ID   SHUT_ADE05              Reviewed;         807 AA.
AC   P24933; P03268;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 1.
DT   04-NOV-2026, entry version 91.
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 5 (HAdV-5) (Human adenovirus 5).
OC   Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Polisuviricotina;
OC   Pharingeaviricetes; Rowavirales; Adenoviridae; Mastadenovirus;
OC   Mastadenovirus caesari; Human mastadenovirus C.
OX   NCBI_TaxID=28285;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1727603; DOI=10.1016/0042-6822(92)90082-z;
RA   Chroboczek J., Bieber F., Jacrot B.;
RT   "The sequence of the genome of adenovirus type 5 and its comparison with
RT   the genome of adenovirus type 2.";
RL   Virology 186:280-285(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-593.
RX   PubMed=6117824; DOI=10.1093/nar/9.18.4439;
RA   Kruijer W., van Schaik F.M.A., Sussenbach J.S.;
RT   "Structure and organization of the gene coding for the DNA binding protein
RT   of adenovirus type 5.";
RL   Nucleic Acids Res. 9:4439-4457(1981).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=23142869; DOI=10.1038/nmeth.2227;
RA   Evans V.C., Barker G., Heesom K.J., Fan J., Bessant C., Matthews D.A.;
RT   "De novo derivation of proteomes from transcriptomes for transcript and
RT   protein identification.";
RL   Nat. Methods 9:1207-1211(2012).
RN   [4]
RP   SUBCELLULAR LOCATION.
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   METHYLATION AT ARG/GLY REGION.
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   [6]
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       {ECO:0000255|HAMAP-Rule:MF_04060}.
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}.
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}.
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; M73260; AAA96412.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; X02997; CAA26756.1; -; Genomic_DNA.
DR   PIR; A39449; WMAD15.
DR   RefSeq; AP_000214.1; AC_000008.1.
DR   AlphaFoldDB; P24933; -.
DR   SMR; P24933; -.
DR   IntAct; P24933; 1.
DR   Proteomes; UP000004992; Segment.
DR   GO; GO:0043657; C:host cell; IEA:GOC.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0046729; C:viral procapsid; IMP:CACAO.
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:symbiont-mediated suppression of host gene expression; IEA:UniProtKB-UniRule.
DR   GO; GO:0039606; P:symbiont-mediated suppression of host translation initiation; IEA:UniProtKB-KW.
DR   GO; GO:0039704; P:viral translational shunt; ISS: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..807
FT                   /note="Shutoff protein"
FT                   /id="PRO_0000221856"
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..807
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        16..29
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        59..70
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        79..88
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        726..743
FT                   /note="Gly residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        744..755
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        756..765
FT                   /note="Basic 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   MOD_RES         682
FT                   /note="Phosphotyrosine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04060"
SQ   SEQUENCE   807 AA;  90213 MW;  CF17561EDA7CBADF CRC64;
     MESVEKKDSL TAPSEFATTA STDAANAPTT FPVEAPPLEE EEVIIEQDPG FVSEDDEDRS
     VPTEDKKQDQ DNAEANEEQV GRGDERHGDY LDVGDDVLLK HLQRQCAIIC DALQERSDVP
     LAIADVSLAY ERHLFSPRVP PKRQENGTCE PNPRLNFYPV FAVPEVLATY HIFFQNCKIP
     LSCRANRSRA DKQLALRQGA VIPDIASLNE VPKIFEGLGR DEKRAANALQ QENSENESHS
     GVLVELEGDN ARLAVLKRSI EVTHFAYPAL NLPPKVMSTV MSELIVRRAQ PLERDANLQE
     QTEEGLPAVG DEQLARWLQT REPADLEERR KLMMAAVLVT VELECMQRFF ADPEMQRKLE
     ETLHYTFRQG YVRQACKISN VELCNLVSYL GILHENRLGQ NVLHSTLKGE ARRDYVRDCV
     YLFLCYTWQT AMGVWQQCLE ECNLKELQKL LKQNLKDLWT AFNERSVAAH LADIIFPERL
     LKTLQQGLPD FTSQSMLQNF RNFILERSGI LPATCCALPS DFVPIKYREC PPPLWGHCYL
     LQLANYLAYH SDIMEDVSGD GLLECHCRCN LCTPHRSLVC NSQLLNESQI IGTFELQGPS
     PDEKSAAPGL KLTPGLWTSA YLRKFVPEDY HAHEIRFYED QSRPPNAELT ACVITQGHIL
     GQLQAINKAR QEFLLRKGRG VYLDPQSGEE LNPIPPPPQP YQQQPRALAS QDGTQKEAAA
     AAATHGRGGI LGQSGRGGFG RGGGGHDGRL GEPRRGSFRG RRGVRRNTVT LGRIPLAGAP
     EIGNRFQHGY NLRSSGAAGT ARSPTQP
//