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UniProtKB/Swiss-Prot Q9HC16 (ABC3G_HUMAN)
Last modified
July 22, 2008.
Version 65.
History...
Clusters with 100%,
90%,
50% identity |
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Names and origin
| Protein names | Recommended name: DNA dC->dU-editing enzyme APOBEC-3G EC=3.5.4.- Alternative name(s): APOBEC-related cytidine deaminase Short name=ARCD Short name=APOBEC-related protein ARP-9 CEM-15 Short name=CEM15 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 384 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | DNA deaminase (cytidine deaminase) that mediates a form of innate resistance to retroviral infections (at least to HIV-1 infection) by triggering G-to-A hypermutation in the newly synthesized viral DNA. The replacements C-to-U in the minus strand DNA of HIV-1 during reverse transcription, leads to G-to-A transitions in the plus strand. The inhibition of viral replication is either due to the degradation of the minus strand before its integration or to the lethality of the hypermutations. Modification of both DNA strands is not excluded. This antiviral activity is neutralized by the virion infectivity factor (VIF), that prevents the incorporation of APOBEC3G into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome. APOBEC3G binds a variety of RNAs, but does not display detectable APOB, NF1 and NAT1 mRNA editing. |
| Cofactor | Zinc. |
| Subunit structure | Homodimer. Interacts with APOBEC3B, APOBEC3F and HIV-1 VIF in a species specific manner. |
| Subcellular location | Cytoplasm. Nucleus. Note= Mainly cytoplasmic. Small amount are found in the nucleus. During HIV-1 infection, virion-encapsidated in absence of HIV-1 VIF. |
| 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. |
| Post-translational modification | Ubiquitinated in the presence of HIV-1 VIF. Association with VIF targets the protein for proteolysis by the ubiquitin-dependent proteasome pathway. |
| Miscellaneous | Inhibits also the infectivity of retroviral particles only distantly related to HIV-1, such as the simian immunodeficiency virus (SIV), the equine infectious anemia virus (EIAV) and the murine leukemia virus (MLV). HIV-1 does not replicate productively in nonhuman primates with the exception of the chimpanzee. The primates APOBEC3G (rhesus macaque, chimpanzee and African green monkey) are active against HIV-1 without VIF. Only the chimpanzee APOBEC3G is inhibited by HIV-1 VIF. 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. |
| Sequence similarities | Belongs to the cytidine and deoxycytidylate deaminase family. |
| Sequence caution | The sequence CAB45274.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| vif | P12504 | 1 | EBI-717839,EBI-779991 | From a different organism. |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | |||||
| Isoform 1 (identifier: Q9HC16-1) 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. | |||||
| Isoform 2 (identifier: Q9HC16-2) The sequence of this isoform differs from the canonical sequence as follows: 1-67: Missing. 195-384: Missing. | |||||
| Notes: May be due to a competing donor and acceptor splice sites and intron retentions. No experimental confirmation available. | |||||
| Isoform 3 (identifier: Q9HC16-3) The sequence of this isoform differs from the canonical sequence as follows: 58-79: VYSELKYHPEMRFFHWFSKWRK → VPPGLQSLCRQELSQLGKQTTH 80-384: Missing. | |||||
| Notes: May be due to a competing donor splice site. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | ||||
Molecule processing | ||||||||
|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 384 | 384 | DNA dC->dU-editing enzyme APOBEC-3G | |||||
Sites | ||||||||
| Active site | 259 | 1 | Proton donor By similarity | |||||
| Metal binding | 65 | 1 | Zinc By similarity | |||||
| Metal binding | 97 | 1 | Zinc By similarity | |||||
| Metal binding | 100 | 1 | Zinc By similarity | |||||
| Metal binding | 257 | 1 | Zinc By similarity | |||||
| Metal binding | 288 | 1 | Zinc By similarity | |||||
| Metal binding | 291 | 1 | Zinc By similarity | |||||
Natural variations | ||||||||
| Alternative sequence | 1 – 67 | 67 | Missing in isoform 2. | |||||
| Alternative sequence | 58 – 79 | 22 | VYSEL…SKWRK → VPPGLQSLCRQELSQLGKQT TH in isoform 3. | |||||
| Alternative sequence | 80 – 384 | 305 | Missing in isoform 3. | |||||
| Alternative sequence | 195 – 384 | 190 | Missing in isoform 2. | |||||
| Natural variant | 186 | 1 | H → R: dbSNP rs8177832. | |||||
| Natural variant | 275 | 1 | Q → E: dbSNP rs17496046. | |||||
Experimental info | ||||||||
| Mutagenesis | 67 | 1 | E → Q: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 81 | 1 | H → A: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 85 | 1 | E → Q: Does not decrease cytidine deaminase activity | |||||
