SHFL_HUMAN
ID SHFL_HUMAN Reviewed; 291 AA.
AC Q9NUL5; A8MQT9; Q4G188; Q8IYH6; Q8N8V1;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Shiftless antiviral inhibitor of ribosomal frameshifting protein {ECO:0000305};
DE Short=SFL {ECO:0000303|PubMed:30682371};
DE Short=SHFL {ECO:0000305};
DE AltName: Full=Interferon-regulated antiviral protein {ECO:0000303|PubMed:27974568};
DE Short=IRAV {ECO:0000303|PubMed:27974568};
DE AltName: Full=Repressor of yield of DENV protein {ECO:0000303|PubMed:26735137};
DE Short=RyDEN {ECO:0000303|PubMed:26735137};
GN Name=SHFL {ECO:0000312|HGNC:HGNC:25649};
GN Synonyms=C19orf66, FLJ11286 {ECO:0000303|PubMed:27974568},
GN IRAV {ECO:0000303|PubMed:27974568}, RYDEN {ECO:0000303|PubMed:26735137},
GN SFL {ECO:0000303|PubMed:30682371};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver, and Placenta;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Lymph, Pancreas, and Testis;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION,
RP INDUCTION, INTERACTION WITH PABPC1, IDENTIFICATION IN A COMPLEX WITH PABPC1
RP AND LARP1, MUTAGENESIS OF 121-ARG--ARG-137, NUCLEAR LOCALIZATION SIGNAL,
RP AND NUCLEAR EXPORT SIGNAL.
RX PubMed=26735137; DOI=10.1371/journal.ppat.1005357;
RA Suzuki Y., Chin W.X., Han Q., Ichiyama K., Lee C.H., Eyo Z.W., Ebina H.,
RA Takahashi H., Takahashi C., Tan B.H., Hishiki T., Ohba K., Matsuyama T.,
RA Koyanagi Y., Tan Y.J., Sawasaki T., Chu J.J., Vasudevan S.G., Sano K.,
RA Yamamoto N.;
RT "Characterization of RyDEN (C19orf66) as an interferon-stimulated cellular
RT inhibitor against dengue virus replication.";
RL PLoS Pathog. 12:E1005357-E1005357(2016).
RN [8]
RP FUNCTION, INDUCTION BY DENV VIRUS, SUBCELLULAR LOCATION, INTERACTION WITH
RP ELAV1; MOV10 AND UPF1, RNA-BINDING, AND INTERACTION WITH NS3 AND NS4A
RP (MICROBIAL INFECTION).
RX PubMed=27974568; DOI=10.1128/jvi.01606-16;
RA Balinsky C.A., Schmeisser H., Wells A.I., Ganesan S., Jin T., Singh K.,
RA Zoon K.C.;
RT "IRAV (FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity
RT against Dengue Virus, Interacts with MOV10.";
RL J. Virol. 91:0-0(2017).
RN [9]
RP FUNCTION, FUNCTION (ISOFORM 4), INDUCTION BY IFN, ALTERNATIVE SPLICING,
RP RIBOSOMES-BINDING, INTERACTION WITH GSPT1, AND RNA-BINDING.
RX PubMed=30682371; DOI=10.1016/j.cell.2018.12.030;
RA Wang X., Xuan Y., Han Y., Ding X., Ye K., Yang F., Gao P., Goff S.P.,
RA Gao G.;
RT "Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of
RT Programmed -1 Ribosomal Frameshifting.";
RL Cell 176:625.E14-635.E14(2019).
RN [10]
RP FUNCTION.
RX PubMed=30944177; DOI=10.1128/jvi.00373-19;
RA Rodriguez W., Srivastav K., Muller M.;
RT "C19ORF66 Broadly Escapes Virus-Induced Endonuclease Cleavage and Restricts
RT Kaposi's Sarcoma-Associated Herpesvirus.";
RL J. Virol. 93:0-0(2019).
