ID V_PIV5 Reviewed; 222 AA. AC P11207; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 02-SEP-2026, entry version 134. DE RecName: Full=Non-structural protein V; GN Name=P/V; OS Parainfluenza virus 5 (strain W3) (PIV5) (Simian virus 5). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; OC Monjiviricetes; Mononegavirales; Paramyxoviridae; Rubulavirinae; OC Orthorubulavirus; Orthorubulavirus mammalis; Mammalian orthorubulavirus 5. OX NCBI_TaxID=11208; OH NCBI_TaxID=9615; Canis lupus familiaris (Dog) (Canis familiaris). OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND RNA EDITING. RX PubMed=3044614; DOI=10.1016/s0092-8674(88)91285-8; RA Thomas S.M., Lamb R.A., Paterson R.G.; RT "Two mRNAs that differ by two nontemplated nucleotides encode the amino RT coterminal proteins P and V of the paramyxovirus SV5."; RL Cell 54:891-902(1988). RN [2] RP INTERACTION WITH PROTEIN NP. RX PubMed=8862406; DOI=10.1006/viro.1996.0513; RA Randall R.E., Bermingham A.; RT "NP:P and NP:V interactions of the paramyxovirus simian virus 5 examined RT using a novel protein:protein capture assay."; RL Virology 224:121-129(1996). RN [3] RP RNA-BINDING. RX PubMed=9400618; DOI=10.1006/viro.1997.8866; RA Lin G.Y., Paterson R.G., Lamb R.A.; RT "The RNA binding region of the paramyxovirus SV5 V and P proteins."; RL Virology 238:460-469(1997). RN [4] RP INTERACTION WITH HUMAN IFIH1/MDA5, AND INTERFERON EVASION. RX PubMed=15563593; DOI=10.1073/pnas.0407639101; RA Andrejeva J., Childs K.S., Young D.F., Carlos T.S., Stock N., Goodbourn S., RA Randall R.E.; RT "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, RT mda-5, and inhibit its activation of the IFN-beta promoter."; RL Proc. Natl. Acad. Sci. U.S.A. 101:17264-17269(2004). RN [5] RP UBIQUITINATION OF HUMAN STAT1 AND HUMAN STAT2. RX PubMed=15604442; DOI=10.1099/vir.0.80263-0; RA Precious B., Young D.F., Andrejeva L., Goodbourn S., Randall R.E.; RT "In vitro and in vivo specificity of ubiquitination and degradation of RT STAT1 and STAT2 by the V proteins of the paramyxoviruses simian virus 5 and RT human parainfluenza virus type 2."; RL J. Gen. Virol. 86:151-158(2005). RN [6] RP FUNCTION. RX PubMed=15950997; DOI=10.1016/j.virol.2005.05.014; RA Lin Y., Horvath F., Aligo J.A., Wilson R., He B.; RT "The role of simian virus 5 V protein on viral RNA synthesis."; RL Virology 338:270-280(2005). RN [7] RP INTERACTION WITH HUMAN DDB1 AND HUMAN STAT2. RX PubMed=16227264; DOI=10.1128/jvi.79.21.13434-13441.2005; RA Precious B., Childs K., Fitzpatrick-Swallow V., Goodbourn S., Randall R.E.; RT "Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to RT facilitate the ubiquitination of STAT1."; RL J. Virol. 79:13434-13441(2005). RN [8] RP FUNCTION, AND INTERACTION WITH HOST DHX58. RX PubMed=22301134; DOI=10.1128/jvi.06405-11; RA Childs K., Randall R., Goodbourn S.; RT "Paramyxovirus V proteins interact with the RNA Helicase LGP2 to inhibit RT RIG-I-dependent interferon induction."; RL J. Virol. 86:3411-3421(2012). RN [9] RP FUNCTION, INTERACTION WITH HOST TRIM25, AND INTERACTION WITH HOST RIGI. RX PubMed=29321315; DOI=10.1128/jvi.01960-17; RA Sanchez-Aparicio M.T., Feinman L.J., Garcia-Sastre A., Shaw M.L.; RT "Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex RT and Inhibit RIG-I Signaling."; RL J. Virol. 