SHUT_ADE02
ID SHUT_ADE02 Reviewed; 805 AA.
AC P24932; P03268;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 25-MAY-2022, entry version 69.
DE RecName: Full=Shutoff protein {ECO:0000255|HAMAP-Rule:MF_04060};
DE AltName: Full=100 kDa protein {ECO:0000255|HAMAP-Rule:MF_04060};
DE Short=p100K {ECO:0000255|HAMAP-Rule:MF_04060};
DE AltName: Full=100K-chaperone protein {ECO:0000255|HAMAP-Rule:MF_04060};
DE AltName: Full=L4-100K {ECO:0000255|HAMAP-Rule:MF_04060};
DE AltName: Full=Shutoff protein 100K {ECO:0000255|HAMAP-Rule:MF_04060};
GN Name=L4 {ECO:0000255|HAMAP-Rule:MF_04060};
OS Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2).
OC Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; Adenoviridae; Mastadenovirus.
OX NCBI_TaxID=10515;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-509.
RX PubMed=6334081; DOI=10.1016/s0021-9258(18)89839-8;
RA Roberts R.J., O'Neill K.E., Yen C.E.;
RT "DNA sequences from the adenovirus 2 genome.";
RL J. Biol. Chem. 259:13968-13975(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 510-805.
RX PubMed=478297; DOI=10.1016/0378-1119(79)90081-7;
RA Galibert F., Herisse J., Courtois G.;
RT "Nucleotide sequence of the EcoRI-F fragment of adenovirus 2 genome.";
RL Gene 6:1-22(1979).
RN [3]
RP FUNCTION, AND INTERACTION WITH HEXON PROTEIN.
RX PubMed=7159928; DOI=10.1016/0092-8674(82)90134-9;
RA Cepko C.L., Sharp P.A.;
RT "Assembly of adenovirus major capsid protein is mediated by a nonvirion
RT protein.";
RL Cell 31:407-415(1982).
RN [4]
RP SUBCELLULAR LOCATION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=14633984; DOI=10.1093/emboj/cdg614;
RA Wodrich H., Guan T., Cingolani G., Von Seggern D., Nemerow G., Gerace L.;
RT "Switch from capsid protein import to adenovirus assembly by cleavage of
RT nuclear transport signals.";
RL EMBO J. 22:6245-6255(2003).
RN [5]
RP FUNCTION, AND INTERACTION WITH HOST EIF4G AND VIRAL MRNAS.
RX PubMed=15314025; DOI=10.1101/gad.1212504;
RA Xi Q., Cuesta R., Schneider R.J.;
RT "Tethering of eIF4G to adenoviral mRNAs by viral 100k protein drives
RT ribosome shunting.";
RL Genes Dev. 18:1997-2009(2004).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST EIF4G.
RX PubMed=15220445; DOI=10.1128/jvi.78.14.7707-7716.2004;
RA Cuesta R., Xi Q., Schneider R.J.;
RT "Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by
RT the adenovirus 100-kilodalton protein.";
RL J. Virol. 78:7707-7716(2004).
RN [7]
RP STRUCTURE BY ELECTRON MICROSCOPY, FUNCTION, SUBUNIT, AND INTERACTION WITH
RP HEXON PROTEIN.
RX PubMed=16081097; DOI=10.1016/j.jmb.2005.06.070;
RA Hong S.S., Szolajska E., Schoehn G., Franqueville L., Myhre S.,
RA Lindholm L., Ruigrok R.W., Boulanger P., Chroboczek J.;
RT "The 100K-chaperone protein from adenovirus serotype 2 (Subgroup C) assists
RT in trimerization and nuclear localization of hexons from subgroups C and B
RT adenoviruses.";
RL J. Mol. Biol. 352:125-138(2005).
RN [8]
RP FUNCTION, PHOSPHORYLATION AT TYR-365 AND TYR-682, AND MUTAGENESIS OF
RP TYR-365 AND TYR-682.
