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Protein

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

Gene

APOBEC3H

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. The A3H-var/haplotype 2 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 T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons.10 Publications

Miscellaneous

APOBEC3H from old world monkeys has retained its antiviral activity, while it is lost in other primates.
It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.

Catalytic activityi

Cytidine + H2O = uridine + NH3.

Cofactori

Zn2+By similarity

Activity 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)DescriptionActionsGraphical viewLength
Metal bindingi54ZincBy similarity1
Active sitei56Proton donorBy similarity1
Metal bindingi85ZincBy similarity1
Metal bindingi88ZincBy similarity1

GO - Molecular functioni

  • cytidine deaminase activity Source: UniProtKB
  • RNA binding Source: GO_Central
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processAntiviral defense, Immunity, Innate immunity
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-72200 mRNA Editing: C to U Conversion
R-HSA-75094 Formation of the Editosome

Names & Taxonomyi

Protein namesi
Recommended name:
DNA dC->dU-editing enzyme APOBEC-3H (EC:3.5.4.-)
Alternative name(s):
APOBEC-related protein 10
Short name:
ARP-10
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H
Short name:
A3H
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100298.15
HGNCiHGNC:24100 APOBEC3H
MIMi610976 gene
neXtProtiNX_Q6NTF7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi56E → Q: Reduces the ability to inhibit the retrotransposition of LINE-1 elements. 1 Publication1

Organism-specific databases

DisGeNETi164668
OpenTargetsiENSG00000100298
PharmGKBiPA162376694

Polymorphism and mutation databases

BioMutaiAPOBEC3H
DMDMi205371798

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002916631 – 200DNA dC->dU-editing enzyme APOBEC-3HAdd BLAST200

Proteomic databases

PaxDbiQ6NTF7
PeptideAtlasiQ6NTF7
PRIDEiQ6NTF7
ProteomicsDBi66670
66671 [Q6NTF7-2]
66672 [Q6NTF7-3]

PTM databases

iPTMnetiQ6NTF7
PhosphoSitePlusiQ6NTF7

Expressioni

Tissue specificityi

Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung, testis, ovary, fetal liver and skin.2 Publications

Gene expression databases

BgeeiENSG00000100298 Expressed in 82 organ(s), highest expression level in blood
CleanExiHS_APOBEC3H
ExpressionAtlasiQ6NTF7 baseline and differential

Organism-specific databases

HPAiHPA021492

Interactioni

Subunit structurei

Interacts with AGO1, AGO2 and AGO3.1 Publication

Protein-protein interaction databases

BioGridi127899, 1 interactor
STRINGi9606.ENSP00000385741

Structurei

Secondary structure

1200
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6NTF7
SMRiQ6NTF7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 126CMP/dCMP-type deaminasePROSITE-ProRule annotationAdd BLAST123

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili160 – 182Sequence analysisAdd BLAST23

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410JBA1 Eukaryota
ENOG41119MS LUCA
GeneTreeiENSGT00530000062933
HOGENOMiHOG000033754
HOVERGENiHBG050434
KOiK18750
OMAiNKIKSMG
OrthoDBiEOG091G0IUK
PhylomeDBiQ6NTF7
TreeFamiTF331356

Family and domain databases

InterProiView protein in InterPro
IPR016192 APOBEC/CMP_deaminase_Zn-bd
IPR013158 APOBEC_N
IPR002125 CMP_dCMP_dom
IPR016193 Cytidine_deaminase-like
PfamiView protein in Pfam
PF08210 APOBEC_N, 1 hit
SUPFAMiSSF53927 SSF53927, 1 hit
PROSITEiView protein in PROSITE
PS00903 CYT_DCMP_DEAMINASES_1, 1 hit
PS51747 CYT_DCMP_DEAMINASES_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6NTF7-1) [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
MALLTAETFR LQFNNKRRLR RPYYPRKALL CYQLTPQNGS TPTRGYFENK
60 70 80 90 100
KKCHAEICFI NEIKSMGLDE TQCYQVTCYL TWSPCSSCAW ELVDFIKAHD
110 120 130 140 150
HLNLGIFASR LYYHWCKPQQ KGLRLLCGSQ VPVEVMGFPE FADCWENFVD
160 170 180 190 200
HEKPLSFNPY KMLEELDKNS RAIKRRLERI KIPGVRAQGR YMDILCDAEV
Note: No experimental confirmation available.
Length:200
Mass (Da):23,532
Last modified:September 12, 2018 - v4
Checksum:i67A9E01382CC9388
GO
Isoform 2 (identifier: Q6NTF7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-200: IPGVRAQGRYMDILCDAEV → S

