Full text data of ZC3HAV1
ZC3HAV1
(ZC3HDC2)
[Confidence: low (only semi-automatic identification from reviews)]
Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13; ARTD13; Zinc finger CCCH domain-containing protein 2; Zinc finger antiviral protein; ZAP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Zinc finger CCCH-type antiviral protein 1 (ADP-ribosyltransferase diphtheria toxin-like 13; ARTD13; Zinc finger CCCH domain-containing protein 2; Zinc finger antiviral protein; ZAP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q7Z2W4
ID ZCCHV_HUMAN Reviewed; 902 AA.
AC Q7Z2W4; A4D1R2; A4D1S4; Q8IW57; Q8TAJ3; Q96N79; Q9H8R9; Q9P0Y7;
read moreDT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 3.
DT 22-JAN-2014, entry version 105.
DE RecName: Full=Zinc finger CCCH-type antiviral protein 1;
DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 13;
DE Short=ARTD13;
DE AltName: Full=Zinc finger CCCH domain-containing protein 2;
DE AltName: Full=Zinc finger antiviral protein;
DE Short=ZAP;
GN Name=ZC3HAV1; Synonyms=ZC3HDC2; ORFNames=PRO1677;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT
RP GLN-565.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Zhou G., Wei H., Bi J., Xu W., Zai Y.,
RA Feng F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 5 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND
RP VARIANTS LYS-485; GLN-565 AND GLU-701.
RC TISSUE=Kidney, and Ovarian carcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP GLU-701 AND ILE-851.
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
RP VARIANTS GLU-701 AND ILE-851.
RC TISSUE=Brain, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP FUNCTION.
RX PubMed=18225958; DOI=10.1371/journal.pgen.0040021;
RA Kerns J.A., Emerman M., Malik H.S.;
RT "Positive selection and increased antiviral activity associated with
RT the PARP-containing isoform of human zinc-finger antiviral protein.";
RL PLoS Genet. 4:E21-E21(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271; THR-273; SER-275;
RP SER-284; SER-302; SER-378; SER-387 AND THR-393, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP REVIEW.
RX PubMed=18418085;
RA Zhu Y., Gao G.;
RT "ZAP-mediated mRNA degradation.";
RL RNA Biol. 5:65-67(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257; SER-284; SER-335;
RP SER-387 AND THR-393, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES,
RP RNA-BINDING, AND DOMAIN N-TERMINAL.
RX PubMed=20451500; DOI=10.1016/j.bbrc.2010.04.164;
RA Jeong M.S., Kim E.J., Jang S.B.;
RT "Expression and RNA-binding of human zinc-finger antiviral protein.";
RL Biochem. Biophys. Res. Commun. 396:696-702(2010).
RN [17]
RP SUBUNIT.
RX PubMed=20181706; DOI=10.1128/JVI.02018-09;
RA Law L.M., Albin O.R., Carroll J.W., Jones C.T., Rice C.M.,
RA Macdonald M.R.;
RT "Identification of a dominant negative inhibitor of human zinc finger
RT antiviral protein reveals a functional endogenous pool and critical
RT homotypic interactions.";
RL J. Virol. 84:4504-4512(2010).
RN [18]
RP INTERACTION WITH DHX30.
RX PubMed=21204022; DOI=10.1007/s13238-010-0117-8;
RA Ye P., Liu S., Zhu Y., Chen G., Gao G.;
RT "DEXH-Box protein DHX30 is required for optimal function of the zinc-
RT finger antiviral protein.";
RL Protein Cell 1:956-964(2010).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284; SER-302; SER-335;
RP SER-378; THR-393 AND SER-492, PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-572 (ISOFORM 3), AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP NOMENCLATURE.
RX PubMed=20106667; DOI=10.1016/j.tibs.2009.12.003;
RA Hottiger M.O., Hassa P.O., Luscher B., Schuler H., Koch-Nolte F.;
RT "Toward a unified nomenclature for mammalian ADP-
RT ribosyltransferases.";
RL Trends Biochem. Sci. 35:208-219(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP REVIEW.
RX PubMed=21169998; DOI=10.1038/ni0111-11;
RA Liu H.M., Gale M. Jr.;
RT "ZAPS electrifies RIG-I signaling.";
RL Nat. Immunol. 12:11-12(2011).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH
RP DDX58/RIG-I.
RX PubMed=21102435; DOI=10.1038/ni.1963;
RA Hayakawa S., Shiratori S., Yamato H., Kameyama T., Kitatsuji C.,
RA Kashigi F., Goto S., Kameoka S., Fujikura D., Yamada T., Mizutani T.,
RA Kazumata M., Sato M., Tanaka J., Asaka M., Ohba Y., Miyazaki T.,
RA Imamura M., Takaoka A.;
RT "ZAPS is a potent stimulator of signaling mediated by the RNA helicase
RT RIG-I during antiviral responses.";
RL Nat. Immunol. 12:37-44(2011).
RN [24]
RP FUNCTION, AND INTERACTION WITH EXOSC3; EXOSC7; PARN; DCP2; DCP1A AND
RP XRN1.
RX PubMed=21876179; DOI=10.1073/pnas.1101676108;
RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L.,
RA Zheng Y.T., Gao G.;
RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively
RT targeting multiply spliced viral mRNAs for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP FUNCTION.
RX PubMed=22720057; DOI=10.1371/journal.pone.0039159;
RA Wang X., Tu F., Zhu Y., Gao G.;
RT "Zinc-finger antiviral protein inhibits XMRV infection.";
RL PLoS ONE 7:E39159-E39159(2012).
