Q6NTF7 (ABC3H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:

APOBEC3H

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

General annotation (Comments)

Function	DNA cytidine deaminase which may provide cellular innate resistance to a specific panel of genetic invaders including endogenous retroelements and a subset of viruses. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10
Catalytic activity	Cytidine + H2O = uridine + NH3.
Cofactor	Zinc By similarity.
Subcellular location	Nucleus. Cytoplasm. Note: Mostly nuclear.
Tissue specificity	Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung, testis, ovary, fetal liver and skin. Ref.5 Ref.9
Polymorphism	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.
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.
Sequence similarities	Belongs to the cytidine and deoxycytidylate deaminase family.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA cytosine deamination Inferred from direct assay Ref.5. Source: UniProtKB negative regulation of retroviral genome replication Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of transposition Inferred from direct assay Ref.7Ref.10. Source: UniProtKB response to virus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay Ref.7. Source: UniProtKB nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular function	cytidine deaminase activity Inferred from direct assay Ref.5. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6NTF7-1)

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: No experimental confirmation available.

Isoform 2 (identifier: Q6NTF7-2)

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

Isoform 3 (identifier: Q6NTF7-3)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 200	200	DNA dC->dU-editing enzyme APOBEC-3H		PRO_0000291663
Regions
	Coiled coil	160 – 182	23	Potential
Sites
	Active site	56	1	Proton donor By similarity
	Metal binding	54	1	Zinc By similarity
	Metal binding	85	1	Zinc By similarity
	Metal binding	88	1	Zinc By similarity
Natural variations
	Alternative sequence	182 – 200	19	IPGVR…CDAEV → S in isoform 2.		VSP_035034
	Alternative sequence	182 – 200	19	IPGVR…CDAEV → QS in isoform 3.		VSP_039975
	Natural variant	15	1	Missing Decreases protein stability.		VAR_065622
	Natural variant	18	1	R → L. Ref.1 Corresponds to variant rs139293 [ dbSNP | Ensembl ].		VAR_032835
	Natural variant	105	1	G → 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. Ref.1 Ref.7 Corresponds to variant rs139297 [ dbSNP | Ensembl ].		VAR_032836
	Natural variant	121	1	K → E in allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction. Corresponds to variant rs139298 [ dbSNP | Ensembl ].		VAR_032837
	Natural variant	121	1	K → N. Corresponds to variant rs139299 [ dbSNP | Ensembl ].		VAR_032838
	Natural variant	178	1	E → D in allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction. Ref.1 Corresponds to variant rs139302 [ dbSNP | Ensembl ].		VAR_032839
Experimental info
	Mutagenesis	56	1	E → Q: Reduces the ability to inhibit the retrotransposition of LINE-1 elements. Ref.8
	Sequence conflict	121	1	K → D in CAG30367. Ref.1
	Sequence conflict	140	1	K → E in CAG30367. Ref.1
	Sequence conflict	140	1	K → E in AAH69023. Ref.3
	Sequence conflict	140	1	K → E in BQ052182. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 3. Checksum: 6F89E0138CC29386	FASTA	200	23,531
	10 20 30 40 50 60 MALLTAETFR LQFNNKRRLR RPYYPRKALL CYQLTPQNGS TPTRGYFENK KKCHAEICFI 70 80 90 100 110 120 NEIKSMGLDE TQCYQVTCYL TWSPCSSCAW ELVDFIKAHD HLNLGIFASR LYYHWCKPQQ 130 140 150 160 170 180 KGLRLLCGSQ VPVEVMGFPK FADCWENFVD HEKPLSFNPY KMLEELDKNS RAIKRRLERI 190 200 KIPGVRAQGR YMDILCDAEV
	Isoform 2 [UniParc]. Checksum: 96BDB820405132F0	FASTA	182	21,530
