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O41965

- DEN_MHV68

UniProt

O41965 - DEN_MHV68

Protein

Deneddylase

Gene

ORF64

Organism
Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68)
Status
Reviewed - Annotation score: 3 out of 5- Protein inferred from homologyi
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    • History
      Entry version 39 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      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
    Sitei20 – 201Important for catalytic activityPROSITE-ProRule annotation
    Active sitei33 – 331PROSITE-ProRule annotation
    Active sitei163 – 1631PROSITE-ProRule annotation
    Active sitei165 – 1651PROSITE-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
    OrganismiMurid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68)
    Taxonomic identifieri33708 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeGammaherpesvirinaeRhadinovirus
    Virus hostiApodemus sylvaticus (European woodmouse) [TaxID: 10129]

    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 – 24572457DeneddylasePRO_0000406915Add
    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

    DIPiDIP-47224N.
    IntActiO41965. 1 interaction.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 224212Peptidase C76PROSITE-ProRule annotationAdd
    BLAST
    Repeati426 – 44924LRR 1Add
    BLAST
    Repeati1017 – 104226LRR 2Add
    BLAST
    Repeati1254 – 127724LRR 3Add
    BLAST
    Repeati1662 – 168524LRR 4Add
    BLAST
    Repeati1699 – 172123LRR 5Add
    BLAST
    Repeati1740 – 176324LRR 6Add
    BLAST
    Repeati1801 – 182727LRR 7Add
    BLAST
    Repeati2046 – 207126LRR 8Add
    BLAST

    Sequence similaritiesi

    Belongs to the herpesviridae deneddylase family.Curated
    Contains 8 LRR (leucine-rich) repeats.Curated
    Contains 1 peptidase C76 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil, Leucine-rich repeat, 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.

