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P04413

- US03_HHV11

UniProt

P04413 - US03_HHV11

Protein

Serine/threonine-protein kinase US3

Gene

US3

Organism
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 84 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      Previous versions | rss
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    Functioni

    Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of apoptosis. Phosphorylates UL31 and UL34, two critical regulators of capsid budding from nucleus to endoplasmic reticulum, thereby facilitating virion egress. Modulates and redistributes host components of the nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix protein MATR3. Phosphorylates envelope glycoprotein B (gB), probably to direct it to the cell surface. Promotes virus intracellular spread by restructuring host cell cytoskeleton. Blocks host apoptosis to extend cell survival and allow efficient viral replication. Promotes viral gene expression by phosphorylating host HDAC2 to reduce viral genome silencing.8 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei220 – 2201ATPPROSITE-ProRule annotation
    Active sitei305 – 3051Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi197 – 2059ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. modulation by virus of host apoptotic process Source: UniProtKB-KW
    2. modulation by virus of host chromatin organization Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Host-virus interaction, Modulation of host cell apoptosis by virus, Modulation of host chromatin by virus

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase US3 (EC:2.7.11.1)
    Gene namesi
    Name:US3
    OrganismiHuman herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
    Taxonomic identifieri10299 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeAlphaherpesvirinaeSimplexvirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000009294: Genome

    Subcellular locationi

    Host cytoplasm By similarity. Host nucleus By similarity

    GO - Cellular componenti

    1. host cell cytoplasm Source: UniProtKB-SubCell
    2. host cell nucleus Source: UniProtKB-SubCell
    3. viral tegument Source: CACAO

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi147 – 1471S → A: Complete loss of autophosphorylation. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 481481Serine/threonine-protein kinase US3PRO_0000086180Add
    BLAST

    Post-translational modificationi

    Phosphorylated by UL13; this phosphorylation regulates subsequent phosphorylation of UL31 and UL34 by US3. Autophosphorylated.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Interactioni

    Protein-protein interaction databases

    IntActiP04413. 29 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP04413.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini191 – 478288Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P04413-1 [UniParc]FASTAAdd to Basket

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    MACRKFCRVY GGQGRRKEEA VPPETKPSRV FPHGPFYTPA EDACLDSPPP    50
    ETPKPSHTTP PSEAERLCHL QEILAQMYGN QDYPIEDDPS ADAADDVDED 100
    APDDVAYPEE YAEELFLPGD ATGPLIGAND HIPPPCGASP PGIRRRSRDE 150
    IGATGFTAEE LDAMDREAAR AISRGGKPPS TMAKLVTGMG FTIHGALTPG 200
    SEGCVFDSSH PDYPQRVIVK AGWYTSTSHE ARLLRRLDHP AILPLLDLHV 250
    VSGVTCLVLP KYQADLYTYL SRRLNPLGRP QIAAVSRQLL SAVDYIHRQG 300
    IIHRDIKTEN IFINTPEDIC LGDFGAACFV QGSRSSPFPY GIAGTIDTNA 350
    PEVLAGDPYT TTVDIWSAGL VIFETAVHNA SLFSAPRGPK RGPCDSQITR 400
    IIRQAQVHVD EFSPHPESRL TSRYRSRAAG NNRPPYTRPA WTRYYKMDID 450
    VEYLVCKALT FDGALRPSAA ELLCLPLFQQ K 481
    Length:481
    Mass (Da):52,835
    Last modified:August 13, 1987 - v1
    Checksum:i71838AB0483BE055
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L00036 Genomic DNA. Translation: AAA96685.1.
    X14112 Genomic DNA. Translation: CAA32280.1.
    X02138 Genomic DNA. Translation: CAA26057.1.
    PIRiA00656. TVBE17.
    RefSeqiNP_044665.1. NC_001806.1.

    Genome annotation databases

    GeneIDi2703401.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L00036 Genomic DNA. Translation: AAA96685.1 .
    X14112 Genomic DNA. Translation: CAA32280.1 .
    X02138 Genomic DNA. Translation: CAA26057.1 .
    PIRi A00656. TVBE17.
    RefSeqi NP_044665.1. NC_001806.1.

    3D structure databases

    ProteinModelPortali P04413.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P04413. 29 interactions.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 2703401.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1."
      McGeoch D.J., Dolan A., Donald S., Rixon F.J.
      J. Mol. Biol. 181:1-13(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The herpesvirus protein kinase: a new departure in protein phosphorylation?"
      Leader D.P., Purves F.C.
      Trends Biochem. Sci. 13:244-246(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    3. "The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene."
      Purves F.C., Spector D., Roizman B.
      J. Virol. 65:5757-5764(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF UL34.
      Strain: F.
    4. "The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus."
      Leopardi R., Van Sant C., Roizman B.
      Proc. Natl. Acad. Sci. U.S.A. 94:7891-7896(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
      Strain: F.
    5. "Identification of proteins phosphorylated directly by the Us3 protein kinase encoded by herpes simplex virus 1."
      Kato A., Yamamoto M., Ohno T., Kodaira H., Nishiyama Y., Kawaguchi Y.
      J. Virol. 79:9325-9331(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF UL31; ICP22 AND US9.
      Strain: F.
    6. "Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31."
      Kato A., Yamamoto M., Ohno T., Tanaka M., Sata T., Nishiyama Y., Kawaguchi Y.
      J. Virol. 80:1476-1486(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY UL13.
      Strain: F.
    7. "Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3."
      Leach N., Bjerke S.L., Christensen D.K., Bouchard J.M., Mou F., Park R., Baines J., Haraguchi T., Roller R.J.
      J. Virol. 81:10792-10803(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Identification of a physiological phosphorylation site of the herpes simplex virus 1-encoded protein kinase Us3 which regulates its optimal catalytic activity in vitro and influences its function in infected cells."
      Kato A., Tanaka M., Yamamoto M., Asai R., Sata T., Nishiyama Y., Kawaguchi Y.
      J. Virol. 82:6172-6189(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOPHOSPHORYLATION.
      Strain: F.
    9. "Phosphorylation of the UL31 protein of herpes simplex virus 1 by the US3-encoded kinase regulates localization of the nuclear envelopment complex and egress of nucleocapsids."
      Mou F., Wills E., Baines J.D.
      J. Virol. 83:5181-5191(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
      Strain: F.
    10. "Regulation of the catalytic activity of herpes simplex virus 1 protein kinase Us3 by autophosphorylation and its role in pathogenesis."
      Sagou K., Imai T., Sagara H., Uema M., Kawaguchi Y.
      J. Virol. 83:5773-5783(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF SER-147.
    11. "Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein B by Us3 kinase in vivo and in vitro."
      Imai T., Sagou K., Arii J., Kawaguchi Y.
      J. Virol. 84:153-162(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF GLYCOPROTEIN B.
    12. "Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3 kinases."
      Walters M.S., Kinchington P.R., Banfield B.W., Silverstein S.
      J. Virol. 84:9666-9676(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF HOST HDAC2.
    13. "The alphaherpesvirus US3/ORF66 protein kinases direct phosphorylation of the nuclear matrix protein matrin 3."
      Erazo A., Yee M.B., Banfield B.W., Kinchington P.R.
      J. Virol. 85:568-581(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF HOST MATR3.
      Strain: RC.

    Entry informationi

    Entry nameiUS03_HHV11
    AccessioniPrimary (citable) accession number: P04413
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 84 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3