonuclease H. (Microbial infection) Interacts with hepatitis B virus capsid protein.

Subcellular location. Cytoplasm. Nucleus. P-body.

Tissue specificity. Expressed in spleen, testes, ovary and peripheral blood leukocytes and CD4+ lymphocytes. Also expressed in non-permissive peripheral blood mononuclear cells, and several tumor cell lines; no expression detected in permissive lymphoid and non-lymphoid cell lines. Exists only in the LMM form in peripheral blood-derived resting CD4 T-cells and monocytes, both of which are refractory to HIV-1 infection. LMM is converted to a HMM complex when resting CD4 T-cells are activated or when monocytes are induced to differentiate into macrophages. This change correlates with increased susceptibility of these cells to HIV-1 infection.

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. Deubiquitinated by USP49; leading to stabilization. Phosphorylation at Thr-32 reduces its binding to HIV-1 Vif and subsequent ubiquitination and degradation thus promoting its antiviral activity.

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. Can also be neutralized by simian immunodeficiency virus sooty mangabey monkey virus (SIV-sm) and chimpanzee immunodeficiency virus (SIV-cpz) Vif.

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.

Induction. Up-regulated by IFN-alpha.

Miscellaneous. Accumulation of APOBEC3G induced non-lethal hypermutation could contribute to the genetic variation of primate lentiviral populations. 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 (2)

UniProt ID	Names	Canonical?
Q9HC16-1	1	yes
Q9HC16-3	3

RefSeq proteins (3): NP_001336365, NP_001336366, NP_068594* (*=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)
• EC 3.5.4.B9 — (BRENDA: organisms, substrates, inhibitors, Km, 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 (120 total): mutagenesis site 46, strand 20, helix 17, cross-link 11, binding site 6, region of interest 4, sequence variant 3, domain 2, turn 2, modified residue 2, splice variant 2, sequence conflict 2, chain 1, site 1, active site 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
3V4K	X-RAY DIFFRACTION	1.38
7UXD	X-RAY DIFFRACTION	1.5
4ROW	X-RAY DIFFRACTION	1.7
4ROV	X-RAY DIFFRACTION	1.8
6BUX	X-RAY DIFFRACTION	1.86
5ZVB	X-RAY DIFFRACTION	2
3V4J	X-RAY DIFFRACTION	2.04
3IR2	X-RAY DIFFRACTION	2.25
3E1U	X-RAY DIFFRACTION	2.3
3IQS	X-RAY DIFFRACTION	2.3
5ZVA	X-RAY DIFFRACTION	2.3
8J62	ELECTRON MICROSCOPY	2.5
8CX0	ELECTRON MICROSCOPY	2.7
8H0I	ELECTRON MICROSCOPY	2.8
6BWY	X-RAY DIFFRACTION	2.9
8CX2	ELECTRON MICROSCOPY	3.2
8CX1	ELECTRON MICROSCOPY	3.3
2JYW	SOLUTION NMR
2KBO	SOLUTION NMR
2KEM	SOLUTION NMR
6K3J	SOLUTION NMR
6K3K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC16-F1	88.57	0.65

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 (2): 244 (interaction with dna); 259 (proton donor)

Ligand- & substrate-binding residues (6): 100; 257; 288; 291; 65; 97

Post-translational modifications (13): 32, 218, 42, 52, 63, 150, 163, 249, 270, 297, 301, 303, 334

Mutagenesis-validated functional residues (46):