CC -!- FUNCTION: Antiviral protein which inhibits the replication of
CC viruses by recruiting the cellular RNA degradation machineries to
CC degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE)
CC present in the target viral mRNA, recruits cellular poly(A)-
CC specific ribonuclease PARN to remove the poly(A) tail, and the 3'-
CC 5' exoribonuclease complex exosome to degrade the RNA body from
CC the 3'-end. It also recruits the decapping complex DCP1-DCP2
CC through RNA helicase p72 (DDX17) to remove the cap structure of
CC the viral mRNA to initiate its degradation from the 5'-end. Its
CC target viruses belong to families which include retroviridae:
CC human immunodeficiency virus type 1 (HIV-1), moloney and murine
CC leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV),
CC filoviridae: ebola virus (EBOV) and marburg virus (MARV),
CC togaviridae: sindbis virus (SINV) and Ross river virus (RRV).
CC Specifically targets the multiply spliced but not unspliced or
CC singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more
CC potent viral inhibitor than isoform 2. Isoform 2 acts as a
CC positive regulator of DDX58/RIG-I signaling resulting in
CC activation of the downstream effector IRF3 leading to the
CC expression of type I IFNs and IFN stimulated genes (ISGs).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable;
CC -!- SUBUNIT: Homodimer or homooligomer. Homooligomerization is
CC essential for its antiviral activity. Interacts with EXOSC5 (By
CC similarity). Interacts (via N-terminal domain) with DDX17 in an
CC RNA-independent manner (By similarity). Interacts with EXOSC3,
CC EXOSC7, DCP2 and DCP1A. Interacts with PARN in an RNA-independent
CC manner. Interacts with XRN1 in an RNA-dependent manner. Isoform 2
CC interacts (via zinc-fingers) with DDX58/RIG-I in an RNA-dependent
CC manner. Interacts (via N-terminal domain) with DHX30 (via N-
CC terminus) in an RNA-independent manner.
CC -!- INTERACTION:
CC O95786:DDX58; NbExp=4; IntAct=EBI-922559, EBI-995350;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Nucleus.
CC Note=Localizes in the cytoplasm at steady state, but shuttles
CC between nucleus and cytoplasm in a XPO1-dependent manner (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=ZAPL;
CC IsoId=Q7Z2W4-1; Sequence=Displayed;
CC Name=2; Synonyms=ZAPS;
CC IsoId=Q7Z2W4-2; Sequence=VSP_010269;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q7Z2W4-3; Sequence=VSP_010270, VSP_010271;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 572;
CC Name=4;
CC IsoId=Q7Z2W4-4; Sequence=VSP_010268;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=Q7Z2W4-5; Sequence=VSP_010268, VSP_010269;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: By type I interferon (IFN) and viruses. Isoform 2 is
CC up-regulated by 3'-PPP-RNA.
CC -!- DOMAIN: The N-terminal domain is sufficient to bind to viral RNAs
CC and promote their degradation. The second and fourth zinc fingers
CC are involved in binding to specific viral RNAs.
CC -!- PTM: Phosphorylation at Ser-275 is essential for sequential
CC phosphorylation of Ser-271, Ser-267, Ser-263 and Ser-257 by GSK3-
CC beta. Phosphorylation by GSK3-beta enhances its antiviral activity
CC (By similarity).
CC -!- SIMILARITY: Contains 4 C3H1-type zinc fingers.
CC -!- SIMILARITY: Contains 1 PARP catalytic domain.
CC -!- SIMILARITY: Contains 1 WWE domain.
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DR EMBL; AF138863; AAF61195.1; -; mRNA.
DR EMBL; AK055851; BAB71028.1; -; mRNA.
DR EMBL; AK023350; BAB14537.1; -; mRNA.
DR EMBL; BX571742; CAE11868.1; -; mRNA.
DR EMBL; CH236950; EAL24040.1; -; Genomic_DNA.
DR EMBL; CH236950; EAL24041.1; -; Genomic_DNA.
DR EMBL; BC025308; AAH25308.1; -; mRNA.
DR EMBL; BC027462; AAH27462.1; -; mRNA.
DR EMBL; BC033105; AAH33105.1; -; mRNA.
DR EMBL; BC040956; AAH40956.1; -; mRNA.
DR RefSeq; NP_064504.2; NM_020119.3.
DR RefSeq; NP_078901.3; NM_024625.3.
DR UniGene; Hs.133512; -.
DR PDB; 2X5Y; X-ray; 1.05 A; A=724-896.
DR PDBsum; 2X5Y; -.
DR ProteinModelPortal; Q7Z2W4; -.
DR SMR; Q7Z2W4; 3-225, 726-896.
DR DIP; DIP-37896N; -.
DR IntAct; Q7Z2W4; 8.
DR MINT; MINT-5006396; -.
DR STRING; 9606.ENSP00000242351; -.
DR PhosphoSite; Q7Z2W4; -.
DR DMDM; 223634727; -.
DR PaxDb; Q7Z2W4; -.
DR PRIDE; Q7Z2W4; -.
DR Ensembl; ENST00000242351; ENSP00000242351; ENSG00000105939.
DR Ensembl; ENST00000471652; ENSP00000419855; ENSG00000105939.
DR GeneID; 56829; -.
DR KEGG; hsa:56829; -.
DR UCSC; uc003vun.3; human.
DR CTD; 56829; -.
DR GeneCards; GC07M138728; -.
DR H-InvDB; HIX0007129; -.
DR HGNC; HGNC:23721; ZC3HAV1.
DR HPA; HPA047818; -.
DR MIM; 607312; gene.
DR neXtProt; NX_Q7Z2W4; -.
DR PharmGKB; PA134944289; -.
DR eggNOG; NOG83866; -.
DR HOVERGEN; HBG050384; -.
DR InParanoid; Q7Z2W4; -.
DR KO; K15259; -.
