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Q2HR64

- DEN_HHV8P

UniProt

Q2HR64 - DEN_HHV8P

Protein

Deneddylase

Gene

ORF64

Organism
Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi
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    • History
      Entry version 31 (01 Oct 2014)
      Sequence version 1 (15 May 2007)
      Previous versions | rss
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    Functioni

    Deneddylase that deregulates the host cell cycle S phase to create a favorable environment allowing efficient viral genome replication. Interacts with and deneddylates host cullins including CUL1 and CUL4A, thereby reducing their E3 ubiquitin ligase activity. Inhibition of cullins leads to the stabilization of cullin-RING ligase substrates such as host CDN1A/p21, CDKN1B/p27kip and CDC25A, preventing S phase progression. Additionally, acts as a deubiquitinase and cleaves both 'Lys-48' and 'Lys-63'-linked ubiquitin chains By similarity.By similarity

    Catalytic activityi

    Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei16 – 161Important for catalytic activityPROSITE-ProRule annotation
    Active sitei29 – 291PROSITE-ProRule annotation
    Active sitei159 – 1591PROSITE-ProRule annotation
    Active sitei161 – 1611PROSITE-ProRule annotation

    GO - Molecular functioni

    1. cysteine-type peptidase activity Source: UniProtKB-KW

    GO - Biological processi

    1. modulation by virus of host protein ubiquitination Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Host-virus interaction, Modulation of host ubiquitin pathway by viral deubiquitinase, Modulation of host ubiquitin pathway by virus, Ubl conjugation pathway

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Deneddylase (EC:3.4.19.12, EC:3.4.22.-)
    Alternative name(s):
    Tegument protein VP1-2
    Tegument protein VP1/2
    Gene namesi
    ORF Names:ORF64
    OrganismiHuman herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus)
    Taxonomic identifieri868565 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000000942: Genome

    Subcellular locationi

    Virion tegument. Host cytoplasm. Host nucleus By similarity
    Note: Tightly associated with the capsid.By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus, Virion, Virion tegument

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 26352635DeneddylasePRO_0000406914Add
    BLAST

    Interactioni

    Subunit structurei

    Interacts with host CUL1 and CUL4A; these interactions inhibit the E3 ligase activity of cullins.By similarity

    Protein-protein interaction databases

    IntActiQ2HR64. 3 interactions.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini9 – 223215Peptidase C76PROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili1085 – 111228Sequence AnalysisAdd
    BLAST
    Coiled coili1394 – 142734Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi300 – 32728Gly-richAdd
    BLAST
    Compositional biasi371 – 39323Pro-richAdd
    BLAST
    Compositional biasi427 – 4304Poly-Asp
    Compositional biasi2237 – 2536300Pro-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the herpesviridae deneddylase family.Curated
    Contains 1 peptidase C76 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil, Repeat

    Family and domain databases

    InterProiIPR006928. Pept_C76_UL36-USP.
    [Graphical view]
    PfamiPF04843. Herpes_teg_N. 1 hit.
    [Graphical view]
    PROSITEiPS51521. HTUSP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q2HR64-1 [UniParc]FASTAAdd to Basket

