MATRX_VSIVA
ID MATRX_VSIVA Reviewed; 229 AA.
AC P03519;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 105.
DE RecName: Full=Matrix protein {ECO:0000303|PubMed:6268840};
DE Short=M protein {ECO:0000303|PubMed:6268840};
GN Name=M;
OS Vesicular stomatitis Indiana virus (strain San Juan) (VSIV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae;
OC Vesiculovirus.
OX NCBI_TaxID=11285;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=9913; Bos taurus (Bovine).
OH NCBI_TaxID=58271; Culicoides.
OH NCBI_TaxID=9793; Equus asinus (Donkey) (Equus africanus asinus).
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=252607; Lutzomyia.
OH NCBI_TaxID=7370; Musca domestica (House fly).
OH NCBI_TaxID=7190; Simuliidae (black flies).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6268840; DOI=10.1128/jvi.39.2.519-528.1981;
RA Rose J.K., Gallione C.J.;
RT "Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus
RT G and M proteins determined from cDNA clones containing the complete coding
RT regions.";
RL J. Virol. 39:519-528(1981).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=1850035; DOI=10.1128/jvi.65.5.2622-2628.1991;
RA Rigaut K.D., Birk D.E., Lenard J.;
RT "Intracellular distribution of input vesicular stomatitis virus proteins
RT after uncoating.";
RL J. Virol. 65:2622-2628(1991).
RN [3]
RP PHOSPHORYLATION.
RC STRAIN=Orsay;
RX PubMed=1323702; DOI=10.1128/jvi.66.9.5384-5392.1992;
RA Kaptur P.E., McCreedy B.J. Jr., Lyles D.S.;
RT "Sites of in vivo phosphorylation of vesicular stomatitis virus matrix
RT protein.";
RL J. Virol. 66:5384-5392(1992).
RN [4]
RP MUTAGENESIS OF MET-51.
RX PubMed=9733895; DOI=10.1128/jvi.72.10.8413-8419.1998;
RA Ahmed M., Lyles D.S.;
RT "Effect of vesicular stomatitis virus matrix protein on transcription
RT directed by host RNA polymerases I, II, and III.";
RL J. Virol. 72:8413-8419(1998).
RN [5]
RP INTERACTION WITH NUP98, AND MUTAGENESIS OF 5-LYS--ILE-7; 28-GLU--ASP-30;
RP 42-ASP--SER-44; 52-ASP--TYR-54 AND 61-TYR--LYS-63.
RX PubMed=11106761; DOI=10.1016/s1097-2765(00)00120-9;
RA von Kobbe C., van Deursen J.M., Rodrigues J.P., Sitterlin D., Bachi A.,
RA Wu X., Wilm M., Carmo-Fonseca M., Izaurralde E.;
RT "Vesicular stomatitis virus matrix protein inhibits host cell gene
RT expression by targeting the nucleoporin Nup98.";
RL Mol. Cell 6:1243-1252(2000).
RN [6]
RP ALTERNATIVE INITIATION (ISOFORMS M2 AND M3).
RX PubMed=12134006; DOI=10.1128/jvi.76.16.8011-8018.2002;
RA Jayakar H.R., Whitt M.A.;
RT "Identification of two additional translation products from the matrix (M)
RT gene that contribute to vesicular stomatitis virus cytopathology.";
RL J. Virol. 76:8011-8018(2002).
RN [7]
RP FUNCTION.
RX PubMed=16298982; DOI=10.1099/vir.0.81129-0;
RA Solon J., Gareil O., Bassereau P., Gaudin Y.;
RT "Membrane deformations induced by the matrix protein of vesicular
RT stomatitis virus in a minimal system.";
RL J. Gen. Virol. 86:3357-3363(2005).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST RAE1-NUP98 COMPLEX.
RX PubMed=15629720; DOI=10.1016/j.molcel.2004.11.023;
RA Faria P.A., Chakraborty P., Levay A., Barber G.N., Ezelle H.J., Enninga J.,
RA Arana C., van Deursen J., Fontoura B.M.;
RT "VSV disrupts the Rae1/mrnp41 mRNA nuclear export pathway.";
RL Mol. Cell 17:93-102(2005).
RN [9]
RP DOMAIN LATE-BUDDING.
RX PubMed=15220457; DOI=10.1128/jvi.78.14.7823-7827.2004;
RA Irie T., Licata J.M., Jayakar H.R., Whitt M.A., Bell P., Harty R.N.;
RT "Functional analysis of late-budding domain activity associated with the
RT PSAP motif within the vesicular stomatitis virus M protein.";
RL J. Virol. 78:7823-7827(2004).
RN [10]
RP CYTOPATHICITY.