DR OrthoDB; EOG7P5T0J; -.
DR ChiTaRS; ZC3HAV1; human.
DR EvolutionaryTrace; Q7Z2W4; -.
DR GeneWiki; ZC3HAV1; -.
DR GenomeRNAi; 56829; -.
DR NextBio; 62226; -.
DR PMAP-CutDB; Q7Z2W4; -.
DR PRO; PR:Q7Z2W4; -.
DR ArrayExpress; Q7Z2W4; -.
DR Bgee; Q7Z2W4; -.
DR CleanEx; HS_ZC3HAV1; -.
DR Genevestigator; Q7Z2W4; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR Gene3D; 3.90.228.10; -; 1.
DR InterPro; IPR012317; Poly(ADP-ribose)pol_cat_dom.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR000571; Znf_CCCH.
DR Pfam; PF00644; PARP; 1.
DR PROSITE; PS51059; PARP_CATALYTIC; 1.
DR PROSITE; PS50918; WWE; 1.
DR PROSITE; PS50103; ZF_C3H1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antiviral defense;
KW Complete proteome; Cytoplasm; Immunity; Innate immunity;
KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; RNA-binding; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 902 Zinc finger CCCH-type antiviral protein
FT 1.
FT /FTId=PRO_0000211343.
FT DOMAIN 594 681 WWE.
FT DOMAIN 716 902 PARP catalytic.
FT ZN_FING 73 86 C3H1-type 1.
FT ZN_FING 88 110 C3H1-type 2.
FT ZN_FING 150 172 C3H1-type 3.
FT ZN_FING 169 193 C3H1-type 4.
FT REGION 2 254 N-terminal domain.
FT REGION 224 254 Binding to EXOSC5 (By similarity).
FT MOTIF 69 76 Nuclear localization signal (By
FT similarity).
FT MOTIF 285 292 Nuclear export signal (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 257 257 Phosphoserine; by GSK3-beta.
FT MOD_RES 263 263 Phosphoserine; by GSK3-beta (By
FT similarity).
FT MOD_RES 267 267 Phosphoserine; by GSK3-beta (By
FT similarity).
FT MOD_RES 271 271 Phosphoserine; by GSK3-beta.
FT MOD_RES 273 273 Phosphothreonine.
FT MOD_RES 275 275 Phosphoserine.
FT MOD_RES 284 284 Phosphoserine.
FT MOD_RES 302 302 Phosphoserine.
FT MOD_RES 327 327 Phosphoserine (By similarity).
FT MOD_RES 335 335 Phosphoserine.
FT MOD_RES 378 378 Phosphoserine.
FT MOD_RES 387 387 Phosphoserine.
FT MOD_RES 393 393 Phosphothreonine.
FT MOD_RES 492 492 Phosphoserine.
FT VAR_SEQ 1 539 Missing (in isoform 4 and isoform 5).
FT /FTId=VSP_010268.
FT VAR_SEQ 491 624 DSLSDVTSTTSSRVDDHDSEEICLDHLCKGCPLNGSCSKVH
FT FHLPYRWQMLIGKTWTDFEHMETIEKGYCNPGIHLCSVGSY
FT TINFRVMSCDSFPIRRLSTPSSVTKPANSVFTTKWIWYWKN
FT ESGTWIQYGEE -> GKYKGKTLWASTFVHDIPNGSSQVVD
FT KTTDVEKTGATGFGLTMAVKAEKDMLCTGSQSLRNLVPTTP
FT GESTAPAQVSTLPQSPAALSSSNRAAVWGAQGQNCTQVPVS
FT SASELTRKTTGSAQCKSLKDKGASVS (in isoform
FT 3).
FT /FTId=VSP_010270.
FT VAR_SEQ 625 902 Missing (in isoform 3).
FT /FTId=VSP_010271.
FT VAR_SEQ 699 902 DHQPAKTSSVSLTATFRPQEDFCFLSSKKYKLSEIHHLHPE
FT YVRVSEHFKASMKNFKIEKIKKIENSELLDKFTWKKSQMKE
FT EGKLLFYATSRAYVESICSNNFDSFLHETHENKYGKGIYFA
FT KDAIYSHKNCPYDAKNVVMFVAQVLVGKFTEGNITYTSPPP
FT QFDSCVDTRSNPSVFVIFQKDQVYPQYVIEYTEDKACVIS
FT -> E (in isoform 2 and isoform 5).
FT /FTId=VSP_010269.
FT VARIANT 485 485 R -> K (in dbSNP:rs2236426).
FT /FTId=VAR_018454.
FT VARIANT 565 565 H -> Q (in dbSNP:rs2297241).
FT /FTId=VAR_018455.
FT VARIANT 701 701 Q -> E (in dbSNP:rs2297236).
FT /FTId=VAR_054319.
FT VARIANT 851 851 T -> I (in dbSNP:rs3735007).
FT /FTId=VAR_018456.
FT CONFLICT 245 245 A -> T (in Ref. 3; CAE11868).
