Q3UPF5 (ZCCHV_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger CCCH-type antiviral protein 1

Alternative name(s):
ADP-ribosyltransferase diphtheria toxin-like 13
Short name=ARTD13

Gene names

Name:

Zc3hav1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	946 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). Ref.8
Subunit structure	Homodimer or homooligomer. Homooligomerization is essential for its antiviral activity By similarity. Interacts with EXOSC5 By similarity. Interacts (via N-terminal domain) with DDX17 in an RNA-independent manner By similarity. Interacts with EXOSC3, EXOSC7, DCP2 and DCP1A By similarity. Interacts with PARN in an RNA-independent manner By similarity. Interacts with XRN1 in an RNA-dependent manner By similarity. Interacts (via N-terminal domain) with DHX30 (via N-terminus) in an RNA-independent manner By similarity. Isoform 2 interacts (via zinc-fingers) with DDX58/RIG-I in an RNA-dependent manner By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Localizes in the cytoplasm at steady state, but shuttles between nucleus and cytoplasm in a XPO1-dependent manner By similarity.
Domain	The N-terminal domain is sufficient to bind to viral RNAs and promote their degradation. The second and fourth zinc fingers are involved in binding to specific viral RNAs By similarity.
Post-translational modification	Phosphorylation at Ser-273 is essential for sequential phosphorylation of Ser-269, Ser-265, Ser-262 and Ser-257 by GSK3-beta. Phosphorylation by GSK3-beta enhances its antiviral activity By similarity.
Sequence similarities	Contains 2 C3H1-type zinc fingers. Contains 1 PARP catalytic domain. Contains 1 WWE domain.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Innate immunity
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding RNA-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to exogenous dsRNA Inferred from direct assay Ref.8. Source: MGI defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of viral genome replication Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ATPase activity Inferred from sequence orthology Ref.8. Source: MGI positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence orthology Ref.8. Source: MGI positive regulation of RIG-I signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of interferon-alpha production Inferred from electronic annotation. Source: Compara positive regulation of interferon-beta production Inferred from electronic annotation. Source: Compara positive regulation of mRNA catabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of type I interferon production Inferred from direct assay Ref.8. Source: MGI response to virus Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara cytoplasm Inferred from sequence orthology Ref.8. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	DEAD/H-box RNA helicase binding Inferred from sequence orthology Ref.8. Source: MGI NAD+ ADP-ribosyltransferase activity Inferred from electronic annotation. Source: InterPro RNA binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q3UPF5-1)

Also known as: ZAPL;

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: Q3UPF5-2)

Also known as: ZAPS;

The sequence of this isoform differs from the canonical sequence as follows:
     789-789: D → E
     790-946: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 946	946	Zinc finger CCCH-type antiviral protein 1		PRO_0000331461
Regions
	Domain	684 – 771	88	WWE
	Domain	805 – 946	142	PARP catalytic
	Zinc finger	73 – 86	14	C3H1-type 1
	Zinc finger	87 – 113	27	C3H1-type 1
	Zinc finger	150 – 172	23	C3H1-type 3
	Zinc finger	173 – 194	22	C3H1-type 2
	Region	1 – 254	254	N-terminal domain
	Region	224 – 254	31	Binding to EXOSC5 By similarity
	Motif	69 – 76	8	Nuclear localization signal By similarity
	Motif	283 – 290	8	Nuclear export signal By similarity
	Motif	412 – 413	2	Nuclear localization signal Potential
	Compositional bias	572 – 576	5	Poly-Met
Amino acid modifications
	Modified residue	257	1	Phosphoserine; by GSK3-beta By similarity
	Modified residue	262	1	Phosphoserine; by GSK3-beta By similarity
	Modified residue	265	1	Phosphoserine; by GSK3-beta By similarity
	Modified residue	269	1	Phosphoserine; by GSK3-beta Ref.5
	Modified residue	273	1	Phosphoserine By similarity
	Modified residue	324	1	Phosphoserine Ref.3 Ref.6
	Modified residue	350	1	Phosphoserine Ref.4
	Modified residue	508	1	Phosphotyrosine Ref.2 Ref.7
	Modified residue	553	1	Phosphoserine Ref.7
	Modified residue	583	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	789	1	D → E in isoform 2.		VSP_033213
	Alternative sequence	790 – 946	157	Missing in isoform 2.		VSP_033214

