C_SENDH
ID C_SENDH Reviewed; 215 AA.
AC P04861;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 23-FEB-2022, entry version 70.
DE RecName: Full=Protein C';
GN Name=P/V/C;
OS Sendai virus (strain Harris) (SeV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Paramyxoviridae; Orthoparamyxovirinae;
OC Respirovirus.
OX NCBI_TaxID=11196;
OH NCBI_TaxID=10144; Cavia cutleri (Guinea pig).
OH NCBI_TaxID=36483; Cricetidae sp. (Hamster).
OH NCBI_TaxID=10090; Mus musculus (Mouse).
OH NCBI_TaxID=10116; Rattus norvegicus (Rat).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6317203; DOI=10.1016/0092-8674(83)90115-0;
RA Giorgi C., Blumberg B.M., Kolakofsky D.;
RT "Sendai virus contains overlapping genes expressed from a single mRNA.";
RL Cell 35:829-836(1983).
RN [2]
RP PROTEIN SEQUENCE OF N-TERMINUS, AND ALTERNATIVE INITIATION.
RX PubMed=2834203; DOI=10.1002/j.1460-2075.1988.tb02806.x;
RA Curran J., Kolakofsky D.;
RT "Ribosomal initiation from an ACG codon in the Sendai virus P/C mRNA.";
RL EMBO J. 7:245-251(1988).
RN [3]
RP MUTAGENESIS OF PHE-181.
RX PubMed=9400614; DOI=10.1006/viro.1997.8836;
RA Garcin D., Itoh M., Kolakofsky D.;
RT "A point mutation in the Sendai virus accessory C proteins attenuates
RT virulence for mice, but not virus growth in cell culture.";
RL Virology 238:424-431(1997).
RN [4]
RP PROTEOLYTIC PROCESSING.
RX PubMed=14739274; DOI=10.1074/jbc.m312391200;
RA de Breyne S., Monney R.S., Curran J.;
RT "Proteolytic processing and translation initiation: two independent
RT mechanisms for the expression of the Sendai virus Y proteins.";
RL J. Biol. Chem. 279:16571-16580(2004).
RN [5]
RP DOMAIN.
RX PubMed=15280488; DOI=10.1128/jvi.78.16.8799-8811.2004;
RA Garcin D., Marq J.B., Iseni F., Martin S., Kolakofsky D.;
RT "A short peptide at the amino terminus of the Sendai virus C protein acts
RT as an independent element that induces STAT1 instability.";
RL J. Virol. 78:8799-8811(2004).
CC -!- FUNCTION: The different products prevent the establishment of cellular
CC antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta)
CC and IFN-gamma signaling pathways. They inhibit IFN-alpha/beta induced
CC tyrosine phosphorylation of STAT1 and STAT2. Blocking the IFN-
CC alpha/beta pathway requires binding to STAT1 in the cytoplasm. They
CC inhibit IFN-gamma induced serine phosphorylation of STAT1. Block the
CC IFN-gamma pathway by binding to and stabilizing the parallel form of
CC the STAT1 dimer, further inducing high-molecular-weight complex
CC formation and inhibition of transcription by IFN-gamma. May also have a
CC role in preventing the cell to enter apoptosis. Modulate regulation of
CC viral transcription and replication. Overexpression inhibits the viral
CC RNA polymerase. The absence of all C', C, Y1 and Y2 proteins leads to
CC viral delayed growth. Plays an important role in virion particles
CC release. Modulates virion shape. {ECO:0000250|UniProtKB:P04862}.
CC -!- SUBUNIT: The different isoforms interact (via C-terminus) with
CC unphosphorylated and phosphorylated human STAT1 (via N-terminus),
CC favoring the formation of parallel STAT1 homodimers. The different
CC isoforms do not interact with host STAT2. C protein interacts with L
CC protein; this interaction has an inhibitory effect on viral
CC transcription and replication. {ECO:0000250|UniProtKB:P04862}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:P04862}.
CC Note=Protein C' seems to localize around the Golgi.
