SH_HRSS2
ID SH_HRSS2 Reviewed; 64 AA.
AC P0DOE4; P04852;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Small hydrophobic protein {ECO:0000303|PubMed:22621926};
DE AltName: Full=Small protein 1A;
GN Name=SH {ECO:0000303|PubMed:22621926};
GN Synonyms=1A {ECO:0000250|UniProtKB:P0DOE5};
OS Human respiratory syncytial virus A (strain S-2) (HRSV-S2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX NCBI_TaxID=410078;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9032893; DOI=10.1016/s0264-410x(96)00136-3;
RA Tolley K.P., Marriott A.C., Simpson A., Plows D.J., Matthews D.A.,
RA Longhurst S.J., Evans J.E., Johnson J.L., Cane P.A., Easton A.J.,
RA Pringle C.R.;
RT "Identification of mutations contributing to the reduced virulence of a
RT modified strain of respiratory syncytial virus.";
RL Vaccine 14:1637-1646(1996).
RN [2]
RP FUNCTION, HOMOPENTAMERIZATION, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP MUTAGENESIS OF HIS-22 AND HIS-51, AND TOPOLOGY.
RX PubMed=22621926; DOI=10.1074/jbc.m111.332791;
RA Gan S.W., Tan E., Lin X., Yu D., Wang J., Tan G.M., Vararattanavech A.,
RA Yeo C.Y., Soon C.H., Soong T.W., Pervushin K., Torres J.;
RT "The small hydrophobic protein of the human respiratory syncytial virus
RT forms pentameric ion channels.";
RL J. Biol. Chem. 287:24671-24689(2012).
RN [3]
RP SUBCELLULAR LOCATION, INTERACTION WITH BCAP31, AND REGION.
RX PubMed=25854864; DOI=10.1016/j.virol.2015.03.034;
RA Li Y., Jain N., Limpanawat S., To J., Quistgaard E.M., Nordlund P.,
RA Thanabalu T., Torres J.;
RT "Interaction between human BAP31 and respiratory syncytial virus small
RT hydrophobic (SH) protein.";
RL Virology 482:105-110(2015).
RN [4]
RP STRUCTURE BY NMR OF 38-64, FUNCTION, MUTAGENESIS OF ILE-21; HIS-22; ALA-39
RP AND HIS-51, ACTIVITY REGULATION, AND REGION.
RX PubMed=25100835; DOI=10.1128/jvi.00839-14;
RA Li Y., To J., Verdia-Baguena C., Dossena S., Surya W., Huang M.,
RA Paulmichl M., Liu D.X., Aguilella V.M., Torres J.;
RT "Inhibition of the human respiratory syncytial virus small hydrophobic
RT protein and structural variations in a bicelle environment.";
RL J. Virol. 88:11899-11914(2014).
CC -!- FUNCTION: Viroporin that forms a homopentameric ion channel displaying
CC low ion selectivity. May play a role in virus morphogenesis and
CC pathogenicity at various stages of the viral life cycle. Accumulates at
CC the membrane of the Golgi apparatus in infected cells and may
CC facilitate virus release by modifying the secretory pathway. May
CC enhance host membrane permeability and disrupt cellular ion
CC homeostasis, which can be sensed as damage-associated molecular
CC patterns/danger signals, triggering NLRP3 inflammasome activation and
CC inflammatory immune response. Also inhibits host TNFA-mediated
CC signaling pathway and may delay apoptosis, allowing time for the virus
CC to replicate. {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- ACTIVITY REGULATION: Channel activity is inhibited by copper. Also
CC inhibited by small-molecule pyronin B. {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- SUBUNIT: Homopentamer forming a funnel-like pore. Interacts with
CC glycoprotein G; this interaction occurs on the surface of virion
CC particles and infected cells. Interacts with host BCAP31 (via C-
CC terminus); this interaction is direct. {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000250|UniProtKB:P0DOE5};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P0DOE5}.
CC Host cell membrane {ECO:0000250|UniProtKB:P0DOE5}; Single-pass type II
CC membrane protein {ECO:0000250|UniProtKB:P0DOE5}. Host Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:P0DOE5}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:P0DOE5}. Host endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:P0DOE5}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:P0DOE5}. Note=Present in very small
CC amount in the virion. Detected in lipid rafts of host Golgi apparatus
CC membrane. {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=SH {ECO:0000250|UniProtKB:P0DOE5};
CC IsoId=P0DOE4-1; Sequence=Displayed;
CC Name=SHt {ECO:0000250|UniProtKB:P0DOE5};
CC IsoId=P0DOE4-2; Sequence=VSP_058891;
CC -!- PTM: Four species of SH have been detected in infected cell cytoplasm:
CC a 7.5 kDa non-glycosylated form (SH0), a 13-15 kDa form that contains
CC one or two N-linked carbohydrate side chains of the high-mannose type
CC (SHg), a 21-30 kDa polylactosaminoglycan-modified form of the protein
CC (SHp), and the isoform generated by alternative translational
CC initiation. Of these different forms, SH0 is by far the most abundant
CC protein detected during virus infection.
