ID MU1_REOVL Reviewed; 708 AA. AC P11077; Q85657; Q8QR20; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 4. DT 24-JAN-2024, entry version 134. DE RecName: Full=Outer capsid protein mu-1; DE Short=Mu1; DE Contains: DE RecName: Full=Outer capsid protein mu-1N; DE Contains: DE RecName: Full=Outer capsid protein mu-1C; GN Name=M2; OS Reovirus type 1 (strain Lang) (T1L) (Mammalian orthoreovirus 1). OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes; OC Reovirales; Spinareoviridae; Orthoreovirus; Mammalian orthoreovirus. OX NCBI_TaxID=10884; OH NCBI_TaxID=40674; Mammalia. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=3363862; DOI=10.1016/0042-6822(88)90629-0; RA Tarlow O., McCorquodale J.G., McCrae M.A.; RT "Molecular cloning and sequencing of the gene (M2) encoding the major RT virion structural protein (mu 1-mu 1C) of serotypes 1 and 3 of mammalian RT reovirus."; RL Virology 164:141-146(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3354208; DOI=10.1016/0042-6822(88)90301-7; RA Wiener J.R., Joklik W.K.; RT "Evolution of reovirus genes: a comparison of serotype 1, 2, and 3 M2 RT genome segments, which encode the major structural capsid protein mu 1C."; RL Virology 163:603-613(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Isolate T1/Human/Ohio/1953; RX PubMed=10196289; DOI=10.1128/jvi.73.5.3941-3950.1999; RA Chandran K., Walker S.B., Chen Y., Contreras C.M., Schiff L.A., Baker T.S., RA Nibert M.L.; RT "In vitro recoating of reovirus cores with baculovirus-expressed outer- RT capsid proteins mu1 and sigma3."; RL J. Virol. 73:3941-3950(1999). RN [4] RP PROTEOLYTIC PROCESSING. RX PubMed=1328674; DOI=10.1128/jvi.66.11.6408-6418.1992; RA Nibert M.L., Fields B.N.; RT "A carboxy-terminal fragment of protein mu 1/mu 1C is present in infectious RT subvirion particles of mammalian reoviruses and is proposed to have a role RT in penetration."; RL J. Virol. 66:6408-6418(1992). RN [5] RP FUNCTION. RX PubMed=11007773; DOI=10.1074/jbc.m004562200; RA Farsetta D.L., Chandran K., Nibert M.L.; RT "Transcriptional activities of reovirus RNA polymerase in recoated cores. RT Initiation and elongation are regulated by separate mechanisms."; RL J. Biol. Chem. 275:39693-39701(2000). RN [6] RP FUNCTION, AND MUTAGENESIS OF ASN-42. RX PubMed=15280481; DOI=10.1128/jvi.78.16.8732-8745.2004; RA Odegard A.L., Chandran K., Zhang X., Parker J.S.L., Baker T.S., RA Nibert M.L.; RT "Putative autocleavage of outer capsid protein micro1, allowing release of RT myristoylated peptide micro1N during particle uncoating, is critical for RT cell entry by reovirus."; RL J. Virol. 78:8732-8745(2004). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16912293; DOI=10.1128/jvi.02601-05; RA Coffey C.M., Sheh A., Kim I.S., Chandran K., Nibert M.L., Parker J.S.L.; RT "Reovirus outer capsid protein micro1 induces apoptosis and associates with RT lipid droplets, endoplasmic reticulum, and mitochondria."; RL J. Virol. 80:8422-8438(2006). RN [8] RP FUNCTION. RX PubMed=17005655; DOI=10.1128/jvi.01343-06; RA Zhang L., Chandran K., Nibert M.L., Harrison S.C.; RT "Reovirus mu1 structural rearrangements that mediate membrane RT penetration."; RL J. Virol. 80:12367-12376(2006). RN [9] RP FUNCTION, AND MUTAGENESIS OF ASN-42. RX PubMed=18369316; DOI=10.1038/emboj.2008.60; RA Ivanovic T., Agosto M.A., Zhang L., Chandran K., Harrison S.C., RA Nibert M.L.; RT "Peptides released from reovirus outer capsid form membrane pores that RT recruit virus particles."; RL EMBO J. 27:1289-1298(2008). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH SIGMA-3. RX PubMed=11832217; DOI=10.1016/s0092-8674(02)00612-8; RA Liemann S., Chandran K., Baker T.S., Nibert M.L., Harrison S.C.; RT "Structure of the reovirus membrane-penetration protein, Mu1, in a complex RT with is protector protein, Sigma3."; RL Cell 108:283-295(2002). RN [11] RP STRUCTURE BY ELECTRON MICROSCOPY (7.0 ANGSTROMS). RX PubMed=16216585; DOI=10.1016/j.str.2005.07.012; RA Zhang X., Ji Y., Zhang L., Harrison S.C., Marinescu D.C., Nibert M.L., RA Baker T.S.; RT "Features of reovirus outer capsid protein mu1 revealed by electron RT cryomicroscopy and image reconstruction of the virion at 7.0 Angstrom RT resolution."; RL Structure 13:1545-1557(2005). CC -!- FUNCTION: Major outer capsid protein involved in host cell membrane CC penetration. In the endocytic compartment, outer-capsid protein sigma-3 CC is removed by cathepsin proteases, which exposes the viral membrane- CC penetration protein mu-1. Both myristoylated peptides mu-1N and phi are CC released during infectious subvirion particles (ISVP) formation in the CC endosome. They associate with host membranes and mu-1N induces CC permeabilization and delivery of transcriptionally active viral CC particles into the host cell cytoplasm. Seems to induce apoptosis in CC the host cell. CC -!