RX PubMed=12692256; DOI=10.1128/jvi.77.9.5524-5528.2003;
RA Kopecky S.A., Lyles D.S.;
RT "The cell-rounding activity of the vesicular stomatitis virus matrix
RT protein is due to the induction of cell death.";
RL J. Virol. 77:5524-5528(2003).
RN [11]
RP DOMAIN LATE-BUDDING.
RX PubMed=16188963; DOI=10.1128/jvi.79.20.12617-12622.2005;
RA Irie T., Harty R.N.;
RT "L-domain flanking sequences are important for host interactions and
RT efficient budding of vesicular stomatitis virus recombinants.";
RL J. Virol. 79:12617-12622(2005).
RN [12]
RP MUTAGENESIS OF 121-ALA--ALA-124.
RX PubMed=16571787; DOI=10.1128/jvi.80.8.3701-3711.2006;
RA Connor J.H., McKenzie M.O., Lyles D.S.;
RT "Role of residues 121 to 124 of vesicular stomatitis virus matrix protein
RT in virus assembly and virus-host interaction.";
RL J. Virol. 80:3701-3711(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH HOST DYNAMIN.
RX PubMed=20943988; DOI=10.1128/jvi.01400-10;
RA Raux H., Obiang L., Richard N., Harper F., Blondel D., Gaudin Y.;
RT "The matrix protein of vesicular stomatitis virus binds dynamin for
RT efficient viral assembly.";
RL J. Virol. 84:12609-12618(2010).
RN [14]
RP INTERACTION WITH HOST NEDD4 AND TSG101, AND MUTAGENESIS OF LEU-4; TYR-27
RP AND PRO-40.
RC STRAIN=Indiana (Orsay);
RX PubMed=22190013; DOI=10.1099/vir.0.039800-0;
RA Obiang L., Raux H., Ouldali M., Blondel D., Gaudin Y.;
RT "Phenotypes of vesicular stomatitis virus mutants with mutations in the
RT PSAP motif of the matrix protein.";
RL J. Gen. Virol. 93:857-865(2012).
RN [15]
RP FUNCTION, INTERACTION WITH HOST GTF2H5, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF MET-51; ILE-96; GLU-156; ARG-159 AND ARG-160.
RX PubMed=28888655; DOI=10.1016/j.vetmic.2017.07.020;
RA Pan W., Song D., He W., Lu H., Lan Y., Tong J., Gao F., Zhao K.;
RT "The matrix protein of vesicular stomatitis virus inhibits host-directed
RT transcription of target genes via interaction with the TFIIH subunit p8.";
RL Vet. Microbiol. 208:82-88(2017).
RN [16]
RP INTERACTION WITH HOST NDUFAF4, AND MUTAGENESIS OF 156-GLU-HIS-157; GLU-156
RP AND 180-ASP-GLU-181.
RX PubMed=33635491; DOI=10.1007/s11262-021-01833-0;
RA Pan W., Shen Z., Wang H., He H.;
RT "The host cellular protein Ndufaf4 interacts with the vesicular stomatitis
RT virus M protein and affects viral propagation.";
RL Virus Genes 57:250-257(2021).
RN [17]
RP VARIANT ALA-133, FUNCTION, AND INTERACTION WITH HUMAN RAE1-NUP98 COMPLEX.
RC STRAIN=pVSV1(+)-GFP;
RX PubMed=33849972; DOI=10.1128/mbio.00065-21;
RA Addetia A., Lieberman N.A.P., Phung Q., Hsiang T.Y., Xie H.,
RA Roychoudhury P., Shrestha L., Loprieno M.A., Huang M.L., Gale M. Jr.,
RA Jerome K.R., Greninger A.L.;
RT "SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through
RT Interactions with Rae1 and Nup98.";
RL MBio 12:0-0(2021).
CC -!- FUNCTION: Plays a major role in assembly and budding of virion, by
CC recruiting cellular partners of the ESCRT complexes that play a key
CC role in releasing the budding particle from the host membrane.
CC Condensates the ribonucleocapsid core during virus assembly.
CC {ECO:0000269|PubMed:16298982, ECO:0000269|PubMed:20943988}.
CC -!- FUNCTION: Inhibits mRNA nuclear export through direct interaction with
CC host RAE1-NUP98 complex, thereby preventing interferon signaling and
CC establishment of antiviral state in infected cells (PubMed:15629720,
CC PubMed:33849972). Induces cell-rounding, cytoskeleton disorganization
CC and apoptosis in infected cell (PubMed:15629720). Inhibits host
CC transcription, possibly through interaction with host DNA repair factor
CC IIH/TFIIH GTF2H5 subunit (PubMed:28888655).