RX PubMed=15827182; DOI=10.1128/jvi.79.9.5676-5683.2005;
RA Xi Q., Cuesta R., Schneider R.J.;
RT "Regulation of translation by ribosome shunting through phosphotyrosine-
RT dependent coupling of adenovirus protein 100k to viral mRNAs.";
RL J. Virol. 79:5676-5683(2005).
RN [9]
RP METHYLATION AT ARG/GLY REGION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=19264777; DOI=10.1128/jvi.02493-08;
RA Koyuncu O.O., Dobner T.;
RT "Arginine methylation of human adenovirus type 5 L4 100-kilodalton protein
RT is required for efficient virus production.";
RL J. Virol. 83:4778-4790(2009).
RN [10]
RP REVIEW.
RX PubMed=21655914; DOI=10.1007/s00018-011-0740-4;
RA Szolajska E., Chroboczek J.;
RT "Faithful chaperones.";
RL Cell. Mol. Life Sci. 68:3307-3322(2011).
CC -!- FUNCTION: Protein that inhibits host translation while promoting late
CC viral translation by ribosome shunting. Blocks host cap-dependent
CC translation by binding to eIF4G, displacing MKNK1 from cap initiation
CC complexes and preventing EIF4E phosphorylation. Binds to the tripartite
CC leader sequence of viral late mRNAs and recruits host eIF4G,
CC PABPC1/poly-A binding protein and 40S ribosomes subunits on viral
CC mRNAs, allowing ribosome shunting and efficient translation of late
CC viral mRNAs even though conventional translation via ribosome scanning
CC from the cap has been shut off in the host cell. During assembly, acts
CC as a chaperone protein that helps hexon proteins assembly into trimers
CC (Probable). {ECO:0000255|HAMAP-Rule:MF_04060,
CC ECO:0000305|PubMed:15220445, ECO:0000305|PubMed:15314025,
CC ECO:0000305|PubMed:15827182, ECO:0000305|PubMed:16081097,
CC ECO:0000305|PubMed:7159928}.
CC -!- SUBUNIT: Monomer. Interacts with hexon protein; this interaction allows
CC chaperoning and trimerization of hexon proteins. Interacts (via N-
CC terminus) with host initiation factor EIF4G (via C-terminus). Interacts
CC (via RRM domain) with viral mRNAs that contain the tripartite leader;
CC this interaction allows ribosome shunting and expression of viral late
CC mRNAs. {ECO:0000255|HAMAP-Rule:MF_04060, ECO:0000269|PubMed:15220445,
CC ECO:0000269|PubMed:15314025, ECO:0000269|PubMed:16081097,
CC ECO:0000269|PubMed:7159928}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04060,
CC ECO:0000269|PubMed:14633984}.
CC -!- INDUCTION: Expressed in the late phase of the viral replicative cycle.
CC {ECO:0000255|HAMAP-Rule:MF_04060}.
CC -!- PTM: Might be cleaved by the viral protease. {ECO:0000255|HAMAP-
CC Rule:MF_04060}.
CC -!- PTM: Phosphorylated. Tyrosine phosphorylation enhances preferential
CC binding to tripartite leader mRNAs and allows ribosome shunting.
CC {ECO:0000255|HAMAP-Rule:MF_04060, ECO:0000269|PubMed:15827182}.
CC -!- PTM: Methylated. Asymmetric dimethylation by host PRMT1 of the Arg/Gly-
CC rich region may regulate shutoff protein binding to hexon and promote
CC the capsid assembly in the nucleus. {ECO:0000255|HAMAP-Rule:MF_04060,
CC ECO:0000269|PubMed:19264777}.
CC -!- MISCELLANEOUS: All late proteins expressed from the major late promoter
CC are produced by alternative splicing and alternative polyadenylation of
CC the same gene giving rise to non-overlapping ORFs. A leader sequence is
CC present in the N-terminus of all these mRNAs and is recognized by the
CC viral shutoff protein to provide expression although conventional
CC translation via ribosome scanning from the cap has been shut off in the
CC host cell. {ECO:0000255|HAMAP-Rule:MF_04060}.
