C_SENDZ
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 23-FEB-2022, entry version 82.
DE RecName: Full=C' protein;
GN Name=P/V/C;
OS Sendai virus (strain Z) (SeV) (Sendai virus (strain HVJ)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Paramyxoviridae; Orthoparamyxovirinae;
OC Respirovirus.
OX NCBI_TaxID=11198;
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=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 RNA
RT and the predicted amino acid sequences of viral NP, P and C proteins.";
RL Nucleic Acids Res. 11:7317-7330(1983).
RN [2]
RP SUBCELLULAR LOCATION.
RX 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 C'
RT proteins by antibodies against synthetic peptides.";
RL Virus Res. 6:109-121(1986).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=2171459; DOI=10.1007/bf01316677;
RA Yamada H., Hayata S., Omata-Yamada T., Taira H., Mizumoto K., 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 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 viral
RT RNA synthesis.";
RL Virology 235:261-270(1997).
RN [5]
RP FUNCTION.
RX PubMed=10823869; 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 to
RT virus assembly as an additional role.";
RL J. Virol. 74:5619-5628(2000).
RN [6]
RP FUNCTION.
RX PubMed=11264369; 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 both
RT counteracting the antiviral action of interferons and inhibiting viral RNA
RT synthesis.";
RL J. Virol. 75:3802-3810(2001).
RN [7]
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 [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 AND
RP 203-GLU-GLU-204.
RX 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 correlation
RT between L polymerase binding and inhibition of viral RNA synthesis.";
RL Virology 288:96-108(2001).
RN [9]
RP FUNCTION.
RX 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 dephosphorylation
RT processes of Stat1.";
RL FEBS Lett. 511:139-144(2002).
RN [10]
RP FUNCTION.
RX 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 of
RT the C proteins.";
RL Microbes Infect. 5:373-378(2003).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF 88-LYS--ASP-91; 125-GLU-GLU-126;
RP 150-MET-ASP-153; 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 that
RT are critically involved in its interferon antagonism and RNA synthesis
RT down-regulation.";
RL J. Virol. 78:7443-7454(2004).
RN [12]
RP FUNCTION.
RX PubMed=15231380; DOI=10.1016/j.virol.2004.04.019;
RA Sugahara F., Uchiyama T., Watanabe H., Shimazu Y., Kuwayama M., Fujii Y.,
RA 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 protein.";
RL Virology 325:1-10(2004).
RN [13]
RP FUNCTION, 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 protein
RT mutant with no STAT1-binding ability.";
RL FEBS Lett. 567:291-296(2004).
RN [14] {ECO:0007744|PDB:3WWT}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 109-215, INTERACTION WITH HUMAN
RP STAT1, AND FUNCTION.
RX PubMed=26339056; DOI=10.1128/jvi.01887-15;
RA Oda K., Matoba Y., Irie T., Kawabata R., Fukushi M., Sugiyama M.,
RA Sakaguchi T.;
RT "Structural basis of the inhibition of STAT1 activity by Sendai virus C
RT protein.";
RL J. Virol. 89:11487-11499(2015).
CC -!- FUNCTION: The different isoforms 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 (HMWC)
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:0000269|PubMed:10823869,
CC ECO:0000269|PubMed:11264369, ECO:0000269|PubMed:11821064,
CC ECO:0000269|PubMed:12737992, ECO:0000269|PubMed:15178339,
CC ECO:0000269|PubMed:15220418, ECO:0000269|PubMed:15231380,
CC ECO:0000269|PubMed:26339056}.
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 (PubMed:11442634,
CC PubMed:26339056). The different isoforms do not interact with host
CC STAT2 (PubMed:11442634, PubMed:26339056). C protein interacts with L
CC protein; this interaction has an inhibitory effect on viral
CC transcription and replication (PubMed:9281506, PubMed:11543662).
CC {ECO:0000269|PubMed:11442634, ECO:0000269|PubMed:11543662,
CC ECO:0000269|PubMed:26339056, ECO:0000269|PubMed:9281506}.
CC -!- INTERACTION:
CC P04862; Q60680: Chuk; Xeno; NbExp=2; IntAct=EBI-8848010, EBI-646245;
CC -!- SUBCELLULAR LOCATION: [Isoform C' protein]: Host cytoplasm
CC {ECO:0000269|PubMed:2171459, ECO:0000269|PubMed:3026113}. Note=Protein
CC C' seems to localize around the Golgi. {ECO:0000269|PubMed:3026113}.
CC -!- SUBCELLULAR LOCATION: [Isoform C protein]: Host cytoplasm
CC {ECO:0000269|PubMed:2171459, ECO:0000269|PubMed:3026113}. Virion.
CC Note=The C protein is found in virion at a ratio of approximately 40
CC molecules per virion, presumably associated with the nucleocapsid.
