P03087 (VP1_SV40) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Major capsid protein VP1 Alternative name(s): Major structural protein VP1
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	362 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	Forms an icosahedral capsid with a T=7 symmetry and a 40 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Binds to N-glycolylneuraminic analog of the ganglioside GM1 on the cell surface to provide virion attachment to target cell. Once attached, the virion is internalized by caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. The assembly takes place in the cell nucleus. Encapsulates the genomic DNA and participates in rearranging nucleosomes around the viral DNA. The viral progenies exit the cells by lytic release.
Subunit structure	Homomultimer; disulfide-linked. The virus capsid is composed of 72 icosahedral units, each one composed of five disulfide-linked copies of VP1. Interacts with agnoprotein By similarity. Interacts with minor capsid proteins VP2 and VP3. Interacts with host HSPA8; this interaction probably participates in virus assembly. Interacts with host SP1; this interaction enhances the efficiency of viral packaging. Ref.7 Ref.8 Ref.10 Ref.13 Ref.15
Subcellular location	Virion. Host nucleus. Host endoplasmic reticulum. Note: Following host cell entry, the virion enters into the endoplasmic reticulum through a calveolar-dependent pathway. Then, viral DNA is translocated to the nucleus. Shortly after synthesis, a nuclear localization signal directs VP1 to the cell nucleus where virion assembly occurs.
Domain	The intrinsically disordered C-terminal region interacts with neighboring pentamers. The unstructured nature of this region allows to make different interactions depending on the stuctural context: pentamers present at the 12 icosahedral fivefold axes bind five pentamers, whereas pentamers present at the 60 icosahedral six-fold axes interact with six pentamers. A DNA-binding domain overlapping a bipartite nuclear localization signal is present in the N-terminal region of the protein and is required for efficient virus formation.
Sequence similarities	Belongs to the polyomaviruses coat protein VP1 family.

Ontologies

Keywords
Biological process	Caveolin-mediated endocytosis of virus by host Host-virus interaction Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host Virus entry into host cell
Cellular component	Host endoplasmic reticulum Host nucleus Virion
Coding sequence diversity	Alternative initiation Alternative splicing
Developmental stage	Late protein
Molecular function	Capsid protein T=7 icosahedral capsid protein
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via caveolae-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	T=7 icosahedral viral capsid Inferred from electronic annotation. Source: UniProtKB-KW host cell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	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 VP1 (identifier: P03087-1)

Also known as: Major capsid protein VP1;

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 (16s mRNA).

Isoform VP2 (identifier: P03093-1)

Also known as: Minor capsid protein VP2;

The sequence of this isoform can be found in the external entry P03093.
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 (19s mRNA).

Isoform VP3 (identifier: P03093-2)

Also known as: Minor capsid protein VP3;

The sequence of this isoform can be found in the external entry P03093.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

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 can be found in the external entry P03093.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

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

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 – 362

361

Major capsid protein VP1

PRO_0000115028

Regions

Region

302 – 362

61

Intrinsically disordered

Motif

5 – 19

15

Bipartite nuclear localization signal

Amino acid modifications

Modified residue

338

1

Phosphothreonine; by host Ref.5

Disulfide bond

10

Interchain Ref.7 Ref.15

Disulfide bond

105

Interchain Ref.7 Ref.15

Disulfide bond

208

Interchain Ref.7 Ref.15

Natural variations

Natural variant

99

1

I → L in strain: 776.

Experimental info

Mutagenesis

49

1

E → A: 99% loss of infectivity ex vivo. Ref.11

Mutagenesis

50

1

C → S: No effect on infectivity ex vivo. Ref.12

Mutagenesis

88

1

C → S: 99% loss of infectivity ex vivo. Ref.12

Mutagenesis

158

1

E → K or R: Complete loss of infectivity ex vivo, defective in nuclear entry. Ref.14

Mutagenesis

161

1

E → K or R: 95% loss of infectivity ex vivo. Ref.14

Mutagenesis

217

1

E → K or R: 99% loss of infectivity ex vivo. Ref.11

Mutagenesis

244

1

V → E: Complete loss of infectivity ex vivo. Ref.13

Mutagenesis

246

1

L → E: Complete loss of infectivity ex vivo. Ref.13

Mutagenesis

255

1

C → S: Complete loss of infectivity ex vivo. Ref.12

Mutagenesis

268

1

C → S: No effect on infectivity ex vivo. Ref.12

Mutagenesis

331

1

E → K or R: Complete loss of infectivity ex vivo, defective in adsorbing to cells. Ref.11

Secondary structure

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362

Helix Strand Turn

Details...