CC -!- SIMILARITY: Belongs to the adenoviridae shutoff protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04060}.
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DR EMBL; J01917; AAA92218.1; -; Genomic_DNA.
DR PIR; B03838; WMADL2.
DR RefSeq; AP_000178.1; AC_000007.1.
DR RefSeq; NP_040528.1; NC_001405.1.
DR iPTMnet; P24932; -.
DR GeneID; 2653005; -.
DR KEGG; vg:2653005; -.
DR Proteomes; UP000008167; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019060; P:intracellular transport of viral protein in host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-UniRule.
DR GO; GO:0039704; P:viral translational shunt; IDA:UniProtKB.
DR HAMAP; MF_04060; ADV_SHUT; 1.
DR InterPro; IPR003381; L4.
DR Pfam; PF02438; Adeno_100; 1.
PE 1: Evidence at protein level;
KW Chaperone; Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host translation shutoff by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host-virus interaction;
KW Inhibition of eukaryotic host translation factors by virus; Late protein;
KW Methylation; Phosphoprotein; Reference proteome; RNA-binding;
KW Translational shunt; Transport.
FT CHAIN 1..805
FT /note="Shutoff protein"
FT /id="PRO_0000221855"
FT DOMAIN 348..466
FT /note="RRM"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04060"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 280..345
FT /note="Binding to host EIF4G"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04060"
FT REGION 684..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..53
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 54..88
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 785..805
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 365
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04060,
FT ECO:0000269|PubMed:15827182"
FT MOD_RES 682
FT /note="Phosphotyrosine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04060,
FT ECO:0000269|PubMed:15827182"
FT MUTAGEN 365
FT /note="Y->F: Almost complete inhibition of ribosome
FT shunting; when associated with F-682."
FT /evidence="ECO:0000269|PubMed:15827182"
FT MUTAGEN 682
FT /note="Y->F: Almost complete inhibition of ribosome
FT shunting; when associated with F-365."
FT /evidence="ECO:0000269|PubMed:15827182"
SQ SEQUENCE 805 AA; 90138 MW; 4C772CF19CA4C573 CRC64;
MESVEKEDSL TAPFEFATTA STDAANAPTT FPVEAPPLEE EEVIIEQDPG FVSEDDEDRS
VPTEDKKQDQ DDAEANEEQV GRGDQRHGDY LDVGDDVLLK HLQRQCAIIC DALQERSDVP
LAIADVSLAY ERHLFSPRVP PKRQENGTCE PNPRLNFYPV FAVPEVLATY HIFFQNCKIP
LSCRANRSRA DKQLALRQGA VIPDIASLDE VPKIFEGLGR DEKRAANALQ QENSENESHC
GVLVELEGDN ARLAVLKRSI EVTHFAYPAL NLPPKVMSTV MSELIVRRAR PLERDANLQE
QTEEGLPAVG DEQLARWLET REPADLEERR KLMMAAVLVT VELECMQRFF ADPEMQRKLE
ETLHYTFRQG YVRQACKISN VELCNLVSYL GILHENRLGQ NVLHSTLKGE ARRDYVRDCV
YLFLCYTWQT AMGVWQQCLE ERNLKELQKL LKQNLKDLWT AFNERSVAAH LADIIFPERL
LKTLQQGLPD FTSQSMLQNF RNFILERSGI LPATCCALPS DFVPIKYREC PPPLWGHCYL
LQLANYLAYH SDIMEDVSGD GLLECHCRCN LCTPHRSLVC NSQLLSESQI IGTFELQGPS
PDEKSAAPGL KLTPGLWTSA YLRKFVPEDY HAHEIRFYED QSRPPNAELT ACVITQGHIL
GQLQAINKAR QEFLLRKGRG VYLDPQSGEE LNPIPPPPQP YQQPRALASQ DGTQKEAAAA
AAATHGRGGI LGQSGRGGFG RGGGDDGRLG QPRRSFRGRR GVRRNTVTLG RIPLAGAPEI
GNRSQHRYNL RSSGAAGTAC SPTQP
