APOBEC3H apolipoprotein B mRNA editing enzyme catalytic subunit 3H [Homo sapiens (human)] - Gene

Summary

Official Symbol: APOBEC3Hprovided by HGNC
Official Full Name: apolipoprotein B mRNA editing enzyme catalytic subunit 3Hprovided by HGNC
Primary source: HGNC:HGNC:24100
See related: Ensembl:ENSG00000100298 MIM:610976; AllianceGenome:HGNC:24100
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: A3H; ARP10; ARP-10
Summary: This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistence to human immunodeficiency virus type 1 infection in certain populations. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]
Expression: Broad expression in lymph node (RPKM 1.2), colon (RPKM 1.0) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (39097244..39104067)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (39567663..39574409)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (39493249..39500072)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential Activity of APOBEC3F, APOBEC3G, and APOBEC3H in the Restriction of HIV-2.
Title: Differential Activity of APOBEC3F, APOBEC3G, and APOBEC3H in the Restriction of HIV-2.
Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma.
Title: Association between APOBEC3H-Mediated Demethylation and Immune Landscape in Head and Neck Squamous Carcinoma.
genetic variations in APOBEC3 genes may affect the efficiency of hepatitis b virus elimination in humans.
Title: Different antiviral activities of natural APOBEC3C, APOBEC3G, and APOBEC3H variants against hepatitis B virus.
APOBEC3 proteins APOBEC3F (A3F), APOBEC3G (A3G), and APOBEC3H (A3H) are host restriction factors that inhibit HIV-1 through DNA cytidine deaminase-dependent and -independent mechanisms and have either one (A3H) or two (A3F and A3G) zinc-binding domains.
Title: Flexibility in Nucleic Acid Binding Is Central to APOBEC3H Antiviral Activity.
These findings suggested that there was no relationship between A3A, A3B and A3H single nucleotide polymorphisms and chronic hepatitis B progression or hepatocellular carcinoma development in the Han Chinese population.
Title: Associations between the single nucleotide polymorphisms of APOBEC3A, APOBEC3B and APOBEC3H, and chronic hepatitis B progression and hepatocellular carcinoma in a Chinese population.
APOBEC3A, APOBEC3B, and APOBEC3H, demonstrated the highest transcript expression in recessive dystrophic epidermolysis bullosa (RDEB) squamous cell carcinoma (SCC) compared with normal skin and for all SCC subtypes analyzed. Furthermore, the proportion of APOBEC mutations associated with APOBEC3A was greater than the context associated with APOBEC3B.
Title: APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa.
Data demonstrate that the cellular RNA bound by APOBEC3H does not completely inhibit enzyme activity, in contrast to other APOBEC family members. Despite degradation of the cellular RNA, an approximately 12-nt RNA remains bound to the enzyme, even in the presence of ssDNA. The RNA-mediated dimer is disrupted by mutating W115 on loop 7 or R175 and R176 on helix 6, but this also disrupts protein stability.
Title: RNA-Mediated Dimerization of the Human Deoxycytidine Deaminase APOBEC3H Influences Enzyme Activity and Interaction with Nucleic Acids.
Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H
Title: Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H.
we reveal the 2.20-A crystal structure of the chimpanzee A3H (cpzA3H) dimer bound to a short double-stranded RNA (dsRNA), which appears to be similar to two recently reported structures of pig-tailed macaque A3H and human A3H
Title: Structural basis of chimpanzee APOBEC3H dimerization stabilized by double-stranded RNA.
APOBEC3H has a structural zipcode for subcellular localization and selecting viral substrates for restriction.
Title: APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 for Restriction.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 (delta Vif) replication is restricted by APOBEC3H haplotypes II and V with similar efficiences, but by different mechanisms	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	A3H hapI-GKE and hapII-RDD variants are packaged into virions through an association with the matrix-capsid region (amino acids 10-277) and with the NC region (amino acids 378-432) of Gag in an RNA-dependent manner, respectively	PubMed
Vif	vif	The combination of N48H and GDAK60-63EKGE results in a hyperfunctional Vif protein capable of fully inhibiting stable APOBEC3H-hapII	PubMed
	vif	Single mutations I31V, R33G, K36R, and K50R in HIV-1 Vif from NL4-3 sufficiently reduce or abolish their ability to cause G2 arrest, but induce APOBEC3H degradation	PubMed
	vif	HIV-1 Vif proteins from NL4-3, SG3, and C2 have the ability to induce G2 arrest in HEK293T cells, but are defective in inducing APOBEC3H degradation when compared to HIV-1 Vif from HXB2	PubMed
	vif	A3H interacts with both HIV-1 Vif(IIIB) and Vif(HXB2) in cells and in vitro, but Vif(IIIB) fails to degrade A3H and Vif(HXB2) H48N mutant reduces its ability to degrade A3H in cells	PubMed
	vif	A histidine at position 48 (48H) in HIV-1 Vif confers activity against A3H-hapII, while an asparagine (48N) abolishes its anti-A3H activity	PubMed
	vif	A glutamic acid at position 121 (121E) renders A3H-hapII sensitivity to both LAI and NL4-3 Vif proteins, while a lysine (121K) results in resistance of A3H-hapII to both Vif alleles	PubMed
	vif	CBF-beta-mediated increase of HIV-1 Vif steady-state levels results in decreased cellular levels of all Vif-sensitive APOBEC proteins (A3C, A3D, A3F, A3G, and A3H haplotype II)	PubMed
	vif	APOBEC3H variants encoding a SNP cluster (G105R, K121D and E178D, hapII-RDD) restrict human immunodeficiency virus type 1 (HIV-1) more efficiently than wild-type APOBEC3H (hapI-GKE). All APOBEC3H variants are resistant to HIV-1 Vif	PubMed
	vif	Once expression is optimized and stabilized, human A3H can significantly reduce HIV-1 infectivity. HIV-1 Vif fails to suppress A3H activity	PubMed
	vif	The interaction of HIV-1 Vif(HXB2) with A3H induces polyubiquitination of A3H at K63 position	PubMed
	vif	HIV-1 Vif variants from subtype F are highly effective in counteracting A3H hapII. Two residues in the amino-terminal region of Vif (positions 39F and 48H) from HIV-1 subtype F are necessary for association of Vif with A3H hapII	PubMed
	vif	HIV-1 Vif 39F efficiently inhibits A3H-hapII, but Vif 39V is defective in counteracting A3H-hapII. Mutation at position 39F to the different residues (C, E, G, H, I, K, L, S, T, and V) is inactive against A3H-hapII, but only 39Y can counteract A3H-hapII	PubMed
	vif	Human T cell line CEM.NKR clones display inhibition of HIV-1 replication although these clones retain low levels of A3DE, A3F, A3G, and A3H expression, suggesting that a novel restriction factor distinct from APOBEC3s exists in CEM.NKR cells	PubMed
	vif	G105R and K121E residues are important for A3H (HapI) stability and increased antiviral activity and for the resistance of A3H (HapI) to Vif, respectively	PubMed
	vif	HIV-1 Vif targets A3H (HapII) for proteasome-mediated degradation. L64, I66, Y69, and L72 residues in Vif are required for Vif-mediated A3H degradation	PubMed
nucleocapsid	gag	A3H (HapVII) virion packaging is dependent on a (112)YYXW(115) motif, which binds HIV-1 nucleocapsid in an RNA-dependent manner. A single Y112A mutation completely disrupts A3H virion incorporation	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables cytidine deaminase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytidine deaminase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxycytidine deaminase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA cytosine deamination	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA cytosine deamination	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA demethylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in clearance of foreign intracellular DNA	IDA Inferred from Direct Assay more info	PubMed
involved_in cytidine deamination	IEA Inferred from Electronic Annotation more info
involved_in cytidine to uridine editing	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to virus	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation by host of viral genome replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate	IDA Inferred from Direct Assay more info	PubMed
involved_in retrotransposon silencing	IDA Inferred from Direct Assay more info	PubMed
involved_in retrotransposon silencing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in P-body	IBA Inferred from Biological aspect of Ancestor more info
located_in P-body	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA dC->dU-editing enzyme APOBEC-3H