RN [11]
RP FUNCTION, INDUCTION BY IFN, INTERACTION WITH ZIKA VIRUS PROTEIN NS3
RP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=32150556; DOI=10.1371/journal.pntd.0008083;
RA Wu Y., Yang X., Yao Z., Dong X., Zhang D., Hu Y., Zhang S., Lin J.,
RA Chen J., An S., Ye H., Zhang S., Qiu Z., He Z., Huang M., Wei G., Zhu X.;
RT "C19orf66 interrupts Zika virus replication by inducing lysosomal
RT degradation of viral NS3.";
RL PLoS Negl. Trop. Dis. 14:e0008083-e0008083(2020).
RN [12]
RP FUNCTION, AND INDUCTION BY IFN.
RX PubMed=32294532; DOI=10.1016/j.jhep.2020.03.047;
RA Kinast V., Plociennikowska A., Angga K., Bracht T., Todt D., Brown R.J.P.,
RA Boldanova T., Zhang Y., Brueggemann Y., Friesland M., Engelmann M.,
RA Vieyres G., Broering R., Vondran F.W.R., Heim M.H., Sitek B.,
RA Bartenschlager R., Pietschmann T., Steinmann E.;
RT "C19orf66 is an interferon-induced inhibitor of HCV replication that
RT restricts formation of the viral replication organelle.";
RL J. Hepatol. 73:549-558(2020).
CC -!- FUNCTION: Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a
CC variety of mRNAs from viruses, such as HIV1, and cellular genes, such
CC as PEG10. Interacts with the -1PRF signal of target mRNA and
CC translating ribosomes and causes premature translation termination at
CC the frameshifting site (PubMed:30682371). Regulates HIV1 GAG-POL
CC expression by inhibiting -1PRF (PubMed:30682371). Exhibits antiviral
CC activity against dengue virus (DENV) and can inhibit the replication of
CC all DENV serotypes. May block the protein translation of DENV RNA via
CC its association with cellular mRNA-binding proteins and viral RNA.
CC Interrupts also Zika virus replication by promoting viral NS3
CC degradation via a lysosome-dependent pathway (PubMed:32150556). Can
CC also limit the replication of hepatitis C virus (HCV) by restricting
CC formation of viral replication organelle, West Nile virus (WNV),
CC Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes
CC virus type 8 (HHV-8) and human adenovirus (PubMed:26735137,
CC PubMed:27974568, PubMed:30944177, PubMed:32294532). Binds nucleic acids
CC with a higher affinity for ssRNA and ssDNA than for dsDNA
CC (PubMed:27974568). {ECO:0000269|PubMed:26735137,
CC ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:30682371,
CC ECO:0000269|PubMed:30944177, ECO:0000269|PubMed:32150556,
CC ECO:0000269|PubMed:32294532}.
CC -!- FUNCTION: Isoform 4 does not inhibit programmed ribosomal frameshifting
CC (-1PRF). Does not bind to ribosomes. {ECO:0000269|PubMed:30682371}.
CC -!- SUBUNIT: Interacts with PABPC1 (PubMed:26735137). Found in a complex
CC with PABPC1 and LARP1 (PubMed:26735137). Interacts with ELAV1, MOV10
CC and UPF1; the interactions increase in presence of RNA
CC (PubMed:27974568). Binds to ribosomes (PubMed:30682371). Interacts with
CC GSPT1 (PubMed:30682371). {ECO:0000269|PubMed:26735137,
CC ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:30682371}.
CC -!- SUBUNIT: (Microbial infection) Interacts with the human dengue virus
CC DENV proteins NS3 and NS4A. {ECO:0000269|PubMed:27974568}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Zika virus protein NS3;
CC this interaction promotes viral NS3 degradation.
CC {ECO:0000269|PubMed:32150556}.