FT STRAND 729 732
FT HELIX 738 748
FT STRAND 754 763
FT HELIX 765 778
FT STRAND 783 790
FT HELIX 791 793
FT HELIX 794 800
FT HELIX 804 807
FT STRAND 812 814
FT STRAND 816 823
FT HELIX 824 830
FT HELIX 835 837
FT STRAND 838 845
FT STRAND 849 852
FT STRAND 866 869
FT STRAND 871 873
FT STRAND 876 879
FT HELIX 882 884
FT STRAND 885 895
SQ SEQUENCE 902 AA; 101431 MW; 72AB311D23658E24 CRC64;
MADPEVCCFI TKILCAHGGR MALDALLQEI ALSEPQLCEV LQVAGPDRFV VLETGGEAGI
TRSVVATTRA RVCRRKYCQR PCDNLHLCKL NLLGRCNYSQ SERNLCKYSH EVLSEENFKV
LKNHELSGLN KEELAVLLLQ SDPFFMPEIC KSYKGEGRQQ ICNQQPPCSR LHICDHFTRG
NCRFPNCLRS HNLMDRKVLA IMREHGLNPD VVQNIQDICN SKHMQKNPPG PRAPSSHRRN
MAYRARSKSR DRFFQGSQEF LASASASAER SCTPSPDQIS HRASLEDAPV DDLTRKFTYL
GSQDRARPPS GSSKATDLGG TSQAGTSQRF LENGSQEDLL HGNPGSTYLA SNSTSAPNWK
SLTSWTNDQG ARRKTVFSPT LPAARSSLGS LQTPEAVTTR KGTGLLSSDY RIINGKSGTQ
DIQPGPLFNN NADGVATDIT STRSLNYKST SSGHREISSP RIQDAGPASR DVQATGRIAD
DADPRVALVN DSLSDVTSTT SSRVDDHDSE EICLDHLCKG CPLNGSCSKV HFHLPYRWQM
LIGKTWTDFE HMETIEKGYC NPGIHLCSVG SYTINFRVMS CDSFPIRRLS TPSSVTKPAN
SVFTTKWIWY WKNESGTWIQ YGEEKDKRKN SNVDSSYLES LYQSCPRGVV PFQAGSRNYE
LSFQGMIQTN IASKTQKDVI RRPTFVPQWY VQQMKRGPDH QPAKTSSVSL TATFRPQEDF
CFLSSKKYKL SEIHHLHPEY VRVSEHFKAS MKNFKIEKIK KIENSELLDK FTWKKSQMKE
EGKLLFYATS RAYVESICSN NFDSFLHETH ENKYGKGIYF AKDAIYSHKN CPYDAKNVVM
FVAQVLVGKF TEGNITYTSP PPQFDSCVDT RSNPSVFVIF QKDQVYPQYV IEYTEDKACV
IS
//
ID ZCCHV_HUMAN Reviewed; 902 AA.
AC Q7Z2W4; A4D1R2; A4D1S4; Q8IW57; Q8TAJ3; Q96N79; Q9H8R9; Q9P0Y7;
read moreDT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 3.
DT 22-JAN-2014, entry version 105.
DE RecName: Full=Zinc finger CCCH-type antiviral protein 1;
DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 13;
DE Short=ARTD13;
DE AltName: Full=Zinc finger CCCH domain-containing protein 2;
DE AltName: Full=Zinc finger antiviral protein;
DE Short=ZAP;
GN Name=ZC3HAV1; Synonyms=ZC3HDC2; ORFNames=PRO1677;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5), AND VARIANT
RP GLN-565.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Zhou G., Wei H., Bi J., Xu W., Zai Y.,
RA Feng F., Liu M., He F.;
RT "Functional prediction of the coding sequences of 5 new genes deduced
RT by analysis of cDNA clones from human fetal liver.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND
RP VARIANTS LYS-485; GLN-565 AND GLU-701.
RC TISSUE=Kidney, and Ovarian carcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP GLU-701 AND ILE-851.
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND
RP VARIANTS GLU-701 AND ILE-851.
RC TISSUE=Brain, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP FUNCTION.
RX PubMed=18225958; DOI=10.1371/journal.pgen.0040021;
RA Kerns J.A., Emerman M., Malik H.S.;
RT "Positive selection and increased antiviral activity associated with
RT the PARP-containing isoform of human zinc-finger antiviral protein.";
RL PLoS Genet. 4:E21-E21(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-271; THR-273; SER-275;
RP SER-284; SER-302; SER-378; SER-387 AND THR-393, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP REVIEW.
RX PubMed=18418085;
RA Zhu Y., Gao G.;
RT "ZAP-mediated mRNA degradation.";
RL RNA Biol. 5:65-67(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257; SER-284; SER-335;
RP SER-387 AND THR-393, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES,
RP RNA-BINDING, AND DOMAIN N-TERMINAL.
RX PubMed=20451500; DOI=10.1016/j.bbrc.2010.04.164;
RA Jeong M.S., Kim E.J., Jang S.B.;
RT "Expression and RNA-binding of human zinc-finger antiviral protein.";
RL Biochem. Biophys. Res. Commun. 396:696-702(2010).
RN [17]
RP SUBUNIT.
RX PubMed=20181706; DOI=10.1128/JVI.02018-09;
RA Law L.M., Albin O.R., Carroll J.W., Jones C.T., Rice C.M.,
RA Macdonald M.R.;
RT "Identification of a dominant negative inhibitor of human zinc finger
RT antiviral protein reveals a functional endogenous pool and critical
RT homotypic interactions.";
RL J. Virol. 84:4504-4512(2010).
RN [18]
RP INTERACTION WITH DHX30.
RX PubMed=21204022; DOI=10.1007/s13238-010-0117-8;
RA Ye P., Liu S., Zhu Y., Chen G., Gao G.;
RT "DEXH-Box protein DHX30 is required for optimal function of the zinc-
RT finger antiviral protein.";
RL Protein Cell 1:956-964(2010).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284; SER-302; SER-335;
RP SER-378; THR-393 AND SER-492, PHOSPHORYLATION [LARGE SCALE ANALYSIS]
RP AT SER-572 (ISOFORM 3), AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP NOMENCLATURE.
RX PubMed=20106667; DOI=10.1016/j.tibs.2009.12.003;
RA Hottiger M.O., Hassa P.O., Luscher B., Schuler H., Koch-Nolte F.;
RT "Toward a unified nomenclature for mammalian ADP-
RT ribosyltransferases.";
RL Trends Biochem. Sci. 35:208-219(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP REVIEW.
