SH_HRSVA
ID SH_HRSVA Reviewed; 64 AA.
AC P0DOE5; P04852;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 1.
DT 02-JUN-2021, entry version 27.
DE RecName: Full=Small hydrophobic protein {ECO:0000303|PubMed:17494063, ECO:0000303|PubMed:22621926};
DE AltName: Full=Small protein 1A;
GN Name=SH {ECO:0000303|PubMed:17494063, ECO:0000303|PubMed:22621926};
GN Synonyms=1A {ECO:0000303|PubMed:2649692, ECO:0000303|PubMed:3879976};
OS Human respiratory syncytial virus A (strain A2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX NCBI_TaxID=11259;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3879976; DOI=10.1016/0042-6822(85)90259-4;
RA Collins P.L., Wertz G.W.;
RT "The 1A protein gene of human respiratory syncytial virus: nucleotide
RT sequence of the mRNA and a related polycistronic transcript.";
RL Virology 141:283-291(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7747420; DOI=10.1006/viro.1995.1178;
RA Connors M., Crowe J.E. Jr., Firestone C.Y., Murphy B.R., Collins P.L.;
RT "A cold-passaged, attenuated strain of human respiratory syncytial virus
RT contains mutations in the F and L genes.";
RL Virology 208:478-484(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9035372; DOI=10.1007/bf00366988;
RA Crowe J.E. Jr., Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R.;
RT "Acquisition of the ts phenotype by a chemically mutagenized cold-passaged
RT human respiratory syncytial virus vaccine candidate results from the
RT acquisition of a single mutation in the polymerase (L) gene.";
RL Virus Genes 13:269-273(1996).
RN [4]
RP ALTERNATIVE INITIATION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RC STRAIN=A2;
RX PubMed=2649692; DOI=10.1128/jvi.63.5.2019-2029.1989;
RA Olmsted R.A., Collins P.L.;
RT "The 1A protein of respiratory syncytial virus is an integral membrane
RT protein present as multiple, structurally distinct species.";
RL J. Virol. 63:2019-2029(1989).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=A2;
RX PubMed=15105532; DOI=10.1099/vir.0.19769-0;
RA Rixon H.W., Brown G., Aitken J., McDonald T., Graham S., Sugrue R.J.;
RT "The small hydrophobic (SH) protein accumulates within lipid-raft
RT structures of the Golgi complex during respiratory syncytial virus
RT infection.";
RL J. Gen. Virol. 85:1153-1165(2004).
RN [6]
RP PHOSPHORYLATION.
RC STRAIN=A2;
RX PubMed=15659757; DOI=10.1099/vir.0.80563-0;
RA Rixon H.W., Brown G., Murray J.T., Sugrue R.J.;
RT "The respiratory syncytial virus small hydrophobic protein is
RT phosphorylated via a mitogen-activated protein kinase p38-dependent
RT tyrosine kinase activity during virus infection.";
RL J. Gen. Virol. 86:375-384(2005).
RN [7]
RP FUNCTION.
RC STRAIN=A2;
RX PubMed=17494063; DOI=10.1128/jvi.02717-06;
RA Fuentes S., Tran K.C., Luthra P., Teng M.N., He B.;
RT "Function of the respiratory syncytial virus small hydrophobic protein.";
RL J. Virol. 81:8361-8366(2007).
RN [8]
RP INTERACTION WITH GLYCOPROTEIN G.
RC STRAIN=A2;
RX PubMed=18036342; DOI=10.1016/j.bbrc.2007.11.042;
RA Low K.W., Tan T., Ng K., Tan B.H., Sugrue R.J.;
RT "The RSV F and G glycoproteins interact to form a complex on the surface of
RT infected cells.";
RL Biochem. Biophys. Res. Commun. 366:308-313(2008).
RN [9]
RP FUNCTION, AND HOMOPENTAMERIZATION.
RX PubMed=18369195; DOI=10.1110/ps.073366208;
RA Gan S.W., Ng L., Lin X., Gong X., Torres J.;
RT "Structure and ion channel activity of the human respiratory syncytial
RT virus (hRSV) small hydrophobic protein transmembrane domain.";
RL Protein Sci. 17:813-820(2008).
RN [10]
RP FUNCTION, SUBUNIT, ACTIVITY REGULATION, MUTAGENESIS OF HIS-22 AND HIS-51,
RP AND TOPOLOGY.
RC STRAIN=S-2;
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 [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23229815; DOI=10.1136/thoraxjnl-2012-202182;
RA Triantafilou K., Kar S., Vakakis E., Kotecha S., Triantafilou M.;
RT "Human respiratory syncytial virus viroporin SH: a viral recognition
RT pathway used by the host to signal inflammasome activation.";
RL Thorax 68:66-75(2013).
RN [12]
RP SUBCELLULAR LOCATION, INTERACTION WITH BCAP31, AND REGION.
RC STRAIN=S-2;
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 [13]
RP FUNCTION.
RX PubMed=27817112; DOI=10.1007/s00894-016-3150-6;
RA Araujo G.C., Silva R.H., Scott L.P., Araujo A.S., Souza F.P.,
RA de Oliveira R.J.;
RT "Structure and functional dynamics characterization of the ion channel of
RT the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH)
RT transmembrane domain by combining molecular dynamics with excited normal
RT modes.";
RL J. Mol. Model. 22:286-286(2016).
RN [14]
RP STRUCTURE BY NMR OF 38-64, FUNCTION, MUTAGENESIS OF ILE-21; HIS-22; ALA-39
RP AND HIS-51, ACTIVITY REGULATION, AND REGION.