Show »
Length:182
Mass (Da):21,531
Checksum:i96BDB54DF68732F0
GO
Isoform 3 (identifier: Q6NTF7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-200: IPGVRAQGRYMDILCDAEV → QS

Show »
Length:183
Mass (Da):21,659
Checksum:iEC45DDB54DF68732
GO
Isoform 4 (identifier: Q6NTF7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     140-200: EFADCWENFV...YMDILCDAEV → NSRGTCAGSLHGYIV

Note: Gene prediction based on EST data.
Show »
Length:154
Mass (Da):17,782
Checksum:i24B2D720CD100775
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WZI3A0A087WZI3_HUMAN
DNA dC->dU-editing enzyme APOBEC-3H
APOBEC3H
154Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121K → D in CAG30367 (PubMed:15461802).Curated1

Polymorphismi

There are at least 4 different haplotypes in the human population. The allele A3H-var/haplotype 2 encodes a more stable protein which is able to block HIV-1 replication. The displayed allele (haplotype 1) is unstable and inefficient to block HIV-1 replication.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06562215Missing Decreases protein stability. 2 Publications1
Natural variantiVAR_03283518R → L1 PublicationCorresponds to variant dbSNP:rs139293Ensembl.1
Natural variantiVAR_032836105G → R in allele A3H-Var; haplotype 2; allele presenting a higher expression and which is more effective in retrotransposons and HIV-1 restriction; increases protein stability. 2 PublicationsCorresponds to variant dbSNP:rs139297Ensembl.1
Natural variantiVAR_032837121K → E in allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction. Corresponds to variant dbSNP:rs139298Ensembl.1
Natural variantiVAR_032838121K → N. Corresponds to variant dbSNP:rs139299Ensembl.1
Natural variantiVAR_067444140E → K. Corresponds to variant dbSNP:rs139300Ensembl.1
Natural variantiVAR_032839178E → D in allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction. 1 PublicationCorresponds to variant dbSNP:rs139302Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047044140 – 200EFADC…CDAEV → NSRGTCAGSLHGYIV in isoform 4. CuratedAdd BLAST61
Alternative sequenceiVSP_035034182 – 200IPGVR…CDAEV → S in isoform 2. 2 PublicationsAdd BLAST19
Alternative sequenceiVSP_039975182 – 200IPGVR…CDAEV → QS in isoform 3. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ376613 mRNA Translation: ACK77774.1
CR456481 mRNA Translation: CAG30367.3
KC329529 mRNA Translation: AGI04217.1
AL031846 Genomic DNA No translation available.
KF457460 Genomic DNA No translation available.
BC069023 mRNA Translation: AAH69023.1
BQ052182 mRNA No translation available.
CCDSiCCDS13985.1 [Q6NTF7-3]
CCDS54530.1 [Q6NTF7-1]
CCDS54531.1 [Q6NTF7-2]
CCDS54532.1 [Q6NTF7-4]
RefSeqiNP_001159474.2, NM_001166002.2 [Q6NTF7-2]
NP_001159475.2, NM_001166003.2 [Q6NTF7-1]
NP_001159476.2, NM_001166004.2
NP_861438.3, NM_181773.4 [Q6NTF7-3]
XP_011528294.1, XM_011529992.2 [Q6NTF7-1]
UniGeneiHs.440515

