C_SENDN
ID C_SENDN Reviewed; 215 AA.
AC P69738;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 23-FEB-2022, entry version 47.
DE RecName: Full=Protein C';
GN Name=P/V/C;
OS Sendai virus (strain Nagoya) (SeV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Paramyxoviridae; Orthoparamyxovirinae;
OC Respirovirus.
OX NCBI_TaxID=317654;
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].
RA Nishio M.;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=10518019; DOI=10.1016/s0014-5793(99)01241-7;
RA Gotoh B., Takeuchi K., Komatsu T., Yokoo J., Kimura Y., Kurotani A.,
RA Kato A., Nagai Y.;
RT "Knockout of the Sendai virus C gene eliminates the viral ability to
RT prevent the interferon-alpha/beta-mediated responses.";
RL FEBS Lett. 459:205-210(1999).
RN [3]
RP INTERACTION WITH HUMAN STAT1.
RX PubMed=11442634; DOI=10.1046/j.1365-2443.2001.00442.x;
RA Takeuchi K., Komatsu T., Yokoo J., Kato A., Shioda T., Nagai Y., Gotoh B.;
RT "Sendai virus C protein physically associates with Stat1.";
RL Genes Cells 6:545-557(2001).
RN [4]
RP FUNCTION.
RX PubMed=12610111; DOI=10.1128/jvi.77.6.3360-3370.2003;
RA Gotoh B., Takeuchi K., Komatsu T., Yokoo J.;
RT "The STAT2 activation process is a crucial target of Sendai virus C protein
RT for the blockade of alpha interferon signaling.";
RL J. Virol. 77:3360-3370(2003).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF PHE-181.
RX PubMed=14599788; DOI=10.1016/s0042-6822(03)00590-7;
RA Gotoh B., Komatsu T., Takeuchi K., Yokoo J.;
RT "The C-terminal half-fragment of the Sendai virus C protein prevents the
RT gamma-activated factor from binding to a gamma-activated sequence site.";
RL Virology 316:29-40(2003).
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 (By similarity).
CC May also have a role in preventing the cell to enter apoptosis.
CC Modulate regulation of viral transcription and replication.
CC Overexpression inhibits the viral RNA polymerase. The absence of all
CC C', C, Y1 and Y2 proteins leads to viral delayed growth. Plays an
CC important role in virion particles release. Modulates virion shape.
CC {ECO:0000250|UniProtKB:P04862, ECO:0000269|PubMed:12610111,
CC ECO:0000269|PubMed:14599788}.
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';
CC IsoId=P69738-1; Sequence=Displayed;
CC Name=C;
CC IsoId=P69738-2; Sequence=VSP_018939;
CC Name=Y1;
CC IsoId=P69738-3; Sequence=VSP_018940;
CC Name=Y2;
CC IsoId=P69738-4; Sequence=VSP_018941;
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:0000250|UniProtKB:P04861}.
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:0000250|UniProtKB:P04861}.
CC -!- DISRUPTION PHENOTYPE: Knockout of the 4 isoforms completely abolish the
CC ability to suppress the induction of IFN-alpha-stimulated gene products
CC and the subsequent establishment of an anti-viral state.
CC {ECO:0000269|PubMed:10518019}.
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.
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 EMBL; AB195968; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR SMR; P69738; -.
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; IDA:UniProtKB.
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; Host cytoplasm; Host-virus interaction;
KW 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 /evidence="ECO:0000250"
FT CHAIN 2..215
FT /note="Protein C'"
FT /evidence="ECO:0000305"
FT /id="PRO_0000039404"
FT REGION 12..34
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:P04861"
FT REGION 15..22
FT /note="Involved in self-degradation and in host STAT1
FT degradation"
FT /evidence="ECO:0000250|UniProtKB:P04861"
FT VAR_SEQ 1..40
FT /note="Missing (in isoform Y2)"
FT /evidence="ECO:0000305"
FT /id="VSP_018941"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform Y1)"
FT /evidence="ECO:0000305"
FT /id="VSP_018940"
FT VAR_SEQ 1..11
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_018939"
FT MUTAGEN 181
FT /note="F->S: Complete loss of STAT1-binding."
FT /evidence="ECO:0000269|PubMed:14599788"
SQ SEQUENCE 215 AA; 25219 MW; 51C41BB9BEB9AECD CRC64;
MASATLTAWI KMPSFLKKIL KLRGRRQEDE SRSRMLSDSS MLSCRVNQLT SEGTEAGSTT
PSTLPKDQAL LIEPKVRAKE KSQHRRPKII DQVRRVESLG EQASQRQKHM LETLINKIYT
GPLGEELVQT LYLRIWTMEE TPESLKILQM REDIRDQVLK MKTERWLRTL IRGEKTKLKD
FQKRYEEVHP YLMKEKVEQV IMEEAWSLAA HIVQE