RX PubMed=21169998; DOI=10.1038/ni0111-11;
RA Liu H.M., Gale M. Jr.;
RT "ZAPS electrifies RIG-I signaling.";
RL Nat. Immunol. 12:11-12(2011).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH
RP DDX58/RIG-I.
RX PubMed=21102435; DOI=10.1038/ni.1963;
RA Hayakawa S., Shiratori S., Yamato H., Kameyama T., Kitatsuji C.,
RA Kashigi F., Goto S., Kameoka S., Fujikura D., Yamada T., Mizutani T.,
RA Kazumata M., Sato M., Tanaka J., Asaka M., Ohba Y., Miyazaki T.,
RA Imamura M., Takaoka A.;
RT "ZAPS is a potent stimulator of signaling mediated by the RNA helicase
RT RIG-I during antiviral responses.";
RL Nat. Immunol. 12:37-44(2011).
RN [24]
RP FUNCTION, AND INTERACTION WITH EXOSC3; EXOSC7; PARN; DCP2; DCP1A AND
RP XRN1.
RX PubMed=21876179; DOI=10.1073/pnas.1101676108;
RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L.,
RA Zheng Y.T., Gao G.;
RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively
RT targeting multiply spliced viral mRNAs for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP FUNCTION.
RX PubMed=22720057; DOI=10.1371/journal.pone.0039159;
RA Wang X., Tu F., Zhu Y., Gao G.;
RT "Zinc-finger antiviral protein inhibits XMRV infection.";
RL PLoS ONE 7:E39159-E39159(2012).
CC -!- FUNCTION: Antiviral protein which inhibits the replication of
CC viruses by recruiting the cellular RNA degradation machineries to
CC degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE)
CC present in the target viral mRNA, recruits cellular poly(A)-
CC specific ribonuclease PARN to remove the poly(A) tail, and the 3'-
CC 5' exoribonuclease complex exosome to degrade the RNA body from
CC the 3'-end. It also recruits the decapping complex DCP1-DCP2
CC through RNA helicase p72 (DDX17) to remove the cap structure of
CC the viral mRNA to initiate its degradation from the 5'-end. Its
CC target viruses belong to families which include retroviridae:
CC human immunodeficiency virus type 1 (HIV-1), moloney and murine
CC leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV),
CC filoviridae: ebola virus (EBOV) and marburg virus (MARV),
CC togaviridae: sindbis virus (SINV) and Ross river virus (RRV).
CC Specifically targets the multiply spliced but not unspliced or
CC singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more
CC potent viral inhibitor than isoform 2. Isoform 2 acts as a
CC positive regulator of DDX58/RIG-I signaling resulting in
CC activation of the downstream effector IRF3 leading to the
CC expression of type I IFNs and IFN stimulated genes (ISGs).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable;
CC -!- SUBUNIT: Homodimer or homooligomer. Homooligomerization is
CC essential for its antiviral activity. Interacts with EXOSC5 (By
CC similarity). Interacts (via N-terminal domain) with DDX17 in an
CC RNA-independent manner (By similarity). Interacts with EXOSC3,
CC EXOSC7, DCP2 and DCP1A. Interacts with PARN in an RNA-independent
CC manner. Interacts with XRN1 in an RNA-dependent manner. Isoform 2
CC interacts (via zinc-fingers) with DDX58/RIG-I in an RNA-dependent
CC manner. Interacts (via N-terminal domain) with DHX30 (via N-
CC terminus) in an RNA-independent manner.
CC -!- INTERACTION:
CC O95786:DDX58; NbExp=4; IntAct=EBI-922559, EBI-995350;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Nucleus.
CC Note=Localizes in the cytoplasm at steady state, but shuttles
CC between nucleus and cytoplasm in a XPO1-dependent manner (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=ZAPL;
CC IsoId=Q7Z2W4-1; Sequence=Displayed;
CC Name=2; Synonyms=ZAPS;
CC IsoId=Q7Z2W4-2; Sequence=VSP_010269;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q7Z2W4-3; Sequence=VSP_010270, VSP_010271;
CC Note=No experimental confirmation available. Contains a
CC phosphoserine at position 572;
CC Name=4;
CC IsoId=Q7Z2W4-4; Sequence=VSP_010268;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=Q7Z2W4-5; Sequence=VSP_010268, VSP_010269;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: By type I interferon (IFN) and viruses. Isoform 2 is
CC up-regulated by 3'-PPP-RNA.
CC -!- DOMAIN: The N-terminal domain is sufficient to bind to viral RNAs
CC and promote their degradation. The second and fourth zinc fingers
CC are involved in binding to specific viral RNAs.
CC -!- PTM: Phosphorylation at Ser-275 is essential for sequential
CC phosphorylation of Ser-271, Ser-267, Ser-263 and Ser-257 by GSK3-
CC beta. Phosphorylation by GSK3-beta enhances its antiviral activity
CC (By similarity).
CC -!- SIMILARITY: Contains 4 C3H1-type zinc fingers.
CC -!- SIMILARITY: Contains 1 PARP catalytic domain.
CC -!- SIMILARITY: Contains 1 WWE domain.
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DR EMBL; AF138863; AAF61195.1; -; mRNA.
DR EMBL; AK055851; BAB71028.1; -; mRNA.
DR EMBL; AK023350; BAB14537.1; -; mRNA.
DR EMBL; BX571742; CAE11868.1; -; mRNA.
DR EMBL; CH236950; EAL24040.1; -; Genomic_DNA.
DR EMBL; CH236950; EAL24041.1; -; Genomic_DNA.