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ZAPL) [UniParc]. Last modified October 11, 2005. Version 1. Checksum: BE2EFE5FBC6062EA	FASTA	946	106,688
	10 20 30 40 50 60 MTDPEVFCFI TKILCAHGGR MTLEELLGEI SLPEAQLYEL LKAAGPDRFV LLETGDQAGI 70 80 90 100 110 120 TRSVVATTRA RVCRRKYCQR PCDSLHLCKL NLLGRCHYAQ SQRNLCKYSH DVLSEQNFQV 130 140 150 160 170 180 LKNHELSGLN QEELAVLLVQ SDPFFMPEIC KSYKGEGRKQ ICGQPQPCER LHICEHFTRG 190 200 210 220 230 240 NCSYLNCLRS HNLMDRKVLA IMREHGLSSD VVQNIQDICN NKHTRRNPPS MRAPHPHRRG 250 260 270 280 290 300 GAHRDRSKSR DRFHHNSLEV LSTVSPLGSG PPSPDVTGCK DPLEDVSADV TQKFKYLGTQ 310 320 330 340 350 360 DRAQLSSVSS KAAGVRGPSQ MRASQEFLED GDPDGLFSRN RSDSSTSRTS AAGFPLVAAQ 370 380 390 400 410 420 RNEAGAMKMG MPSGHHVEVK GKNEDIDRVP FLNSYIDGVT MEEATVSGIL GKRATDNGLE 430 440 450 460 470 480 EMILSSNHQK SVAKTQDPQT AGRITDSGQD TAFLHSKYEE NPAWPGTSTH NGPNGFSQIM 490 500 510 520 530 540 DETPNVSKSS PTGFGIKSAV TGGKEAVYSG VQSLRSHVLA MPGETTTPVQ GSNRLPPSPL 550 560 570 580 590 600 SSSTSHRVAA SGSPGKSSTH ASVSPASEPS RMMMMMSDPA EYSLCYIVNP VSPRMDDHGL 610 620 630 640 650 660 KEICLDHLYR GCQQVNCNKN HFHLPYRWQL FILPTWMDFQ DMEYIERAYC DPQIEIIVIE 670 680 690 700 710 720 KHRINFKKMT CDSYPIRRLS TPSFVEKTLN SVFTTKWLWY WRNELNEYTQ YGHESPSHTS 730 740 750 760 770 780 SEINSAYLES FFHSCPRGVL QFHAGSQNYE LSFQGMIQTN IASKTQRHVV RRPVFVSSKD 790 800 810 820 830 840 VEQKRRGPDH QPVMPQADAL TLFSSPQRNA STVSSNEYEF IELNNQDEEY AKISEQFKAS 850 860 870 880 890 900 MKQFKIVTIK RIWNQKLWDT FERKKQKMKN KTEMFLFHAV GRIHMDYICK NNFEWILHGN 910 920 930 940 REIRYGKGLC WRRENCDSSH AHGFLEMPLA SLGRTASLDS SGLQRK
	Isoform 2 (ZAPS) [UniParc]. Checksum: 98C5633AE78BD4A5	FASTA	789	88,231
	10 20 30 40 50 60 MTDPEVFCFI TKILCAHGGR MTLEELLGEI SLPEAQLYEL LKAAGPDRFV LLETGDQAGI 70 80 90 100 110 120 TRSVVATTRA RVCRRKYCQR PCDSLHLCKL NLLGRCHYAQ SQRNLCKYSH DVLSEQNFQV 130 140 150 160 170 180 LKNHELSGLN QEELAVLLVQ SDPFFMPEIC KSYKGEGRKQ ICGQPQPCER LHICEHFTRG 190 200 210 220 230 240 NCSYLNCLRS HNLMDRKVLA IMREHGLSSD VVQNIQDICN NKHTRRNPPS MRAPHPHRRG 250 260 270 280 290 300 GAHRDRSKSR DRFHHNSLEV LSTVSPLGSG PPSPDVTGCK DPLEDVSADV TQKFKYLGTQ 310 320 330 340 350 360 DRAQLSSVSS KAAGVRGPSQ MRASQEFLED GDPDGLFSRN RSDSSTSRTS AAGFPLVAAQ 370 380 390 400 410 420 RNEAGAMKMG MPSGHHVEVK GKNEDIDRVP FLNSYIDGVT MEEATVSGIL GKRATDNGLE 430 440 450 460 470 480 EMILSSNHQK SVAKTQDPQT AGRITDSGQD TAFLHSKYEE NPAWPGTSTH NGPNGFSQIM 490 500 510 520 530 540 DETPNVSKSS PTGFGIKSAV TGGKEAVYSG VQSLRSHVLA MPGETTTPVQ GSNRLPPSPL 550 560 570 580 590 600 SSSTSHRVAA SGSPGKSSTH ASVSPASEPS RMMMMMSDPA EYSLCYIVNP VSPRMDDHGL 610 620 630 640 650 660 KEICLDHLYR GCQQVNCNKN HFHLPYRWQL FILPTWMDFQ DMEYIERAYC DPQIEIIVIE 670 680 690 700 710 720 KHRINFKKMT CDSYPIRRLS TPSFVEKTLN SVFTTKWLWY WRNELNEYTQ YGHESPSHTS 730 740 750 760 770 780 SEINSAYLES FFHSCPRGVL QFHAGSQNYE LSFQGMIQTN IASKTQRHVV RRPVFVSSKD VEQKRRGPE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J and NOD. Tissue: Amnion, Cecum, Lung, Spleen and Thymus.
