Reviewed, UniProtKB/Swiss-Prot Q9HC16 (ABC3G_HUMAN)

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

Name:	APOBEC3G
ORF Names:	MDS019

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

Keywords
Biological process	Antiviral defense Host-virus interaction
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
PTM	Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	base conversion or substitution editing Traceable author statement. Source: HGNC innate immune response Inferred from direct assay. Source: HGNC negative regulation of retroviral genome replication Inferred from direct assay. Source: HGNC positive regulation of defense response to virus by host Inferred from direct assay. Source: HGNC transcription, RNA-dependent Inferred from direct assay. Source: HGNC
Cellular component	apolipoprotein B mRNA editing enzyme complex Traceable author statement. Source: HGNC cytosol Ref.16 Inferred from Experiment. Source: Reactome
Molecular function	RNA binding Ref.8 Inferred from direct assay. Source: UniProtKB cytidine deaminase activity Traceable author statement. Source: HGNC protein homodimerization activity Ref.8 Non-traceable author statement. Source: UniProtKB zinc ion binding Ref.8 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 60525DC3B7D903D6	FASTA	384	46,408
	10 20 30 40 50 60 MKPHFRNTVE RMYRDTFSYN FYNRPILSRR NTVWLCYEVK TKGPSRPPLD AKIFRGQVYS 70 80 90 100 110 120 ELKYHPEMRF FHWFSKWRKL HRDQEYEVTW YISWSPCTKC TRDMATFLAE DPKVTLTIFV 130 140 150 160 170 180 ARLYYFWDPD YQEALRSLCQ KRDGPRATMK IMNYDEFQHC WSKFVYSQRE LFEPWNNLPK 190 200 210 220 230 240 YYILLHIMLG EILRHSMDPP TFTFNFNNEP WVRGRHETYL CYEVERMHND TWVLLNQRRG 250 260 270 280 290 300 FLCNQAPHKH GFLEGRHAEL CFLDVIPFWK LDLDQDYRVT CFTSWSPCFS CAQEMAKFIS 310 320 330 340 350 360 KNKHVSLCIF TARIYDDQGR CQEGLRTLAE AGAKISIMTY SEFKHCWDTF VDHQGCPFQP 370 380 WDGLDEHSQD LSGRLRAILQ NQEN
	Isoform 2 [UniParc]. Checksum: F3CC7CC3AA1303E0		127	15,856
	10 20 30 40 50 60 MRFFHWFSKW RKLHRDQEYE VTWYISWSPC TKCTRDMATF LAEDPKVTLT IFVARLYYFW 70 80 90 100 110 120 DPDYQEALRS LCQKRDGPRA TMKIMNYDEF QHCWSKFVYS QRELFEPWNN LPKYYILLHI MLGEILR
	Isoform 3 [UniParc]. Checksum: 359E8ACA44AB074A		79	9,386
	10 20 30 40 50 60 MKPHFRNTVE RMYRDTFSYN FYNRPILSRR NTVWLCYEVK TKGPSRPPLD AKIFRGQVPP 70 GLQSLCRQEL SQLGKQTTH

References

	« Hide 'large scale' referencesShow '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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., 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. , 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: 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.,