P03093 (VP2_SV40) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Minor capsid protein VP2 Alternative name(s): Minor structural protein VP2
Organism	Simian virus 40 (SV40) [Reference proteome]
Taxonomic identifier	10633 [NCBI]
Taxonomic lineage	Viruses › dsDNA viruses, no RNA stage › Polyomaviridae › Polyomavirus
Virus host	Macaca (macaques) [TaxID: 9539]

Protein attributes

Sequence length	352 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Isoform VP2 is a structural protein that resides within the core of the capsid surrounded by 72 VP1 pentamers. Following virus endocytosis and trafficking to the endoplasmic reticulum, VP2 and VP3 form oligomers and integrate into the endoplasmic reticulum membrane. Heterooligomer VP2-VP3 may create a viroporin for transporting the viral genome across the endoplasmic reticulum membrane to the cytoplasm. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2 or Vp3 nuclear localization signal (shared C-terminus). Plays a role in virion assembly within the nucleus in particular through a DNA-binding domain located in the C-terminal region. A N-terminal myristoylation suggests a scaffold function for virion assembly. The viral progenies exit the cells by lytic release. Isoform VP2 may repress SP1 activation of the SV40 early promoter, via specific protein-protein and protein-DNA interactions. Ref.10 Ref.12 Ref.14 Isoform VP3 is a structural protein that resides within the core of the capsid surrounded by 72 VP1 pentamers. Following virus entry, VP2 and VP3 form oligomers and integrate into the endoplasmic reticulum membrane. Heterooligomer VP2-VP3 may create a viroporin for transporting the viral genome across the endoplasmic reticulum membrane. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2 or Vp3 nuclear localization signal (shared C-terminus)Isoform VP3 represses SP1 activation of the SV40 early promoter, via specific protein-protein and protein-DNA interactions. SP1 additionally participates in recruiting VP3 to the SV40 minichromosome during SV40 assembly. Isoform VP3 plays a role in virion assembly within the nucleus. May initiate host cell lysis when associated with VP4. Ref.10 Ref.12 Ref.14 Isoform VP4 is a viroporin inducing perforation of cellular membranes to trigger virus progeny release. Forms pores of 3 nm inner diameter. VP4 is expressed about 24 hours after the late structural proteins and is not incorporated into the mature virion. Ref.10 Ref.12 Ref.14
Subunit structure	Isoform VP2 forms homooligomers, and heterooligomers with VP3 in the endoplasmic reticulum membrane. Isoform VP2 interacts (via D1 domain) with VP1. Isoform VP3 interacts (via D1 domain) with VP1. VP4 oligomerizes with VP3 in the nucleus. Isoform VP3 (via C-terminus) interacts with host SP1, this is probably also the case for VP2; this interaction represses SP1 activation of the SV40 early promoter and participates in virion assembly. Interacts (via nuclear localization signal) with host importin alpha2-beta heterodimer. Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location	Isoform VP2: Virion. Host nucleus Ref.5. Host endoplasmic reticulum. Host endoplasmic reticulum membrane. Note: Following host cell entry, the virion enters into the endoplasmic reticulum through a calveolar-dependent pathway. Then, isoform VP2 integrates into the endoplasmic reticulum membrane and participates in the translocation of viral DNA to the nucleus. Shortly after synthesis, a nuclear localization signal directs isoform VP2 to the cell nucleus where virion assembly occurs. Ref.5 Isoform VP3: Virion. Host nucleus Ref.5. Host endoplasmic reticulum. Host endoplasmic reticulum membrane. Note: Following host cell entry, the virion enters into the endoplasmic reticulum through a calveolar-dependent pathway. Then, isoform VP3 integrates into the endoplasmic reticulum membrane and participates in the translocation of viral DNA to the nucleus. Shortly after synthesis, a nuclear localization signal directs isoform VP3 to the cell nucleus where virion assembly occurs. Ref.5 Isoform VP4: Host nucleus Ref.5.
Domain	The D1 region of isoform VP2 and isoform VP3 is necessary and sufficient to direct the interaction with VP1. The basic-rich C-terminal region of isoforms VP2 and VP3 is sufficient for DNA-binding and may cause compaction of the DNA. The transmembrane region is only used when isoform VP2 and isoform VP3 form oligomers and integrate into the endoplasmic reticulum membrane.
Sequence similarities	Belongs to the polyomaviruses capsid protein VP2 family.

Ontologies

Keywords
Biological process	Cytolysis Host-virus interaction Viral penetration into host nucleus Virus entry into host cell
Cellular component	Host endoplasmic reticulum Host membrane Host nucleus Membrane Virion
Coding sequence diversity	Alternative initiation Alternative splicing
Developmental stage	Late protein
Domain	Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Capsid protein
PTM	Lipoprotein Myristate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytolysis Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW viral penetration into host nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Isoform VP2 (identifier: P03093-1)

Also known as: Minor capsid protein VP2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Produced by alternative splicing of the late mRNA (19s mRNA).

