Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

D5LX59 (DEN_HCMVT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 26, 2013. Version 9. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Deneddylase

EC=3.4.19.12
EC=3.4.22.-
Alternative name(s):
Tegument protein VP1-2
Tegument protein VP1/2
Gene names
ORF Names:UL48
OrganismHuman cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5)
Taxonomic identifier10363 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeBetaherpesvirinaeCytomegalovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length2242 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Catalytic activity

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).

Subunit structure

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

Subcellular location

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

Sequence similarities

Belongs to the herpesviridae deneddylase family.

Contains 1 peptidase C76 domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 22422242Deneddylase
PRO_0000406913

Regions

Domain4 – 226223Peptidase C76
Coiled coil545 – 57228 Potential
Coiled coil766 – 79328 Potential
Coiled coil1168 – 120134 Potential
Coiled coil1241 – 127333 Potential
Compositional bias244 – 2474Poly-Thr
Compositional bias315 – 3206Poly-Ser
Compositional bias326 – 3294Poly-Ser
Compositional bias786 – 7905Poly-Glu
Compositional bias1922 – 193110Poly-Thr
Compositional bias2134 – 21385Poly-Ala

Sites

Active site241 By similarity
Active site1601 By similarity
Active site1621 By similarity

Experimental info

Mutagenesis241C → S: Complete loss of DUB activity. Ref.2
Mutagenesis1621H → A: Complete loss of DUB activity. Ref.2

Sequences

Sequence LengthMass (Da)Tools
D5LX59 [UniParc].

Last modified June 15, 2010. Version 1.
Checksum: 209FE3CF7502FDAA

FASTA2,242253,365
        10         20         30         40         50         60 
MKVTQASCHQ GDIARFGARA GNQCVCNGIM FLHALHLGGT SAVLQTEALD AIMEEGARLD 

        70         80         90        100        110        120 
ARLERELQKK LPAGGRLPVY RLGDEVPRRL ESRFGRTVHA LSRPFNGTTE TCDLDGYMCP 

       130        140        150        160        170        180 
GIFDFLRYAH AKPRPTYVLV TVNSLARAVV FTEDHMLVFD PHSSAECHNA AVYHCEGLHQ 

       190        200        210        220        230        240 
VLMVLTGFGV QLSPAFYYEA LFLYMLDVAT VPEAEIAARL VSTYRDRDID LTGVVRESAD 

       250        260        270        280        290        300 
TAATTTTAAP SLPPLPDPIV DPGCPPGVAP SIPVYDPSSS PKKTPEKRRK DLSGSKHGGK 

       310        320        330        340        350        360 
KKPPSTTSKT LATASSSSPS AIAAASSSSA VPPSYSCGEG ALPALGRYQQ LVDEVEQELK 

       370        380        390        400        410        420 
ALTLPPLPAN TSAWTLHAAG TESGANAATA TAPSFDEAFL TDRLQQLIIH AVNQRSCLRR 

       430        440        450        460        470        480 
PCGPQSAAQQ AVRAYLGLSK KLDAFLLNWL HHGLDLRRMH DYLSHKTTKG TYSTLDRALL 

       490        500        510        520        530        540 
EKMQVVFDPY GRQHGPALIA WVEEMLRYVE SKPTNELSQR LQRFVTKRPM PVSDSFVCLR 

       550        560        570        580        590        600 
PVDFQRLTQV IEQRRRVLQR QREEYHGVYE HLAGLITSID IHDLDASDLN RREILKALQP 

       610        620        630        640        650        660 
LDDNAKQELF RLGNAKMLEL QMDLDRLSTQ LLTRVHNHIL NGFLPVEDLK QMERVVEQVL 

       670        680        690        700        710        720 
RLFYDLRDLK LCDGSYEEGF VVIREQLSYL MTGTVRDNVP LLQEILQLRH AYQQATQQNE 

       730        740        750        760        770        780 
GRLTQIHDLL HVIETLVRDP GSRGSALTLA LVQEQLAQLE ALGGLQLPEV QQRLQNAQLA 

       790        800        810        820        830        840 
LSRLYEEEEE TQRFLDGLSY DDPPTEQTIK RHPQLREMLR RDEQTRLRLI NAVLSMFHTL 

       850        860        870        880        890        900 
VMRLARDESP RPTFFDAVSL LLQQLPPDSH EREDLRAANA TYAQMVKKLE QIEKAGTGAS 

       910        920        930        940        950        960 
EKRFQALREL VYFFRNHEYF FQHMVGRLGV GPQVTELYER YQHEMEEQHL ERLEREWQEE 

       970        980        990       1000       1010       1020 
AGKLTVTSVE DVQRVLARAP SHRVMHQMQQ TLTTKMQDFL DKEKRKQEEQ QRQLLDGYQK 