DR EMBL; BC025308; AAH25308.1; -; mRNA.
DR EMBL; BC027462; AAH27462.1; -; mRNA.
DR EMBL; BC033105; AAH33105.1; -; mRNA.
DR EMBL; BC040956; AAH40956.1; -; mRNA.
DR RefSeq; NP_064504.2; NM_020119.3.
DR RefSeq; NP_078901.3; NM_024625.3.
DR UniGene; Hs.133512; -.
DR PDB; 2X5Y; X-ray; 1.05 A; A=724-896.
DR PDBsum; 2X5Y; -.
DR ProteinModelPortal; Q7Z2W4; -.
DR SMR; Q7Z2W4; 3-225, 726-896.
DR DIP; DIP-37896N; -.
DR IntAct; Q7Z2W4; 8.
DR MINT; MINT-5006396; -.
DR STRING; 9606.ENSP00000242351; -.
DR PhosphoSite; Q7Z2W4; -.
DR DMDM; 223634727; -.
DR PaxDb; Q7Z2W4; -.
DR PRIDE; Q7Z2W4; -.
DR Ensembl; ENST00000242351; ENSP00000242351; ENSG00000105939.
DR Ensembl; ENST00000471652; ENSP00000419855; ENSG00000105939.
DR GeneID; 56829; -.
DR KEGG; hsa:56829; -.
DR UCSC; uc003vun.3; human.
DR CTD; 56829; -.
DR GeneCards; GC07M138728; -.
DR H-InvDB; HIX0007129; -.
DR HGNC; HGNC:23721; ZC3HAV1.
DR HPA; HPA047818; -.
DR MIM; 607312; gene.
DR neXtProt; NX_Q7Z2W4; -.
DR PharmGKB; PA134944289; -.
DR eggNOG; NOG83866; -.
DR HOVERGEN; HBG050384; -.
DR InParanoid; Q7Z2W4; -.
DR KO; K15259; -.
DR OrthoDB; EOG7P5T0J; -.
DR ChiTaRS; ZC3HAV1; human.
DR EvolutionaryTrace; Q7Z2W4; -.
DR GeneWiki; ZC3HAV1; -.
DR GenomeRNAi; 56829; -.
DR NextBio; 62226; -.
DR PMAP-CutDB; Q7Z2W4; -.
DR PRO; PR:Q7Z2W4; -.
DR ArrayExpress; Q7Z2W4; -.
DR Bgee; Q7Z2W4; -.
DR CleanEx; HS_ZC3HAV1; -.
DR Genevestigator; Q7Z2W4; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:1900246; P:positive regulation of RIG-I signaling pathway; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR Gene3D; 3.90.228.10; -; 1.
DR InterPro; IPR012317; Poly(ADP-ribose)pol_cat_dom.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR000571; Znf_CCCH.
DR Pfam; PF00644; PARP; 1.
DR PROSITE; PS51059; PARP_CATALYTIC; 1.
DR PROSITE; PS50918; WWE; 1.
DR PROSITE; PS50103; ZF_C3H1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antiviral defense;
KW Complete proteome; Cytoplasm; Immunity; Innate immunity;
KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; RNA-binding; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 902 Zinc finger CCCH-type antiviral protein
FT 1.
FT /FTId=PRO_0000211343.
FT DOMAIN 594 681 WWE.
FT DOMAIN 716 902 PARP catalytic.
FT ZN_FING 73 86 C3H1-type 1.
FT ZN_FING 88 110 C3H1-type 2.
FT ZN_FING 150 172 C3H1-type 3.
FT ZN_FING 169 193 C3H1-type 4.
FT REGION 2 254 N-terminal domain.
FT REGION 224 254 Binding to EXOSC5 (By similarity).
FT MOTIF 69 76 Nuclear localization signal (By
FT similarity).
FT MOTIF 285 292 Nuclear export signal (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 257 257 Phosphoserine; by GSK3-beta.
FT MOD_RES 263 263 Phosphoserine; by GSK3-beta (By
FT similarity).
FT MOD_RES 267 267 Phosphoserine; by GSK3-beta (By
FT similarity).
FT MOD_RES 271 271 Phosphoserine; by GSK3-beta.
FT MOD_RES 273 273 Phosphothreonine.
FT MOD_RES 275 275 Phosphoserine.
FT MOD_RES 284 284 Phosphoserine.
FT MOD_RES 302 302 Phosphoserine.
FT MOD_RES 327 327 Phosphoserine (By similarity).
FT MOD_RES 335 335 Phosphoserine.
FT MOD_RES 378 378 Phosphoserine.
FT MOD_RES 387 387 Phosphoserine.
FT MOD_RES 393 393 Phosphothreonine.
FT MOD_RES 492 492 Phosphoserine.
FT VAR_SEQ 1 539 Missing (in isoform 4 and isoform 5).
FT /FTId=VSP_010268.
FT VAR_SEQ 491 624 DSLSDVTSTTSSRVDDHDSEEICLDHLCKGCPLNGSCSKVH
FT FHLPYRWQMLIGKTWTDFEHMETIEKGYCNPGIHLCSVGSY
FT TINFRVMSCDSFPIRRLSTPSSVTKPANSVFTTKWIWYWKN
FT ESGTWIQYGEE -> GKYKGKTLWASTFVHDIPNGSSQVVD
FT KTTDVEKTGATGFGLTMAVKAEKDMLCTGSQSLRNLVPTTP
FT GESTAPAQVSTLPQSPAALSSSNRAAVWGAQGQNCTQVPVS
FT SASELTRKTTGSAQCKSLKDKGASVS (in isoform
FT 3).
FT /FTId=VSP_010270.
FT VAR_SEQ 625 902 Missing (in isoform 3).