RC STRAIN=S-2;
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 (PubMed:18369195, PubMed:22621926, PubMed:25100835,
CC PubMed:27817112). 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
CC (PubMed:15105532, PubMed:23229815). May enhance host membrane
CC permeability and disrupt cellular ion homeostasis, which can be sensed
CC as damage-associated molecular patterns/danger signals, triggering
CC NLRP3 inflammasome activation and inflammatory immune response
CC (PubMed:23229815). Also inhibits host TNFA-mediated signaling pathway
CC and may delay apoptosis, allowing time for the virus to replicate
CC (PubMed:17494063). {ECO:0000269|PubMed:15105532,
CC ECO:0000269|PubMed:17494063, ECO:0000269|PubMed:18369195,
CC ECO:0000269|PubMed:22621926, ECO:0000269|PubMed:23229815,
CC ECO:0000269|PubMed:25100835, ECO:0000269|PubMed:27817112}.
CC -!- ACTIVITY REGULATION: Channel activity is inhibited by copper
CC (PubMed:22621926). Also inhibited by small-molecule pyronin B
CC (PubMed:25100835). {ECO:0000269|PubMed:22621926,
CC ECO:0000269|PubMed:25100835}.
CC -!- SUBUNIT: Homopentamer forming a funnel-like pore (PubMed:18036342,
CC PubMed:18369195, PubMed:22621926). Interacts with glycoprotein G; this
CC interaction occurs on the surface of virion particles and infected
CC cells (PubMed:18036342). Interacts with host BCAP31 (via C-terminus);
CC this interaction is direct (PubMed:25854864).
CC {ECO:0000269|PubMed:18036342, ECO:0000269|PubMed:18369195,
CC ECO:0000269|PubMed:22621926, ECO:0000269|PubMed:25854864}.
CC -!- INTERACTION:
CC P0DOE5; P0DOE5: SH; NbExp=4; IntAct=EBI-7973466, EBI-7973466;
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000305|PubMed:2649692};
CC Single-pass type II membrane protein {ECO:0000305}. Host cell membrane
CC {ECO:0000269|PubMed:2649692}; Single-pass type II membrane protein
CC {ECO:0000305}. Host Golgi apparatus membrane
CC {ECO:0000269|PubMed:15105532, ECO:0000269|PubMed:23229815}; Single-pass
CC type II membrane protein. Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15105532, ECO:0000269|PubMed:25854864}; Single-pass
CC type II membrane protein. Note=Present in very small amount in the
CC virion. Detected in lipid rafts of host Golgi apparatus membrane.
CC {ECO:0000269|PubMed:15105532}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=SH {ECO:0000269|PubMed:2649692};
CC IsoId=P0DOE5-1; Sequence=Displayed;
CC Name=SHt {ECO:0000269|PubMed:2649692};
CC IsoId=P0DOE5-2; Sequence=VSP_029056;
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 (PubMed:2649692). Of these different forms, SH0 is by far
CC the most abundant protein detected during virus infection
CC (PubMed:2649692). {ECO:0000269|PubMed:2649692}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000269|PubMed:15659757}.
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:0000269|PubMed:2649692}.
CC -!- SIMILARITY: Belongs to the orthopneumovirus small hydrophobic protein
CC family. {ECO:0000305}.
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DR EMBL; M11486; AAB59856.1; -; Genomic_RNA.
DR EMBL; U50362; AAB86662.1; -; Genomic_RNA.
DR EMBL; U50363; AAB86674.1; -; Genomic_RNA.
DR EMBL; U63644; AAC55968.1; -; Genomic_RNA.
DR PIR; A04031; P1NZAR.
DR PDB; 2NB7; NMR; -; A=1-14.
DR PDB; 2NB8; NMR; -; A=38-64.
DR PDBsum; 2NB7; -.
DR PDBsum; 2NB8; -.
DR SMR; P0DOE5; -.
DR MINT; P0DOE5; -.
DR Proteomes; UP000007678; Genome.
DR Proteomes; UP000134464; Genome.
DR Proteomes; UP000181145; Genome.
DR Proteomes; UP000181262; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0044178; C:host cell Golgi membrane; IDA:UniProtKB.
DR GO; GO:0020002; C:host cell plasma membrane; IDA:UniProtKB.
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:0005261; F:cation channel activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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 GO; GO:0019050; P:suppression by virus of host apoptotic process; IMP:UniProtKB.
DR InterPro; IPR005327; SHP.
DR Pfam; PF03579; SHP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activation of host caspases by virus; Alternative initiation;
KW Glycoprotein; Host cell membrane; Host endoplasmic reticulum;
KW Host Golgi apparatus; Host membrane; Host-virus interaction; Ion channel;
KW Ion transport; Membrane; Modulation of host cell apoptosis by virus;
KW Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Transport; Viral ion channel; Virion.
FT CHAIN 1..64
FT /note="Small hydrophobic protein"
FT /id="PRO_0000142869"
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:0000269|PubMed:27817112"
FT SITE 51
FT /note="Involved in opening and closing mechanism of the
FT pentameric structure"
FT /evidence="ECO:0000269|PubMed:27817112"
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_029056"
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. Reduces 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"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:2NB7"
FT HELIX 6..13
FT /evidence="ECO:0007829|PDB:2NB7"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:2NB8"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2NB8"
SQ SEQUENCE 64 AA; 7536 MW; 02C92E27F227E66B CRC64;
MENTSITIEF SSKFWPYFTL IHMITTIISL LIIISIMIAI LNKLCEYNVF HNKTFELPRA
RVNT