Position	Phenotype
67	loss of cytidine deaminase activity and significant decrease in antiviral activity; when associated with a-259.
67	no effect on cytidine deaminase and antiviral activity.
67	decreases cytidine deaminase activity.
74	remains sensitive to hiv-1 vif and able to bind vif.
80	remains sensitive to hiv-1 vif and able to bind vif.
81	decreases cytidine deaminase activity.
85	does not decrease cytidine deaminase activity.
86	remains sensitive to hiv-1 vif and able to bind vif.
97	decreases cytidine deaminase activity.
100	decreases cytidine deaminase activity.
107	remains sensitive to hiv-1 vif and able to bind vif.
128	resistant to hiv-1 vif with complete loss of vif-induced ubiquitination and degradation and vif binding.
210	nearly abolished catalytic efficiency of cytidine deaminase activity.
213	slightly reduces enzyme activity.
213	reduces enzyme activity.
215	abolishes enzyme activity.
217	modifies the spectrum of action against mobile genetic elements; when associated with k-247.
218	loss of phosphorylation. no effect on cytidine deaminase activity or hiv-1 restriction activity.
218	phosphomimetic mutant which shows loss of cytidine deaminase activity and hiv-1 restriction activity.
221	does not decrease cytidine deaminase activity.
244	abolishes enzyme activity.
245	nearly abolished cytidine deaminase activity.
247	modifies the spectrum of action against mobile genetic elements; when associated with k-217.
248	improved catalytic efficiency of cytidine deaminase activity.
250	improved catalytic efficiency of cytidine deaminase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-180585	Vif-mediated degradation of APOBEC3G
R-HSA-180689	APOBEC3G mediated resistance to HIV-1 infection

MSigDB gene sets: 208 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_DNA_MODIFICATION, REACTOME_HIV_INFECTION, ONKEN_UVEAL_MELANOMA_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_RNA_MODIFICATION, REACTOME_VIF_MEDIATED_DEGRADATION_OF_APOBEC3G, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (14): 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), 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), defense response to symbiont (GO:0140546)

GO Molecular Function (9): RNA binding (GO:0003723), cytidine deaminase activity (GO:0004126), zinc ion binding (GO:0008270), dCTP deaminase activity (GO:0008829), 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 (6): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), apolipoprotein B mRNA editing enzyme complex (GO:0030895), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Host Interactions of HIV factors	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	2
deaminase activity	2
cellular anatomical structure	2
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
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
defense response to other organism	1
nucleic acid binding	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

1944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOBEC3G	CUL5	Q93034	956
APOBEC3G	CDA	P32320	945
APOBEC3G	BST2	Q10589	939
APOBEC3G	TRIM5	Q9C035	920
APOBEC3G	HDAC6	Q9UBN7	887
APOBEC3G	SAMHD1	Q9Y3Z3	876
APOBEC3G	ELOB	Q15370	813
APOBEC3G	APOB	P04114	801
APOBEC3G	APOBEC4	Q8WW27	788
APOBEC3G	CBFB	Q13951	774
APOBEC3G	CD4	P01730	762
APOBEC3G	SMARCA2	P51531	750
APOBEC3G	MOV10	Q9HCE1	739
APOBEC3G	CCR5	P51681	727
APOBEC3G	ELOC	Q15369	706

IntAct

23 interactions, top by confidence:

A	B	Type	Score
APOBEC3G	APOBEC3G	psi-mi:“MI:0915”(physical association)	0.610
APOBEC3G	APOBEC3G	psi-mi:“MI:0407”(direct interaction)	0.610
APOBEC3G	vif	psi-mi:“MI:0915”(physical association)	0.590
APOBEC3G	PRKACA	psi-mi:“MI:0915”(physical association)	0.540
APOBEC3G	PRKACA	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
gag	APOBEC3G	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3F	APOBEC3G	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3G	CEBPB	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3G		psi-mi:“MI:0915”(physical association)	0.400
APOBEC3G	N	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3G	vif	psi-mi:“MI:0915”(physical association)	0.400
APOBEC3G	C	psi-mi:“MI:2364”(proximity)	0.270
PTN	APOBEC3G	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (93): vpr (Affinity Capture-Western), vif (Affinity Capture-Western), vif (Reconstituted Complex), vif (Co-fractionation), APOBEC3G (Biochemical Activity), APOBEC3G (Biochemical Activity), APOBEC3G (Affinity Capture-Western), HDAC6 (Affinity Capture-Western), APOBEC3G (Affinity Capture-Western), vif (Affinity Capture-Western), vif (Reconstituted Complex), HDAC6 (Reconstituted Complex), APOBEC3G (Affinity Capture-Western), MAP3K5 (Affinity Capture-Western), vif (Affinity Capture-Western)

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

3 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	APOBEC3G	phosphorylation
APOBEC3G	up-regulates	“Clearance_of_foreign intracellular_DNA”
NEDD4	“up-regulates activity”	APOBEC3G	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