CC -!- INTERACTION:
CC Q9NUL5; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-10313866, EBI-10173507;
CC Q9NUL5; A2RRN7: CADPS; NbExp=3; IntAct=EBI-10313866, EBI-10179719;
CC Q9NUL5; Q96JN2-2: CCDC136; NbExp=3; IntAct=EBI-10313866, EBI-10171416;
CC Q9NUL5; Q6PGQ1: DRICH1; NbExp=3; IntAct=EBI-10313866, EBI-10253641;
CC Q9NUL5; Q96EV8: DTNBP1; NbExp=3; IntAct=EBI-10313866, EBI-465804;
CC Q9NUL5; Q13422: IKZF1; NbExp=3; IntAct=EBI-10313866, EBI-745305;
CC Q9NUL5; Q6A162: KRT40; NbExp=3; IntAct=EBI-10313866, EBI-10171697;
CC Q9NUL5; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-10313866, EBI-10172150;
CC Q9NUL5; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-10313866, EBI-10172290;
CC Q9NUL5; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-10313866, EBI-10171774;
CC Q9NUL5; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-10313866, EBI-10172052;
CC Q9NUL5; P0C7H8: KRTAP2-3; NbExp=3; IntAct=EBI-10313866, EBI-10196781;
CC Q9NUL5; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-10313866, EBI-739863;
CC Q9NUL5; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-10313866, EBI-10172511;
CC Q9NUL5; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-10313866, EBI-3958099;
CC Q9NUL5; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-10313866, EBI-1044640;
CC Q9NUL5; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-10313866, EBI-741037;
CC Q9NUL5; P43355: MAGEA1; NbExp=3; IntAct=EBI-10313866, EBI-740978;
CC Q9NUL5; Q99750: MDFI; NbExp=3; IntAct=EBI-10313866, EBI-724076;
CC Q9NUL5; P50222: MEOX2; NbExp=3; IntAct=EBI-10313866, EBI-748397;
CC Q9NUL5; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-10313866, EBI-10172526;
CC Q9NUL5; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-10313866, EBI-742948;
CC Q9NUL5; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10313866, EBI-945833;
CC Q9NUL5; Q5VU43: PDE4DIP; NbExp=3; IntAct=EBI-10313866, EBI-1105124;
CC Q9NUL5; O43597: SPRY2; NbExp=3; IntAct=EBI-10313866, EBI-742487;
CC Q9NUL5; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-10313866, EBI-2212028;
CC Q9NUL5; P15884: TCF4; NbExp=3; IntAct=EBI-10313866, EBI-533224;
CC Q9NUL5; P54274: TERF1; NbExp=2; IntAct=EBI-10313866, EBI-710997;
CC Q9NUL5; Q63HR2: TNS2; NbExp=4; IntAct=EBI-10313866, EBI-949753;
CC Q9NUL5; Q13077: TRAF1; NbExp=3; IntAct=EBI-10313866, EBI-359224;
CC Q9NUL5-3; G5E9A7: DMWD; NbExp=3; IntAct=EBI-22000547, EBI-10976677;
CC Q9NUL5-3; P28799: GRN; NbExp=3; IntAct=EBI-22000547, EBI-747754;
CC Q9NUL5-3; P04792: HSPB1; NbExp=3; IntAct=EBI-22000547, EBI-352682;
CC Q9NUL5-3; O60333-2: KIF1B; NbExp=3; IntAct=EBI-22000547, EBI-10975473;
CC Q9NUL5-3; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-22000547, EBI-396669;
CC Q9NUL5-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-22000547, EBI-5235340;
CC Q9NUL5-3; O76024: WFS1; NbExp=3; IntAct=EBI-22000547, EBI-720609;
CC Q9NUL5-4; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-11955083, EBI-10173507;
CC Q9NUL5-4; O95273: CCNDBP1; NbExp=3; IntAct=EBI-11955083, EBI-748961;
CC Q9NUL5-4; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11955083, EBI-3867333;
CC Q9NUL5-4; Q6PGQ1: DRICH1; NbExp=3; IntAct=EBI-11955083, EBI-10253641;
CC Q9NUL5-4; Q92997: DVL3; NbExp=3; IntAct=EBI-11955083, EBI-739789;
CC Q9NUL5-4; Q5TD97: FHL5; NbExp=3; IntAct=EBI-11955083, EBI-750641;
CC Q9NUL5-4; O75031: HSF2BP; NbExp=3; IntAct=EBI-11955083, EBI-7116203;