FT /FTId=VSP_010271.
FT VAR_SEQ 699 902 DHQPAKTSSVSLTATFRPQEDFCFLSSKKYKLSEIHHLHPE
FT YVRVSEHFKASMKNFKIEKIKKIENSELLDKFTWKKSQMKE
FT EGKLLFYATSRAYVESICSNNFDSFLHETHENKYGKGIYFA
FT KDAIYSHKNCPYDAKNVVMFVAQVLVGKFTEGNITYTSPPP
FT QFDSCVDTRSNPSVFVIFQKDQVYPQYVIEYTEDKACVIS
FT -> E (in isoform 2 and isoform 5).
FT /FTId=VSP_010269.
FT VARIANT 485 485 R -> K (in dbSNP:rs2236426).
FT /FTId=VAR_018454.
FT VARIANT 565 565 H -> Q (in dbSNP:rs2297241).
FT /FTId=VAR_018455.
FT VARIANT 701 701 Q -> E (in dbSNP:rs2297236).
FT /FTId=VAR_054319.
FT VARIANT 851 851 T -> I (in dbSNP:rs3735007).
FT /FTId=VAR_018456.
FT CONFLICT 245 245 A -> T (in Ref. 3; CAE11868).
FT STRAND 729 732
FT HELIX 738 748
FT STRAND 754 763
FT HELIX 765 778
FT STRAND 783 790
FT HELIX 791 793
FT HELIX 794 800
FT HELIX 804 807
FT STRAND 812 814
FT STRAND 816 823
FT HELIX 824 830
FT HELIX 835 837
FT STRAND 838 845
FT STRAND 849 852
FT STRAND 866 869
FT STRAND 871 873
FT STRAND 876 879
FT HELIX 882 884
FT STRAND 885 895
SQ SEQUENCE 902 AA; 101431 MW; 72AB311D23658E24 CRC64;
MADPEVCCFI TKILCAHGGR MALDALLQEI ALSEPQLCEV LQVAGPDRFV VLETGGEAGI
TRSVVATTRA RVCRRKYCQR PCDNLHLCKL NLLGRCNYSQ SERNLCKYSH EVLSEENFKV
LKNHELSGLN KEELAVLLLQ SDPFFMPEIC KSYKGEGRQQ ICNQQPPCSR LHICDHFTRG
NCRFPNCLRS HNLMDRKVLA IMREHGLNPD VVQNIQDICN SKHMQKNPPG PRAPSSHRRN
MAYRARSKSR DRFFQGSQEF LASASASAER SCTPSPDQIS HRASLEDAPV DDLTRKFTYL
GSQDRARPPS GSSKATDLGG TSQAGTSQRF LENGSQEDLL HGNPGSTYLA SNSTSAPNWK
SLTSWTNDQG ARRKTVFSPT LPAARSSLGS LQTPEAVTTR KGTGLLSSDY RIINGKSGTQ
DIQPGPLFNN NADGVATDIT STRSLNYKST SSGHREISSP RIQDAGPASR DVQATGRIAD
DADPRVALVN DSLSDVTSTT SSRVDDHDSE EICLDHLCKG CPLNGSCSKV HFHLPYRWQM
LIGKTWTDFE HMETIEKGYC NPGIHLCSVG SYTINFRVMS CDSFPIRRLS TPSSVTKPAN
SVFTTKWIWY WKNESGTWIQ YGEEKDKRKN SNVDSSYLES LYQSCPRGVV PFQAGSRNYE
LSFQGMIQTN IASKTQKDVI RRPTFVPQWY VQQMKRGPDH QPAKTSSVSL TATFRPQEDF
CFLSSKKYKL SEIHHLHPEY VRVSEHFKAS MKNFKIEKIK KIENSELLDK FTWKKSQMKE
EGKLLFYATS RAYVESICSN NFDSFLHETH ENKYGKGIYF AKDAIYSHKN CPYDAKNVVM
FVAQVLVGKF TEGNITYTSP PPQFDSCVDT RSNPSVFVIF QKDQVYPQYV IEYTEDKACV
IS
//
MIM
607312
*RECORD*
*FIELD* NO
607312
*FIELD* TI
*607312 ZINC FINGER CCCH DOMAIN-CONTAINING ANTIVIRAL PROTEIN 1; ZC3HAV1
;;ZINC FINGER ANTIVIRAL PROTEIN; ZAP
read more*FIELD* TX
DESCRIPTION
ZC3HAV1 is a CCCH-type zinc finger protein that prevents infection by
retroviruses.
CLONING
In their analysis of genes expressed in human fetal liver, Yu et al.
(2001) identified ZC3HAV1, which they called ZAP, as a 1,524-bp cDNA
(GenBank GENBANK AF138863) with an open reading frame of 264 amino
acids.
Gao et al. (2002) screened mammalian cDNA libraries for genes that
prevent infection by a genetically marked retrovirus. Virus-resistant
cells were selected from pools of transduced clones, and an active
antiviral cDNA was recovered. The gene encodes a CCCH-type zinc finger
protein designated ZAP for 'zinc finger antiviral protein.' Gao et al.
(2002) cloned a full-length rat Zap cDNA, which contained 776 codons.
Northern blot analysis of rat Zap showed that mRNA was highly expressed
in kidney and liver, but undetectable in brain and testis. Two mRNAs
(3.5 and 4.5 kb) were observed in most tissues, possibly corresponding
to alternative splice variants. Expression of the gene caused profound
and specific loss of viral mRNAs from the cytoplasm of rat and mouse
cells without affecting the levels of nuclear mRNAs. This observation
suggested the existence of a previously unknown machinery for the
inhibition of virus replication, targeting a step in viral gene
expression.
