M21_HMPVC
ID M21_HMPVC Reviewed; 187 AA.
AC Q6WB97;
DT 15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 64.
DE RecName: Full=Protein M2-1;
DE AltName: Full=Envelope-associated 22 kDa protein;
GN Name=M2-1;
OS Human metapneumovirus (strain CAN97-83) (HMPV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Metapneumovirus.
OX NCBI_TaxID=694067;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=14592754; DOI=10.1016/s0042-6822(03)00528-2;
RA Biacchesi S., Skiadopoulos M.H., Boivin G., Hanson C.T., Murphy B.R.,
RA Collins P.L., Buchholz U.J.;
RT "Genetic diversity between human metapneumovirus subgroups.";
RL Virology 315:1-9(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=16306583; DOI=10.1128/jvi.79.24.15114-15122.2005;
RA Pham Q.N., Biacchesi S., Skiadopoulos M.H., Murphy B.R., Collins P.L.,
RA Buchholz U.J.;
RT "Chimeric recombinant human metapneumoviruses with the nucleoprotein or
RT phosphoprotein open reading frame replaced by that of avian metapneumovirus
RT exhibit improved growth in vitro and attenuation in vivo.";
RL J. Virol. 79:15114-15122(2005).
RN [3]
RP FUNCTION.
RC STRAIN=CAN97-83;
RX PubMed=15890897; DOI=10.1128/jvi.79.11.6588-6597.2005;
RA Buchholz U.J., Biacchesi S., Pham Q.N., Tran K.C., Yang L., Luongo C.L.,
RA Skiadopoulos M.H., Murphy B.R., Collins P.L.;
RT "Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus:
RT effects on RNA synthesis, attenuation, and immunogenicity.";
RL J. Virol. 79:6588-6597(2005).
RN [4]
RP DOMAIN, AND MUTAGENESIS OF CYS-7; CYS-15; CYS-21 AND HIS-25.
RC STRAIN=NL/1/00;
RX PubMed=25855728; DOI=10.1128/jvi.03488-14;
RA Cai H., Zhang Y., Ma Y., Sun J., Liang X., Li J.;
RT "Zinc binding activity of human metapneumovirus M2-1 protein is
RT indispensable for viral replication and pathogenesis in vivo.";
RL J. Virol. 89:6391-6405(2015).
RN [5]
RP PHOSPHORYLATION AT SER-57 AND SER-60.
RC STRAIN=NL/1/00;
RX PubMed=27252537; DOI=10.1128/jvi.00755-16;
RA Cai H., Zhang Y., Lu M., Liang X., Jennings R., Niewiesk S., Li J.;
RT "Phosphorylation of Human Metapneumovirus M2-1 Protein Upregulates Viral
RT Replication and Pathogenesis.";
RL J. Virol. 90:7323-7338(2016).
CC -!- FUNCTION: Essential for viral replication in vivo (PubMed:15890897).
CC Plays a role in the association of the matrix protein with the
CC nucleocapsid, which initiates assembly and budding (By similarity).
CC {ECO:0000250|UniProtKB:P04545, ECO:0000269|PubMed:15890897}.
CC -!- SUBUNIT: Homotetramer. The homotetramer interacts with RNA. Interacts
CC with the phosphoprotein (P); this interaction is required for protein
CC M2-1 function, localization in host inclusion bodies. Interacts with
CC the nucleoprotein (N). Interacts with the matrix protein (M); this
CC interaction directs M localization to cytoplasmic inclusions comprising
CC viral proteins L, N, P, and M2-1 and mediates M association with the
CC nucleocapsid. {ECO:0000250|UniProtKB:P04545}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P04545}. Host
CC cytoplasm {ECO:0000250|UniProtKB:P04545}. Host nucleus
CC {ECO:0000250|UniProtKB:P04545}. Note=Localizes in cytoplasmic inclusion
CC bodies substructures called inclusion bodies associated granules
CC (IBAGs). Forms a layer between the matrix and nucleocapsid.
CC {ECO:0000250|UniProtKB:P04545}.