Helix

33 – 37

5

Beta strand

45 – 52

8

Helix

61 – 63

3

Helix

83 – 85

3

Beta strand

90 – 95

6

Beta strand

105 – 121

17

Helix

123 – 127

5

Beta strand

130 – 132

3

Beta strand

135 – 137

3

Beta strand

145 – 147

3

Beta strand

149 – 158

10

Beta strand

161 – 164

4

Helix

185 – 188

4

Helix

192 – 194

3

Beta strand

195 – 197

3

Turn

201 – 203

3

Turn

206 – 208

3

Beta strand

209 – 211

3

Turn

213 – 215

3

Beta strand

219 – 226

8

Beta strand

234 – 240

7

Helix

256 – 258

3

Beta strand

259 – 272

14

Beta strand

278 – 282

5

Beta strand

285 – 297

13

Beta strand

304 – 306

3

Helix

324 – 326

3

Beta strand

348 – 351

4

Beta strand

353 – 359

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform VP1 (Major capsid protein VP1) [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 81C28EB7EA51D398	FASTA	362	39,906
	10 20 30 40 50 60 MAPTKRKGSC PGAAPKKPKE PVQVPKLVIK GGIEVLGVKT GVDSFTEVEC FLNPQMGNPD 70 80 90 100 110 120 EHQKGLSKSL AAEKQFTDDS PDKEQLPCYS VARIPLPNIN EDLTCGNILM WEAVTVKTEV 130 140 150 160 170 180 IGVTAMLNLH SGTQKTHENG AGKPIQGSNF HFFAVGGEPL ELQGVLANYR TKYPAQTVTP 190 200 210 220 230 240 KNATVDSQQM NTDHKAVLDK DNAYPVECWV PDPSKNENTR YFGTYTGGEN VPPVLHITNT 250 260 270 280 290 300 ATTVLLDEQG VGPLCKADSL YVSAVDICGL FTNTSGTQQW KGLPRYFKIT LRKRSVKNPY 310 320 330 340 350 360 PISFLLSDLI NRRTQRVDGQ PMIGMSSQVE EVRVYEDTEE LPGDPDMIRY IDEFGQTTTR MQ
	Isoform VP2 (Minor capsid protein VP2) [UniParc]. See P03093.		–	–
	Isoform VP3 (Minor capsid protein VP3) [UniParc]. See P03093.		–	–
	Isoform VP4 (Viroporin VP4) [UniParc]. See P03093.		–	–
	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]	"Correlation of the protein and nucleic acid sequences for the major structural protein of simian virus 40." Kempe T.D., Beattie W.G., Weissman S., Konigsberg W. J. Biol. Chem. 254:7561-7569(1979) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE.
[4]	"An electron microscope study of the development of SV40 virus." Granboulan N., Tournier P., Wicker R., Bernhard W. J. Cell Biol. 17:423-441(1963) [PubMed] [Europe PMC] [Abstract] Cited for: VIRION ASSEMBLY.
[5]	"Epitopes on the major capsid protein of simian virus 40." Babe L.M., Brew K., Matsuura S.E., Scott W.A. J. Biol. Chem. 264:2665-2671(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-338.
[6]	"Analysis of a nuclear localization signal of simian virus 40 major capsid protein Vp1." Ishii N., Minami N., Chen E.Y., Medina A.L., Chico M.M., Kasamatsu H. J. Virol. 70:1317-1322(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR LOCALIZATION SIGNAL.
[7]	"Cys9, Cys104 and Cys207 of simian virus 40 Vp1 are essential for inter-pentamer disulfide-linkage and stabilization in cell-free lysates." Jao C.C., Weidman M.K., Perez A.R., Gharakhanian E. J. Gen. Virol. 80:2481-2489(1999) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS IN INTER-PENTAMER.
[8]	"HSC70 interactions with SV40 viral proteins differ between permissive and nonpermissive mammalian cells." Sainis L., Angelidis C., Pagoulatos G.N., Lazaridis L. Cell Stress Chaperones 5:132-138(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST HSPA8.
[9]	"Simian virus 40 Vp1 DNA-binding domain is functionally separable from the overlapping nuclear localization signal and is required for effective virion formation and full viability." Li P.P., Nakanishi A., Shum D., Sun P.C., Salazar A.M., Fernandez C.F., Chan S.W., Kasamatsu H. J. Virol. 75:7321-7329(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING, NUCLEAR LOCALIZATION SIGNAL.
