P31941 (ABC3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable DNA dC->dU-editing enzyme APOBEC-3A
EC=3.5.4.-

Alternative name(s):
Phorbolin-1

Gene names

Name:

APOBEC3A

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	199 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Single-stranded DNA cytidine deaminase involved in foreign DNA clearance. May trigger C-to-U hypermutation in exogenous DNA leading to its degradation. Provides cellular innate resistance to a specific panel of genetic invaders including endogenous retroelements and a subset of viruses. May have a preference for cytidines in a C-C sequence context. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation. Ref.1 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14
Catalytic activity	Cytidine + H2O = uridine + NH3. Ref.9 Ref.10 Ref.11 Ref.14
Cofactor	Zinc By similarity.
Subcellular location	Nucleus. Cytoplasm Ref.9 Ref.14.
Tissue specificity	Expressed in peripherical leukocytes with higher expression in CD14-positive phagocytic cells. Also detected in non-lymphoid tissues including lung and adipose tissues. Also detected in keratinocytes. Ref.6 Ref.9 Ref.11 Ref.12
Induction	Up-regulated by interferon and CpG single-stranded DNA (at protein level). Ref.10 Ref.11
Miscellaneous	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.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative initiation Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA cytosine deamination Inferred from direct assay Ref.9Ref.14. Source: UniProtKB DNA demethylation Inferred from direct assay Ref.13. Source: UniProtKB cellular response to xenobiotic stimulus Inferred from direct assay Ref.11. Source: UniProtKB clearance of foreign intracellular DNA by conversion of DNA cytidine to uridine Inferred from direct assay Ref.11. Source: UniProtKB defense response to virus Inferred from direct assay Ref.14. Source: UniProtKB innate immune response Inferred from direct assay Ref.14. Source: UniProtKB negative regulation of transposition Inferred from direct assay Ref.9Ref.11Ref.14. Source: UniProtKB negative regulation of viral genome replication Inferred from direct assay Ref.9. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay Ref.9Ref.14. Source: UniProtKB nucleus Inferred from direct assay Ref.9Ref.14. Source: UniProtKB
Molecular function	cytidine deaminase activity Inferred from direct assay Ref.9Ref.14. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: P31941-1)

Also known as: Phorbolin-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.

Note: Enzymatically active.

Isoform 2 (identifier: P31941-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: Missing.

