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P12473

- VP4_ROTRH

UniProt

P12473 - VP4_ROTRH

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Protein
Outer capsid protein VP4
Gene
N/A
Organism
Rotavirus A (strain Monkey/United States/RRV/1980 G3-P5B[3]-I2-R2-C3-M3-A9-Nx-T3-E3-H6) (RV-A)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. It is subsequently lost, together with VP7, following virus entry into the host cell. Rotavirus attachment and entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. In sialic acid-dependent and/or integrin-dependent strains, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.1 Publication
Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment.1 Publication
VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei231 – 2322Cleavage By similarity
Sitei247 – 2482Cleavage

GO - Biological processi

  1. permeabilization of host organelle membrane involved in viral entry into host cell Source: UniProtKB-KW
  2. virion attachment to host cell Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hemagglutinin

Keywords - Biological processi

Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Viral penetration via permeabilization of host membrane, Virus entry into host cell

Protein family/group databases

TCDBi1.G.19.1.1. the rotavirus pore-forming membrane fusion complex (rotavirus mfc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Outer capsid protein VP4
Alternative name(s):
Hemagglutinin
Cleaved into the following 2 chains:
OrganismiRotavirus A (strain Monkey/United States/RRV/1980 G3-P5B[3]-I2-R2-C3-M3-A9-Nx-T3-E3-H6) (RV-A)
Taxonomic identifieri10969 [NCBI]
Taxonomic lineageiVirusesdsRNA virusesReoviridaeSedoreovirinaeRotavirusRotavirus A
Virus hostiMacaca mulatta (Rhesus macaque) [TaxID: 9544]

Subcellular locationi

Chain Outer capsid protein VP4 : Virion. Host rough endoplasmic reticulum Reviewed prediction
Note: Immature double-layered particles assembled in the cytoplasm bud across the membrane of the endoplasmic reticulum, acquiring during this process a transient lipid membrane that is modified with the ER resident viral glycoproteins NSP4 and VP7; these enveloped particles also contain VP4. As the particles move towards the interior of the ER cisternae, the transient lipid membrane and the non-structural protein NSP4 are lost, while the virus surface proteins VP4 and VP7 rearrange to form the outermost virus protein layer, yielding mature infectious triple-layered particles.
Chain Outer capsid protein VP8* : Virion
Note: Outer capsid protein.
Chain Outer capsid protein VP5* : Virion
Note: Outer capsid protein.

GO - Cellular componenti

  1. host cell rough endoplasmic reticulum Source: UniProtKB-SubCell
  2. viral outer capsid Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host endoplasmic reticulum, Outer capsid protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 776776Outer capsid protein VP4
PRO_0000041108Add
BLAST
Chaini1 – 231231Outer capsid protein VP8* Reviewed prediction
PRO_0000041109Add
BLAST
Chaini248 – 776529Outer capsid protein VP5* Reviewed prediction
PRO_0000041110Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi32 – 321N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi56 – 561N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi97 – 971N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi111 – 1111N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi149 – 1491N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi183 – 1831N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi198 – 1981N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi203 ↔ 216 Reviewed prediction
Disulfide bondi318 ↔ 380 Reviewed prediction

Post-translational modificationi

Proteolytic cleavage by trypsin results in activation of VP4 functions and greatly increases infectivity. The penetration into the host cell is dependent on trypsin treatment of VP4. It produces two peptides, VP5* and VP8* that remain associated with the virion.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

