Reviewed, UniProtKB/Swiss-Prot P04862 (C_SENDZ)

Names and origin

Protein names

Recommended name:
    Protein C'
Cleaved into the following 3 chains:
    1- Recommended name:
            Protein C
    2- Recommended name:
            Protein Y1
    3- Recommended name:
            Protein Y2

Gene names

Name:

P/V/C

Organism

Sendai virus (strain Z) (SeV) (Sendai virus (strain HVJ)) [Complete proteome]

Taxonomic identifier

11198 [NCBI]

Taxonomic lineage

Viruses › ssRNA negative-strand viruses › Mononegavirales › Paramyxoviridae › Paramyxovirinae › Respirovirus

Virus host

Mus musculus (Mouse) [TaxID: 10090]
Rattus norvegicus (Rat) [TaxID: 10116]
Cavia cutleri (Guinea pig) [TaxID: 10144]
Cricetidae sp. (Hamster) [TaxID: 36483]

Protein attributes

Sequence length	215 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The different products prevent the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways. They inhibit IFN-alpha/beta induced tyrosine phosphorylation of STAT1 and STAT2. Blocking the IFN-alpha/beta pathway requires binding to STAT1 in the cytoplasm. They inhibit IFN-gamma induced serine phosphorylation of STAT1. Block the IFN-gamma pathway in a STAT1-binding independent mechanism, preventing the GAF (tyrosine-phosphorylated STAT1 dimer) to bind its promoter in the nucleus. May also have a role in preventing the cell to enter apoptosis. Modulate regulation of viral transcription and replication. Overexpression inhibits the viral RNA polymerase. The absence of all C', C, Y1 and Y2 proteins leads to viral delayed growth. Plays an important role in virion particles release. Modulates virion shape. Ref.5 Ref.6 Ref.9 Ref.10 Ref.12 Ref.13
Subunit structure	The different products bind the N-terminal part of unphosphorylated and phosphorylated human STAT1, preventing the formation of STAT1 homodimers and STAT1/STAT2 heterodimers By similarity. The binding of C protein to L protein has an inhibitory effect on viral transcription and replication.
Subcellular location	Host cytoplasm By similarity. Note: Protein C' seems to localize around the Golgi By similarity.
Post-translational modification	Y1 and Y2 proteins are produced not only by alternative initiation, but also by preoteolytic cleavage of C'. Only alternative initiation is detected in vitro, whereas in vivo cleavage seems to be predominant By similarity.
Miscellaneous	The C protein is found in virion at a ratio of approximately 40 molecules per virion, presumably associated with the nucleocapsid. The P/V/C gene has two overlapping open reading frames. One encodes the P/V/W proteins and the other the C/Y proteins.
Sequence similarities	Belongs to the respirovirus protein C family.
Caution	The C' protein uses an unusual ACG start codon.

Ontologies

Keywords
Biological process	Host-virus interaction Interferon antiviral system evasion
Cellular component	Cytoplasm
Coding sequence diversity	Alternative initiation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative initiation. [Align] [Select]

Isoform C' (identifier: P04862-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: The initiator methionine is coded by an unusual start codon ACG.

Isoform C (identifier: P04862-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-11: Missing.

Note: Most abundant isoform in infected cells.

Isoform Y1 (identifier: P04862-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Note: No experimental confirmation available.

Isoform Y2 (identifier: P04862-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host By similarity
	Chain	2 – 215	214	Protein C'		PRO_0000039411
Natural variations
	Alternative sequence	1 – 40	40	Missing in isoform Y2.		VSP_018946
	Alternative sequence	1 – 34	34	Missing in isoform Y1.		VSP_018945
	Alternative sequence	1 – 11	11	Missing in isoform C.		VSP_018944
Experimental info
	Mutagenesis	28 – 30	3	EDE → AAA: 11% loss of binding to L protein in protein C'.
	Mutagenesis	88 – 91	4	KIID → AIIA: Complete loss of STAT1-binding and RNA synthesis inhibition by C protein. 80% loss of binding to L protein in protein C'.
	Mutagenesis	125 – 126	2	EE → AA: Complete loss of STAT1-binding in protein C. No effect on binding to L protein in protein C'.
	Mutagenesis	140 – 143	4	ETPE → ATPA: 60% loss of binding to L protein in protein C'.
	Mutagenesis	150 – 153	4	MRED → AREA: Complete loss of STAT1-binding and RNA synthesis inhibition by C protein.
	Mutagenesis	162 – 165	4	KTER → ATAA: Complete loss of STAT1-binding, anti-IFN activity and RNA synthesis inhibition by protein C. 67% loss of binding to L protein in C' protein. Ref.11
	Mutagenesis	168	1	R → A: 63% loss of binding to L protein in protein C'. Ref.8
	Mutagenesis	172 – 174	3	RGE → AGA: 10% loss of binding to L protein. Ref.8
	Mutagenesis	181	1	F → S: Complete loss of STAT1-binding by C protein. 49% loss of binding to L protein. Ref.13 Ref.8
	Mutagenesis	184 – 187	4	RYEE → AYAA: Complete loss of STAT1-binding and RNA synthesis inhibition by C protein. 62% loss of binding to L protein. Ref.11 Ref.8
	Mutagenesis	203 – 204	2	EE → AA: 17% loss of binding to L protein.