CC -!- DOMAIN: Contains a zinc-finger domain on its N-terminus essential for
CC its function (PubMed:25855728). Contains an oligomerization domain (By
CC similarity). The central globular core is responsible for binding to
CC RNA and phosphoprotein (By similarity). {ECO:0000250|UniProtKB:P04545,
CC ECO:0000269|PubMed:25855728}.
CC -!- PTM: Phosphorylated by host in infected cells (PubMed:27252537).
CC Phosphorylation is not essential for zinc binding activity and
CC oligomerization, but zinc binding activity is necessary for the
CC phosphorylation and oligomerization (PubMed:27252537). Phosphorylation
CC up-regulates viral RNA synthesis, replication, and pathogenesis in vivo
CC (PubMed:27252537). {ECO:0000269|PubMed:27252537}.
CC -!- SIMILARITY: Belongs to the pneumoviridae M2-1 protein family.
CC {ECO:0000305}.
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DR EMBL; AY297749; AAQ67696.1; -; Genomic_RNA.
DR RefSeq; YP_012609.1; NC_004148.2.
DR SMR; Q6WB97; -.
DR PRIDE; Q6WB97; -.
DR Proteomes; UP000001398; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0046782; P:regulation of viral transcription; IEA:InterPro.
DR InterPro; IPR009452; Pneumovirus_M2-1.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR Pfam; PF06436; Pneumovirus_M2; 1.
DR Pfam; PF00642; zf-CCCH; 1.
DR PIRSF; PIRSF003913; Matrix_glycop-M2_paramyxo; 1.
DR SMART; SM00356; ZnF_C3H1; 1.
DR SUPFAM; SSF90229; SSF90229; 1.
DR PROSITE; PS50103; ZF_C3H1; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host nucleus; Metal-binding; Phosphoprotein;
KW Reference proteome; RNA-binding; Virion; Zinc; Zinc-finger.
FT CHAIN 1..187
FT /note="Protein M2-1"
FT /id="PRO_0000394812"
FT ZN_FING 1..28
FT /note="C3H1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723,
FT ECO:0000269|PubMed:25855728"
FT REGION 32..49
FT /note="Oligomerization"
FT /evidence="ECO:0000250|UniProtKB:P04545"
FT REGION 75..167
FT /note="Globular core"
FT /evidence="ECO:0000250|UniProtKB:P04545"
FT SITE 8
FT /note="Involved in RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P04545"
FT SITE 23
FT /note="Involved in RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P04545"
FT SITE 91
FT /note="Involved in RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P04545"
FT SITE 149
FT /note="Involved in RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P04545"
FT MOD_RES 57
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:27252537"
FT MOD_RES 60
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:27252537"
FT MUTAGEN 7
FT /note="C->S: 58% loss of zinc binding and loss of
FT homotetramerization. Delayed viral replication."
FT /evidence="ECO:0000269|PubMed:25855728"
FT MUTAGEN 15
FT /note="C->S: 62% loss of zinc binding and loss of
FT homotetramerization. Delayed viral replication."
FT /evidence="ECO:0000269|PubMed:25855728"
FT MUTAGEN 21
FT /note="C->S: Almost complete loss of zinc binding and loss
FT of homotetramerization. Delayed viral replication."
FT /evidence="ECO:0000269|PubMed:25855728"
FT MUTAGEN 25
FT /note="H->L: Almost complete loss of zinc binding and loss
FT of homotetramerization. Delayed viral replication."
FT /evidence="ECO:0000269|PubMed:25855728"
SQ SEQUENCE 187 AA; 21234 MW; 70FD9F9C665CCAE2 CRC64;
MSRKAPCKYE VRGKCNRGSE CKFNHNYWSW PDRYLLIRSN YLLNQLLRNT DRADGLSIIS
GAGREDRTQD FVLGSTNVVQ GYIDDNQSIT KAAACYSLHN IIKQLQEVEV RQARDSKLSD
SKHVALHNLI LSYMEMSKTP ASLINNLKRL PREKLKKLAK LIIDLSAGAD NDSSYALQDS
ESINQVQ