971 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39079154:A:G	donor_gain	1.0000
22:39081469:A:AG	acceptor_gain	1.0000
22:39081470:G:GA	acceptor_gain	1.0000
22:39081470:GA:G	acceptor_gain	1.0000
22:39086274:TCTA:T	acceptor_loss	1.0000
22:39086275:CTA:C	acceptor_loss	1.0000
22:39086276:TA:T	acceptor_loss	1.0000
22:39086277:A:AG	acceptor_gain	1.0000
22:39086277:AG:A	acceptor_gain	1.0000
22:39086278:G:A	acceptor_loss	1.0000
22:39086278:G:GA	acceptor_gain	1.0000
22:39086278:GG:G	acceptor_gain	1.0000
22:39086278:GGCT:G	acceptor_gain	1.0000
22:39086423:G:GT	donor_gain	1.0000
22:39086424:A:T	donor_gain	1.0000
22:39086499:G:GT	donor_gain	1.0000
22:39086565:GTG:G	donor_gain	1.0000
22:39080928:CCCA:C	acceptor_loss	0.9900
22:39080929:CCA:C	acceptor_loss	0.9900
22:39080930:CAGGT:C	acceptor_loss	0.9900
22:39080932:G:GC	acceptor_loss	0.9900
22:39080932:GGT:G	acceptor_gain	0.9900
22:39081224:GACG:G	donor_gain	0.9900
22:39081227:GGT:G	donor_loss	0.9900
22:39081228:G:GG	donor_gain	0.9900
22:39081229:T:A	donor_loss	0.9900
22:39081470:GAA:G	acceptor_gain	0.9900
22:39081470:GAAT:G	acceptor_gain	0.9900
22:39081581:CTCAG:C	donor_loss	0.9900
22:39081582:TCAGG:T	donor_loss	0.9900

AlphaMissense

2579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39086399:A:C	S286R	0.984
22:39086401:C:A	S286R	0.984
22:39086401:C:G	S286R	0.984
22:39081494:T:C	F164L	0.983
22:39081496:C:A	F164L	0.983
22:39081496:C:G	F164L	0.983
22:39087013:T:C	F343L	0.983
22:39087015:T:A	F343L	0.983
22:39087015:T:G	F343L	0.983
22:39081473:T:C	F157L	0.981
22:39081475:T:A	F157L	0.981
22:39081475:T:G	F157L	0.981
22:39078963:T:C	F17L	0.980
22:39078965:C:A	F17L	0.980
22:39078965:C:G	F17L	0.980
22:39083753:T:C	F202L	0.980
22:39083755:C:A	F202L	0.980
22:39083755:C:G	F202L	0.980
22:39087034:T:C	F350L	0.979
22:39087036:T:A	F350L	0.979
22:39087036:T:G	F350L	0.979
22:39081044:A:C	S95R	0.978
22:39081046:C:A	S95R	0.978
22:39081046:C:G	S95R	0.978
22:39083765:T:C	F206L	0.978
22:39083767:T:A	F206L	0.978
22:39083767:T:G	F206L	0.978
22:39078975:T:C	F21L	0.977
22:39078977:T:A	F21L	0.977
22:39078977:T:G	F21L	0.977

dbSNP variants (sampled 300 via entrez): RS1000243581 (22:39076889 G>A), RS1000300520 (22:39087386 T>G), RS1001118858 (22:39083496 T>C), RS1001583704 (22:39082565 G>A), RS1001807433 (22:39087683 G>T), RS1001919152 (22:39083741 G>A), RS1001970306 (22:39087952 C>T), RS1002187124 (22:39075953 CAGA>C), RS1002303509 (22:39084183 A>G), RS1002677418 (22:39078352 G>C), RS1002740385 (22:39082878 C>A,T), RS1002813555 (22:39078086 C>T), RS1002911400 (22:39082543 G>A), RS1003700120 (22:39087797 G>A), RS1004879619 (22:39088011 G>A)

Disease associations

OMIM: gene MIM:607113 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001725_110	Inflammatory bowel disease	4.000000e-33
GCST006585_2355	Blood protein levels	4.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741217 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 21,957 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,278
CHEMBL3561076	TRIMETAZIDINE DIHYDROCHLORIDE	4	280
CHEMBL474579	CEFOTETAN	4	15,647
CHEMBL1716983	ENISAMIUM IODIDE	3	1
CHEMBL1257065	STILONIUM IODIDE	2	751