Sequences

	Sequence		Length	Mass (Da)
	Isoform C' [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 506F01080EB9BEDC	FASTA	215	25,189
	10 20 30 40 50 60 MASATLTAWI KMPSFLKKIL KLRGRRQEDE SRSRMLSDSS MLSCRVNQLT SEGTEAGSTT 70 80 90 100 110 120 PSTLPKDQAL LIEPKVRAKE KSQHRRPKII DQVRRVESLG EQASQRQKHM LETLINKIYT 130 140 150 160 170 180 GPLGEELVQT LYLRIWAMEE TPESLKILQM REDIRDQVLK MKTERWLRTL IRGEKTKLKD 190 200 210 FQKRYEEVHP YLMKEKVEQV IMEEAWSLAA HIVQE
	Isoform C. Checksum: 3F4AAEC228222857	FASTA	204	24,015
	10 20 30 40 50 60 MPSFLKKILK LRGRRQEDES RSRMLSDSSM LSCRVNQLTS EGTEAGSTTP STLPKDQALL 70 80 90 100 110 120 IEPKVRAKEK SQHRRPKIID QVRRVESLGE QASQRQKHML ETLINKIYTG PLGEELVQTL 130 140 150 160 170 180 YLRIWAMEET PESLKILQMR EDIRDQVLKM KTERWLRTLI RGEKTKLKDF QKRYEEVHPY 190 200 LMKEKVEQVI MEEAWSLAAH IVQE
	Isoform Y1. Checksum: 0817DE79BF6130E7	FASTA	181	21,202
	10 20 30 40 50 60 MLSDSSMLSC RVNQLTSEGT EAGSTTPSTL PKDQALLIEP KVRAKEKSQH RRPKIIDQVR 70 80 90 100 110 120 RVESLGEQAS QRQKHMLETL INKIYTGPLG EELVQTLYLR IWAMEETPES LKILQMREDI 130 140 150 160 170 180 RDQVLKMKTE RWLRTLIRGE KTKLKDFQKR YEEVHPYLMK EKVEQVIMEE AWSLAAHIVQ E
	Isoform Y2. Checksum: 2767937BC46BAA50	FASTA	175	20,581
	10 20 30 40 50 60 MLSCRVNQLT SEGTEAGSTT PSTLPKDQAL LIEPKVRAKE KSQHRRPKII DQVRRVESLG 70 80 90 100 110 120 EQASQRQKHM LETLINKIYT GPLGEELVQT LYLRIWAMEE TPESLKILQM REDIRDQVLK 130 140 150 160 170 MKTERWLRTL IRGEKTKLKD FQKRYEEVHP YLMKEKVEQV IMEEAWSLAA HIVQE