CC Q9NUL5-4; Q0VD86: INCA1; NbExp=3; IntAct=EBI-11955083, EBI-6509505;
CC Q9NUL5-4; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-11955083, EBI-2796400;
CC Q9NUL5-4; Q15323: KRT31; NbExp=3; IntAct=EBI-11955083, EBI-948001;
CC Q9NUL5-4; Q6A162: KRT40; NbExp=3; IntAct=EBI-11955083, EBI-10171697;
CC Q9NUL5-4; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-11955083, EBI-11959885;
CC Q9NUL5-4; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-11955083, EBI-11749135;
CC Q9NUL5-4; Q9BYS1: KRTAP1-5; NbExp=3; IntAct=EBI-11955083, EBI-11741292;
CC Q9NUL5-4; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-11955083, EBI-10172150;
CC Q9NUL5-4; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-11955083, EBI-10172290;
CC Q9NUL5-4; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-11955083, EBI-10171774;
CC Q9NUL5-4; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-11955083, EBI-10172052;
CC Q9NUL5-4; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-11955083, EBI-11953334;
CC Q9NUL5-4; Q9BYP8: KRTAP17-1; NbExp=3; IntAct=EBI-11955083, EBI-11988175;
CC Q9NUL5-4; Q9BYR9: KRTAP2-4; NbExp=3; IntAct=EBI-11955083, EBI-14065470;
CC Q9NUL5-4; Q9BYQ6: KRTAP4-11; NbExp=5; IntAct=EBI-11955083, EBI-10302392;
CC Q9NUL5-4; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-11955083, EBI-739863;
CC Q9NUL5-4; Q9BYR3: KRTAP4-4; NbExp=3; IntAct=EBI-11955083, EBI-11958132;
CC Q9NUL5-4; Q9BYR2: KRTAP4-5; NbExp=3; IntAct=EBI-11955083, EBI-11993254;
CC Q9NUL5-4; Q6L8G8: KRTAP5-7; NbExp=3; IntAct=EBI-11955083, EBI-11987425;
CC Q9NUL5-4; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-11955083, EBI-3958099;
CC Q9NUL5-4; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-11955083, EBI-1044640;
CC Q9NUL5-4; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-11955083, EBI-1043191;
CC Q9NUL5-4; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-11955083, EBI-739832;
CC Q9NUL5-4; Q96LR2: LURAP1; NbExp=3; IntAct=EBI-11955083, EBI-741355;
CC Q9NUL5-4; Q99750: MDFI; NbExp=3; IntAct=EBI-11955083, EBI-724076;
CC Q9NUL5-4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11955083, EBI-16439278;
CC Q9NUL5-4; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-11955083, EBI-11522433;
CC Q9NUL5-4; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-11955083, EBI-22310682;
CC Q9NUL5-4; Q92824-2: PCSK5; NbExp=3; IntAct=EBI-11955083, EBI-11956269;
CC Q9NUL5-4; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-11955083, EBI-79165;
CC Q9NUL5-4; Q15172: PPP2R5A; NbExp=3; IntAct=EBI-11955083, EBI-641666;
CC Q9NUL5-4; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-11955083, EBI-11955083;
CC Q9NUL5-4; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-11955083, EBI-2212028;
CC Q9NUL5-4; Q6N022: TENM4; NbExp=3; IntAct=EBI-11955083, EBI-12827077;
CC Q9NUL5-4; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11955083, EBI-11741437;
CC Q9NUL5-4; Q13077: TRAF1; NbExp=3; IntAct=EBI-11955083, EBI-359224;
CC Q9NUL5-4; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-11955083, EBI-492476;
CC Q9NUL5-4; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-11955083, EBI-5235829;
CC Q9NUL5-4; Q2TAL6: VWC2; NbExp=3; IntAct=EBI-11955083, EBI-11957238;
CC Q9NUL5-4; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-11955083, EBI-5667516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26735137,
CC ECO:0000269|PubMed:32150556}. Nucleus {ECO:0000269|PubMed:26735137}.