VP4 is a homotrimer Reviewed prediction. VP4 adopts a dimeric appearance above the capsid surface, while forming a trimeric base anchored inside the capsid layer. Only hints of the third molecule are observed above the capsid surface. It probably performs a series of molecular rearrangements during viral entry. Prior to trypsin cleavage, it is flexible. The priming trypsin cleavage triggers its rearrangement into rigid spikes with approximate two-fold symmetry of their protruding parts. After an unknown second triggering event, cleaved VP4 may undergo another rearrangement, in which two VP5* subunits fold back on themselves and join a third subunit to form a tightly associated trimer, shaped like a folded umbrella. VP5* is a homotrimer Reviewed prediction. The trimer is coiled-coil stabilized by its C-terminus, however, its N-terminus, known as antigen domain or "body", seems to be flexible allowing it to self-associate either as a dimer or a trimer. The two- to three-fold reorganization and fold-back of VP5* may be linked to membrane penetration, by exposing its hydrophobic region. Interacts with host ITGA2 (via ITAG2 I-domain); this interaction occurs when ITGA2 is part of the integrin heterodimer ITGA2/ITGB1. Interacts with host integrin heterodimer ITGA4/ITGB1 and ITGA4/ITGB7.3 Publications

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi66 – 694
Beta strandi71 – 744
Beta strandi80 – 845
Beta strandi88 – 969
Beta strandi98 – 1003
Beta strandi102 – 1087
Beta strandi110 – 12112
Beta strandi124 – 1329
Beta strandi135 – 14713
Beta strandi153 – 16210
Beta strandi165 – 1706
Beta strandi173 – 1808
Beta strandi185 – 1906
Helixi194 – 1963
Beta strandi198 – 2036
Beta strandi205 – 2095
Helixi210 – 2123
Helixi213 – 22210
Beta strandi249 – 25810
Beta strandi260 – 27516
Beta strandi278 – 2836
Beta strandi290 – 2978
Beta strandi299 – 3079
Beta strandi310 – 32213
Beta strandi324 – 3296
Beta strandi338 – 3458
Beta strandi350 – 35910
Helixi360 – 3623
Beta strandi367 – 3759
Beta strandi378 – 3814
Beta strandi384 – 3863
Beta strandi390 – 3923
Beta strandi396 – 3994
Beta strandi401 – 41515
Beta strandi420 – 43213
Beta strandi437 – 4393
Beta strandi449 – 4546
Turni455 – 4584
Beta strandi462 – 47514
Helixi492 – 51221
Turni513 – 5197

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1KQRX-ray1.40A62-224[»]
1KRINMR-A46-231[»]
1SLQX-ray3.20A/B/C/D/E/F248-525[»]
2B4HX-ray1.60A/B248-479[»]
2B4IX-ray2.00A/B/C248-479[»]
2P3IX-ray1.75A64-224[»]
2P3JX-ray1.90A64-224[»]
2P3KX-ray1.56A64-224[»]
3TB0X-ray2.00A64-224[»]

Miscellaneous databases

EvolutionaryTraceiP12473.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni248 – 480233Antigen domain
Add
BLAST
Regioni308 – 3103DGE motif; interaction with ITGA2/ITGB1 heterodimer By similarity
Regioni389 – 40921Hydrophobic; possible role in virus entry into host cell Reviewed prediction
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili484 – 51835 Reviewed prediction
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi560 – 61657Ser-rich
Add
BLAST

Sequence similaritiesi

Belongs to the rotavirus VP4 family.

Keywords - Domaini

Coiled coil

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
InterProiIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000416. Haemagglutinin_VP4.
[Graphical view]
PfamiPF00426. VP4_haemagglut. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P12473-1 [UniParc]FASTAAdd to Basket