Names: APOBEC-related protein 10; apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3H

NP_001159474.2

EC 3.5.4.38

NP_001159475.2

EC 3.5.4.38

NP_001159476.2

EC 3.5.4.38

NP_861438.3

EC 3.5.4.38

XP_011528292.1

EC 3.5.4.38

XP_011528293.1

EC 3.5.4.38

XP_011528294.1

EC 3.5.4.38

XP_054181176.1

EC 3.5.4.38

XP_054181177.1

EC 3.5.4.38

XP_054181178.1

EC 3.5.4.38

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001166002.3 → NP_001159474.2 DNA dC->dU-editing enzyme APOBEC-3H isoform SV-182

See identical proteins and their annotated locations for NP_001159474.2

Status: REVIEWED

Description

Transcript Variant: This variant (SV-182) lacks an alternate exon and uses an alternate splice site, resulting in an alternate 3' coding region and 3' UTR, compared to variant SV-200. The encoded isoform (SV-182) has a distinct C-terminus and is shorter than isoform SV-200.

Source sequence(s)

BC069023

Consensus CDS

CCDS54531.1

UniProtKB/TrEMBL

B7TQM4, B7TQM7

Related

ENSP00000216123.5, ENST00000348946.8

Conserved Domains (1) summary

pfam08210
Location:27 → 179

APOBEC_N; APOBEC-like N-terminal domain
NM_001166003.3 → NP_001159475.2 DNA dC->dU-editing enzyme APOBEC-3H isoform SV-200

See identical proteins and their annotated locations for NP_001159475.2

Status: REVIEWED

Description

Transcript Variant: This variant (SV-200) represents the longest transcript and encodes the longest isoform (SV-200).

