VL2_HPV16
ID VL2_HPV16 Reviewed; 473 AA.
AC P03107; Q71BI1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Minor capsid protein L2 {ECO:0000255|HAMAP-Rule:MF_04003};
GN Name=L2 {ECO:0000255|HAMAP-Rule:MF_04003};
OS Human papillomavirus type 16.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=333760;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2990099; DOI=10.1016/0042-6822(85)90214-4;
RA Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W.G.;
RT "Human papillomavirus type 16 DNA sequence.";
RL Virology 145:181-185(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate European German 131;
RA Terai M., Fu L., Ma Z., Burk R.D.;
RT "Cloning and sequencing of non-European human papillomavirus (HPV) variant
RT complete genomes from cervicovaginal cells by an overlapping PCR method.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH PROTEIN L1, AND PHOSPHORYLATION.
RX PubMed=1662690; DOI=10.1099/0022-1317-72-12-2981;
RA Xi S.Z., Banks L.M.;
RT "Baculovirus expression of the human papillomavirus type 16 capsid
RT proteins: detection of L1-L2 protein complexes.";
RL J. Gen. Virol. 72:2981-2988(1991).
RN [4]
RP INTERACTION WITH HUMAN GADD45GIP1.
RC TISSUE=Keratinocyte;
RX PubMed=12482659; DOI=10.1006/viro.2002.1670;
RA Goernemann J., Hofmann T.G., Will H., Mueller M.;
RT "Interaction of human papillomavirus type 16 L2 with cellular proteins:
RT identification of novel nuclear body-associated proteins.";
RL Virology 303:69-78(2002).
RN [5]
RP DNA-BINDING.
RX PubMed=8289365; DOI=10.1128/jvi.68.2.619-625.1994;
RA Zhou J., Sun X.Y., Louis K., Frazer I.H.;
RT "Interaction of human papillomavirus (HPV) type 16 capsid proteins with HPV
RT DNA requires an intact L2 N-terminal sequence.";
RL J. Virol. 68:619-625(1994).
RN [6]
RP FUNCTION.
RX PubMed=8553535; DOI=10.1006/viro.1995.0044;
RA Heino P., Dillner J., Schwartz S.;
RT "Human papillomavirus type 16 capsid proteins produced from recombinant
RT Semliki Forest virus assemble into virus-like particles.";
RL Virology 214:349-359(1995).
RN [7]
RP INTERACTION WITH HOST HSPA8.
RX PubMed=15140951; DOI=10.1128/jvi.78.11.5546-5553.2004;
RA Florin L., Becker K.A., Sapp C., Lambert C., Sirma H., Muller M.,
RA Streeck R.E., Sapp M.;
RT "Nuclear translocation of papillomavirus minor capsid protein L2 requires
RT Hsc70.";
RL J. Virol. 78:5546-5553(2004).
RN [8]
RP FUNCTION, INTERACTION WITH IMPORTINS KPNB2 AND KPNB3, AND NUCLEAR
RP LOCALIZATION SIGNALS.
RX PubMed=15507604; DOI=10.1128/jvi.78.22.12179-12188.2004;
RA Darshan M.S., Lucchi J., Harding E., Moroianu J.;
RT "The l2 minor capsid protein of human papillomavirus type 16 interacts with
RT a network of nuclear import receptors.";
RL J. Virol. 78:12179-12188(2004).
RN [9]
RP FUNCTION, AND INTERACTION WITH E2.
RX PubMed=15681049; DOI=10.1016/j.virusres.2004.07.004;
RA Okoye A., Cordano P., Taylor E.R., Morgan I.M., Everett R., Campo M.S.;
RT "Human papillomavirus 16 L2 inhibits the transcriptional activation
RT function, but not the DNA replication function, of HPV-16 E2.";
RL Virus Res. 108:1-14(2005).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=19095951; DOI=10.2353/ajpath.2009.080588;
RA Lin Z., Yemelyanova A.V., Gambhira R., Jagu S., Meyers C., Kirnbauer R.,
RA Ronnett B.M., Gravitt P.E., Roden R.B.;
RT "Expression pattern and subcellular localization of human papillomavirus
RT minor capsid protein L2.";
RL Am. J. Pathol. 174:136-143(2009).
RN [11]
RP MUTAGENESIS OF CYS-22 AND CYS-28, AND DISULFIDE BOND.
RX PubMed=19214230; DOI=10.1371/journal.pone.0004463;
RA Campos S.K., Ozbun M.A.;
RT "Two highly conserved cysteine residues in HPV16 L2 form an intramolecular
RT disulfide bond and are critical for infectivity in human keratinocytes.";
RL PLoS ONE 4:E4463-E4463(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH HUMAN DYNLT1.