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

Binding affinities (BindingDB)

645 measured of 944 human assays (1000 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
MLS000082581	EC50	0.0948 nM
5-cyclopentylidene-2-sulfanylidene-1,3-thiazolidin-4-one	IC50	240 nM
4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thione	IC50	250 nM
6-bromo-N-piperonyl-pyrazolo[1,5-a]pyrimidine-2-carboxamide	IC50	363 nM
SMR000285999	EC50	560 nM
MLS000689390	EC50	880 nM
MLS001208265	IC50	892 nM
3-chloranyl-N-(3-morpholin-4-ylpropyl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	950 nM
1,4-Benzoquinone	KI	955 nM
MLS000708819	EC50	970 nM
trimethyl-[2-[oxo-(1-phenylcyclopentyl)methoxy]ethyl]ammonium;iodide	IC50	1060 nM
MLS000036597	IC50	1070 nM
MLS001212885	IC50	1080 nM
SMR000305231	IC50	1140 nM
SMR000595764	IC50	1190 nM
1-ethyl-5-methyl-4-[(phenylsulfonyl)methyl]-1,3-dihydro-2H-imidazol-2-one	IC50	1230 nM
cid_6294434	IC50	1240 nM
cid_6603239	IC50	1300 nM
cid_16682258	IC50	1310 nM
ethyl 5-(diethylamino)-2-hydroxyimino-pentanoate;iodanylmethane	IC50	1350 nM
SMR000279529	IC50	1390 nM
SMR000283917	IC50	1440 nM
3-(4-fluorophenyl)-4,5-dihydro-1,2-oxazole-5-carboxylic acid	EC50	1450 nM
3-pyridinecarboxylic acid (3-acetyl-4-oxido-2-quinoxalin-4-iumyl)methyl ester	IC50	1480 nM
2-{(E)-2-[3-Methoxy-4-(o-tolylcarbamoyl-methoxy)-phenyl]-vinyl}-1-methyl-pyridinium	IC50	1560 nM
2-[[5-[[2-(3-chloroanilino)-4-thiazolyl]methyl]-4-(3-methoxypropyl)-1,2,4-triazol-3-yl]thio]acetic acid cyclohexyl ester	IC50	1560 nM
SMR000198590	IC50	1580 nM
1-phenyl-1-cyclopentanecarboxylic acid 3-(4-methyl-4-morpholin-4-iumyl)propyl ester;iodide	IC50	1610 nM
SMR000306192	IC50	1610 nM
MLS001183995	IC50	1610 nM
3-[(2-methyl-5-oxidanylidene-3-phenyl-4H-imidazol-4-yl)diazenyl]benzoic acid	EC50	1640 nM
MLS000065559	IC50	1640 nM
MLS000565397	IC50	1660 nM
SMR000173748	IC50	1670 nM
2-(4,6-dimethyl-3-oxidanylidene-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-(3-fluorophenyl)ethanamide	EC50	1720 nM
2-(3-keto-4,6-dimethyl-isothiazolo[5,4-b]pyridin-2-yl)-N-propyl-acetamide	EC50	1750 nM
MLS000689393	EC50	1750 nM
1-cyclohexyloxy-3-(2-ethyl-3-methyl-benzimidazol-3-ium-1-yl)propan-2-ol;iodide	IC50	1750 nM
3,4-dimethyl-1-(2H-tetrazol-5-yl)-6-pyrano[2,3-c]pyrazolone	IC50	1760 nM
(1,3-dimethyl-1H-imidazol-3-ium-2-yl)methyl methylcarbamate	IC50	1760 nM
1-O-tert-butyl 2-O-[2-oxo-2-(4-phenylphenyl)ethyl] 4-hydroxypyrrolidine-1,2-dicarboxylate	IC50	1790 nM
1-heptylpyridin-4-imine;hydroiodide	IC50	1830 nM
cid_14262872	IC50	1850 nM
2-Cyano-3-(2-methyl-1H-indol-3-yl)-N-(1-phenyl-ethyl)-acrylamide	IC50	1870 nM
[(2Z)-2-(1,3-dioxolan-4-ylidene)ethyl]-trimethylammonium;iodide	IC50	1890 nM
SMR000518608	IC50	1890 nM
MLS000333810	IC50	1910 nM
cid_6473547	IC50	1910 nM
MLS000688171	IC50	1930 nM
(8S)-7-(3,3-diphenylpropanoyl)-3-[3-(2-methylprop-2-enoylamino)phenyl]-1-oxa-2,7-diazaspiro[4.4]non-2-ene-8-carboxamide	EC50	1940 nM