    O41965-1 [UniParc]FASTAAdd to Basket

    « Hide

    MALPASLAGF RIEGTASTNQ ADCKFGENAG AQCLSNCIIY LMSSYFNNEA     50
    PITETHDLNK VLKFGAELDS NLRKLGLLSP GQYAQLDHVP CYVQTRKWSG 100
    FIYTSAEMFG LLGMPADISD SCITSLRDLL TANYSNTIQY ILYICGQKSG 150
    AIIIQGGRYT MFDPHCLKDI PESPAHVLST SDPDALIKYV GGVSREYTAC 200
    FLYFVPGHIS PKNYIMSHYK VISFSDLHGS KIILEEYDLP TTNQSFCSSP 250
    QASSSPDPEV GSLLKYMSKA KRKRYPMSCG EEWTDANKKR KESGRTPPEK 300
    MTHPLPSPDI IDLTMDDDVI DLTGDDDMED ESEGDREAEP DRSGTSLPSV 350
    TLPNLAAVDQ LLNSLTLPGH VPSFPALVDT DTGESYRLTR ALHQLKNVLQ 400
    QVLEIGVVSD SDYTPTEALN VLNYLMAWSK QLQIKNDDIK LLINSNLQIE 450
    KLFTLLKNNL ISDPNLADHV QAKVCACLPA MHANRATDLQ KILLHCKNLT 500
    RALEISKSSL DIKDIITTFT ESFPQDFFCV CSVEEANNLV STVQDLKRVV 550
    SNNMALTSEQ DARFKALMLS VLNNTDPPAS LGPIYLETET RTPLLSSAIQ 600
    EAVKAIEKDT VETLSELISN IPSENAIETT FVPPVRTLLK NVTTLLTVIN 650
    ACVERAEIRT PEIDSSQQQL SYIGRELSKI IDETWPERAF REPVHVLDIF 700
    QKTSSHLNDL KKKMADSESL DKILSEINQT LKAIQDKAAS PALINTLSDY 750
    IKNATVLAQA SDPRLVEIQS QVTTLTTSTS YIESLLQKIN IRTLPEVIPQ 800
    LQAATKTEQG QLSLAAMNLS LIQITNSLIN EALSSIHARS HNHLSNTFFN 850
    SLNSLMGLAD IPGREDLIKT MESIMAVQEE LVDCDDMECV EKGLTTFKYI 900
    KSSIRQYKFD KSFKTKIYLI ITSEVRDLTK IKTDKQLEAW KQDVADFTPA 950
    SIDDLNLFLD KAPTKTARSY ATRQLKHFRD DLIKEQEMET ETTPVPSTAE 1000
    IERAIDLKIK ATWDKILTNL RDLTFHHIAP GDWQVLLTVF NDHKSALFTK 1050
    MGGELLKALQ GLTAYVDSIL TPLLASQLPQ GQRYVAPNSD WVETFDQNVK 1100
    YYLRTFHLPR VSEQLDDLER KTLLLTKLVK FTDLSQSLIG THLEKDWSIY 1150
    QKLFNSLLTV YNDHLIKTKT EVHAFLDKIA SDPLLEPQAH PDLQKITQLF 1200
    TEQEIIEINT LPDIFKESIK NNEKHYIASY QTEMKVFTSM VDAALAKKTQ 1250
    STTEYNTHLL KIVNNMLVQA PPYAASHPIS SDAISYITSL VRDKHLLEKL 1300
    SYAESLKNFN WLSRLITIIL TNCHPSHKQH LQTLLDEILS REQTLTPLVA 1350
    LEDNANQSPT ERTLQAALTT LNVERVLGRA TTFQKWKSQL QELEEAVKTT 1400
    TQVSLLIQTI SSLHDKTVTE MDPTILSSHS QALADKLKEL LALKPSLDET 1450
    TMSLFHGMKA YAQFKHYFVQ HYVITQPKIF DAYPLSHHGT VSSSGGHQAT 1500
    KFNPLMRLKA FSMVTDVKKM SVWREINTTV DPTGHTFIPA PPTPAMPPIH 1550
    YNVLFSSFLQ AEAINLALNS NQPPTKKFGL LPGLMDARVG VQGAMLLDNQ 1600
    WNDISTNSAK LLDHYVRSEL TPNSLTNSQF AAMTVFAHAM AMVTPHINST 1650
    RATIFPSKAI VLNQLQFLKL CLTMWPKFSG GLLRAPSFER VVQLARATLP 1700
    TLLLSAPRNT LNHFLANNYR PTDTLPNTEA LLFYPNQHPL VNLEKLLLTS 1750
    SPFHALSTSV LNTRISMLVW GILSLSEAVL QQLWDSLYQE SATFTTYIDL 1800
    LRHLSAMNHK NSTLTTSTSL PQNNGPVVYS YGHTAGTTVA TLEGSHPLDD 1850
    GGQNIPMTLF EFVIFAIILK LKFHVFYTQE KALVNTQLGP LHLITHALDG 1900
    TGDTEPFKTY ISIPPQKYNG LGNLQQFCSQ DEIQIFQRQH EWLVGVTKQT 1950
    SFSNEDLFIV LASADNKVLS VHTFNPPINS LESETPEIVA APIQESWPKE 2000
    ITTVSFWDKP ALEKSPQELI TEVSLVAEIF SGSAIFNTFP PSYKMVSHTP 2050
    SLHVETHQLE NLSITEGTPP TSPPLPDSTT QDHMEEPDNK QAKPPYQMTS 2100
    PMKENTSTSG RPARSPSPSP PVLTPIKPII PIPQATPTMP ILSPFTPRLL 2150
    PAAVKKHQNG AVWGHSGSLP PTHIQSSTPG PAQNTRDSGR RQIVSPVITI 2200
    LPGTKAGADS AGQNTSHKDI SAYSPPPASK KTDRPSDTHV TAPLFSKSKL 2250
    VTPRPAAKTD TGTFGPLLGH EKPPVTDLTA PVEPGHPSKV SPIIHLKPSN 2300
    TGDRDPHPIS DDEDSKQPPV PDTSRDKAQS RWKTPKQRPQ NIFPPPKHED 2350
    DVPVTAPQPQ GRKILVGGRQ LPSLVYNPPT LRDIKTGMSD DKNPEPCVKE 2400
    NPPGVTHDPP LRIQHMEQTV NSSKYNVLLF IEKIIKSVHD HSSYMLSTLK 2450
    RIKQLYI 2457
    Length:2,457
    Mass (Da):273,538
    Last modified:January 1, 1998 - v1
    Checksum:i6AE1D5E1821BAAD1
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U97553 Genomic DNA. Translation: AAB66417.1.
    AF105037 Genomic DNA. Translation: AAF19328.1.
    RefSeqiNP_044902.1. NC_001826.2.

    Genome annotation databases

    GeneIDi1497174.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U97553 Genomic DNA. Translation: AAB66417.1 .
    AF105037 Genomic DNA. Translation: AAF19328.1 .
    RefSeqi NP_044902.1. NC_001826.2.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-47224N.
    IntActi O41965. 1 interaction.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 1497174.

    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. "Complete sequence and genomic analysis of murine gammaherpesvirus 68."
      Virgin H.W. IV, Latreille P., Wamsley P., Hallsworth K., Weck K.E., Dal Canto A.J., Speck S.H.
      J. Virol. 71:5894-5904(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: G2.4 and WUMS.
    2. "A functional ubiquitin-specific protease embedded in the large tegument protein (ORF64) of murine gammaherpesvirus 68 is active during the course of infection."
      Gredmark S., Schlieker C., Quesada V., Spooner E., Ploegh H.L.
      J. Virol. 81:10300-10309(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiDEN_MHV68
    AccessioniPrimary (citable) accession number: O41965
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 5, 2011
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 39 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    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