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Protein

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

Gene

APOBEC3D

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

Functioni

DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. Exhibits antiviral activity against vif-deficient HIV-1. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single-or double-stranded RNA. May inhibit the mobility of LTR and non-LTR retrotransposons.6 Publications

Catalytic activityi

Cytidine + H2O = uridine + NH3.

Cofactori

Zn2+By similarity

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi78 – 781ZincBy similarity
Metal bindingi109 – 1091ZincBy similarity
Metal bindingi112 – 1121ZincBy similarity
Metal bindingi262 – 2621ZincBy similarity
Active sitei264 – 2641Proton donorBy similarity
Metal bindingi293 – 2931ZincBy similarity
Metal bindingi296 – 2961ZincBy similarity

GO - Molecular functioni

GO - Biological processi

  • defense response to virus Source: UniProtKB
  • DNA cytosine deamination Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • negative regulation of single stranded viral RNA replication via double stranded DNA intermediate Source: UniProtKB
  • negative regulation of transposition Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
DNA dC->dU-editing enzyme APOBEC-3D (EC:3.5.4.-)
Short name:
A3D
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:17354. APOBEC3D.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic mRNA processing body Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24894.

Polymorphism and mutation databases

DMDMi48474596.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 386386DNA dC->dU-editing enzyme APOBEC-3DPRO_0000171756Add
BLAST

Proteomic databases

EPDiQ96AK3.
MaxQBiQ96AK3.
PaxDbiQ96AK3.
PRIDEiQ96AK3.

PTM databases

iPTMnetiQ96AK3.
PhosphoSiteiQ96AK3.

Expressioni

Tissue specificityi

Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung.1 Publication

Gene expression databases

BgeeiQ96AK3.
ExpressionAtlasiQ96AK3. baseline and differential.
GenevisibleiQ96AK3. HS.

Organism-specific databases

HPAiHPA055116.

Interactioni

Protein-protein interaction databases

IntActiQ96AK3. 2 interactions.
STRINGi9606.ENSP00000216099.

Structurei

3D structure databases

ProteinModelPortaliQ96AK3.
SMRiQ96AK3. Positions 5-386.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 145117CMP/dCMP-type deaminase 1PROSITE-ProRule annotationAdd
BLAST
Domaini187 – 334148CMP/dCMP-type deaminase 2PROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410JBA1. Eukaryota.
ENOG41119MS. LUCA.
GeneTreeiENSGT00530000062933.
HOGENOMiHOG000033755.
HOVERGENiHBG050434.
OMAiFEYCWDN.
PhylomeDBiQ96AK3.
TreeFamiTF331356.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q96AK3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPQIRNPME RMYRDTFYDN FENEPILYGR SYTWLCYEVK IKRGRSNLLW
60 70 80 90 100
DTGVFRGPVL PKRQSNHRQE VYFRFENHAE MCFLSWFCGN RLPANRRFQI
110 120 130 140 150
TWFVSWNPCL PCVVKVTKFL AEHPNVTLTI SAARLYYYRD RDWRWVLLRL
160 170 180 190 200
HKAGARVKIM DYEDFAYCWE NFVCNEGQPF MPWYKFDDNY ASLHRTLKEI
210 220 230 240 250
LRNPMEAMYP HIFYFHFKNL LKACGRNESW LCFTMEVTKH HSAVFRKRGV
260 270 280 290 300
FRNQVDPETH CHAERCFLSW FCDDILSPNT NYEVTWYTSW SPCPECAGEV
310 320 330 340 350
AEFLARHSNV NLTIFTARLC YFWDTDYQEG LCSLSQEGAS VKIMGYKDFV
360 370 380
SCWKNFVYSD DEPFKPWKGL QTNFRLLKRR LREILQ
Length:386
Mass (Da):46,598
Last modified:December 1, 2001 - v1
Checksum:i94C7253BDCC85B22
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL022318 Genomic DNA. Translation: CAI17899.1.
CCDSiCCDS46709.1.
UniGeneiHs.629775.
Hs.658626.

Genome annotation databases

EnsembliENST00000216099; ENSP00000216099; ENSG00000243811.
ENST00000381568; ENSP00000370980; ENSG00000243811.
UCSCiuc003awt.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL022318 Genomic DNA. Translation: CAI17899.1.
CCDSiCCDS46709.1.
UniGeneiHs.629775.
Hs.658626.