ChEMBL bioactivities

642 potent at pChembl≥5 of 966 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.46	IC50	345	nM	CHEMBL1310492
6.42	IC50	376	nM	CHEMBL1455989
6.27	IC50	539	nM	CHEMBL1498363
6.26	IC50	550	nM	CHEMBL1498363
6.22	IC50	601	nM	CHEMBL1312653
6.16	IC50	695	nM	CHEMBL1503187
6.16	IC50	693	nM	CHEMBL510505
6.16	IC50	695	nM	CHEMBL290545
6.13	IC50	732	nM	CHEMBL1499970
6.09	IC50	814	nM	CHEMBL3196851
6.09	IC50	808	nM	CHEMBL1499970
6.08	IC50	835	nM	CHEMBL290545
6.07	IC50	858	nM	CHEMBL1447034
6.05	IC50	884	nM	CHEMBL255881
6.05	IC50	892	nM	CHEMBL289356
6.03	IC50	936	nM	CHEMBL1466798
6.00	IC50	989	nM	CHEMBL1567396
6.00	IC50	992	nM	CHEMBL1511078
5.96	IC50	1100	nM	CHEMBL1724713
5.95	IC50	1120	nM	CHEMBL1362702
5.92	IC50	1190	nM	CHEMBL1537130
5.92	IC50	1200	nM	CHEMBL290545
5.92	IC50	1200	nM	CHEMBL1412746
5.92	IC50	1190	nM	CHEMBL1334528
5.91	IC50	1220	nM	CHEMBL1334528
5.90	IC50	1260	nM	CHEMBL3207528
5.89	IC50	1290	nM	CHEMBL1342158
5.88	IC50	1310	nM	CHEMBL1379279
5.88	IC50	1320	nM	CHEMBL1389035
5.87	IC50	1350	nM	CHEMBL1587985
5.85	IC50	1420	nM	CHEMBL1341547
5.84	IC50	1450	nM	CHEMBL1498363
5.83	IC50	1470	nM	CHEMBL1412746
5.83	IC50	1470	nM	CHEMBL1501432
5.82	IC50	1500	nM	CHEMBL1727425
5.82	IC50	1503	nM	CHEMBL1503187
5.81	IC50	1540	nM	CHEMBL1511826
5.81	IC50	1550	nM	CHEMBL3209322
5.81	IC50	1560	nM	CHEMBL3198803
5.80	IC50	1600	nM	CHEMBL1412746
5.78	IC50	1660	nM	GLAUCINE METHIODIDE
5.78	IC50	1650	nM	CHEMBL1377153
5.77	IC50	1700	nM	CHEMBL1310492
5.76	IC50	1730	nM	CHEMBL1976824
5.76	IC50	1720	nM	CHEMBL1551307
5.76	IC50	1750	nM	CHEMBL1706030
5.75	IC50	1790	nM	CHEMBL3190345
5.75	IC50	1780	nM	CHEMBL3191118
5.74	IC50	1810	nM	CHEMBL3197232
5.74	IC50	1840	nM	CHEMBL1378796

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation	3
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	3
Aflatoxin B1	increases expression, affects expression	3
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
Benzo(a)pyrene	increases methylation, increases expression	2
Nickel	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
MRK 003	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Azacitidine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Demecolcine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1

ChEMBL screening assays

31 unique, capped per target: 23 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1217305	Binding	Binding affinity to human recombinant APOBEC3G at 20 ug/ml	Baculiferins A-O, O-sulfated pyrrole alkaloids with anti-HIV-1 activity, from the Chinese marine sponge Iotrochota baculifera. — Bioorg Med Chem
CHEMBL1738408	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of small molecule APOBEC3G DNA Deaminase Inhibitors via a fluorescence-based single-stranded DNA deaminase assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_W645	293T/APOBEC3G	Transformed cell line	Female
CVCL_W646	HeLa-APOBEC3G	Cancer cell line	Female

Clinical trials (associated diseases)

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