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D5LX59

- DEN_HCMVT

UniProt

D5LX59 - DEN_HCMVT

Protein

Deneddylase

Gene

UL48

Organism
Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 11 (01 Oct 2014)
      Sequence version 1 (15 Jun 2010)
      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
    Active sitei24 – 241PROSITE-ProRule annotation
    Active sitei160 – 1601PROSITE-ProRule annotation
    Active sitei162 – 1621PROSITE-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:UL48
    OrganismiHuman cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5)
    Taxonomic identifieri10363 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeBetaherpesvirinaeCytomegalovirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]

    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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi24 – 241C → S: Complete loss of DUB activity. 1 Publication
    Mutagenesisi162 – 1621H → A: Complete loss of DUB activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 22422242DeneddylasePRO_0000406913Add
    BLAST

    Interactioni

    Subunit structurei

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

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 226223Peptidase C76PROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili545 – 57228Sequence AnalysisAdd
    BLAST
    Coiled coili766 – 79328Sequence AnalysisAdd
    BLAST
    Coiled coili1168 – 120134Sequence AnalysisAdd
    BLAST
    Coiled coili1241 – 127333Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi244 – 2474Poly-Thr
    Compositional biasi315 – 3206Poly-Ser
    Compositional biasi326 – 3294Poly-Ser
    Compositional biasi786 – 7905Poly-Glu
    Compositional biasi1922 – 193110Poly-Thr
    Compositional biasi2134 – 21385Poly-Ala

    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.