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    MAAQPLYMEG MASTHQANCI FGEHAGSQCL SNCVMYLASS YYNSETPLVD     50
    RASLDDVLEQ GMRLDLLLRK SGMLGFRQYA QLHHIPGFLR TDDWATKIFQ 100
    SPEFYGLIGQ DAAIREPFIE SLRSVLSRNY AGTVQYLIII CQSKAGAIVV 150
    KDKTYYMFDP HCIPNIPNSP AHVIKTNDVG VLLPYIATHD TEYTGCFLYF 200
    IPHDYISPEH YIANHYRTIV FEELHGPRMD ISRGVESCSI TEITSPSVSP 250
    APSEAPLRRD STQSQDETRP RRPRVVIPPY DPTDRPRPPH QDRPPEQAAG 300
    YGGNKGRGGN KGRGGKTGRG GNEGRGGHQP PDEHQPPHIT AEHMDQSDGQ 350
    GADGDMDSTP ANGETSVTET PGPEPNPPAR PDREPPPTPP ATPGATALLS 400
    DLTATRGQKR KFSSLKESYP IDSPPSDDDD VSQPSQQTAP DTEDIWIDDP 450
    LTPLYPLTDT PSFDITADVT PDNTHPEKAA DGDFTNKTTS TDADRYASAS 500
    QESLGTLVSP YDFTNLDTLL AELGRLGTAQ PIPVIVDRLT SRPFREASAL 550
    QAMDRILTHV VLEYGLVSGY STAAPSKCTH VLQFFILWGE KLGIPTEDAK 600
    TLLESALEIP AMCEIVQQGR LKEPTFSRHI ISKLNPCLES LHATSRQDFK 650
    SLIQAFNAEG IRIASRERET SMAELIETIT ARLKPNFNIV CARQDAQTIQ 700
    DGVGLLRAEV NKRNAQIAQE AAYFENIITA LSTFQPPPQS QQTFEVLPDL 750
    KLRTLVEHLT LVEAQVTTQT VESLQAYLQS AATAEHHLTN VPNVHSILSN 800
    ISNTLKVIDY VIPKFIINTD TLAPYKQQFS YLGGELASMF SLDWPHAPAE 850
    AVEPLPVLTS LRGKIAEALT RQENKNAVDQ ILTDAEGLLK NITDPNGAHF 900
    HAQAVSIPVL ENYVHNAGVL LKGEKSERFS RLKTAIQNLV SSESFITVTL 950
    HSTNLGNLVT NVPKLGEAFT GGPHLLTSPS VRQSLSTLCT TLLRDALDAL 1000
    EKKDPALLGE GTTLALETLL GYGSVQDYKE TVQIISSLVG IQKLVRDQGA 1050
    DKWATAVTRL TDLKSTLATT AIETATKRKL YRLIQRDLKE AQKHETNRAM 1100
    EEWKQKVLAL DNASPERVAT LLQQAPTAKA REFAEKHFKI LLPVPADAPV 1150
    QASPTPMEYS ASPLPDPKDI DRATSIHGEQ AWKKIQQAFK DFNFAVLRPA 1200
    DWDALAAEYQ RRGSPLPAAV GPALSGFLET ILGTLNDIYM DKLRSFLPDA 1250
    QPFQAPPFDW LTPYQDQVSF FLRTIGLPLV RALADKISVQ ALRLSHALQS 1300
    GDLQQATVGT PLELPATEYA RIASNMKSVF NDHGLQVRSE VADYVEAQRA 1350
    DAHTPHVPRP KIQAPKTLIP HPDAIVADGL PAFLKTSLLQ QEAKLLALQR 1400
    ADFESLESDM RAAEAQRKAS REETQRKMAH AITQLLQQAP SAISGRPLSL 1450
    QDPVGFLEGI IYDKVLERES YETGLEGLSW LEQTIKSITV YAPVEEKQRM 1500
    HVLLDEVKKQ RANTETALEL EAAATHGDDA RLLQRAVDEL SPLRVKGGKA 1550
    AVESWRQKIQ TLKSLVQEAE QAGLLLATID TVAGQAQETI SPSTLQGLYQ 1600
    QGQEAMAAIK RFRDSPQLAG LQEKLAELQQ YVKYKKQYLE HFEATQSVVF 1650
    TAFPLTQEVT IPALHYAGPF DNLERLSRYL HIGQTQPAPG QWLLTLPTFD 1700
    PTRPACVPAG GHEPPLHRQV VFSSFLEAQI RLALSVAGPV PGRGLPGTPQ 1750
    IRRGVEAAAC FLHQWDEISR LLPEVLDTFF HNAPLPAESS SNAFLAMCVL 1800
    THLVYLAGRA VLGPREPEHA APDAYPREVA LAPRDLTYLL LAMWPSWISA 1850
    ILKQPSHAEA AHACLVTLPT MLKAVPYLTL EASAGPLPAD MRHFATPEAR 1900
    LFFPARWHHV NVQEKLWLRN DFMSLCHRSP GRARIAVLVW AVTCLDPEVI 1950
    RQLWSTLRPL TADESDTASG LLRVLVEMEF GPPPKTPRRE AVAPGATLPP 2000
    YPYGLATGER LVGQAQERSG GAGKMPVSGF EIVLGALLFR APLRIFSTAS 2050
    THRISDFEGG FQILTPLLDC CPDREPFASL AAAPRRTVPL GDPCANIHTP 2100
    EEIQIFARQA AWLQYTFANY QIPSTDNPIP IVVLNANNNL ENSYIPRDRK 2150
    ADPLRPFYVV PLKPQGRWPE IMTTATTPCR LPTSPEEAGS QFARLLQSQV 2200
    SATWSDIFSR VPERLAPNAP QKSSQTMSEI HEVAATPPLT ITPNKPTGTP 2250
    HVSPEADPIT ERKRGQQPKI VADNMPSRIL PSLPTPKPRE PRITLPHALP 2300
    VISPPAHRPS PIPHLPAPQV TEPKGVLQSK RGTLVLRPAA VIDPRKPVSA 2350
    PITRYERTAL QPPRTEGEGR RPPDTQPVTL TFRLPPTAPT PATAALETKT 2400
    TPPSTPPHAI DISPPQTPPM STSPHARDTS PPAEKRAAPV IRVMAPTQPS 2450
    GEARVKRVEI EQGLSTRNEA PPLERSNHAV PAVTPRRTVA REIRIPPEIK 2500
    AGWDTAPDIP LPHSSPESSP PTSPQPIRVD DKSPLPNLVE RYARGFLDTP 2550
    SVEVMSLENQ DIAVDPGLLT RRIPSVVPMP HPIMWSPIVP ISLQNTDIDT 2600
    AKITLISFIR RIKQKVAALS ASLAETVDRI KKWYL 2635
    Length:2,635
    Mass (Da):289,691
    Last modified:May 15, 2007 - v1
    Checksum:i00070132EA8139AF
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF148805 Genomic DNA. Translation: ABD28919.1.
    RefSeqiYP_001129421.1. NC_009333.1.

    Genome annotation databases

    GeneIDi4961441.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF148805 Genomic DNA. Translation: ABD28919.1 .
    RefSeqi YP_001129421.1. NC_009333.1.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q2HR64. 3 interactions.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 4961441.

    Family and domain databases

    InterProi IPR006928. Pept_C76_UL36-USP.
    [Graphical view ]
    Pfami PF04843. Herpes_teg_N. 1 hit.
    [Graphical view ]
    PROSITEi PS51521. HTUSP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview."
      Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.
      J. Gen. Virol. 87:1781-1804(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. "Kaposi's sarcoma-associated herpesvirus encodes a viral deubiquitinase."
      Gonzalez C.M., Wang L., Damania B.
      J. Virol. 83:10224-10233(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiDEN_HHV8P
    AccessioniPrimary (citable) accession number: Q2HR64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 5, 2011
    Last sequence update: May 15, 2007
    Last modified: October 1, 2014
    This is version 31 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. Peptidase families
      Classification of peptidase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3