References

[1]	"Sequence of 3,687 nucleotides from the 3' end of Sendai virus genome RNA and the predicted amino acid sequences of viral NP, P and C proteins." Shioda T., Hidaka Y., Kanda T., Shibuta H., Nomoto A., Iwasaki K. Nucleic Acids Res. 11:7317-7330(1983) [PubMed: 6316257] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Localization and characterization of Sendai virus nonstructural C and C' proteins by antibodies against synthetic peptides." Portner A., Gupta K.C., Seyer J.M., Beachey E.H., Kingsbury D.W. Virus Res. 6:109-121(1986) [PubMed: 3026113] [Abstract] Cited for: SUBCELLULAR LOCATION OF C' AND C PROTEINS.
[3]	"Association of the Sendai virus C protein with nucleocapsids." Yamada H., Hayata S., Omata-Yamada T., Taira H., Mizumoto K., Iwasaki K. Arch. Virol. 113:245-253(1990) [PubMed: 2171459] [Abstract] Cited for: SUBCELLULAR LOCATION, ASSOCIATION WITH NUCLEOCAPSID.
[4]	"The Sendai virus C protein binds the L polymerase protein to inhibit viral RNA synthesis." Horikami S.M., Hector R.E., Smallwood S., Moyer S.A. Virology 235:261-270(1997) [PubMed: 9281506] [Abstract] Cited for: INTERACTION WITH L PROTEIN.
[5]	"Versatility of the accessory C proteins of Sendai virus: contribution to virus assembly as an additional role." Hasan M.K., Kato A., Muranaka M., Yamaguchi R., Sakai Y., Hatano I., Tashiro M., Nagai Y. J. Virol. 74:5619-5628(2000) [PubMed: 10823869] [Abstract] Cited for: FUNCTION IN VIRUS ASSEMBLY.
[6]	"Y2, the smallest of the Sendai virus C proteins, is fully capable of both counteracting the antiviral action of interferons and inhibiting viral RNA synthesis." Kato A., Ohnishi Y., Kohase M., Saito S., Tashiro M., Nagai Y. J. Virol. 75:3802-3810(2001) [PubMed: 11264369] [Abstract] Cited for: FUNCTION OF Y2 PROTEIN.
[7]	"Sendai virus C protein physically associates with Stat1." Takeuchi K., Komatsu T., Yokoo J., Kato A., Shioda T., Nagai Y., Gotoh B. Genes Cells 6:545-557(2001) [PubMed: 11442634] [Abstract] Cited for: INTERACTION WITH HUMAN STAT1.
[8]	"Sendai virus wild-type and mutant C proteins show a direct correlation between L polymerase binding and inhibition of viral RNA synthesis." Grogan C.C., Moyer S.A. Virology 288:96-108(2001) [PubMed: 11543662] [Abstract] Cited for: INTERACTION WITH L PROTEIN, MUTAGENESIS OF 28-GLU--GLU-30; 88-LYS--ASP-91; 125-GLU-GLU-126; 140-GLU--GLU-143; 150-MET-ASP-153; 162-LYS--ARG-165; ARG-168; 172-ARG--GLU-174; PHE-181; 184-GLU--GLU-187 AND 203-GLU-GLU-204.
[9]	"Sendai virus C protein impairs both phosphorylation and dephosphorylation processes of Stat1." Komatsu T., Takeuchi K., Yokoo J., Gotoh B. FEBS Lett. 511:139-144(2002) [PubMed: 11821064] [Abstract] Cited for: FUNCTION OF C PROTEIN.
[10]	"Virus multiplication and induction of apoptosis by Sendai virus: role of the C proteins." Koyama A.H., Irie H., Kato A., Nagai Y., Adachi A. Microbes Infect. 5:373-378(2003) [PubMed: 12737992] [Abstract] Cited for: FUNCTION IN APOPTOSIS SUPPRESSION.
[11]	"Characterization of the amino acid residues of Sendai virus C protein that are critically involved in its interferon antagonism and RNA synthesis down-regulation." Kato A., Cortese-Grogan C., Moyer S.A., Sugahara F., Sakaguchi T., Kubota T., Otsuki N., Kohase M., Tashiro M., Nagai Y. J. Virol. 78:7443-7454(2004) [PubMed: 15220418] [Abstract] Cited for: MUTAGENESIS OF 88-LYS--ASP-91; 125-GLU-GLU-126; 150-MET-ASP-153; 162-LYS--ARG-165 AND 184-GLU--GLU-187.
[12]	"Paramyxovirus Sendai virus-like particle formation by expression of multiple viral proteins and acceleration of its release by C protein." Sugahara F., Uchiyama T., Watanabe H., Shimazu Y., Kuwayama M., Fujii Y., Kiyotani K., Adachi A., Kohno N., Yoshida T., Sakaguchi T. Virology 325:1-10(2004) [PubMed: 15231380] [Abstract] Cited for: FUNCTION IN BUDDING.
[13]	"Inhibition of the gamma interferon response by a Sendai virus C protein mutant with no STAT1-binding ability." Gotoh B., Takeuchi K., Komatsu T. FEBS Lett. 567:291-296(2004) [PubMed: 15178339] [Abstract] Cited for: FUNCTION OF C PROTEIN, MUTAGENESIS OF PHE-181.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X00087 Genomic RNA. Translation: CAA24947.1.
PIR	MNNZSV. A04041.
3D structure databases
ModBase	Search...
Family and domain databases
InterPro	IPR002608. Paramyxo_C. [Graphical view]
Pfam	PF01692. Paramyxo_C. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

C_SENDZ

Accession

Primary (citable) accession number: P04862

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 50 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)