[10]	"Cellular transcription factor Sp1 recruits simian virus 40 capsid proteins to the viral packaging signal, ses." Gordon-Shaag A., Ben-Nun-Shaul O., Roitman V., Yosef Y., Oppenheim A. J. Virol. 76:5915-5924(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST SP1.
[11]	"Importance of Vp1 calcium-binding residues in assembly, cell entry, and nuclear entry of simian virus 40." Li P.P., Naknanishi A., Tran M.A., Ishizu K., Kawano M., Phillips M., Handa H., Liddington R.C., Kasamatsu H. J. Virol. 77:7527-7538(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLU-49; GLU-217 AND GLU-331.
[12]	"Cys254 and Cys49/Cys87of simian virus 40 Vp1 are essential in formation of infectious virions." Gharakhanian E., Mana W., Norng M. Virus Res. 107:21-25(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-50; CYS-88; CYS-255 AND CYS-268.
[13]	"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 VP2 AND VP3, MUTAGENESIS OF VAL-244 AND LEU-246.
[14]	"Importance of calcium-binding site 2 in simian virus 40 infection." Li P.P., Nguyen A.P., Qu Q., Jafri Q.H., Aungsumart S., Cheng R.H., Kasamatsu H. J. Virol. 81:6099-6105(2007) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLU-158 AND GLU-161.
[15]	"Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells." Schelhaas M., Malmstroem J., Pelkmans L., Haugstetter J., Ellgaard L., Gruenewald K., Helenius A. Cell 131:516-529(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ISOMERIZATION OF DISULFIDE BONDS.
[16]	"The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry." Neu U., Stehle T., Atwood W.J. Virology 384:389-399(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[17]	"Structure of simian virus 40 at 3.8-A resolution." Liddinngton R.C., Yan Y., Moulai J., Sahli R., Benjamin T.L., Harrison S.C. Nature 354:278-284(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS).
[18]	"The structure of simian virus 40 refined at 3.1-A resolution." Stehle T., Gamblin S.J., Yan Y., Harrison S.C. Structure 4:165-182(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 2-362.
[19]	"Structural basis of GM1 ganglioside recognition by simian virus 40." Neu U., Woellner K., Gauglitz G., Stehle T. Proc. Natl. Acad. Sci. U.S.A. 105:5219-5224(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 31-298.
+	Additional computationally mapped references.

Web resources

Virus Particle ExploreR db

Icosahedral capsid structure

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02400 Genomic DNA. Translation: AAB59923.1.

PIR

A31426.
VVVP14. E03631.

RefSeq

YP_003708381.1. NC_001669.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SVA	X-ray	3.10	1/2/3/4/5/6	2-362	[»]
3BWQ	X-ray	2.30	A/B/C/D/E	31-298	[»]
3BWR	X-ray	2.25	A/B/C/D/E	31-298	[»]

DisProt

DP00182.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29870N.

IntAct

P03087. 1 interaction.

MINT

MINT-238076.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

1489530.

Phylogenomic databases

ProtClustDB

PHA2614.

Family and domain databases

Gene3D

2.60.175.10. 1 hit.

InterPro

IPR000662. Capsid_VP1_Polyomavir.
IPR011222. dsDNA_vir_gr_I_capsid.
[Graphical view]

Pfam

PF00718. Polyoma_coat. 1 hit.
[Graphical view]

PIRSF

PIRSF003376. Capsid_VP1_Polyomavir. 1 hit.

SUPFAM

SSF88648. dsDNA_vir_gr_I_capsid. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P03087.

Entry information

Entry name

VP1_SV40

Accession

Primary (citable) accession number: P03087

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 25, 2008
Last modified:	April 3, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program