RX PubMed=21166973; DOI=10.1111/j.1462-5822.2010.01515.x;
RA Schneider M.A., Spoden G.A., Florin L., Lambert C.;
RT "Identification of the dynein light chains required for human
RT papillomavirus infection.";
RL Cell. Microbiol. 13:32-46(2011).
RN [13]
RP CLEAVAGE BY HOST FURIN.
RX PubMed=26569287; DOI=10.3390/v7112910;
RA Cruz L., Biryukov J., Conway M.J., Meyers C.;
RT "Cleavage of the HPV16 minor capsid protein L2 during virion morphogenesis
RT ablates the requirement for cellular furin during De Novo infection.";
RL Viruses 7:5813-5830(2015).
RN [14]
RP FUNCTION, INTERACTION WITH HOST VPS35 AND VPS29, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 446-PHE--LEU-448 AND 452-TYR--LEU-455.
RX PubMed=25693203; DOI=10.1371/journal.ppat.1004699;
RA Popa A., Zhang W., Harrison M.S., Goodner K., Kazakov T., Goodwin E.C.,
RA Lipovsky A., Burd C.G., DiMaio D.;
RT "Direct binding of retromer to human papillomavirus type 16 minor capsid
RT protein L2 mediates endosome exit during viral infection.";
RL PLoS Pathog. 11:E1004699-E1004699(2015).
RN [15]
RP FUNCTION, INTERACTION WITH HOST VPS35, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF LYS-457.
RX PubMed=30122350; DOI=10.1016/j.cell.2018.07.031;
RA Zhang P., Monteiro da Silva G., Deatherage C., Burd C., DiMaio D.;
RT "Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human
RT Papillomavirus L2 Protein to Trigger Retrograde Trafficking.";
RL Cell 0:0-0(2018).
CC -!- FUNCTION: Minor protein of the capsid that localizes along the inner
CC surface of the virion, within the central cavities beneath the L1
CC pentamers. Plays a role in capsid stabilization through interaction
CC with the major capsid protein L1. Once the virion enters the host cell,
CC L2 escorts the genomic DNA into the nucleus by promoting escape from
CC the endosomal compartments and traffic through the host Golgi network.
CC Mechanistically, the C-terminus of L2 possesses a cell-penetrating
CC peptide that protudes from the host endosome, interacts with host
CC cytoplasmic retromer cargo and thereby mediates the capsid delivery to
CC the host trans-Golgi network. Plays a role through its interaction with
CC host dynein in the intracellular microtubule-dependent transport of
CC viral capsid toward the nucleus. Mediates the viral genome import into
CC the nucleus through binding to host importins. Once within the nucleus,
CC L2 localizes viral genomes to host PML bodies in order to activate
CC early gene expression for establishment of infection. Later on,
CC promotes late gene expression by interacting with the viral E2 protein
CC and by inhibiting its transcriptional activation functions. During
CC virion assembly, encapsidates the genome by direct interaction with the
CC viral DNA. {ECO:0000255|HAMAP-Rule:MF_04003,
CC ECO:0000269|PubMed:15507604, ECO:0000269|PubMed:15681049,
CC ECO:0000269|PubMed:21166973, ECO:0000269|PubMed:25693203,
CC ECO:0000269|PubMed:30122350, ECO:0000269|PubMed:8553535}.
CC -!- SUBUNIT: Interacts with major capsid protein L1. Interacts with E2;
CC this interaction inhibits E2 transcriptional activity but not the DNA
CC replication function E2. Interacts with host GADD45GIP1. Interacts with
CC host HSPA8; this interaction is required for L2 nuclear translocation.
CC Interacts with host importins KPNB2 and KPNB3. Forms a complex with
CC importin alpha2-beta1 heterodimers via interaction with the importin
CC alpha2 adapter. Interacts with host DYNLT1; this interaction is
CC essential for virus intracellular transport during entry. Interacts
CC (via C-terminus) with host retromer subunits VPS35 AND VPS29.
CC {ECO:0000255|HAMAP-Rule:MF_04003, ECO:0000269|PubMed:12482659,
CC ECO:0000269|PubMed:15140951, ECO:0000269|PubMed:15507604,
CC ECO:0000269|PubMed:15681049, ECO:0000269|PubMed:1662690,
CC ECO:0000269|PubMed:21166973, ECO:0000269|PubMed:25693203,
CC ECO:0000269|PubMed:30122350}.
CC -!- INTERACTION:
CC P03107; P52292: KPNA2; Xeno; NbExp=3; IntAct=EBI-7362531, EBI-349938;
CC P03107; Q14974: KPNB1; Xeno; NbExp=2; IntAct=EBI-7362531, EBI-286758;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04003,
CC ECO:0000269|PubMed:19095951}. Host nucleus {ECO:0000255|HAMAP-
CC Rule:MF_04003, ECO:0000269|PubMed:19095951}. Host early endosome
CC {ECO:0000269|PubMed:25693203, ECO:0000269|PubMed:30122350}. Host Golgi
CC apparatus {ECO:0000269|PubMed:25693203, ECO:0000269|PubMed:30122350}.
