ID   C_SENDZ                 Reviewed;         215 AA.
AC   P04862;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   16-JUN-2009, entry version 50.
DE   RecName: Full=Protein C';
DE   Contains:
DE     RecName: Full=Protein C;
DE   Contains:
DE     RecName: Full=Protein Y1;
DE   Contains:
DE     RecName: Full=Protein Y2;
GN   Name=P/V/C;
OS   Sendai virus (strain Z) (SeV) (Sendai virus (strain HVJ)).
OC   Viruses; ssRNA negative-strand viruses; Mononegavirales;
OC   Paramyxoviridae; Paramyxovirinae; Respirovirus.
OX   NCBI_TaxID=11198;
OH   NCBI_TaxID=10090; Mus musculus (Mouse).
OH   NCBI_TaxID=10116; Rattus norvegicus (Rat).
OH   NCBI_TaxID=10144; Cavia cutleri (Guinea pig).
OH   NCBI_TaxID=36483; Cricetidae sp. (Hamster).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   MEDLINE=84069769; PubMed=6316257; DOI=10.1093/nar/11.21.7317;
RA   Shioda T., Hidaka Y., Kanda T., Shibuta H., Nomoto A., Iwasaki K.;
RT   "Sequence of 3,687 nucleotides from the 3' end of Sendai virus genome
RT   RNA and the predicted amino acid sequences of viral NP, P and C
RT   proteins.";
RL   Nucleic Acids Res. 11:7317-7330(1983).
RN   [2]
RP   SUBCELLULAR LOCATION OF C' AND C PROTEINS.
RX   MEDLINE=87096152; PubMed=3026113; DOI=10.1016/0168-1702(86)90043-2;
RA   Portner A., Gupta K.C., Seyer J.M., Beachey E.H., Kingsbury D.W.;
RT   "Localization and characterization of Sendai virus nonstructural C and
RT   C' proteins by antibodies against synthetic peptides.";
RL   Virus Res. 6:109-121(1986).
RN   [3]
RP   SUBCELLULAR LOCATION, AND ASSOCIATION WITH NUCLEOCAPSID.
RX   MEDLINE=91024577; PubMed=2171459; DOI=10.1007/BF01316677;
RA   Yamada H., Hayata S., Omata-Yamada T., Taira H., Mizumoto K.,
RA   Iwasaki K.;
RT   "Association of the Sendai virus C protein with nucleocapsids.";
RL   Arch. Virol. 113:245-253(1990).
RN   [4]
RP   INTERACTION WITH L PROTEIN.
RX   MEDLINE=97428574; PubMed=9281506; DOI=10.1006/viro.1997.8702;
RA   Horikami S.M., Hector R.E., Smallwood S., Moyer S.A.;
RT   "The Sendai virus C protein binds the L polymerase protein to inhibit
RT   viral RNA synthesis.";
RL   Virology 235:261-270(1997).
RN   [5]
RP   FUNCTION IN VIRUS ASSEMBLY.
RX   MEDLINE=20283821; PubMed=10823869;
RX   DOI=10.1128/JVI.74.12.5619-5628.2000;
RA   Hasan M.K., Kato A., Muranaka M., Yamaguchi R., Sakai Y., Hatano I.,
RA   Tashiro M., Nagai Y.;
RT   "Versatility of the accessory C proteins of Sendai virus: contribution
RT   to virus assembly as an additional role.";
RL   J. Virol. 74:5619-5628(2000).
RN   [6]
RP   FUNCTION OF Y2 PROTEIN.
RX   MEDLINE=21165290; PubMed=11264369;
RX   DOI=10.1128/JVI.75.8.3802-3810.2001;
RA   Kato A., Ohnishi Y., Kohase M., Saito S., Tashiro M., Nagai Y.;
RT   "Y2, the smallest of the Sendai virus C proteins, is fully capable of
RT   both counteracting the antiviral action of interferons and inhibiting
RT   viral RNA synthesis.";
RL   J. Virol. 75:3802-3810(2001).
RN   [7]
RP   INTERACTION WITH HUMAN STAT1.
RX   MEDLINE=21336297; PubMed=11442634;
RX   DOI=10.1046/j.1365-2443.2001.00442.x;
RA   Takeuchi K., Komatsu T., Yokoo J., Kato A., Shioda T., Nagai Y.,
RA   Gotoh B.;
RT   "Sendai virus C protein physically associates with Stat1.";
RL   Genes Cells 6:545-557(2001).