[2]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508, MASS SPECTROMETRY. Tissue: Mast cell.
[3]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, MASS SPECTROMETRY. Tissue: Liver.
[4]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, MASS SPECTROMETRY. Tissue: Liver.
[5]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269, MASS SPECTROMETRY. Tissue: Melanoma.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324, MASS SPECTROMETRY. Tissue: Macrophage.
[7]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508 AND SER-553, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[8]	"ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses." Hayakawa S., Shiratori S., Yamato H., Kameyama T., Kitatsuji C., Kashigi F., Goto S., Kameoka S., Fujikura D., Yamada T., Mizutani T., Kazumata M., Sato M., Tanaka J., Asaka M., Ohba Y., Miyazaki T., Imamura M., Takaoka A. Nat. Immunol. 12:37-44(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK004770 mRNA. Translation: BAB23549.1. AK080334 mRNA. Translation: BAC37881.1. AK143568 mRNA. Translation: BAE25440.1. AK169402 mRNA. Translation: BAE41148.1. AK172379 mRNA. Translation: BAE42974.1. AK020263 mRNA. Translation: BAB32047.2.
IPI	IPI00136572. IPI00163030.
RefSeq	NP_082697.1. NM_028421.1. NP_083140.1. NM_028864.2.
UniGene	Mm.25243. Mm.486484.
3D structure databases
ProteinModelPortal	Q3UPF5.
SMR	Q3UPF5. Positions 3-225, 817-922.
ModBase	Search...
PTM databases
PhosphoSite	Q3UPF5.
Proteomic databases
PaxDb	Q3UPF5.
PRIDE	Q3UPF5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000031850; ENSMUSP00000031850; ENSMUSG00000029826.
GeneID	78781.
KEGG	mmu:78781.
UCSC	uc009bjz.2. mouse. uc009bka.1. mouse.
Organism-specific databases
CTD	56829.
MGI	MGI:1926031. Zc3hav1.
Phylogenomic databases
eggNOG	NOG83866.
GeneTree	ENSGT00700000104297.
HOGENOM	HOG000236279.
HOVERGEN	HBG050384.
KO	K15259.
OrthoDB	EOG4HHP1P.
Gene expression databases
ArrayExpress	Q3UPF5.
Bgee	Q3UPF5.
Genevestigator	Q3UPF5.
Family and domain databases
InterPro	IPR012317. Poly(ADP-ribose)pol_cat_dom. IPR004170. WWE-dom. IPR000571. Znf_CCCH. [Graphical view]
Pfam	PF00644. PARP. 1 hit. [Graphical view]
PROSITE	PS51059. PARP_CATALYTIC. 1 hit. PS50918. WWE. 1 hit. PS50103. ZF_C3H1. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	349482.
SOURCE	Search...

Entry information

Entry name

ZCCHV_MOUSE

Accession

Primary (citable) accession number: Q3UPF5
Secondary accession number(s): Q9CTU4, Q9DBS7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 29, 2008
Last sequence update:	October 11, 2005
Last modified:	May 1, 2013
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program