CC -!- PTM: Highly phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04003,
CC ECO:0000269|PubMed:1662690}.
CC -!- MISCELLANEOUS: HPV16, in comparison to HPV types 6 and 11, is more
CC often associated with malignant genital cancers in humans.
CC -!- SIMILARITY: Belongs to the papillomaviridae L2 protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04003}.
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DR EMBL; K02718; AAA46942.1; -; Genomic_DNA.
DR EMBL; AF536179; AAQ10718.1; -; Genomic_DNA.
DR PIR; A03649; P2WLHS.
DR BioGRID; 4263560; 6.
DR ELM; P03107; -.
DR IntAct; P03107; 4.
DR MINT; P03107; -.
DR TCDB; 1.A.86.1.1; the human papilloma virus type 16 (hpv16) l2 viroporin (l2 viroporin) family.
DR PRIDE; P03107; -.
DR ABCD; P03107; 2 sequenced antibodies.
DR Proteomes; UP000009251; Genome.
DR Proteomes; UP000106302; Genome.
DR GO; GO:0044174; C:host cell endosome; IEA:UniProtKB-KW.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR GO; GO:0075521; P:microtubule-dependent intracellular transport of viral material towards nucleus; IEA:UniProtKB-UniRule.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-KW.
DR HAMAP; MF_04003; PPV_L2; 1.
DR InterPro; IPR000784; Late_L2.
DR Pfam; PF00513; Late_protein_L2; 1.
PE 1: Evidence at protein level;
KW Capsid protein; Cytoplasmic inwards viral transport; Disulfide bond;
KW DNA-binding; Host endosome; Host Golgi apparatus; Host nucleus;
KW Host-virus interaction; Late protein; Microtubular inwards viral transport;
KW Phosphoprotein; Reference proteome; Viral penetration into host nucleus;
KW Virion; Virus entry into host cell.
FT CHAIN 1..473
FT /note="Minor capsid protein L2"
FT /id="PRO_0000133583"
FT MOTIF 1..13
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04003,
FT ECO:0000305|PubMed:15507604"
FT MOTIF 454..462
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04003,
FT ECO:0000305|PubMed:15507604"
FT DISULFID 22..28
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04003,
FT ECO:0000269|PubMed:19214230"
FT MUTAGEN 22
FT /note="C->S: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:19214230"
FT MUTAGEN 28
FT /note="C->S: Complete loss of infectivity."
FT /evidence="ECO:0000269|PubMed:19214230"
FT MUTAGEN 446..448
FT /note="FYL->AAA: Complete loss of interaction with host
FT VPS35."
FT /evidence="ECO:0000269|PubMed:25693203"
FT MUTAGEN 452..455
FT /note="YYML->AAAA: Complete loss of interaction with host
FT VPS35."
FT /evidence="ECO:0000269|PubMed:25693203"
FT MUTAGEN 457
FT /note="K->R: Complete loss of host Golgi localization."
FT /evidence="ECO:0000269|PubMed:30122350"
FT CONFLICT 43
FT /note="E -> D (in Ref. 2; AAQ10718)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="S -> P (in Ref. 2; AAQ10718)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="S -> L (in Ref. 2; AAQ10718)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 473 AA; 50688 MW; 18E64E793D760744 CRC64;
MRHKRSAKRT KRASATQLYK TCKQAGTCPP DIIPKVEGKT IAEQILQYGS MGVFFGGLGI
GTGSGTGGRT GYIPLGTRPP TATDTLAPVR PPLTVDPVGP SDPSIVSLVE ETSFIDAGAP
TSVPSIPPDV SGFSITTSTD TTPAILDINN TVTTVTTHNN PTFTDPSVLQ PPTPAETGGH
FTLSSSTIST HNYEEIPMDT FIVSTNPNTV TSSTPIPGSR PVARLGLYSR TTQQVKVVDP
AFVTTPTKLI TYDNPAYEGI DVDNTLYFSS NDNSINIAPD PDFLDIVALH RPALTSRRTG
IRYSRIGNKQ TLRTRSGKSI GAKVHYYYDL STIDPAEEIE LQTITPSTYT TTSHAASPTS
INNGLYDIYA DDFITDTSTT PVPSVPSTSL SGYIPANTTI PFGGAYNIPL VSGPDIPINI
TDQAPSLIPI VPGSPQYTII ADAGDFYLHP SYYMLRKRRK RLPYFFSDVS LAA