CC Cytoplasm, P-body {ECO:0000269|PubMed:27974568}. Note=Predominantly
CC found in the cytoplasm (PubMed:26735137). After infection, relocalizes
CC to the DENV replication complex in perinuclear regions
CC (PubMed:27974568). {ECO:0000269|PubMed:26735137,
CC ECO:0000269|PubMed:27974568}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=SFL {ECO:0000303|PubMed:30682371};
CC IsoId=Q9NUL5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NUL5-2; Sequence=VSP_031272;
CC Name=3;
CC IsoId=Q9NUL5-3; Sequence=VSP_031273;
CC Name=4; Synonyms=SFLS {ECO:0000303|PubMed:30682371};
CC IsoId=Q9NUL5-4; Sequence=VSP_031274;
CC -!- INDUCTION: Up-regulated by interferon (IFN) treatment (PubMed:26735137,
CC PubMed:27974568, PubMed:30682371, PubMed:32294532). Expression
CC increases in response to DENV infection in an IFN-dependent manner
CC (PubMed:27974568). {ECO:0000269|PubMed:26735137,
CC ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:30682371}.
CC -!- SIMILARITY: Belongs to the SHFL family. {ECO:0000305}.
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DR EMBL; AK002148; BAA92109.1; -; mRNA.
DR EMBL; AK096142; BAC04710.1; -; mRNA.
DR EMBL; AC020931; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84066.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84068.1; -; Genomic_DNA.
DR EMBL; CH471106; EAW84069.1; -; Genomic_DNA.
DR EMBL; BC010847; AAH10847.1; -; mRNA.
DR EMBL; BC026180; AAH26180.1; -; mRNA.
DR EMBL; BC035817; AAH35817.1; -; mRNA.
DR CCDS; CCDS45957.1; -. [Q9NUL5-1]
DR CCDS; CCDS77231.1; -. [Q9NUL5-4]
DR RefSeq; NP_001295206.1; NM_001308277.1. [Q9NUL5-4]
DR RefSeq; NP_060851.2; NM_018381.3. [Q9NUL5-1]
DR RefSeq; XP_016882423.1; XM_017026934.1.
DR AlphaFoldDB; Q9NUL5; -.
DR SMR; Q9NUL5; -.
DR BioGRID; 120618; 93.
DR CORUM; Q9NUL5; -.
DR IntAct; Q9NUL5; 73.
DR STRING; 9606.ENSP00000253110; -.
DR iPTMnet; Q9NUL5; -.
DR PhosphoSitePlus; Q9NUL5; -.
DR BioMuta; C19orf66; -.
DR DMDM; 172044675; -.
DR EPD; Q9NUL5; -.
DR jPOST; Q9NUL5; -.
DR MassIVE; Q9NUL5; -.
DR MaxQB; Q9NUL5; -.
DR PaxDb; Q9NUL5; -.
DR PeptideAtlas; Q9NUL5; -.
DR PRIDE; Q9NUL5; -.
DR ProteomicsDB; 82688; -. [Q9NUL5-1]
DR ProteomicsDB; 82689; -. [Q9NUL5-2]
DR ProteomicsDB; 82690; -. [Q9NUL5-3]
DR ProteomicsDB; 82691; -. [Q9NUL5-4]
DR Antibodypedia; 51349; 37 antibodies from 11 providers.
DR DNASU; 55337; -.
DR Ensembl; ENST00000253110.16; ENSP00000253110.10; ENSG00000130813.18. [Q9NUL5-1]
DR Ensembl; ENST00000397881.7; ENSP00000380978.3; ENSG00000130813.18. [Q9NUL5-2]
DR Ensembl; ENST00000591813.5; ENSP00000467182.1; ENSG00000130813.18. [Q9NUL5-4]
DR GeneID; 55337; -.
DR KEGG; hsa:55337; -.
DR MANE-Select; ENST00000253110.16; ENSP00000253110.10; NM_018381.4; NP_060851.2.
DR UCSC; uc002mmu.5; human. [Q9NUL5-1]
DR CTD; 55337; -.
DR DisGeNET; 55337; -.
DR GeneCards; SHFL; -.
DR HGNC; HGNC:25649; SHFL.