By database searching with evolutionarily conserved sequences in the
TIPARP gene (612480), Katoh and Katoh (2003) identified 2 human genes,
FLJ22693 (PARP12; 612481) and ZC3HAV1, encoding deduced proteins with
the same conserved domains: a WWE domain, a PARP-like domain, and a TPH
domain. The N-terminal domain of the TPH domain in all 3 genes contains
a CCCH-type zinc finger. Katoh and Katoh (2003) noted that PARP12 and
ZCH3HAV1 share 27.5% and 26% overall amino acid sequence identity with
TIPARP, respectively. They stated that the deduced ZC3HAV1 protein
contains 902 amino acids.
MAPPING
Yu et al. (2001) assigned the human ZAP gene to chromosome 7. By
analysis of mouse genomic sequences, Gao et al. (2002) mapped the Zap
gene to chromosome 6.
*FIELD* RF
1. Gao, G.; Guo, X.; Goff, S. P.: Inhibition of retroviral RNA production
by ZAP, a CCCH-type zinc finger protein. Science 297: 1703-1706,
2002.
2. Katoh, M.; Katoh, M.: Identification and characterization of human
TIPARP gene within the CCNL amplicon at human chromosome 3q25.31. Int.
J. Oncol. 23: 541-547, 2003.
3. Yu, Y.; Zhang, C.; Zhou, G.; Wu, S.; Qu, X.; Wei, H.; Xing, G.;
Dong, C.; Zhai, Y.; Wan, J.; Ouyang, S.; Li, L.; Zhang, S.; Zhou,
K.; Zhang, Y.; Wu, C.; He, F.: Gene expression profiling in human
fetal liver and identification of tissue- and developmental-stage-specific
genes through compiled expression profiles and efficient cloning of
full-length cDNAs. Genome Res. 11: 1392-1403, 2001.
*FIELD* CN
Carol A. Bocchini - updated: 12/16/2008
*FIELD* CD
Ada Hamosh: 10/21/2002
*FIELD* ED
carol: 12/16/2008
wwang: 11/13/2006
alopez: 10/21/2002
*RECORD*
*FIELD* NO
607312
*FIELD* TI
*607312 ZINC FINGER CCCH DOMAIN-CONTAINING ANTIVIRAL PROTEIN 1; ZC3HAV1
;;ZINC FINGER ANTIVIRAL PROTEIN; ZAP
read more*FIELD* TX
DESCRIPTION
ZC3HAV1 is a CCCH-type zinc finger protein that prevents infection by
retroviruses.
CLONING
In their analysis of genes expressed in human fetal liver, Yu et al.
(2001) identified ZC3HAV1, which they called ZAP, as a 1,524-bp cDNA
(GenBank GENBANK AF138863) with an open reading frame of 264 amino
acids.
Gao et al. (2002) screened mammalian cDNA libraries for genes that
prevent infection by a genetically marked retrovirus. Virus-resistant
cells were selected from pools of transduced clones, and an active
antiviral cDNA was recovered. The gene encodes a CCCH-type zinc finger
protein designated ZAP for 'zinc finger antiviral protein.' Gao et al.
(2002) cloned a full-length rat Zap cDNA, which contained 776 codons.
Northern blot analysis of rat Zap showed that mRNA was highly expressed
in kidney and liver, but undetectable in brain and testis. Two mRNAs
(3.5 and 4.5 kb) were observed in most tissues, possibly corresponding
to alternative splice variants. Expression of the gene caused profound
and specific loss of viral mRNAs from the cytoplasm of rat and mouse
cells without affecting the levels of nuclear mRNAs. This observation
suggested the existence of a previously unknown machinery for the
inhibition of virus replication, targeting a step in viral gene
expression.
By database searching with evolutionarily conserved sequences in the
TIPARP gene (612480), Katoh and Katoh (2003) identified 2 human genes,
FLJ22693 (PARP12; 612481) and ZC3HAV1, encoding deduced proteins with
the same conserved domains: a WWE domain, a PARP-like domain, and a TPH
domain. The N-terminal domain of the TPH domain in all 3 genes contains
a CCCH-type zinc finger. Katoh and Katoh (2003) noted that PARP12 and
ZCH3HAV1 share 27.5% and 26% overall amino acid sequence identity with
TIPARP, respectively. They stated that the deduced ZC3HAV1 protein
contains 902 amino acids.
MAPPING
Yu et al. (2001) assigned the human ZAP gene to chromosome 7. By
analysis of mouse genomic sequences, Gao et al. (2002) mapped the Zap
gene to chromosome 6.
*FIELD* RF
1. Gao, G.; Guo, X.; Goff, S. P.: Inhibition of retroviral RNA production
by ZAP, a CCCH-type zinc finger protein. Science 297: 1703-1706,
2002.
2. Katoh, M.; Katoh, M.: Identification and characterization of human
TIPARP gene within the CCNL amplicon at human chromosome 3q25.31. Int.
J. Oncol. 23: 541-547, 2003.
3. Yu, Y.; Zhang, C.; Zhou, G.; Wu, S.; Qu, X.; Wei, H.; Xing, G.;
Dong, C.; Zhai, Y.; Wan, J.; Ouyang, S.; Li, L.; Zhang, S.; Zhou,
K.; Zhang, Y.; Wu, C.; He, F.: Gene expression profiling in human
fetal liver and identification of tissue- and developmental-stage-specific
genes through compiled expression profiles and efficient cloning of
full-length cDNAs. Genome Res. 11: 1392-1403, 2001.
*FIELD* CN
Carol A. Bocchini - updated: 12/16/2008
*FIELD* CD
Ada Hamosh: 10/21/2002
*FIELD* ED
carol: 12/16/2008
wwang: 11/13/2006
alopez: 10/21/2002