Note: Enzymatically active.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 199	199	Probable DNA dC->dU-editing enzyme APOBEC-3A		PRO_0000171752
Sites
	Active site	72	1	Proton donor By similarity
	Metal binding	70	1	Zinc; catalytic By similarity
	Metal binding	101	1	Zinc; catalytic By similarity
	Metal binding	106	1	Zinc; catalytic By similarity
Natural variations
	Alternative sequence	1 – 12	12	Missing in isoform 2.		VSP_041723
	Natural variant	19	1	T → A. Corresponds to variant rs17000556 [ dbSNP | Ensembl ].		VAR_048721
Experimental info
	Mutagenesis	28	1	R → E: No effect on deaminase activity despite an altered restriction activity towards genetic invaders. Ref.14
	Mutagenesis	29	1	H → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	30	1	K → F: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	57	1	N → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	60	1	K → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	69	1	R → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	70	1	H → R: Altered deaminase activity. Ref.9
	Mutagenesis	72	1	E → Q: Altered deaminase activity and restriction activity towards genetic invaders. Ref.9 Ref.14
	Mutagenesis	98	1	W → L: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	106	1	C → S: Altered deaminase activity. Ref.9
	Mutagenesis	128	1	R → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	130	1	Y → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	131	1	D → N: No effect on deaminase activity despite an altered restriction activity towards genetic invaders. Ref.14
	Mutagenesis	133	1	D → N: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14
	Mutagenesis	136	1	Y → A: Altered deaminase activity and restriction activity towards genetic invaders. Ref.14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Phorbolin-1) [UniParc]. Last modified January 11, 2001. Version 3. Checksum: 42E99E0D7DF7AA14	FASTA	199	23,012
	10 20 30 40 50 60 MEASPASGPR HLMDPHIFTS NFNNGIGRHK TYLCYEVERL DNGTSVKMDQ HRGFLHNQAK 70 80 90 100 110 120 NLLCGFYGRH AELRFLDLVP SLQLDPAQIY RVTWFISWSP CFSWGCAGEV RAFLQENTHV 130 140 150 160 170 180 RLRIFAARIY DYDPLYKEAL QMLRDAGAQV SIMTYDEFKH CWDTFVDHQG CPFQPWDGLD 190 EHSQALSGRL RAILQNQGN
	Isoform 2 [UniParc]. Checksum: C7901DFD6A693D9D	FASTA	187	21,778
	10 20 30 40 50 60 MDPHIFTSNF NNGIGRHKTY LCYEVERLDN GTSVKMDQHR GFLHNQAKNL LCGFYGRHAE 70 80 90 100 110 120 LRFLDLVPSL QLDPAQIYRV TWFISWSPCF SWGCAGEVRA FLQENTHVRL RIFAARIYDY 130 140 150 160 170 180 DPLYKEALQM LRDAGAQVSI MTYDEFKHCW DTFVDHQGCP FQPWDGLDEH SQALSGRLRA ILQNQGN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1." Madsen P.P., Anant S., Rasmussen H.H., Gromov P., Vorum H., Dumanski J.P., Tommerup N., Collins J.E., Wright C.L., Dunham I., Macginnitie A.J., Davidson N.O., Celis J.E. J. Invest. Dermatol. 113:162-169(1999) [PubMed: 10469298] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-27; 31-35; 53-60; 112-123; 129-137 AND 192-198, FUNCTION. Tissue: Keratinocyte.
[2]	"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:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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].
[4]	"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]. Tissue: Brain.
[5]	"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes." Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J. Electrophoresis 13:960-969(1992) [PubMed: 1286667] [Abstract] Cited for: PROTEIN SEQUENCE OF 53-60; 112-121 AND 129-137. Tissue: Keratinocyte.
[6]	"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.
[7]	"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: 12683974] [Abstract] Cited for: REVIEW ON APOBEC FAMILIES.
[8]	"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 HOST DEFENSE.
[9]	"APOBEC3A is a potent inhibitor of adeno-associated virus and retrotransposons." Chen H., Lilley C.E., Yu Q., Lee D.V., Chou J., Narvaiza I., Landau N.R., Weitzman M.D. Curr. Biol. 16:480-485(2006) [PubMed: 16527742] [Abstract] Cited for: FUNCTION IN HOST DEFENSE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-70; GLU-72 AND CYS-106, TISSUE SPECIFICITY.
[10]	"Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms." Thielen B.K., McNevin J.P., McElrath M.J., Hunt B.V., Klein K.C., Lingappa J.R. J. Biol. Chem. 285:27753-27766(2010) [PubMed: 20615867] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INDUCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[11]	"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: 20062055] [Abstract] Cited for: FUNCTION IN FOREIGN DNA CLEARANCE, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, INDUCTION.
[12]	"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: 20308164] [Abstract] Cited for: TISSUE SPECIFICITY.
[13]	"Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain." Guo J.U., Su Y., Zhong C., Ming G.L., Song H. Cell 145:423-434(2011) [PubMed: 21496894] [Abstract] Cited for: FUNCTION IN DNA DEMETHYLATION.
[14]	"Structure-function analyses point to a polynucleotide-accommodating groove essential for APOBEC3A restriction activities." Bulliard Y., Narvaiza I., Bertero A., Peddi S., Roehrig U.F., Ortiz M., Zoete V., Castro-Diaz N., Turelli P., Telenti A., Michielin O., Weitzman M.D., Trono D. J. Virol. 85:1765-1776(2011) [PubMed: 21123384] [Abstract] Cited for: FUNCTION IN HOST DEFENSE, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-28; HIS-29; LYS-30; ASN-57; LYS-60; ARG-69; GLU-72; TRP-98; ARG-128; TYR-130; ASP-131; ASP-133 AND TYR-136.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U03891 mRNA. Translation: AAA03706.2. CR456393 mRNA. Translation: CAG30279.1. AL022318 Genomic DNA. Translation: CAI17897.1. BC126416 mRNA. Translation: AAI26417.1.
IPI	IPI00013876. IPI01025690.
PIR	G01233.
RefSeq	NP_001180218.1. NM_001193289.1. NP_663745.1. NM_145699.3.
UniGene	Hs.226307.
3D structure databases
ProteinModelPortal	P31941.
SMR	P31941. Positions 10-199.
ModBase	Search...
Protein-protein interaction databases
STRING	P31941.
Polymorphism databases
DMDM	12644206.
2D gel databases
Aarhus/Ghent-2DPAGE	2116. IEF.
Proteomic databases
PRIDE	P31941.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000249116; ENSP00000249116; ENSG00000128383. ENST00000402255; ENSP00000384359; ENSG00000128383.
GeneID	200315.
KEGG	hsa:200315.
UCSC	uc003awn.1. human.
Organism-specific databases
CTD	200315.
GeneCards	GC22P039348.
HGNC	HGNC:17343. APOBEC3A.
HPA	HPA043237.
MIM	607109. gene.
neXtProt	NX_P31941.
PharmGKB	PA24891.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000062933.
HOGENOM	HBG716052.
HOVERGEN	HBG050434.
InParanoid	P31941.
OMA	IAIMTSK.
OrthoDB	EOG480HX1.
PhylomeDB	P31941.
Gene expression databases
ArrayExpress	P31941.
Bgee	P31941.
CleanEx	HS_APOBEC3A.
Genevestigator	P31941.
GermOnline	ENSG00000128383. Homo sapiens.
Family and domain databases
InterPro	IPR016192. APOBEC/CMP_deaminase_Zn-bd. IPR007904. APOBEC_C. IPR013158. APOBEC_N. IPR016193. Cytidine_deaminase-like. [Graphical view]
KO	K01500.
Pfam	PF05240. APOBEC_C. 1 hit. PF08210. APOBEC_N. 1 hit. [Graphical view]
SUPFAM	SSF53927. Cytidine_deaminase-like. 1 hit.
PROSITE	PS00903. CYT_DCMP_DEAMINASES. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	89887.
SOURCE	Search...

Entry information

Entry name

ABC3A_HUMAN

Accession

Primary (citable) accession number: P31941
Secondary accession number(s): A0AVM1 , Q12807, Q5JZ93, Q9UH18

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	January 11, 2001
Last modified:	January 25, 2012
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.