      1030       1040       1050       1060       1070       1080 
KVQQDLQRVV DAVKGEMLST IPHQPLEATL ELLLGLDQRA QPLLDKFNQD LLSALQQLSK 

      1090       1100       1110       1120       1130       1140 
KLDGRINECL HGVLTGDVER RCHPHREAAM QTQASLNHLD QVLGPQLLIH ETQQALQHAV 

      1150       1160       1170       1180       1190       1200 
HQAQFIEKCQ QGDPTTAITG SEFESDFARY RSSQQKMEGQ LQETRQQMTE TSERLDRSLR 

      1210       1220       1230       1240       1250       1260 
QDPGSSSVTR VPEKPFKGQE LAGRITPPPV DFQRPVFKTL LDQQADAARK ALSDEADLLN 

      1270       1280       1290       1300       1310       1320 
QKVQTQLRQR DEQLSTAQNL WTDLVTRHKM SGGLDVTTPD AKALMEKPLE TLRELLGKAT 

      1330       1340       1350       1360       1370       1380 
QQLPYLSAER TVRWMLAFLE EALAQITADP THPHHGSRTH YRNLQQQAVE SAVTLAHQIE 

      1390       1400       1410       1420       1430       1440 
QNAACENFIA QHQEATANGA STPRVDMVQA VEAVWQRLEP GRVAGGAARH QKVQELLQRL 

      1450       1460       1470       1480       1490       1500 
GQTLGDLELQ ETLATEYFAL LHGIQTFSYG LDFRSQLEKI RDLRTRFAEL AKRRGTRLSN 

      1510       1520       1530       1540       1550       1560 
EGALPNPRKP QATTSLGAFT RGLNALERHV QLGHQYLLNK LNGSSLVYRL EDIPSVLPPT 

      1570       1580       1590       1600       1610       1620 
HETDPALIMR DRLRRLCFAR HHDTFLEVVD VFGMRQIVTQ AGEPIHLVTD YGNVAFKYLA 

      1630       1640       1650       1660       1670       1680 
LRDDGRPLAW RRRCSGGGLK NVVTTRYKAI TVAVAVCQTL RTFWPQISQY DLRPYLTQHQ 

      1690       1700       1710       1720       1730       1740 
SHTHPAETHT LHNLKLFCYL VSTAWHQRID TQQELTAADR VGSGEGGDVG EQRPGRGTVL 

      1750       1760       1770       1780       1790       1800 
RLSLQEFCVL IAALYPEYIY TVLKYPVQMS LPSLTAHLHQ DVIHAVVNNT HKMPPDHLPE 

      1810       1820       1830       1840       1850       1860 
QVKAFCITPT QWPAMQLNKL FWENKLVQQL CQVGPQKSTP PLGKLWLYAM ATLVFPQDML 

      1870       1880       1890       1900       1910       1920 
QCLWLELKPQ YAETYASVSE LVQTLFQIFT QQCEMVTEGY TQPQLPTGEP VLQMIRVRRQ 

      1930       1940       1950       1960       1970       1980 
DTTTTDTNTT TEPGLLDVFI QTETALDYAL GSWLFGIPVC LGVHVADLLK GQRVLVARHL 

      1990       2000       2010       2020       2030       2040 
EYTSRDRDFL RIQRSRDLNL SQLLQDTWTE TPLEHCWLQA QIRRLRDYLR FPTRLEFIPL 

      2050       2060       2070       2080       2090       2100 
VIYNAQDHTV VRVLRPPSTF EQDHSRLVLD EAFPIFPLYD QDDNSSADNV AASGAAPTPP 

      2110       2120       2130       2140       2150       2160 
VPFNRVPVNI QFLRENPPPI ARVQQPPRRH RHRAAAAADD DGQIDHVQDD TSRTADSALV 

      2170       2180       2190       2200       2210       2220 
STAFGGSVFQ ENRLGETPLC RDELVAVAPG AASTSFASPP ITVLTQNVLS ALEILRLVRL 

      2230       2240 
NLRQLAQSVQ DTIQHMRFLY LL 

« Hide

References

« Hide 'large scale' references
[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
GU980198 Genomic DNA. Translation: ADE88055.1.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR006928. Pept_C76_UL36-USP.
[Graphical view]
PfamPF04843. Herpes_teg_N. 1 hit.
[Graphical view]
PROSITEPS51521. HTUSP. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameDEN_HCMVT
AccessionPrimary (citable) accession number: D5LX59
Entry history
Integrated into UniProtKB/Swiss-Prot: April 5, 2011
Last sequence update: June 15, 2010
Last modified: June 26, 2013
This is version 9 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries