ID   HOLIN_BPP21             Reviewed;          71 AA.
AC   P27360;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   12-AUG-2020, entry version 53.
DE   RecName: Full=Antiholin {ECO:0000303|PubMed:10361276};
GN   Name=S;
OS   Enterobacteria phage P21 (Bacteriophage 21) (Bacteriophage P21).
OC   Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC   Caudovirales; Siphoviridae; Lambdavirus.
OX   NCBI_TaxID=10711;
OH   NCBI_TaxID=562; Escherichia coli.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], MUTAGENESIS OF MET-1 AND MET-4, SUBUNIT,
RP   AND ALTERNATIVE INITIATION.
RX   PubMed=2019562; DOI=10.1128/jb.173.9.2897-2905.1991;
RA   Bonovich M.T., Young R.;
RT   "Dual start motif in two lambdoid S genes unrelated to lambda S.";
RL   J. Bacteriol. 173:2897-2905(1991).
RN   [2]
RP   CHARACTERIZATION, ALTERNATIVE INITIATION, FUNCTION (ISOFORM ANTIHOLIN), AND
RP   MUTAGENESIS OF LYS-2.
RX   PubMed=10361276; DOI=10.1046/j.1365-2958.1999.01385.x;
RA   Barenboim M., Chang C.Y., dib Hajj F., Young R.;
RT   "Characterization of the dual start motif of a class II holin gene.";
RL   Mol. Microbiol. 32:715-727(1999).
RN   [3]
RP   FUNCTION (ISOFORM HOLIN).
RX   PubMed=17827300; DOI=10.1128/jb.00847-07;
RA   Park T., Struck D.K., Dankenbring C.A., Young R.;
RT   "The pinholin of lambdoid phage 21: control of lysis by membrane
RT   depolarization.";
RL   J. Bacteriol. 189:9135-9139(2007).
RN   [4]
RP   FUNCTION (ISOFORM HOLIN), SUBUNIT, AND TOPOLOGY.
RX   PubMed=19861547; DOI=10.1073/pnas.0907941106;
RA   Pang T., Savva C.G., Fleming K.G., Struck D.K., Young R.;
RT   "Structure of the lethal phage pinhole.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:18966-18971(2009).
RN   [5]
RP   FUNCTION (ISOFORM HOLIN).
RX   PubMed=23671069; DOI=10.1073/pnas.1222283110;
RA   Pang T., Fleming T.C., Pogliano K., Young R.;
RT   "Visualization of pinholin lesions in vivo.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:E2054-E2063(2013).
RN   [6]
RP   DOMAIN.
RX   PubMed=30528914; DOI=10.1016/j.ab.2018.12.003;
RA   Drew D.L. Jr., Ahammad T., Serafin R.A., Butcher B.J., Clowes K.R.,
RA   Drake Z., Sahu I.D., McCarrick R.M., Lorigan G.A.;
RT   "Solid phase synthesis and spectroscopic characterization of the active and
RT   inactive forms of bacteriophage S21 pinholin protein.";
RL   Anal. Biochem. 567:14-20(2019).
CC   -!- FUNCTION: [Isoform Holin]: Accumulates harmlessly in the cytoplasmic
CC       membrane until it reaches a critical concentration that triggers the
CC       formation of nanometer-scale pores (pinholes) causing host cell
CC       membrane depolarization and endolysin refolding and release into the
CC       periplasmic space (PubMed:19861547, PubMed:17827300, PubMed:23671069).
CC       Once the pinholin has permeabilized the host cell membrane, the SAR-
CC       endolysin is released into the periplasm and breaks down the
CC       peptidoglycan layer (PubMed:19861547, PubMed:17827300). Determines the
CC       precise timing of host cell lysis (PubMed:23671069). Participates with
CC       the SAR-endolysin and spanin proteins in the sequential events which
CC       lead to the programmed host cell lysis releasing the mature viral
CC       particles from the host cell (Probable) (PubMed:17827300).
CC       {ECO:0000269|PubMed:17827300, ECO:0000269|PubMed:19861547,
CC       ECO:0000269|PubMed:23671069, ECO:0000305|PubMed:10361276}.
CC   -!- FUNCTION: [Isoform Antiholin]: Counteracts the aggregation of the holin
CC       molecules and thus of pore formation. {ECO:0000305|PubMed:10361276}.
CC   -!- SUBUNIT: [Isoform Holin]: Homoheptamer; forms small heptameric channels
CC       of about 2 nm (pinholes) (PubMed:19861547). Interacts with isoform
CC       Antiholin; this interaction blocks the holin homomultimerization and
CC       delays host cell lysis (Probable). {ECO:0000269|PubMed:19861547,
CC       ECO:0000305|PubMed:2019562}.
CC   -!- INTERACTION:
CC       P27360; P27360: S; NbExp=4; IntAct=EBI-15616242, EBI-15616242;
CC   -!- SUBCELLULAR LOCATION: Host cell inner membrane
CC       {ECO:0000250|UniProtKB:P03705}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Classified as a class II holin.
CC       {ECO:0000303|PubMed:10361276, ECO:0000303|PubMed:2019562}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Antiholin {ECO:0000303|PubMed:10361276,
CC       ECO:0000303|PubMed:2019562}; Synonyms=S71;
CC         IsoId=P27360-1; Sequence=Displayed;
CC       Name=Holin {ECO:0000303|PubMed:10361276, ECO:0000303|PubMed:2019562};
CC       Synonyms=S68, Pinholin;
CC         IsoId=P27360-2; Sequence=VSP_058889;
CC   -!- DOMAIN: The N-terminal transmembrane domain seems to be externalized
CC       during the pinhole formation. {ECO:0000269|PubMed:30528914}.
CC   -!- MISCELLANEOUS: [Isoform Holin]: Antiholin and Holin ratio is about 1:2.
CC       {ECO:0000269|PubMed:10361276}.
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DR   EMBL; M65239; AAA32349.1; -; Genomic_DNA.
DR   SMR; P27360; -.
DR   DIP; DIP-49009N; -.
DR   TCDB; 1.E.1.1.1; the p21 holin s (p21 holin) family.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0034291; F:canonical holin activity; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR   GO; GO:0044659; P:viral release from host cell by cytolysis; IDA:UniProtKB.
DR   InterPro; IPR007054; Lysis_S.
DR   Pfam; PF04971; Phage_holin_2_1; 1.
DR   PIRSF; PIRSF030786; Lysis_S; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; Cytolysis; Host cell inner membrane;
KW   Host cell lysis by virus; Host cell membrane; Host membrane; Membrane;
KW   Transmembrane; Transmembrane helix; Viral release from host cell.
FT   CHAIN           1..71
FT                   /note="Antiholin"
FT                   /id="PRO_0000077654"
FT   TOPO_DOM        1..6
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:19861547"
FT   TRANSMEM        7..27
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        28..37
FT                   /note="Periplasmic"
FT                   /evidence="ECO:0000305|PubMed:19861547"
FT   TRANSMEM        38..58
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        59..71
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305|PubMed:19861547"
FT   VAR_SEQ         1..3
FT                   /note="Missing (in isoform Holin)"
FT                   /evidence="ECO:0000269|PubMed:2019562"
FT                   /id="VSP_058889"
FT   MUTAGEN         1
FT                   /note="M->L: No effect on lysis activity."
FT                   /evidence="ECO:0000269|PubMed:2019562"
FT   MUTAGEN         2
FT                   /note="K->R,S,T: Decrease in lysis inhibition by isoform
FT                   Antiholin."
FT                   /evidence="ECO:0000269|PubMed:10361276"
FT   MUTAGEN         4
FT                   /note="M->L: Complete loss of lysis activity."
FT                   /evidence="ECO:0000269|PubMed:2019562"
SQ   SEQUENCE   71 AA;  7893 MW;  8690A8F25234A3E2 CRC64;
     MKSMDKISTG IAYGTSAGSA GYWFLQWLDQ VSPSQWAAIG VLGSLVLGFL TYLTNLYFKI
     REDRRKAARG E