- FUNCTION: The viral outer shell polypeptides, of which mu-1 is one, CC impose structural constraints that prevent elongation of nascent CC transcripts by the RNA-dependent RNA polymerase lambda-3. CC -!- SUBUNIT: Heterohexamer of three sigma-3 and three Mu-1 proteins. CC {ECO:0000269|PubMed:11832217}. CC -!- SUBCELLULAR LOCATION: [Outer capsid protein mu-1]: Virion. Host cell CC membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Host endoplasmic CC reticulum. Host mitochondrion. Note=Found in the outer capsid. Seems to CC associate with cell membranes. This association is enhanced by CC myristoylation (By similarity). {ECO:0000250}. CC -!- DOMAIN: The C-terminal region, phi, determines both targeting to CC intracellular membranes and induction of apoptosis. {ECO:0000305}. CC -!- PTM: Cleaved during the endosomal proteolytic disassembly of the outer CC capsid. Mu-1 is proteolytically cleaved into mu-1N and mu-1C during the CC maturation step to generate the ISVP. Cleavage of mu-1 to mu-1C is CC dependent on myristoylation and binding to sigma-3 protein. Mu-1C is CC further cleaved into delta (59 kDa), and phi (13 kDa) segments during CC entry into the host cell cytoplasm. {ECO:0000269|PubMed:1328674}. CC -!- PTM: Mu-1 and mu-1N are N-terminally myristoylated. This acylation is CC essential for the membrane fusion activity (By similarity). CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the orthoreovirus mu-1 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; M19407; AAA47237.1; -; Genomic_RNA. DR EMBL; M19345; AAA47236.1; -; mRNA. DR EMBL; AF490617; AAM10735.1; -; mRNA. DR PIR; A28607; M2XR2L. DR PIR; A28612; M2XR1L. DR PDB; 1JMU; X-ray; 2.80 A; A/C/E=2-42, B/D/F=43-708. DR PDB; 2CSE; EM; 7.00 A; A/B/C/J/K/L/P/Q/R/T=1-708. DR PDB; 6XF8; EM; 6.50 A; F/K=43-675. DR PDB; 6ZTY; EM; -; H/I/J=10-675. DR PDB; 6ZTZ; EM; -; K/L/M=10-675. DR PDBsum; 1JMU; -. DR PDBsum; 2CSE; -. DR PDBsum; 6XF8; -. DR PDBsum; 6ZTY; -. DR PDBsum; 6ZTZ; -. DR EMDB; EMD-22166; -. DR SMR; P11077; -. DR IntAct; P11077; 1. DR MEROPS; N07.001; -. DR GlyCosmos; P11077; 7 sites, No reported glycans. DR EvolutionaryTrace; P11077; -. DR Proteomes; UP000007253; Genome. DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0019028; C:viral capsid; IDA:CACAO. DR GO; GO:0039624; C:viral outer capsid; IEA:UniProtKB-KW. DR GO; GO:0046812; F:host cell surface binding; IEA:InterPro. DR GO; GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; IEA:UniProtKB-KW. DR GO; GO:0099008; P:viral entry via permeabilization of inner membrane; IEA:UniProtKB-KW. DR Gene3D; 2.60.120.420; Membrane penetration protein mu1, Chain B, domain 4; 1. DR Gene3D; 3.90.1370.10; Protein mu-1, chain B, domain 1; 1. DR Gene3D; 1.10.2040.10; Protein mu-1, chain B, domain 2; 1. DR Gene3D; 1.10.2050.10; Protein mu-1, chain B, domain 3; 1. DR InterPro; IPR009113; Mu1/VP4. DR InterPro; IPR036256; Mu1/VP4_sf. DR InterPro; IPR015961; Mu1_membr_pen_domI. DR InterPro; IPR015962; Mu1_membr_pen_domII. DR InterPro; IPR044937; Mu1_membr_pen_domIII. DR InterPro; IPR015960; Mu1_membr_pen_domIV. DR Pfam; PF05993; Reovirus_M2; 1. DR SUPFAM; SSF69908; Membrane penetration protein mu1; 1. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Capsid protein; Glycoprotein; Host cell membrane; KW Host endoplasmic reticulum; Host membrane; Host mitochondrion; Lipoprotein; KW Membrane; Myristate; Outer capsid protein; Reference proteome; KW Viral penetration into host cytoplasm; KW Viral penetration via permeabilization of host membrane; Virion; KW Virus entry into host cell. FT INIT_MET 1 FT /note="Removed; by host" FT /evidence="ECO:0000250" FT CHAIN 2..708 FT /note="Outer capsid protein mu-1" FT /id="PRO_0000040662" FT CHAIN 2..42 FT /note="Outer capsid protein mu-1N" FT /id="PRO_0000344980" FT CHAIN 43..708 FT /note="Outer capsid protein mu-1C" FT /id="PRO_0000040664" FT REGION 674..708 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 42..43 FT /note="Cleavage" FT /evidence="ECO:0000250" FT LIPID 2 FT /note="N-myristoyl glycine; by host" FT /evidence="ECO:0000250" FT CARBOHYD 12 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 81 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 458 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 482 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 528 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 659 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT MUTAGEN 42 FT /note="N->A: Complete loss of mu-1N cleavage and host FT membrane penetration." FT /evidence="ECO:0000269|PubMed:15280481, FT ECO:0000269|PubMed:18369316" FT CONFLICT 3 FT /note="N -> T (in Ref. 1; AAA47237)" FT /evidence="ECO:0000305" FT CONFLICT 237..238 FT /note="AV -> LL (in Ref. 1; AAA47237)" FT /evidence="ECO:0000305" FT CONFLICT 272 FT /note="P -> L (in Ref. 2; AAA47236)" FT /evidence="ECO:0000305" FT CONFLICT 284 FT /note="K -> R (in Ref. 2; AAA47236)" FT /evidence="ECO:0000305" FT CONFLICT 644 FT /note="V -> M (in Ref. 1; AAA47237)" FT /evidence="ECO:0000305" FT STRAND 15..17 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 24..26 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 38..41 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 45..55 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 60..62 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 63..65 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 105..119 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 122..127 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 137..140 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 142..151 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 152..156 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 159..166 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 168..198 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 204..207 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 212..222 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:6ZTZ" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 233..243 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 245..248 FT /evidence="ECO:0007829|PDB:6ZTY" FT TURN 252..254 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 264..270 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 274..276 FT /evidence="ECO:0007829|PDB:6ZTY" FT HELIX 279..296 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 298..301 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 309..312 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:1JMU" FT TURN 323..325 FT /evidence="ECO:0007829|PDB:1JMU" FT TURN 328..330 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 334..336 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 339..341 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 344..351 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 356..362 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 366..369 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 371..373 FT /evidence="ECO:0007829|PDB:6ZTZ" FT STRAND 375..381 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 398..408 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 410..412 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 416..418 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 420..429 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 441..443 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 448..452 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 454..457 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 465..476 FT /evidence="ECO:0007829|PDB:1JMU" FT TURN 480..482 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 490..498 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 503..505 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 508..513 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 515..518 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 524..529 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 535..553 FT /evidence="ECO:0007829|PDB:1JMU" FT TURN 563..565 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 566..575 FT /evidence="ECO:0007829|PDB:1JMU" FT STRAND 581..583 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 589..605 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 607..611 FT /evidence="ECO:0007829|PDB:1JMU" FT TURN 616..619 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 621..636 FT /evidence="ECO:0007829|PDB:1JMU" FT HELIX 644..671 FT /evidence="ECO:0007829|PDB:1JMU" SQ SEQUENCE 708 AA; 76233 MW; 12F3839798DF355F CRC64; MGNASSIVQT INVTGDGNVF KPSAETSSTA VPSLSLSPGM LNPGGVPWIA IGDETSVTSP GALRRMTSKD IPETAIINTD NSSGAVPSES ALVPYNDEPL VVVTEHAIAN FTKAEMALEF NREFLDKLRV LSVSPKYSDL LTYVDCYVGV SARQALNNFQ KQVPVITPTR QTMYVDSIQA ALKALEKWEI DLRVAQTLLP TNVPIGEVSC PMQSVVKLLD DQLPDDSLIR RYPKEAAVAL AKRNGGIQWM DVSEGTVMNE AVNAVAASAL APSASAPPLE EKSKLTEQAM DLVTAAEPEI IASLVPVPAP VFAIPPKPAD YNVRTLKIDE ATWLRMIPKT MGTPFQIQVT DNTGTNWHLN LRGGTRVVNL DQIAPMRFVL DLGGKSYKET SWDPNGKKVG FIVFQSKIPF ELWTAASQIG QATVVNYVQL YAEDSSFTAQ SIIATTSLAY NYEPEQLNKT DPEMNYYLLA TFIDSAAITP TNMTQPDVWD ALLTMSPLSA GEVTVKGAVV SEVVPAELIG SYTPESLNAS LPNDAARCMI DRASKIAEAI KIDDDAGPDE YSPNSVPIQG QLAISQLETG YGVRIFNPKG ILSKIASRAM QAFIGDPSTI ITQAAPVLSD KNNWIALAQG VKTSLRTKSL SAGVKTAVSK LSSSESIQNW TQGFLDKVST HFPAPKPDCP TNGDGSEPSA RRVKRDSYAG VVKRGYTR //