92:0-0(2018). RN [10] {ECO:0007744|PDB:2B5L} RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) IN COMPLEX WITH ZN(2+), AND RP FUNCTION. RX PubMed=16413485; DOI=10.1016/j.cell.2005.10.033; RA Li T., Chen X., Garbutt K.C., Zhou P., Zheng N.; RT "Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack RT of a propeller cluster in ubiquitin ligase."; RL Cell 124:105-117(2006). RN [11] {ECO:0007744|PDB:2HYE} RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) IN COMPLEX WITH HUMAN CUL4A; DDB1 AND RP ROC1, AND FUNCTION. RX PubMed=16964240; DOI=10.1038/nature05175; RA Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.; RT "Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase RT machinery."; RL Nature 443:590-593(2006). RN [12] {ECO:0007744|PDB:4I1S} RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 168-219 IN COMPLEX WITH ZN(2+). RX PubMed=23328395; DOI=10.1126/science.1230949; RA Motz C., Schuhmann K.M., Kirchhofer A., Moldt M., Witte G., RA Conzelmann K.K., Hopfner K.P.; RT "Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to RT inhibit antiviral signaling."; RL Science 339:690-693(2013). CC -!- FUNCTION: Plays an essential role in the inhibition of host immune CC response. Prevents the establishment of cellular antiviral state by CC blocking interferon-alpha/beta (IFN-alpha/beta) production and CC signaling pathway. Interacts with host IFIH1/MDA5 and DHX58/LGP2 to CC inhibit the transduction pathway involved in the activation of IFN-beta CC promoter, thus protecting the virus against cell antiviral state. CC Efficiently blocks type I IFN signaling following infection by behaving CC as a substrate receptor for CUL4-DDB1 E3 ligase complex and targeting CC host STAT1 for proteasomal degradation. Blocks the type I interferon CC signaling pathway by disrupting the RIG-I signaling pathway (By CC similarity). {ECO:0000250|UniProtKB:Q9EMA9, CC ECO:0000269|PubMed:15950997, ECO:0000269|PubMed:16413485, CC ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:22301134}. CC -!- SUBUNIT: Interacts with host DDB1, STAT2 and IFIH1/MDA5. Interacts with CC host RIGI regulatory protein (via CARDs domain) and host TRIM25 (via CC SPRY domain); these interactions prevent TRIM25-mediated ubiquitination CC of RIG-I and disrupts downstream RIG-I signaling (PubMed:29321315). CC {ECO:0000269|PubMed:15563593, ECO:0000269|PubMed:16227264, CC ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:22301134, CC ECO:0000269|PubMed:29321315, ECO:0000269|PubMed:8862406}. CC -!- INTERACTION: CC P11207; Q16531: DDB1; Xeno; NbExp=4; IntAct=EBI-6148694, EBI-350322; CC P11207; Q96C10: DHX58; Xeno; NbExp=2; IntAct=EBI-6148694, EBI-744193; CC P11207; Q8R5F7-1: Ifih1; Xeno; NbExp=3; IntAct=EBI-6148694, EBI-16019291; CC P11207; Q9BYX4: IFIH1; Xeno; NbExp=3; IntAct=EBI-6148694, EBI-6115771; CC P11207; A7LCX1: MDA5; Xeno; NbExp=2; IntAct=EBI-6148694, EBI-16032125; CC P11207; P52630: STAT2; Xeno; NbExp=2; IntAct=EBI-6148694, EBI-1546963; CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250}. CC -!- RNA EDITING: Modified_positions=164 {ECO:0000269|PubMed:3044614}; CC Note=Partially edited. RNA editing at this position consists of an CC insertion of two guanine nucleotides. The sequence displayed here is CC the V protein, derived from the unedited RNA. The edited RNA gives rise CC to the P protein (AC P11208).; CC -!