	10 20 30 40 50 60 MALLTAETFR LQFNNKRRLR RPYYPRKALL CYQLTPQNGS TPTRGYFENK KKCHAEICFI 70 80 90 100 110 120 NEIKSMGLDE TQCYQVTCYL TWSPCSSCAW ELVDFIKAHD HLNLGIFASR LYYHWCKPQQ 130 140 150 160 170 180 KGLRLLCGSQ VPVEVMGFPK FADCWENFVD HEKPLSFNPY KMLEELDKNS RAIKRRLERI KS
	Isoform 3 [UniParc]. Checksum: EC45DDB820405132	FASTA	183	21,658
	10 20 30 40 50 60 MALLTAETFR LQFNNKRRLR RPYYPRKALL CYQLTPQNGS TPTRGYFENK KKCHAEICFI 70 80 90 100 110 120 NEIKSMGLDE TQCYQVTCYL TWSPCSSCAW ELVDFIKAHD HLNLGIFASR LYYHWCKPQQ 130 140 150 160 170 180 KGLRLLCGSQ VPVEVMGFPK FADCWENFVD HEKPLSFNPY KMLEELDKNS RAIKRRLERI KQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 2), VARIANTS ASN-15 DEL; LEU-18; ARG-105 AND ASP-178.
[2]	"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].
[3]	"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 2 AND 3). Tissue: Astrocyte.
[4]	"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 FAMILY.
[5]	"Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H." OhAinle M., Kerns J.A., Malik H.S., Emerman M. J. Virol. 80:3853-3862(2006) [PubMed: 16571802] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]	"Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family." Dang Y., Wang X., Esselman W.J., Zheng Y.-H. J. Virol. 80:10522-10533(2006) [PubMed: 16920826] [Abstract] Cited for: FUNCTION.
[7]	"Antiretroelement activity of APOBEC3H was lost twice in recent human evolution." OhAinle M., Kerns J.A., Li M.M., Malik H.S., Emerman M. Cell Host Microbe 4:249-259(2008) [PubMed: 18779051] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS ASN-15 DEL AND ARG-105.
[8]	"Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1." Tan L., Sarkis P.T., Wang T., Tian C., Yu X.F. FASEB J. 23:279-287(2009) [PubMed: 18827027] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF ALLELE A3H-VAR, MUTAGENESIS OF GLU-56.
[9]	"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.
[10]	"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 RETROTRANSPOSITION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CR456481 mRNA. Translation: CAG30367.3. AL031846 Genomic DNA. Translation: CAQ07272.1. AL031846 Genomic DNA. Translation: CAQ07273.1. BC069023 mRNA. Translation: AAH69023.1. BQ052182 mRNA. No translation available.
IPI	IPI00375550. IPI00472346. IPI00873390.
RefSeq	NP_001159474.1. NM_001166002.1. NP_001159475.1. NM_001166003.1. NP_861438.2. NM_181773.3.
UniGene	Hs.440515.
3D structure databases
ProteinModelPortal	Q6NTF7.
SMR	Q6NTF7. Positions 2-182.
ModBase	Search...
Protein-protein interaction databases
STRING	Q6NTF7.
Polymorphism databases
DMDM	205371798.
Proteomic databases
PRIDE	Q6NTF7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000401756; ENSP00000385741; ENSG00000100298. ENST00000448746; ENSP00000388717; ENSG00000100298.
GeneID	164668.
KEGG	hsa:164668.
Organism-specific databases
CTD	164668.
GeneCards	GC22P039493.
HGNC	HGNC:24100. APOBEC3H.
HPA	HPA021492.
MIM	610976. gene.
neXtProt	NX_Q6NTF7.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13651.
GeneTree	ENSGT00530000062933.
HOVERGEN	HBG050434.
InParanoid	Q6NTF7.
OMA	VTCYLTW.
Gene expression databases
ArrayExpress	Q6NTF7.
Bgee	Q6NTF7.
CleanEx	HS_APOBEC3H.
Genevestigator	Q6NTF7.
Family and domain databases
InterPro	IPR016192. APOBEC/CMP_deaminase_Zn-bd. IPR007904. APOBEC_C. IPR013158. APOBEC_N. IPR016193. Cytidine_deaminase-like. [Graphical view]
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
SOURCE	Search...

Entry information

Entry name

ABC3H_HUMAN

Accession

Primary (citable) accession number: Q6NTF7
Secondary accession number(s): B0QYP0 , B0QYP1, Q5JYL9, Q6IC87

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 26, 2007
Last sequence update:	September 2, 2008
Last modified:	January 25, 2012
This is version 58 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.