3D structure databases

ProteinModelPortaliQ96AK3.
SMRiQ96AK3. Positions 5-386.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ96AK3. 2 interactions.
STRINGi9606.ENSP00000216099.

PTM databases

iPTMnetiQ96AK3.
PhosphoSiteiQ96AK3.

Polymorphism and mutation databases

DMDMi48474596.

Proteomic databases

EPDiQ96AK3.
MaxQBiQ96AK3.
PaxDbiQ96AK3.
PRIDEiQ96AK3.

Protocols and materials databases

DNASUi140564.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216099; ENSP00000216099; ENSG00000243811.
ENST00000381568; ENSP00000370980; ENSG00000243811.
UCSCiuc003awt.5. human.

Organism-specific databases

GeneCardsiAPOBEC3D.
HGNCiHGNC:17354. APOBEC3D.
HPAiHPA055116.
MIMi609900. gene.
neXtProtiNX_Q96AK3.
PharmGKBiPA24894.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBA1. Eukaryota.
ENOG41119MS. LUCA.
GeneTreeiENSGT00530000062933.
HOGENOMiHOG000033755.
HOVERGENiHBG050434.
OMAiFEYCWDN.
PhylomeDBiQ96AK3.
TreeFamiTF331356.

Miscellaneous databases

PROiQ96AK3.
SOURCEiSearch...

Gene expression databases

BgeeiQ96AK3.
ExpressionAtlasiQ96AK3. baseline and differential.
GenevisibleiQ96AK3. HS.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence of human chromosome 22."
    Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M.
    , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
    Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22."
    Jarmuz A., Chester A., Bayliss J., Gisbourne J., Dunham I., Scott J., Navaratnam N.
    Genomics 79:285-296(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: GENE FAMILY ORGANIZATION.
  3. "Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business."
    Wedekind J.E., Dance G.S.C., Sowden M.P., Smith H.C.
    Trends Genet. 19:207-216(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON APOBEC FAMILIES.
  4. Cited for: FUNCTION IN HIV-1 INFECTIVITY.
  5. "The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements."
    Chiu Y.L., Greene W.C.
    Annu. Rev. Immunol. 26:317-353(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. "APOBEC3 proteins mediate the clearance of foreign DNA from human cells."
    Stenglein M.D., Burns M.B., Li M., Lengyel J., Harris R.S.
    Nat. Struct. Mol. Biol. 17:222-229(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN RETROTRANSPOSITION.
  7. "Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction."
    Refsland E.W., Stenglein M.D., Shindo K., Albin J.S., Brown W.L., Harris R.S.
    Nucleic Acids Res. 38:4274-4284(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1."
    Hultquist J.F., Lengyel J.A., Refsland E.W., LaRue R.S., Lackey L., Brown W.L., Harris R.S.
    J. Virol. 85:11220-11234(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HIV-1 RESTRICTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
  9. "Retroelements versus APOBEC3 family members: No great escape from the magnificent seven."
    Arias J.F., Koyama T., Kinomoto M., Tokunaga K.
    Front. Microbiol. 3:275-275(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. "HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies."
    Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.
    J. Virol. 86:11712-11724(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  11. "Endogenous origins of HIV-1 G-to-A hypermutation and restriction in the nonpermissive T cell line CEM2n."
    Refsland E.W., Hultquist J.F., Harris R.S.
    PLoS Pathog. 8:E1002800-E1002800(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HIV-1 RESTRICTION.
  12. Cited for: REVIEW.
  13. "APOBEC3G restricts HIV-1 to a greater extent than APOBEC3F and APOBEC3DE in human primary CD4+ t cells and macrophages."
    Chaipan C., Smith J.L., Hu W.S., Pathak V.K.
    J. Virol. 87:444-453(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HIV-1 RESTRICTION.
  14. "The suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4+ T cells is associated with the inhibition of processive reverse transcription as well as excessive cytidine deamination."
    Gillick K., Pollpeter D., Phalora P., Kim E.Y., Wolinsky S.M., Malim M.H.
    J. Virol. 87:1508-1517(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN HIV-1 RESTRICTION.

Entry informationi

Entry nameiABC3D_HUMAN
AccessioniPrimary (citable) accession number: Q96AK3
Secondary accession number(s): Q5JZ91
, Q7Z2N2, Q7Z2N5, Q7Z2N6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: December 1, 2001
Last modified: June 8, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

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