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MASLIYRQLL TNSYTVDLSD EIQEIGSTKT QNVTINLGPF AQTGYAPVNW    50
GPGETNDSTT VEPVLDGPYQ PTSFNPPVDY WMLLAPTAAG VVVEGTNNTD 100
RWLATILVEP NVTSETRSYT LFGTQEQITI ANASQTQWKF IDVVKTTQNG 150
SYSQYGPLQS TPKLYAVMKH NGKIYTYNGE TPNVTTKYYS TTNYDSVNMT 200
AFCDFYIIPR EEESTCTEYI NNGLPPIQNT RNIVPLALSA RNIISHRAQA 250
NEDIVVSKTS LWKEMQYNRD ITIRFKFASS IVKSGGLGYK WSEISFKPAN 300
YQYTYTRDGE DVTAHTTCSV NGMNDFNFNG GSLPTDFIIS RYEVIKENSY 350
VYVDYWDDSQ AFRNMVYVRS LAANLNSVIC TGGDYSFALP VGQWPVMTGG 400
AVSLHSAGVT LSTQFTDFVS FNSLRFRFRL TVEEPSFSIT RTRVGGLYGL 450
PAAYPNNGKE YYEVAGRLSL ISLVPSNDDY QTPITNSVTV RQDLERQLGE 500
LREEFNALSQ EIAMSQLIYL ALLPLDMFSM FSGIKSTIDA AKSMATSVMK 550
KFKKSGLANS VSTLTDSLSD AASSISRGAS IRSVGSSASA WTDVSTQITD 600
VSSSVSSIST QTSTISRRLR LKEMATQTEG MNFDDISAAV LKTKIDRSTQ 650
ISPNTLPDIV TEASEKFIPN RAYRVINNDE VFEAGTDGRY FAYRVETFDE 700
IPFDVQKFAD LVTDSPVISA IIDFKTLKNL NDNYGISRQQ AFNLLRSDPR 750
VLREFINQDN PIIRNRIEQL IMQCRL 776
Length:776
Mass (Da):86,554
Last modified:March 24, 2009 - v2
Checksum:iC012EB9E3816A3F9
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti109 – 1102EP → VA in strain: Isolate MMU-18006.
Natural varianti146 – 1461T → S in strain: Isolate MMU-18006.
Natural varianti166 – 1661A → G in strain: Isolate MMU-18006.
Natural varianti235 – 2406PLALSA → LALSAS in strain: Isolate MMU-18006.
Natural varianti244 – 2452IS → TY in strain: Isolate MMU-18006.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti73 – 731S → T in AAK52093. 1 Publication
Sequence conflicti132 – 1321N → Y in AAA47345. 1 Publication
Sequence conflicti311 – 3111D → E in AAK52093. 1 Publication
Sequence conflicti338 – 3381I → V in AAK52093. 1 Publication
Sequence conflicti421 – 4211F → L in AAK52093. 1 Publication
Sequence conflicti445 – 4462GG → SR in AAK52093. 1 Publication
Sequence conflicti454 – 4541Y → N in AAK52093. 1 Publication
Sequence conflicti468 – 4681L → F in AAK52093. 1 Publication
Sequence conflicti519 – 5191Y → D in AAK52093. 1 Publication
Sequence conflicti690 – 6901Y → F in AAK52093. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M18736 Genomic RNA. Translation: AAA47345.1.
AY033150 mRNA. Translation: AAK52093.1.
PIRiA31078. VPXRRH.
I25904. VPXRRR.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M18736 Genomic RNA. Translation: AAA47345.1 .
AY033150 mRNA. Translation: AAK52093.1 .
PIRi A31078. VPXRRH.
I25904. VPXRRR.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1KQR X-ray 1.40 A 62-224 [» ]
1KRI NMR - A 46-231 [» ]
1SLQ X-ray 3.20 A/B/C/D/E/F 248-525 [» ]
2B4H X-ray 1.60 A/B 248-479 [» ]
2B4I X-ray 2.00 A/B/C 248-479 [» ]
2P3I X-ray 1.75 A 64-224 [» ]
2P3J X-ray 1.90 A 64-224 [» ]
2P3K X-ray 1.56 A 64-224 [» ]
3TB0 X-ray 2.00 A 64-224 [» ]
ModBasei Search...

Protein family/group databases

TCDBi 1.G.19.1.1. the rotavirus pore-forming membrane fusion complex (rotavirus mfc) family.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P12473.