- SIMILARITY: Belongs to the paramyxoviruses V protein family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J03142; AAA47882.1; -; mRNA. DR EMBL; AF052755; AAC95512.1; -; Genomic_RNA. DR PIR; A31594; MNNZSP. DR PDB; 2B5L; X-ray; 2.85 A; C/D=1-222. DR PDB; 2HYE; X-ray; 3.10 A; B=1-222. DR PDB; 2K48; NMR; -; A=53-89. DR PDB; 4I1S; X-ray; 2.29 A; B=168-219. DR AlphaFoldDB; P11207; -. DR SMR; P11207; -. DR DIP; DIP-48759N; -. DR IntAct; P11207; 12. DR MINT; P11207; -. DR EvolutionaryTrace; P11207; -. DR Proteomes; UP000007232; Segment. DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:1990756; F:ubiquitin-like ligase-substrate adaptor activity; IDA:UniProt. DR GO; GO:0039554; P:symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity; IDA:CACAO. DR GO; GO:0039563; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW. DR GO; GO:0039564; P:symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity; IDA:UniProt. DR GO; GO:0039502; P:symbiont-mediated suppression of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR FunFam; 4.10.80.340:FF:000001; Protein V; 1. DR Gene3D; 4.10.80.340; -; 1. DR InterPro; IPR024279; Paramyx_V_Zn-bd. DR InterPro; IPR025909; Soyouz_module. DR Pfam; PF14313; Soyouz_module; 1. DR Pfam; PF13008; zf-Paramyx-P; 1. PE 1: Evidence at protein level; KW 3D-structure; 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 MDA5 by virus; Inhibition of host RLR pathway by virus; KW Inhibition of host STAT1 by virus; Interferon antiviral system evasion; KW Metal-binding; Reference proteome; RNA editing; RNA-binding; KW Ubl conjugation pathway; Viral immunoevasion; Zinc. FT CHAIN 1..222 FT /note="Non-structural protein V" FT /id="PRO_0000142830" FT REGION 61..107 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 171 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:23328395, FT ECO:0007744|PDB:4I1S" FT BINDING 190 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:23328395, FT ECO:0007744|PDB:2B5L, ECO:0007744|PDB:2HYE, FT ECO:0007744|PDB:4I1S" FT BINDING 194 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:23328395, FT ECO:0007744|PDB:2B5L, ECO:0007744|PDB:2HYE, FT ECO:0007744|PDB:4I1S" FT BINDING 206 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:23328395, ECO:0007744|PDB:2B5L, FT ECO:0007744|PDB:4I1S" FT BINDING 208 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:23328395, FT ECO:0007744|PDB:2B5L, ECO:0007744|PDB:2HYE, FT ECO:0007744|PDB:4I1S" FT BINDING 211 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:23328395, FT ECO:0007744|PDB:2B5L, ECO:0007744|PDB:2HYE, FT ECO:0007744|PDB:4I1S" FT BINDING 215 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:23328395, ECO:0007744|PDB:2B5L, FT ECO:0007744|PDB:4I1S" FT BINDING 218 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:16413485, FT ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:23328395, FT ECO:0007744|PDB:2B5L, ECO:0007744|PDB:2HYE, FT ECO:0007744|PDB:4I1S" FT HELIX 23..32 FT /evidence="ECO:0007829|PDB:2B5L" FT HELIX 53..85 FT /evidence="ECO:0007829|PDB:2K48" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:2B5L" FT HELIX 98..100 FT /evidence="ECO:0007829|PDB:2B5L" FT TURN 101..104 FT /evidence="ECO:0007829|PDB:2B5L" FT STRAND 109..116 FT /evidence="ECO:0007829|PDB:2B5L" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:2B5L" FT HELIX 127..138 FT /evidence="ECO:0007829|PDB:2B5L" FT STRAND 143..146 FT /evidence="ECO:0007829|PDB:2B5L" FT STRAND 164..167 FT /evidence="ECO:0007829|PDB:2B5L" FT STRAND 170..180 FT /evidence="ECO:0007829|PDB:4I1S" FT STRAND 183..192 FT /evidence="ECO:0007829|PDB:4I1S" FT HELIX 204..206 FT /evidence="ECO:0007829|PDB:4I1S" FT STRAND 207..209 FT /evidence="ECO:0007829|PDB:4I1S" FT HELIX 216..218 FT /evidence="ECO:0007829|PDB:4I1S" SQ SEQUENCE 222 AA; 23935 MW; 13D2F1627D15AFA3 CRC64; MDPTDLSFSP DEINKLIETG LNTVEYFTSQ QVTGTSSLGK NTIPPGVTGL LTNAAEAKIQ ESTNHQKGSV GGGAKPKKPR PKIAIVPADD KTVPGKPIPN PLLGLDSTPS TQTVLDLSGK TLPSGSYKGV KLAKFGKENL MTRFIEEPRE NPIATSSPID FKRGRDTGGF HRREYSIGWV GDEVKVTEWC NPSCSPITAA ARRFECTCHQ CPVTCSECER DT //