    D5LX59-1 [UniParc]FASTAAdd to Basket

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    MKVTQASCHQ GDIARFGARA GNQCVCNGIM FLHALHLGGT SAVLQTEALD     50
    AIMEEGARLD ARLERELQKK LPAGGRLPVY RLGDEVPRRL ESRFGRTVHA 100
    LSRPFNGTTE TCDLDGYMCP GIFDFLRYAH AKPRPTYVLV TVNSLARAVV 150
    FTEDHMLVFD PHSSAECHNA AVYHCEGLHQ VLMVLTGFGV QLSPAFYYEA 200
    LFLYMLDVAT VPEAEIAARL VSTYRDRDID LTGVVRESAD TAATTTTAAP 250
    SLPPLPDPIV DPGCPPGVAP SIPVYDPSSS PKKTPEKRRK DLSGSKHGGK 300
    KKPPSTTSKT LATASSSSPS AIAAASSSSA VPPSYSCGEG ALPALGRYQQ 350
    LVDEVEQELK ALTLPPLPAN TSAWTLHAAG TESGANAATA TAPSFDEAFL 400
    TDRLQQLIIH AVNQRSCLRR PCGPQSAAQQ AVRAYLGLSK KLDAFLLNWL 450
    HHGLDLRRMH DYLSHKTTKG TYSTLDRALL EKMQVVFDPY GRQHGPALIA 500
    WVEEMLRYVE SKPTNELSQR LQRFVTKRPM PVSDSFVCLR PVDFQRLTQV 550
    IEQRRRVLQR QREEYHGVYE HLAGLITSID IHDLDASDLN RREILKALQP 600
    LDDNAKQELF RLGNAKMLEL QMDLDRLSTQ LLTRVHNHIL NGFLPVEDLK 650
    QMERVVEQVL RLFYDLRDLK LCDGSYEEGF VVIREQLSYL MTGTVRDNVP 700
    LLQEILQLRH AYQQATQQNE GRLTQIHDLL HVIETLVRDP GSRGSALTLA 750
    LVQEQLAQLE ALGGLQLPEV QQRLQNAQLA LSRLYEEEEE TQRFLDGLSY 800
    DDPPTEQTIK RHPQLREMLR RDEQTRLRLI NAVLSMFHTL VMRLARDESP 850
    RPTFFDAVSL LLQQLPPDSH EREDLRAANA TYAQMVKKLE QIEKAGTGAS 900
    EKRFQALREL VYFFRNHEYF FQHMVGRLGV GPQVTELYER YQHEMEEQHL 950
    ERLEREWQEE AGKLTVTSVE DVQRVLARAP SHRVMHQMQQ TLTTKMQDFL 1000
    DKEKRKQEEQ QRQLLDGYQK KVQQDLQRVV DAVKGEMLST IPHQPLEATL 1050
    ELLLGLDQRA QPLLDKFNQD LLSALQQLSK KLDGRINECL HGVLTGDVER 1100
    RCHPHREAAM QTQASLNHLD QVLGPQLLIH ETQQALQHAV HQAQFIEKCQ 1150
    QGDPTTAITG SEFESDFARY RSSQQKMEGQ LQETRQQMTE TSERLDRSLR 1200
    QDPGSSSVTR VPEKPFKGQE LAGRITPPPV DFQRPVFKTL LDQQADAARK 1250
    ALSDEADLLN QKVQTQLRQR DEQLSTAQNL WTDLVTRHKM SGGLDVTTPD 1300
    AKALMEKPLE TLRELLGKAT QQLPYLSAER TVRWMLAFLE EALAQITADP 1350
    THPHHGSRTH YRNLQQQAVE SAVTLAHQIE QNAACENFIA QHQEATANGA 1400
    STPRVDMVQA VEAVWQRLEP GRVAGGAARH QKVQELLQRL GQTLGDLELQ 1450
    ETLATEYFAL LHGIQTFSYG LDFRSQLEKI RDLRTRFAEL AKRRGTRLSN 1500
    EGALPNPRKP QATTSLGAFT RGLNALERHV QLGHQYLLNK LNGSSLVYRL 1550
    EDIPSVLPPT HETDPALIMR DRLRRLCFAR HHDTFLEVVD VFGMRQIVTQ 1600
    AGEPIHLVTD YGNVAFKYLA LRDDGRPLAW RRRCSGGGLK NVVTTRYKAI 1650
    TVAVAVCQTL RTFWPQISQY DLRPYLTQHQ SHTHPAETHT LHNLKLFCYL 1700
    VSTAWHQRID TQQELTAADR VGSGEGGDVG EQRPGRGTVL RLSLQEFCVL 1750
    IAALYPEYIY TVLKYPVQMS LPSLTAHLHQ DVIHAVVNNT HKMPPDHLPE 1800
    QVKAFCITPT QWPAMQLNKL FWENKLVQQL CQVGPQKSTP PLGKLWLYAM 1850
    ATLVFPQDML QCLWLELKPQ YAETYASVSE LVQTLFQIFT QQCEMVTEGY 1900
    TQPQLPTGEP VLQMIRVRRQ DTTTTDTNTT TEPGLLDVFI QTETALDYAL 1950
    GSWLFGIPVC LGVHVADLLK GQRVLVARHL EYTSRDRDFL RIQRSRDLNL 2000
    SQLLQDTWTE TPLEHCWLQA QIRRLRDYLR FPTRLEFIPL VIYNAQDHTV 2050
    VRVLRPPSTF EQDHSRLVLD EAFPIFPLYD QDDNSSADNV AASGAAPTPP 2100
    VPFNRVPVNI QFLRENPPPI ARVQQPPRRH RHRAAAAADD DGQIDHVQDD 2150
    TSRTADSALV STAFGGSVFQ ENRLGETPLC RDELVAVAPG AASTSFASPP 2200
    ITVLTQNVLS ALEILRLVRL NLRQLAQSVQ DTIQHMRFLY LL 2242
    Length:2,242
    Mass (Da):253,365
    Last modified:June 15, 2010 - v1
    Checksum:i209FE3CF7502FDAA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    GU980198 Genomic DNA. Translation: ADE88055.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    GU980198 Genomic DNA. Translation: ADE88055.1 .

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    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. "Human cytomegalovirus RL11 gene family: variation, recombination and transcription."
      Davison A.J.
      Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: CINCY+Towne.
    2. "Cleavage specificity of the UL48 deubiquitinating protease activity of human cytomegalovirus and the growth of an active-site mutant virus in cultured cells."
      Kim E.T., Oh S.E., Lee Y.O., Gibson W., Ahn J.H.
      J. Virol. 83:12046-12056(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF CYS-24 AND HIS-162.

    Entry informationi

    Entry nameiDEN_HCMVT
    AccessioniPrimary (citable) accession number: D5LX59
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 5, 2011
    Last sequence update: June 15, 2010
    Last modified: October 1, 2014
    This is version 11 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