Family and domain databases

Gene3Di 2.60.120.200. 1 hit.
InterProi IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000416. Haemagglutinin_VP4.
[Graphical view ]
Pfami PF00426. VP4_haemagglut. 1 hit.
[Graphical view ]
SUPFAMi SSF49899. SSF49899. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "The rhesus rotavirus gene encoding protein VP3: location of amino acids involved in homologous and heterologous rotavirus neutralization and identification of a putative fusion region."
    Mackow E.R., Shaw R.D., Matsui S.M., Vo P.T., Dang M.-N., Greenberg H.G.
    Proc. Natl. Acad. Sci. U.S.A. 85:645-649(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Proteolysis of monomeric recombinant rotavirus VP4 yields an oligomeric VP5* core."
    Dormitzer P.R., Greenberg H.B., Harrison S.C.
    J. Virol. 75:7339-7350(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Conservation of amino acid sequence of VP8 and cleavage region of 84-kDa outer capsid protein among rotaviruses recovered from asymptomatic neonatal infection."
    Gorziglia M., Hoshino Y., Buckler-White A., Blumentals I., Glass R., Flores J., Kapikian A.Z., Chanock R.M.
    Proc. Natl. Acad. Sci. U.S.A. 83:7039-7043(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-281.
    Strain: Isolate MMU-18006.
  4. "Location of intrachain disulfide bonds in the VP5* and VP8* trypsin cleavage fragments of the rhesus rotavirus spike protein VP4."
    Patton J.T., Hua J.J., Mansell E.A.
    J. Virol. 67:4848-4855(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  5. "Cleavage of rhesus rotavirus VP4 after arginine 247 is essential for rotavirus-like particle-induced fusion from without."
    Gilbert J.M., Greenberg H.B.
    J. Virol. 72:5323-5327(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC CLEAVAGE SITE.
  6. "Rotaviruses interact with alpha4beta7 and alpha4beta1 integrins by binding the same integrin domains as natural ligands."
    Graham K.L., Fleming F.E., Halasz P., Hewish M.J., Nagesha H.S., Holmes I.H., Takada Y., Coulson B.S.
    J. Gen. Virol. 86:3397-3408(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB1, INTERACTION WITH HUMAN INTEGRIN HETERODIMER ITGA4/ITGB7.
  7. "Alternative intermolecular contacts underlie the rotavirus VP5* two-to three-fold rearrangement."
    Yoder J.D., Dormitzer P.R.
    EMBO J. 25:1559-1568(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  8. "Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell surface and competes with virus for cell binding and infectivity."
    Graham K.L., Takada Y., Coulson B.S.
    J. Gen. Virol. 87:1275-1283(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SIMIAN INTEGRIN HETERODIMER ITGA2/ITGB1.
  9. "Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry."
    Kim I.S., Trask S.D., Babyonyshev M., Dormitzer P.R., Harrison S.C.
    J. Virol. 84:6200-6207(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF VP5*.
  10. "The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site."
    Dormitzer P.R., Sun Z.Y., Wagner G., Harrison S.C.
    EMBO J. 21:885-897(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 62-224, STRUCTURE BY NMR OF 46-231.
  11. "Structural rearrangements in the membrane penetration protein of a non-enveloped virus."
    Dormitzer P.R., Nason E.B., Prasad B.V.V., Harrison S.C.
    Nature 430:1053-1058(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 248-525.
  12. "Rotavirus architecture at subnanometer resolution."
    Li Z., Baker M.L., Jiang W., Estes M.K., Prasad B.V.V.
    J. Virol. 83:1754-1766(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY ELECTRON CRYOMICROSCOPY OF CAPSID SHELL.

Entry informationi

Entry nameiVP4_ROTRH
AccessioniPrimary (citable) accession number: P12473
Secondary accession number(s): P11201
, Q86214, Q86215, Q91HI9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: March 24, 2009
Last modified: September 3, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

In group A rotaviruses, VP4 defines the P serotype.
This strain has been shown to be sialic acid-dependent, and integrin-dependent in cell culture conditions.

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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