CC {ECO:0000250|UniProtKB:P04862}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=4;
CC Name=C' {ECO:0000303|PubMed:2834203};
CC IsoId=P04861-1; Sequence=Displayed;
CC Name=C {ECO:0000303|PubMed:2834203};
CC IsoId=P04861-2; Sequence=VSP_018933;
CC Name=Y1 {ECO:0000303|PubMed:2834203};
CC IsoId=P04861-3; Sequence=VSP_018934;
CC Name=Y2 {ECO:0000303|PubMed:2834203};
CC IsoId=P04861-4; Sequence=VSP_018935;
CC -!- DOMAIN: The disordered region at the N-terminus is involved in C
CC protein self-degradation in trans. This self-degradation of C protein
CC may play a role in the regulation of viral RNA synthesis. The
CC disordered region at the N-terminus is also involved in the host STAT1
CC degradation in order to counteract the host innate antiviral response.
CC {ECO:0000269|PubMed:15280488}.
CC -!- PTM: Y1 and Y2 proteins are produced not only by alternative
CC initiation, but also by proteolytic cleavage of C'. Only alternative
CC initiation is detected in vitro, whereas in vivo cleavage seems to be
CC predominant. {ECO:0000269|PubMed:14739274}.
CC -!- MISCELLANEOUS: The C protein is found in virion at a ratio of
CC approximately 40 molecules per virion, presumably associated with the
CC nucleocapsid. {ECO:0000250|UniProtKB:P04862}.
CC -!- MISCELLANEOUS: The P/V/C gene has two overlapping open reading frames.
CC One encodes the P/V/W proteins and the other the C/Y proteins.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform C']: The initiator methionine is coded by an
CC unusual start codon ACG. {ECO:0000269|PubMed:2834203}.
CC -!- MISCELLANEOUS: [Isoform C]: Most abundant isoform in infected cells.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the respirovirus protein C family.
CC {ECO:0000305}.
CC -!- CAUTION: The C' protein uses an unusual ACG start codon. {ECO:0000305}.
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DR PIR; B28985; MNNZHS.
DR SMR; P04861; -.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; ISS:UniProtKB.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR002608; Paramyxo_C.
DR Pfam; PF01692; Paramyxo_C; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Direct protein sequencing; Host cytoplasm;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host STAT1 by virus; Inhibition of host STAT2 by virus;
KW Interferon antiviral system evasion; Viral immunoevasion.
FT INIT_MET 1
FT /note="Removed; by host"
FT CHAIN 2..215
FT /note="Protein C'"
FT /id="PRO_0000039396"
FT REGION 12..34
FT /note="Disordered"
FT /evidence="ECO:0000269|PubMed:15280488"
FT REGION 15..22
FT /note="Involved in self-degradation and in host STAT1
FT degradation"
FT /evidence="ECO:0000269|PubMed:15280488"
FT REGION 51..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 51..66
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform Y2)"
FT /evidence="ECO:0000269|PubMed:2834203, ECO:0000305"
FT /id="VSP_018935"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform Y1)"
FT /evidence="ECO:0000269|PubMed:2834203, ECO:0000305"
FT /id="VSP_018934"
FT VAR_SEQ 1..11
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000269|PubMed:2834203, ECO:0000305"
FT /id="VSP_018933"
FT MUTAGEN 181
FT /note="F->S: Complete loss of virulence and STAT1-binding."
FT /evidence="ECO:0000269|PubMed:9400614"
SQ SEQUENCE 215 AA; 25187 MW; 35AE39B84E081A6C CRC64;
MASATLTAWI KMPSFLKKIL KLRGRRQEEE SRSRMLSDSS MLSCRVNQLT SEGTEAGSTT
PSTLPKDQAL PIEPKVRAKE KSQHRRPKII DQVRRVESLG EQASQRQKHM LETLINKIYT
GPLGEELVQT LYLRIWAMEE TPESLKILQM REDIRDQVLK MKTERWLRTL IRGEKTKLKD
FQKRYEEVHP YLMKEKVEQV IMEEAWSLAA HIVQE