| Mutagenesis | 97 | 1 | C → A: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 100 | 1 | C → A or S: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 128 | 1 | D → K: Complete loss of VIF-induced degradation | |||||
| Mutagenesis | 221 | 1 | C → S: Does not decrease cytidine deaminase activity | |||||
| Mutagenesis | 257 | 1 | H → A: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 259 | 1 | E → Q: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 288 | 1 | C → A: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 291 | 1 | C → A or S: Decreases cytidine deaminase activity | |||||
| Mutagenesis | 323 | 1 | E → Q: Does not decrease cytidine deaminase activity | |||||
| Sequence conflict | 162 | 1 | S → N Ref.1 | |||||
| Sequence conflict | 370 | 1 | D → Y Ref.1 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity." Kao S., Khan M.A., Miyagi E., Plishka R., Buckler-White A., Strebel K. J. Virol. 77:11398-11407(2003) [PubMed: 14557625] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN HIV-1 INFECTION INHIBITION. Tissue: Kidney. |
| [2] | "Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients." Huang C., Qian B., Tu Y., Gu W., Wang Y., Han Z., Chen Z. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hematopoietic stem cell. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Teratocarcinoma. |
| [4] | "A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [5] | SeattleSNPs program for genomic applications Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-186 AND GLU-275. |
| [6] | "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. Wright H.Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Skin and Uterus. |
| [8] | "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: 11863358] [Abstract] Cited for: GENE FAMILY ORGANIZATION, TISSUE SPECIFICITY, SUBUNIT, RNA-BINDING, ZINC-BINDING. |
| [9] | "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein." Sheehy A.M., Gaddis N.C., Choi J.D., Malim M.H. Nature 418:646-650(2002) [PubMed: 12167863] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION IN HIV-1 INFECTION INHIBITION. Tissue: T-cell lymphoma. |
| [10] | "Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts." Mangeat B., Turelli P., Caron G., Friedli M., Perrin L., Trono D. Nature 424:99-103(2003) [PubMed: 12808466] [Abstract] Cited for: SUBCELLULAR LOCATION, FUNCTION IN DNA C TO U EDITING, MUTAGENESIS OF GLU-67; HIS-81; GLU-85; CYS-97; CYS-100; CYS-221; HIS-257; GLU-259; CYS-288; CYS-291 AND GLU-323. |
| [11] | "DNA deamination mediates innate immunity to retroviral infection." Harris R.S., Bishop K.N., Sheehy A.M., Craig H.M., Petersen-Mahrt S.K., Watt I.N., Neuberger M.S., Malim M.H. Cell 113:803-809(2003) [PubMed: 12809610] [Abstract] Cited for: FUNCTION IN DNA C TO U EDITING, MLV INFECTION INHIBITION. |
| [12] | "The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA." Zhang H., Yang B., Pomerantz R.J., Zhang C., Arunachalam S.C., Gao L. Nature 424:94-98(2003) [PubMed: 12808465] [Abstract] Cited for: FUNCTION IN DNA C TO U EDITING, MUTAGENESIS OF HIS-81; CYS-97; CYS-100; HIS-257; CYS-288 AND CYS-291. |
| [13] | "Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif." Mariani R., Chen D., Schroefelbauer B., Navarro F., Koenig R., Bollman B., Muenk C., Nymark-McMahon H., Landau N.R. Cell 114:21-31(2003) [PubMed: 12859895] [Abstract] Cited for: FUNCTION IN DNA C TO U EDITING, INTERACTION WITH VIF. |
| [14] | "The enzymatic activity of CEM15/Apobec-3G is essential for the regulation of the infectivity of HIV-1 virion but not a sole determinant of its antiviral activity." Shindo K., Takaori-Kondo A., Kobayashi M., Abudu A., Fukunaga K., Uchiyama T. J. Biol. Chem. 278:44412-44416(2003) [PubMed: 12970355] [Abstract] Cited for: FUNCTION IN DNA C TO U EDITING, INFECTION REGULATION OF HIV-1, MUTAGENESIS OF GLU-67; CYS-100; GLU-259 AND CYS-291. Tissue: T-cell lymphoma. |
| [15] | "HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability." Stopak K., de Noronha C., Yonemoto W., Greene W.C. Mol. Cell 12:591-601(2003) [PubMed: 14527406] [Abstract] Cited for: INTERACTION WITH VIF, PROTEASOME MEDIATED DEGRADATION, TRANSLATION INHIBITION. |
| [16] | "HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation." Marin M., Rose K.M., Kozak S.L., Kabat D. Nat. Med. 9:1398-1403(2003) [PubMed: 14528301] [Abstract] Cited for: INTERACTION WITH VIF, UBIQUITINATION. |
| [17] | "The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif." Sheehy A.M., Gaddis N.C., Malim M.H. Nat. Med. 9:1404-1407(2003) [PubMed: 14528300] [Abstract] Cited for: FUNCTION IN DNA C TO U EDITING, UBIQUITINATION. |
| [18] | "Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business." Wedekind J.E., Dance G.S.C., |

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