Genome annotation databases

EnsembliENST00000348946; ENSP00000216123; ENSG00000100298 [Q6NTF7-2]
ENST00000401756; ENSP00000385741; ENSG00000100298 [Q6NTF7-1]
ENST00000442487; ENSP00000411754; ENSG00000100298 [Q6NTF7-3]
ENST00000613677; ENSP00000483689; ENSG00000100298 [Q6NTF7-1]
GeneIDi164668
KEGGihsa:164668
UCSCiuc021wps.2 human [Q6NTF7-1]
uc062ejr.1 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ376613 mRNA Translation: ACK77774.1
CR456481 mRNA Translation: CAG30367.3
KC329529 mRNA Translation: AGI04217.1
AL031846 Genomic DNA No translation available.
KF457460 Genomic DNA No translation available.
BC069023 mRNA Translation: AAH69023.1
BQ052182 mRNA No translation available.
CCDSiCCDS13985.1 [Q6NTF7-3]
CCDS54530.1 [Q6NTF7-1]
CCDS54531.1 [Q6NTF7-2]
CCDS54532.1 [Q6NTF7-4]
RefSeqiNP_001159474.2, NM_001166002.2 [Q6NTF7-2]
NP_001159475.2, NM_001166003.2 [Q6NTF7-1]
NP_001159476.2, NM_001166004.2
NP_861438.3, NM_181773.4 [Q6NTF7-3]
XP_011528294.1, XM_011529992.2 [Q6NTF7-1]
UniGeneiHs.440515

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6B0BX-ray3.28A/E1-181[»]
6BBOX-ray3.43A/E3-181[»]
ProteinModelPortaliQ6NTF7
SMRiQ6NTF7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127899, 1 interactor
STRINGi9606.ENSP00000385741

PTM databases

iPTMnetiQ6NTF7
PhosphoSitePlusiQ6NTF7

Polymorphism and mutation databases

BioMutaiAPOBEC3H
DMDMi205371798

Proteomic databases

PaxDbiQ6NTF7
PeptideAtlasiQ6NTF7
PRIDEiQ6NTF7
ProteomicsDBi66670
66671 [Q6NTF7-2]
66672 [Q6NTF7-3]

Protocols and materials databases

DNASUi164668
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000348946; ENSP00000216123; ENSG00000100298 [Q6NTF7-2]
ENST00000401756; ENSP00000385741; ENSG00000100298 [Q6NTF7-1]
ENST00000442487; ENSP00000411754; ENSG00000100298 [Q6NTF7-3]
ENST00000613677; ENSP00000483689; ENSG00000100298 [Q6NTF7-1]
GeneIDi164668
KEGGihsa:164668
UCSCiuc021wps.2 human [Q6NTF7-1]
uc062ejr.1 human

Organism-specific databases

CTDi164668
DisGeNETi164668
EuPathDBiHostDB:ENSG00000100298.15
GeneCardsiAPOBEC3H
HGNCiHGNC:24100 APOBEC3H
HPAiHPA021492
MIMi610976 gene
neXtProtiNX_Q6NTF7
OpenTargetsiENSG00000100298
PharmGKBiPA162376694
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBA1 Eukaryota
ENOG41119MS LUCA
GeneTreeiENSGT00530000062933
HOGENOMiHOG000033754
HOVERGENiHBG050434
KOiK18750
OMAiNKIKSMG
OrthoDBiEOG091G0IUK
PhylomeDBiQ6NTF7
TreeFamiTF331356

Enzyme and pathway databases

ReactomeiR-HSA-72200 mRNA Editing: C to U Conversion
R-HSA-75094 Formation of the Editosome

Miscellaneous databases

GeneWikiiAPOBEC3H
GenomeRNAii164668
PROiPR:Q6NTF7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100298 Expressed in 82 organ(s), highest expression level in blood
CleanExiHS_APOBEC3H
ExpressionAtlasiQ6NTF7 baseline and differential

Family and domain databases

InterProiView protein in InterPro
IPR016192 APOBEC/CMP_deaminase_Zn-bd
IPR013158 APOBEC_N
IPR002125 CMP_dCMP_dom
IPR016193 Cytidine_deaminase-like
PfamiView protein in Pfam
PF08210 APOBEC_N, 1 hit
SUPFAMiSSF53927 SSF53927, 1 hit
PROSITEiView protein in PROSITE
PS00903 CYT_DCMP_DEAMINASES_1, 1 hit
PS51747 CYT_DCMP_DEAMINASES_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiABC3H_HUMAN
AccessioniPrimary (citable) accession number: Q6NTF7
Secondary accession number(s): B0QYP0
, B0QYP1, B7TQM5, E9PF38, M4W6S4, Q5JYL9, Q6IC87
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: September 12, 2018
Last modified: November 7, 2018
This is version 117 of the entry and version 4 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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