Source sequence(s)

BC069023, BQ054330

Consensus CDS

CCDS54530.1

UniProtKB/Swiss-Prot

B0QYP0, B0QYP1, B7TQM5, E9PF38, M4W6S4, Q5JYL9, Q6IC87, Q6NTF7

UniProtKB/TrEMBL

B7TQM7

Related

ENSP00000385741.1, ENST00000401756.5

Conserved Domains (1) summary

pfam08210
Location:27 → 179

APOBEC_N; APOBEC-like N-terminal domain
NM_001166004.3 → NP_001159476.2 DNA dC->dU-editing enzyme APOBEC-3H isoform SV-154

Status: REVIEWED

Description

Transcript Variant: This variant (SV-154) lacks an alternate exon, resulting in a frameshift in the 3' coding region, compared to variant SV-200. The encoded isoform (SV-154) has a distinct C-terminus and is shorter than isoform SV-200. The 3' UTR of this variant is incomplete due to lack of a 3'-complete supporting transcript and splice site ambiguity in the terminal non-coding exon.

Source sequence(s)

BC069023, BQ054330, FJ376617

Consensus CDS

CCDS54532.1

UniProtKB/TrEMBL

A0A087WZI3, B7TQM9

Related

ENSP00000393520.2, ENST00000421988.6

Conserved Domains (2) summary

cd01283
Location:30 → 121

cytidine_deaminase; Cytidine deaminase zinc-binding domain. These enzymes are Zn dependent. The zinc ion in the active site plays a central role in the proposed catalytic mechanism, activating a water molecule to form a hydroxide ion that performs a nucleophilic attack on ...

pfam05240
Location:120 → 140

APOBEC_C; APOBEC-like C-terminal domain
NM_181773.5 → NP_861438.3 DNA dC->dU-editing enzyme APOBEC-3H isoform SV-183

See identical proteins and their annotated locations for NP_861438.3

Status: REVIEWED

Description

Transcript Variant: This variant (SV-183) lacks an alternate exon, resulting in an alternate 3' coding region and 3' UTR, compared to variant SV-200. The encoded isoform (SV-183) has a distinct C-terminus and is shorter than isoform SV-200

Source sequence(s)

BC069023, BQ052182, BU585251

Consensus CDS

CCDS13985.1

UniProtKB/TrEMBL

B7TQM3, B7TQM6

Related

ENSP00000411754.3, ENST00000442487.8

Conserved Domains (3) summary

cd01283
Location:30 → 121

cytidine_deaminase; Cytidine deaminase zinc-binding domain. These enzymes are Zn dependent. The zinc ion in the active site plays a central role in the proposed catalytic mechanism, activating a water molecule to form a hydroxide ion that performs a nucleophilic attack on ...

pfam05240
Location:120 → 163

APOBEC_C; APOBEC-like C-terminal domain

pfam08210
Location:27 → 179

APOBEC_N; APOBEC-like N-terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

39097244..39104067

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011529990.3 → XP_011528292.1 DNA dC->dU-editing enzyme APOBEC-3H isoform X1

See identical proteins and their annotated locations for XP_011528292.1

UniProtKB/TrEMBL

B7TQM7

Conserved Domains (3) summary

cd01283
Location:30 → 121

cytidine_deaminase; Cytidine deaminase zinc-binding domain. These enzymes are Zn dependent. The zinc ion in the active site plays a central role in the proposed catalytic mechanism, activating a water molecule to form a hydroxide ion that performs a nucleophilic attack on ...

pfam05240
Location:120 → 163

APOBEC_C; APOBEC-like C-terminal domain

pfam08210
Location:27 → 179

APOBEC_N; APOBEC-like N-terminal domain
XM_011529991.4 → XP_011528293.1 DNA dC->dU-editing enzyme APOBEC-3H isoform X1

See identical proteins and their annotated locations for XP_011528293.1

UniProtKB/TrEMBL

B7TQM7

Conserved Domains (3) summary

cd01283
Location:30 → 121

cytidine_deaminase; Cytidine deaminase zinc-binding domain. These enzymes are Zn dependent. The zinc ion in the active site plays a central role in the proposed catalytic mechanism, activating a water molecule to form a hydroxide ion that performs a nucleophilic attack on ...

pfam05240
Location:120 → 163

APOBEC_C; APOBEC-like C-terminal domain

pfam08210
Location:27 → 179

APOBEC_N; APOBEC-like N-terminal domain
XM_011529992.4 → XP_011528294.1 DNA dC->dU-editing enzyme APOBEC-3H isoform X2

See identical proteins and their annotated locations for XP_011528294.1

UniProtKB/Swiss-Prot

B0QYP0, B0QYP1, B7TQM5, E9PF38, M4W6S4, Q5JYL9, Q6IC87, Q6NTF7

UniProtKB/TrEMBL

B7TQM7

Related

ENSP00000483689.1, ENST00000613677.4

Conserved Domains (1) summary

pfam08210
Location:27 → 179

APOBEC_N; APOBEC-like N-terminal domain

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

39567663..39574409

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054325201.1 → XP_054181176.1 DNA dC->dU-editing enzyme APOBEC-3H isoform X1
XM_054325202.1 → XP_054181177.1 DNA dC->dU-editing enzyme APOBEC-3H isoform X1
XM_054325203.1 → XP_054181178.1 DNA dC->dU-editing enzyme APOBEC-3H isoform X2

UniProtKB/TrEMBL

B7TQM8