DR HPA; ENSG00000130813; Tissue enhanced (liver).
DR MIM; 616808; gene.
DR neXtProt; NX_Q9NUL5; -.
DR OpenTargets; ENSG00000130813; -.
DR PharmGKB; PA162378809; -.
DR VEuPathDB; HostDB:ENSG00000130813; -.
DR eggNOG; ENOG502QVND; Eukaryota.
DR GeneTree; ENSGT00390000005065; -.
DR HOGENOM; CLU_087318_0_0_1; -.
DR InParanoid; Q9NUL5; -.
DR OMA; CRKCKVK; -.
DR OrthoDB; 1485595at2759; -.
DR PhylomeDB; Q9NUL5; -.
DR TreeFam; TF337433; -.
DR PathwayCommons; Q9NUL5; -.
DR SignaLink; Q9NUL5; -.
DR BioGRID-ORCS; 55337; 17 hits in 1046 CRISPR screens.
DR ChiTaRS; C19orf66; human.
DR GenomeRNAi; 55337; -.
DR Pharos; Q9NUL5; Tdark.
DR PRO; PR:Q9NUL5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NUL5; protein.
DR Bgee; ENSG00000130813; Expressed in right lobe of liver and 194 other tissues.
DR ExpressionAtlas; Q9NUL5; baseline and differential.
DR Genevisible; Q9NUL5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:1990825; F:sequence-specific mRNA binding; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:2001125; P:negative regulation of translational frameshifting; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0006449; P:regulation of translational termination; IDA:UniProtKB.
DR GO; GO:0035456; P:response to interferon-beta; IDA:UniProtKB.
DR GO; GO:0034341; P:response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB.
DR GO; GO:0034342; P:response to type III interferon; IDA:UniProtKB.
DR GO; GO:0075523; P:viral translational frameshifting; IDA:UniProtKB.
DR InterPro; IPR026795; SHFL.
DR PANTHER; PTHR16135; PTHR16135; 1.
DR Pfam; PF15135; UPF0515; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Antiviral defense; Cytoplasm; Nucleus;
KW Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..291
FT /note="Shiftless antiviral inhibitor of ribosomal
FT frameshifting protein"
FT /id="PRO_0000318701"
FT REGION 51..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 102..150
FT /note="Interaction with PABPC1"
FT /evidence="ECO:0000269|PubMed:26735137"
FT REGION 221..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 270..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 121..137
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:26735137"
FT MOTIF 261..269
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:26735137"
FT COMPBIAS 56..71
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 1..65
FT /note="MSQEGVELEKSVRRLREKFHGKVSSKKAGALMRKFGSDHTGVGRSIVYGVKQ
FT KDGQELSNDLDAQ -> MSQHQQACGICRQE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_031272"
FT VAR_SEQ 164..291
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031273"
FT VAR_SEQ 164..199
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031274"
FT MUTAGEN 121..137
FT /note="RRVPQRKEVSRCRKCRK->AAVPQAAEVSACAACAA: Decreased
FT efficiency in the interaction with PABPC1 and reduced
FT inhibitory activity against DENV replication."
FT /evidence="ECO:0000269|PubMed:26735137"
FT CONFLICT 191
FT /note="W -> R (in Ref. 1; BAA92109)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="S -> P (in Ref. 1; BAA92109)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 291 AA; 33110 MW; D6513814B96BDAF6 CRC64;
MSQEGVELEK SVRRLREKFH GKVSSKKAGA LMRKFGSDHT GVGRSIVYGV KQKDGQELSN
DLDAQDPPED MKQDRDIQAV ATSLLPLTEA NLRMFQRAQD DLIPAVDRQF ACSSCDHVWW
RRVPQRKEVS RCRKCRKRYE PVPADKMWGL AEFHCPKCRH NFRGWAQMGS PSPCYGCGFP
VYPTRILPPR WDRDPDRRST HTHSCSAADC YNRREPHVPG TSCAHPKSRK QNHLPKVLHP
SNPHISSGST VATCLSQGGL LEDLDNLILE DLKEEEEEEE EVEDEEGGPR E