CC {ECO:0000269|PubMed:15629720, ECO:0000269|PubMed:28888655,
CC ECO:0000269|PubMed:33849972}.
CC -!- SUBUNIT: Homomultimer. Interacts with viral nucleocapsid. Interacts
CC with host NEDD4 and TSG101 (PubMed:22190013). Interacts with host
CC dynamin (PubMed:20943988). Interacts with host RAE1-NUP98 complex
CC (PubMed:11106761, PubMed:15629720, PubMed:33849972). Interacts with
CC host NDUFAF4; the interaction inhibits viral propagation and is
CC independent of interferon activation (PubMed:33635491). Interacts with
CC host GTF2H5; the interaction may inhibit host transcription
CC (PubMed:28888655). {ECO:0000269|PubMed:11106761,
CC ECO:0000269|PubMed:15629720, ECO:0000269|PubMed:20943988,
CC ECO:0000269|PubMed:22190013, ECO:0000269|PubMed:28888655,
CC ECO:0000269|PubMed:33635491, ECO:0000269|PubMed:33849972}.
CC -!- SUBCELLULAR LOCATION: Virion membrane; Peripheral membrane protein
CC {ECO:0000269|PubMed:1850035}. Host endomembrane system; Peripheral
CC membrane protein. Host nucleus membrane; Peripheral membrane protein.
CC Host nucleus {ECO:0000269|PubMed:28888655}. Host cytoplasm
CC {ECO:0000269|PubMed:28888655}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=3;
CC Name=M;
CC IsoId=P03519-1; Sequence=Displayed;
CC Name=M2 {ECO:0000303|PubMed:12134006};
CC IsoId=P03519-2; Sequence=VSP_025421;
CC Name=M3 {ECO:0000303|PubMed:12134006};
CC IsoId=P03519-3; Sequence=VSP_025420;
CC -!- DOMAIN: Late-budding domains (L domains) are short sequence motifs
CC essential for viral particle budding. They recruit proteins of the host
CC ESCRT machinery (Endosomal Sorting Complex Required for Transport) or
CC ESCRT-associated proteins. M contains two overlapping L domains: a PPXY
CC motif which interacts with the WW domain 3 of NEDD4 and a PTAP/PSAP
CC motif, which interacts with the UEV domain of TSG101.
CC {ECO:0000269|PubMed:15220457, ECO:0000269|PubMed:16188963}.
CC -!- PTM: Phosphorylated by host. {ECO:0000269|PubMed:1323702}.
CC -!- BIOTECHNOLOGY: VSV is used as an oncolytic agent for cancer therapy,
CC because of his wide host range, rapid replication and mild
CC pathogenicity in humans. VSV used are mutated at M51R in their matrix
CC protein. These mutated viruses cannot successfully infect normal cells,
CC being unable to counteract the antiviral state induced by interferon-
CC alpha in normal cells. Cancer cells are impeded with responsiveness to
CC interferon, and then can be successfully infected and lysed by the
CC virus.
CC -!- MISCELLANEOUS: Most abundant protein in the virion.
CC -!- SIMILARITY: Belongs to the vesiculoviruses matrix protein family.
CC {ECO:0000305}.
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DR EMBL; J02428; AAA48369.1; -; Genomic_RNA.
DR RefSeq; NP_041714.1; NC_001560.1.
DR SMR; P03519; -.
DR ELM; P03519; -.
DR IntAct; P03519; 3.
DR MINT; P03519; -.
DR TCDB; 9.A.73.2.1; the virus matrix protein (vmp) family.
DR DNASU; 1489833; -.
DR GeneID; 1489833; -.
DR KEGG; vg:1489833; -.
DR Proteomes; UP000002327; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044200; C:host cell nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:InterPro.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0039660; F:structural constituent of virion; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0039522; P:suppression by virus of host mRNA export from nucleus; IDA:UniProtKB.
DR GO; GO:0039602; P:suppression by virus of host transcription initiation from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0039702; P:viral budding via host ESCRT complex; IDA:UniProtKB.
DR Gene3D; 3.10.460.10; -; 1.
DR InterPro; IPR009397; Vesiculo_matrix.
DR InterPro; IPR036711; VSV_matrix_sf.
DR Pfam; PF06326; Vesiculo_matrix; 1.
DR SUPFAM; SSF75404; SSF75404; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Apoptosis;
KW Eukaryotic host gene expression shutoff by virus; Host cytoplasm;
KW Host gene expression shutoff by virus; Host membrane;
KW Host mRNA suppression by virus; Host nucleus; Host-virus interaction;
KW Inhibition of host mRNA nuclear export by virus; Membrane; Phosphoprotein;
KW Reference proteome; Viral budding;
KW Viral budding via the host ESCRT complexes; Viral matrix protein;
KW Viral release from host cell; Virion.