RN   [8]
RP   INTERACTION WITH L PROTEIN, AND MUTAGENESIS OF 28-GLU--GLU-30;
RP   88-LYS--ASP-91; 125-GLU-GLU-126; 140-GLU--GLU-143; 150-MET-ASP-153;
RP   162-LYS--ARG-165; ARG-168; 172-ARG--GLU-174; PHE-181; 184-GLU--GLU-187
RP   AND 203-GLU-GLU-204.
RX   MEDLINE=21429748; PubMed=11543662; DOI=10.1006/viro.2001.1068;
RA   Grogan C.C., Moyer S.A.;
RT   "Sendai virus wild-type and mutant C proteins show a direct
RT   correlation between L polymerase binding and inhibition of viral RNA
RT   synthesis.";
RL   Virology 288:96-108(2001).
RN   [9]
RP   FUNCTION OF C PROTEIN.
RX   MEDLINE=21679117; PubMed=11821064; DOI=10.1016/S0014-5793(01)03301-4;
RA   Komatsu T., Takeuchi K., Yokoo J., Gotoh B.;
RT   "Sendai virus C protein impairs both phosphorylation and
RT   dephosphorylation processes of Stat1.";
RL   FEBS Lett. 511:139-144(2002).
RN   [10]
RP   FUNCTION IN APOPTOSIS SUPPRESSION.
RX   MEDLINE=22624087; PubMed=12737992; DOI=10.1016/S1286-4579(03)00043-1;
RA   Koyama A.H., Irie H., Kato A., Nagai Y., Adachi A.;
RT   "Virus multiplication and induction of apoptosis by Sendai virus: role
RT   of the C proteins.";
RL   Microbes Infect. 5:373-378(2003).
RN   [11]
RP   MUTAGENESIS OF 88-LYS--ASP-91; 125-GLU-GLU-126; 150-MET-ASP-153;
RP   162-LYS--ARG-165 AND 184-GLU--GLU-187.
RX   PubMed=15220418; DOI=10.1128/JVI.78.14.7443-7454.2004;
RA   Kato A., Cortese-Grogan C., Moyer S.A., Sugahara F., Sakaguchi T.,
RA   Kubota T., Otsuki N., Kohase M., Tashiro M., Nagai Y.;
RT   "Characterization of the amino acid residues of Sendai virus C protein
RT   that are critically involved in its interferon antagonism and RNA
RT   synthesis down-regulation.";
RL   J. Virol. 78:7443-7454(2004).
RN   [12]
RP   FUNCTION IN BUDDING.
RX   PubMed=15231380; DOI=10.1016/j.virol.2004.04.019;
RA   Sugahara F., Uchiyama T., Watanabe H., Shimazu Y., Kuwayama M.,
RA   Fujii Y., Kiyotani K., Adachi A., Kohno N., Yoshida T., Sakaguchi T.;
RT   "Paramyxovirus Sendai virus-like particle formation by expression of
RT   multiple viral proteins and acceleration of its release by C
RT   protein.";
RL   Virology 325:1-10(2004).
RN   [13]
RP   FUNCTION OF C PROTEIN, AND MUTAGENESIS OF PHE-181.
RX   PubMed=15178339; DOI=10.1016/j.febslet.2004.05.001;
RA   Gotoh B., Takeuchi K., Komatsu T.;
RT   "Inhibition of the gamma interferon response by a Sendai virus C
RT   protein mutant with no STAT1-binding ability.";
RL   FEBS Lett. 567:291-296(2004).
CC   -!- FUNCTION: The different products prevent the establishment of
CC       cellular antiviral state by blocking the interferon-alpha/beta
CC       (IFN-alpha/beta) and IFN-gamma signaling pathways. They inhibit
CC       IFN-alpha/beta induced tyrosine phosphorylation of STAT1 and
CC       STAT2. Blocking the IFN-alpha/beta pathway requires binding to
CC       STAT1 in the cytoplasm. They inhibit IFN-gamma induced serine
CC       phosphorylation of STAT1. Block the IFN-gamma pathway in a STAT1-
CC       binding independent mechanism, preventing the GAF (tyrosine-
CC       phosphorylated STAT1 dimer) to bind its promoter in the nucleus.
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
CC       all C', C, Y1 and Y2 proteins leads to viral delayed growth. Plays
CC       an important role in virion particles release. Modulates virion
CC       shape.
CC   -!- SUBUNIT: The different products bind the N-terminal part of
CC       unphosphorylated and phosphorylated human STAT1, preventing the
CC       formation of STAT1 homodimers and STAT1/STAT2 heterodimers (By
CC       similarity). The binding of C protein to L protein has an
CC       inhibitory effect on viral transcription and replication.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm (By similarity). Note=Protein
CC       C' seems to localize around the Golgi (By similarity).