CC {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- MISCELLANEOUS: [Isoform SHt]: Produced by alternative initiation at
CC Met-23 of isoform SH and gives rise to a 4.6 kDa truncated form of the
CC non-glycosylated protein. {ECO:0000250|UniProtKB:P0DOE5}.
CC -!- SIMILARITY: Belongs to the orthopneumovirus small hydrophobic protein
CC family. {ECO:0000305}.
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DR EMBL; U39661; AAC57035.1; -; Genomic_RNA.
DR EMBL; U39662; AAC57025.1; -; Genomic_RNA.
DR RefSeq; NP_044594.1; NC_001803.1.
DR SMR; P0DOE4; -.
DR GeneID; 1494473; -.
DR KEGG; vg:1494473; -.
DR Proteomes; UP000101899; Genome.
DR Proteomes; UP000113393; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
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:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; IDA:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; IDA:UniProtKB.
DR GO; GO:0039651; P:induction by virus of host cysteine-type endopeptidase activity involved in apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR InterPro; IPR005327; SHP.
DR Pfam; PF03579; SHP; 1.
PE 1: Evidence at protein level;
KW Activation of host caspases by virus; Alternative initiation; Glycoprotein;
KW Host cell membrane; Host endoplasmic reticulum; Host Golgi apparatus;
KW Host membrane; Host-virus interaction; Ion channel; Ion transport;
KW Membrane; Modulation of host cell apoptosis by virus; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Transport; Viral ion channel; Virion.
FT CHAIN 1..64
FT /note="Small hydrophobic protein"
FT /id="PRO_0000439635"
FT TOPO_DOM 1..20
FT /note="Intravirion"
FT /evidence="ECO:0000305|PubMed:22621926"
FT TRANSMEM 21..44
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000269|PubMed:22621926"
FT TOPO_DOM 45..64
FT /note="Virion surface"
FT /evidence="ECO:0000269|PubMed:22621926"
FT REGION 6..15
FT /note="Interaction with host BCAP31"
FT /evidence="ECO:0000269|PubMed:25854864"
FT REGION 38..43
FT /note="Interaction with small-molecule inhibitor"
FT /evidence="ECO:0000269|PubMed:25100835"
FT SITE 22
FT /note="Involved in opening and closing mechanism of the
FT pentameric structure"
FT /evidence="ECO:0000250|UniProtKB:P0DOE5"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..22
FT /note="Missing (in isoform SHt)"
FT /evidence="ECO:0000305"
FT /id="VSP_058891"
FT MUTAGEN 21
FT /note="I->F: Reduces channel activity."
FT /evidence="ECO:0000269|PubMed:25100835"
FT MUTAGEN 21
FT /note="I->Y: Reduces the effect of small-molecule
FT inhibitor."
FT /evidence="ECO:0000269|PubMed:25100835"
FT MUTAGEN 22
FT /note="H->A: Impairs channel activity; when associated with
FT A-51."
FT /evidence="ECO:0000269|PubMed:22621926"
FT MUTAGEN 22
FT /note="H->F: Impairs channel activity; when associated with
FT F-51. Abolishes the effect of small-molecule inhibitor."
FT /evidence="ECO:0000269|PubMed:22621926,
FT ECO:0000269|PubMed:25100835"
FT MUTAGEN 39
FT /note="A->S: Abolishes the effect of small-molecule
FT inhibitor."
FT /evidence="ECO:0000269|PubMed:25100835"
FT MUTAGEN 51
FT /note="H->A: Impairs channel activity; when associated with
FT A-22."
FT /evidence="ECO:0000269|PubMed:22621926"
FT MUTAGEN 51
FT /note="H->F: Impairs channel activity; when associated with
FT F-22."
FT /evidence="ECO:0000269|PubMed:22621926,
FT ECO:0000269|PubMed:25100835"
SQ SEQUENCE 64 AA; 7536 MW; 02C92E27F227E66B CRC64;
MENTSITIEF SSKFWPYFTL IHMITTIISL LIIISIMIAI LNKLCEYNVF HNKTFELPRA
RVNT