CC {ECO:0000269|PubMed:2171459}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=4;
CC Name=C' protein;
CC IsoId=P04862-1; Sequence=Displayed;
CC Name=C protein;
CC IsoId=P04862-2; Sequence=VSP_018944;
CC Name=Y1 protein;
CC IsoId=P04862-3; Sequence=VSP_018945;
CC Name=Y2 protein;
CC IsoId=P04862-4; Sequence=VSP_018946;
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 -!- 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' protein]: The initiator methionine is coded
CC by an unusual start codon ACG.
CC -!- MISCELLANEOUS: [Isoform C protein]: Most abundant isoform in infected
CC cells. {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; X00087; CAA24947.1; -; Genomic_RNA.
DR PIR; A04041; MNNZSV.
DR PDB; 3WWT; X-ray; 2.00 A; B=109-215.
DR PDB; 6KP3; X-ray; 2.20 A; B=109-215.
DR PDBsum; 3WWT; -.
DR PDBsum; 6KP3; -.
DR SMR; P04862; -.
DR IntAct; P04862; 2.
DR MINT; P04862; -.
DR Proteomes; UP000006560; Genome.
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; IDA: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 3D-structure; Alternative initiation; 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; Reference proteome;
KW Viral immunoevasion; Virion.
FT INIT_MET 1
FT /note="Removed; by host"
FT /evidence="ECO:0000250"
FT CHAIN 2..215
FT /note="C' protein"
FT /id="PRO_0000039411"
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 protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_018946"
FT VAR_SEQ 1..34
FT /note="Missing (in isoform Y1 protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_018945"
FT VAR_SEQ 1..11
FT /note="Missing (in isoform C protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_018944"
FT MUTAGEN 28..30
FT /note="EDE->AAA: 11% loss of binding to L protein in
FT protein C'."
FT /evidence="ECO:0000269|PubMed:11543662"
FT MUTAGEN 88..91
FT /note="KIID->AIIA: Complete loss of STAT1-binding and RNA
FT synthesis inhibition by C protein. 80% loss of binding to L
FT protein in protein C'."
FT /evidence="ECO:0000269|PubMed:11543662,
FT ECO:0000269|PubMed:15220418"
FT MUTAGEN 125..126
FT /note="EE->AA: Complete loss of STAT1-binding in protein C.
FT No effect on binding to L protein in protein C'."
FT /evidence="ECO:0000269|PubMed:11543662,
FT ECO:0000269|PubMed:15220418"
FT MUTAGEN 140..143
FT /note="ETPE->ATPA: 60% loss of binding to L protein in
FT protein C'."
FT /evidence="ECO:0000269|PubMed:11543662"
FT MUTAGEN 150..153
FT /note="MRED->AREA: Complete loss of STAT1-binding and RNA
FT synthesis inhibition by C protein."
FT /evidence="ECO:0000269|PubMed:11543662,
FT ECO:0000269|PubMed:15220418"
FT MUTAGEN 162..165
FT /note="KTER->ATAA: Complete loss of STAT1-binding, anti-IFN
FT activity and RNA synthesis inhibition by protein C. 67%
FT loss of binding to L protein in C' protein."
FT /evidence="ECO:0000269|PubMed:11543662,
FT ECO:0000269|PubMed:15220418"
FT MUTAGEN 168
FT /note="R->A: 63% loss of binding to L protein in protein
FT C'."
FT /evidence="ECO:0000269|PubMed:11543662"
FT MUTAGEN 172..174
FT /note="RGE->AGA: 10% loss of binding to L protein."
FT /evidence="ECO:0000269|PubMed:11543662"
FT MUTAGEN 181
FT /note="F->S: Complete loss of STAT1-binding by C protein.
FT 49% loss of binding to L protein."
FT /evidence="ECO:0000269|PubMed:11543662,
FT ECO:0000269|PubMed:15178339"
FT MUTAGEN 184..187
FT /note="RYEE->AYAA: Complete loss of STAT1-binding and RNA
FT synthesis inhibition by C protein. 62% loss of binding to L
FT protein."
FT /evidence="ECO:0000269|PubMed:11543662,
FT ECO:0000269|PubMed:15220418"
FT MUTAGEN 203..204
FT /note="EE->AA: 17% loss of binding to L protein."
FT /evidence="ECO:0000269|PubMed:11543662"
FT HELIX 109..120
FT /evidence="ECO:0007829|PDB:3WWT"
FT HELIX 122..137
FT /evidence="ECO:0007829|PDB:3WWT"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:3WWT"
FT HELIX 152..170
FT /evidence="ECO:0007829|PDB:3WWT"
FT HELIX 180..194
FT /evidence="ECO:0007829|PDB:3WWT"
FT HELIX 196..210
FT /evidence="ECO:0007829|PDB:3WWT"
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