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=4;
CC       Name=C';
CC         IsoId=P04862-1; Sequence=Displayed;
CC         Note=The initiator methionine is coded by an unusual start codon
CC         ACG;
CC       Name=C;
CC         IsoId=P04862-2; Sequence=VSP_018944;
CC         Note=Most abundant isoform in infected cells;
CC       Name=Y1;
CC         IsoId=P04862-3; Sequence=VSP_018945;
CC         Note=No experimental confirmation available;
CC       Name=Y2;
CC         IsoId=P04862-4; Sequence=VSP_018946;
CC         Note=No experimental confirmation available;
CC   -!- PTM: Y1 and Y2 proteins are produced not only by alternative
CC       initiation, but also by preoteolytic cleavage of C'. Only
CC       alternative initiation is detected in vitro, whereas in vivo
CC       cleavage seems to be predominant (By similarity).
CC   -!- MISCELLANEOUS: The C protein is found in virion at a ratio of
CC       approximately 40 molecules per virion, presumably associated with
CC       the nucleocapsid.
CC   -!- MISCELLANEOUS: The P/V/C gene has two overlapping open reading
CC       frames. One encodes the P/V/W proteins and the other the C/Y
CC       proteins.
CC   -!- SIMILARITY: Belongs to the respirovirus protein C family.
CC   -!- CAUTION: The C' protein uses an unusual ACG start codon.
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DR   EMBL; X00087; CAA24947.1; -; Genomic_RNA.
DR   PIR; A04041; MNNZSV.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0030683; P:evasion by virus of host immune response; IEA:UniProtKB-KW.
DR   InterPro; IPR002608; Paramyxo_C.
DR   Pfam; PF01692; Paramyxo_C; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; Complete proteome; Cytoplasm;
KW   Host-virus interaction; Interferon antiviral system evasion.
FT   INIT_MET      1      1       Removed; by host (By similarity).
FT   CHAIN         2    215       Protein C'.
FT                                /FTId=PRO_0000039411.
FT   VAR_SEQ       1     40       Missing (in isoform Y2).
FT                                /FTId=VSP_018946.
FT   VAR_SEQ       1     34       Missing (in isoform Y1).
FT                                /FTId=VSP_018945.
FT   VAR_SEQ       1     11       Missing (in isoform C).
FT                                /FTId=VSP_018944.
FT   MUTAGEN      28     30       EDE->AAA: 11% loss of binding to L
FT                                protein in protein C'.
FT   MUTAGEN      88     91       KIID->AIIA: Complete loss of STAT1-
FT                                binding and RNA synthesis inhibition by C
FT                                protein. 80% loss of binding to L protein
FT                                in protein C'.
FT   MUTAGEN     125    126       EE->AA: Complete loss of STAT1-binding in
FT                                protein C. No effect on binding to L
FT                                protein in protein C'.
FT   MUTAGEN     140    143       ETPE->ATPA: 60% loss of binding to L
FT                                protein in protein C'.
FT   MUTAGEN     150    153       MRED->AREA: Complete loss of STAT1-
FT                                binding and RNA synthesis inhibition by C
FT                                protein.
FT   MUTAGEN     162    165       KTER->ATAA: Complete loss of STAT1-
FT                                binding, anti-IFN activity and RNA
FT                                synthesis inhibition by protein C. 67%
FT                                loss of binding to L protein in C'
FT                                protein.
FT   MUTAGEN     168    168       R->A: 63% loss of binding to L protein in
FT                                protein C'.
FT   MUTAGEN     172    174       RGE->AGA: 10% loss of binding to L
FT                                protein.
FT   MUTAGEN     181    181       F->S: Complete loss of STAT1-binding by C
FT                                protein. 49% loss of binding to L
FT                                protein.
FT   MUTAGEN     184    187       RYEE->AYAA: Complete loss of STAT1-
FT                                binding and RNA synthesis inhibition by C
FT                                protein. 62% loss of binding to L
FT                                protein.
FT   MUTAGEN     203    204       EE->AA: 17% loss of binding to L protein.
SQ   SEQUENCE   215 AA;  25189 MW;  506F01080EB9BEDC CRC64;
     MASATLTAWI KMPSFLKKIL KLRGRRQEDE SRSRMLSDSS MLSCRVNQLT SEGTEAGSTT
     PSTLPKDQAL LIEPKVRAKE KSQHRRPKII DQVRRVESLG EQASQRQKHM LETLINKIYT
     GPLGEELVQT LYLRIWAMEE TPESLKILQM REDIRDQVLK MKTERWLRTL IRGEKTKLKD
     FQKRYEEVHP YLMKEKVEQV IMEEAWSLAA HIVQE
//