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D5LX59

- DEN_HCMVT

UniProt

D5LX59 - DEN_HCMVT

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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

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.1 Publication

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 – 241 By similarity
Active sitei160 – 1601 By similarity
Active sitei162 – 1621 By similarity

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
Complete GO annotation...

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
Complete GO annotation...

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 C76Add
BLAST

Coiled coil

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

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

« Hide

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

« Hide 'large scale' publications
  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: May 14, 2014
This is version 10 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

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