Isoform VP3 (identifier: P03093-2)

Also known as: Minor capsid protein VP3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.

Note: Produced by alternative initiation at Met-119 of isoform VP2.

Isoform VP4 (identifier: P03093-3)

Also known as: Viroporin VP4;

The sequence of this isoform differs from the canonical sequence as follows:
     1-227: Missing.

Note: Produced by alternative initiation at Met-228 of isoform VP2.

Isoform VP1 (identifier: P03087-1)

Also known as: Major capsid protein VP1;

The sequence of this isoform can be found in the external entry P03087.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by alternative splicing of the late mRNA (16s mRNA).

Isoform Agno (identifier: P03084-1)

The sequence of this isoform can be found in the external entry P03084.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Produced by alternative initiation of the late mRNA (16s and 19s mRNAs).

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed; by host
	Chain	2 – 352	351	Minor capsid protein VP2		PRO_0000039223
Regions
	Transmembrane	290 – 310	21	Helical; Potential
	Region	273 – 308	36	D1
	Region	313 – 352	40	DNA-binding
	Motif	316 – 324	9	Nuclear localization signal Ref.6
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine; by host Ref.5
Natural variations
	Alternative sequence	1 – 227	227	Missing in isoform VP4.		VSP_035892
	Alternative sequence	1 – 118	118	Missing in isoform VP3.		VSP_018925
	Natural variant	63	1	I → T in strain: 776.
Experimental info
	Mutagenesis	276 – 277	2	FI → EE: Complete loss of interaction with VP1.
	Mutagenesis	283 – 285	3	PGG → RER: Complete loss of interaction with VP1. Ref.11
	Mutagenesis	296	1	L → E: Partial loss of interaction with VP1. Ref.11
	Mutagenesis	300	1	L → E: Partial loss of interaction with VP1. Ref.11
	Mutagenesis	344	1	K → T: Partial loss of DNA-binding activity. Ref.8
	Mutagenesis	348	1	R → T: Partial loss of DNA-binding activity. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform VP2 (Minor capsid protein VP2) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 79A1C73604646923	FASTA	352	38,539
	10 20 30 40 50 60 MGAALTLLGD LIATVSEAAA ATGFSVAEIA AGEAAAAIEV QLASVATVEG LTTSEAIAAI 70 80 90 100 110 120 GLIPQAYAVI SGAPAAIAGF AALLQTVTGV SAVAQVGYRF FSDWDHKVST VGLYQQPGMA 130 140 150 160 170 180 VDLYRPDDYY DILFPGVQTF VHSVQYLDPR HWGPTLFNAI SQAFWRVIQN DIPRLTSQEL 190 200 210 220 230 240 ERRTQRYLRD SLARFLEETT WTVINAPVNW YNSLQDYYST LSPIRPTMVR QVANREGLQI 250 260 270 280 290 300 SFGHTYDNID EADSIQQVTE RWEAQSQSPN VQSGEFIEKF EAPGGANQRT APQWMLPLLL 310 320 330 340 350 GLYGSVTSAL KAYEDGPNKK KRKLSRGSSQ KTKGTSASAK ARHKRRNRSS RS
	Isoform VP3 (Minor capsid protein VP3) [UniParc]. Checksum: FFF86A591AC3E957	FASTA	234	26,963
	10 20 30 40 50 60 MAVDLYRPDD YYDILFPGVQ TFVHSVQYLD PRHWGPTLFN AISQAFWRVI QNDIPRLTSQ 70 80 90 100 110 120 ELERRTQRYL RDSLARFLEE TTWTVINAPV NWYNSLQDYY STLSPIRPTM VRQVANREGL 130 140 150 160 170 180 QISFGHTYDN IDEADSIQQV TERWEAQSQS PNVQSGEFIE KFEAPGGANQ RTAPQWMLPL 190 200 210 220 230 LLGLYGSVTS ALKAYEDGPN KKKRKLSRGS SQKTKGTSAS AKARHKRRNR SSRS
	Isoform VP4 (Viroporin VP4) [UniParc]. Checksum: 056545C2FBC44A08	FASTA	125	13,922
	10 20 30 40 50 60 MVRQVANREG LQISFGHTYD NIDEADSIQQ VTERWEAQSQ SPNVQSGEFI EKFEAPGGAN 70 80 90 100 110 120 QRTAPQWMLP LLLGLYGSVT SALKAYEDGP NKKKRKLSRG SSQKTKGTSA SAKARHKRRN RSSRS
	Isoform VP1 (Major capsid protein VP1) [UniParc]. See P03087.		–	–
	Isoform Agno [UniParc]. See P03084.		–	–