FT CHAIN 1..229
FT /note="Matrix protein"
FT /id="PRO_0000222857"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 2..4
FT /note="dynamin binding"
FT /evidence="ECO:0000269|PubMed:20943988"
FT MOTIF 24..27
FT /note="PPXY motif"
FT MOTIF 37..40
FT /note="PTAP/PSAP motif"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform M3)"
FT /evidence="ECO:0000305"
FT /id="VSP_025420"
FT VAR_SEQ 1..32
FT /note="Missing (in isoform M2)"
FT /evidence="ECO:0000305"
FT /id="VSP_025421"
FT VARIANT 133
FT /note="T -> A (in strain: pVSV1(+)-GFP)"
FT /evidence="ECO:0000269|PubMed:33849972"
FT MUTAGEN 4
FT /note="L->A: No effect on host NEDD4 or TSG101 binding."
FT /evidence="ECO:0000269|PubMed:11106761"
FT MUTAGEN 5..7
FT /note="KKI->AAA: No effect on mRNA nuclear export
FT inhibition."
FT /evidence="ECO:0000269|PubMed:11106761"
FT MUTAGEN 27
FT /note="Y->A: Partial loss of host NEDD4 binding."
FT /evidence="ECO:0000269|PubMed:22190013"
FT MUTAGEN 28..30
FT /note="EED->AAA: No effect on mRNA nuclear export
FT inhibition."
FT /evidence="ECO:0000269|PubMed:11106761"
FT MUTAGEN 40
FT /note="P->A: Partial loss of host TSG101 binding."
FT /evidence="ECO:0000269|PubMed:22190013"
FT MUTAGEN 42..44
FT /note="DKS->AAA: No effect on mRNA nuclear export
FT inhibition."
FT /evidence="ECO:0000269|PubMed:11106761"
FT MUTAGEN 51
FT /note="M->R: Complete loss of mRNA nuclear export
FT inhibition. Loss of ability to inhibit host transcription."
FT /evidence="ECO:0000269|PubMed:28888655,
FT ECO:0000269|PubMed:9733895"
FT MUTAGEN 52..54
FT /note="DTY->AAA: Complete loss of mRNA nuclear export
FT inhibition."
FT /evidence="ECO:0000269|PubMed:11106761"
FT MUTAGEN 61..63
FT /note="YEK->AAA: No effect on mRNA nuclear export
FT inhibition."
FT /evidence="ECO:0000269|PubMed:11106761"
FT MUTAGEN 96
FT /note="I->A: Loss of mouse GTF2H5 binding. Loss of ability
FT to inhibit host transcription."
FT /evidence="ECO:0000269|PubMed:28888655"
FT MUTAGEN 121..124
FT /note="AVLA->DKQQ: No effect on virion budding. Increase
FT viral-mRNA translation."
FT /evidence="ECO:0000269|PubMed:16571787"
FT MUTAGEN 156..157
FT /note="EH->AA: Loss of host NDUFAF4 binding."
FT /evidence="ECO:0000269|PubMed:33635491"
FT MUTAGEN 156
FT /note="E->A: Loss of host NDUFAF4 binding. Loss of host
FT GTF2H5 binding. Loss of ability to inhibit host
FT transcription."
FT /evidence="ECO:0000269|PubMed:28888655,
FT ECO:0000269|PubMed:33635491"
FT MUTAGEN 159
FT /note="R->A: Loss of host GTF2H5 binding. Loss of ability
FT to inhibit host transcription."
FT /evidence="ECO:0000269|PubMed:28888655"
FT MUTAGEN 160
FT /note="R->A: Loss of host GTF2H5 binding. Loss of ability
FT to inhibit host transcription."
FT /evidence="ECO:0000269|PubMed:28888655"
FT MUTAGEN 180..181
FT /note="DE->AA: Loss of host NDUFAF4 binding."
FT /evidence="ECO:0000269|PubMed:33635491"
SQ SEQUENCE 229 AA; 26094 MW; C89E2ACA4365B847 CRC64;
MSSLKKILGL KGKGKKSKKL GIAPPPYEED TSMEYAPSAP IDKSYFGVDE MDTYDPNQLR
YEKFFFTVKM TVRSNRPFRT YSDVAAAVSH WDHMYIGMAG KRPFYKILAF LGSSNLKATP
AVLADQGQPE YHTHCEGRAY LPHRMGKTPP MLNVPEHFRR PFNIGLYKGT IELTMTIYDD
ESLEAAPMIW DHFNSSKFSD FREKALMFGL IVEKKASGAW VLDSISHFK