References

[1]	"The genome of simian virus 40." Reddy V.B., Thimmappaya B., Dhar R., Subramanian K.N., Zain B.S., Pan J., Ghosh P.K., Celma M.L., Weissman S.M. Science 200:494-502(1978) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Complete nucleotide sequence of SV40 DNA." Fiers W., Contreras R., Haegeman G., Rogiers R., van de Voorde A., van Heuverswyn H., van Herreweghe J., Volckaert G., Ysebaert M. Nature 273:113-120(1978) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 776.
[3]	"Overlapping of the VP2-VP3 gene and the VP1 gene in the SV40 genome." Contreras R., Rogiers R., Van de Voorde A., Fiers W. Cell 12:529-538(1977) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION (ISOFORM VP3).
[4]	"Evidence for 'splicing' of SV40 16S mRNA." Haegeman G., Fiers W. Nature 273:70-73(1978) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[5]	"Myristic acid is coupled to a structural protein of polyoma virus and SV40." Streuli C.H., Griffin B.E. Nature 326:619-622(1987) [PubMed] [Europe PMC] [Abstract] Cited for: MYRISTOYLATION AT GLY-2, SUBCELLULAR LOCATION.
[6]	"Simian virus 40 Vp2/3 small structural proteins harbor their own nuclear transport signal." Clever J., Kasamatsu H. Virology 181:78-90(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNAL.
[7]	"Identification of a DNA binding domain in simian virus 40 capsid proteins Vp2 and Vp3." Clever J., Dean D.A., Kasamatsu H. J. Biol. Chem. 268:20877-20883(1993) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING.
[8]	"Essential role of the Vp2 and Vp3 DNA-binding domain in simian virus 40 morphogenesis." Dean D.A., Li P.P., Lee L.M., Kasamatsu H. J. Virol. 69:1115-1121(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-344 AND ARG-348.
[9]	"The SV40 capsid protein VP3 cooperates with the cellular transcription factor Sp1 in DNA-binding and in regulating viral promoter activity." Gordon-Shaag A., Ben-Nun-Shaul O., Kasamatsu H., Oppenheim A.B., Oppenheim A. J. Mol. Biol. 275:187-195(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST SP1.
[10]	"Interaction of the Vp3 nuclear localization signal with the importin alpha 2/beta heterodimer directs nuclear entry of infecting simian virus 40." Nakanishi A., Shum D., Morioka H., Otsuka E., Kasamatsu H. J. Virol. 76:9368-9377(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH IMPORTIN ALPHA2-BETA HETERODIMER.
[11]	"Identification of amino acid residues within simian virus 40 capsid proteins Vp1, Vp2, and Vp3 that are required for their interaction and for viral infection." Nakanishi A., Nakamura A., Liddington R., Kasamatsu H. J. Virol. 80:8891-8898(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH VP1, MUTAGENESIS OF 276-PHE-ILE-277; 283-PRO--GLY-285; LEU-296 AND LEU-300.
[12]	"SV40 VP2 and VP3 insertion intoER membranes is controlled by the capsid protein VP1: implications for DNA translocation out of the ER." Daniels R., Rusan N.M., Wadsworth P., Hebert D.N. Mol. Cell 24:955-966(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT.
[13]	"A very late viral protein triggers the lytic release of SV40." Daniels R., Sadowicz D., Hebert D.N. PLoS Pathog. 3:E98-E98(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION (ISOFORM VP4).
[14]	"The SV40 late protein VP4 is a viroporin that forms pores to disrupt membranes for viral release." Raghava S., Giorda K.M., Romano F.B., Heuck A.P., Hebert D.N. PLoS Pathog. 7:E1002116-E1002116(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION (ISOFORM VP4).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02400 Genomic DNA. Translation: AAB59921.1. J02400 Genomic DNA. Translation: AAB59922.1.
PIR	VVVP24. A03631.
RefSeq	YP_003708379.1. NC_001669.1. YP_003708380.1. NC_001669.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P03093. 1 interaction.
MINT	MINT-6376721.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1489528. 1489529.
Phylogenomic databases
ProtClustDB	PHA2620.
Family and domain databases
InterPro	IPR001070. Polyoma_coat_VP2. [Graphical view]
Pfam	PF00761. Polyoma_coat2. 1 hit. [Graphical view]
PIRSF	PIRSF003377. Polyoma_coat2. 1 hit.
ProtoNet	Search...

Entry information

Entry name

VP2_SV40

Accession

Primary (citable) accession number: P03093

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 85 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program