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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.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
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-KW
  2. host cell nucleus Source: UniProtKB-KW
  3. viral tegument Source: UniProtKB-KW
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 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

« Hide

        10         20         30         40         50
MKVTQASCHQ GDIARFGARA GNQCVCNGIM FLHALHLGGT SAVLQTEALD
60 70 80 90 100
AIMEEGARLD ARLERELQKK LPAGGRLPVY RLGDEVPRRL ESRFGRTVHA
110 120 130 140 150
LSRPFNGTTE TCDLDGYMCP GIFDFLRYAH AKPRPTYVLV TVNSLARAVV
160 170 180 190 200
FTEDHMLVFD PHSSAECHNA AVYHCEGLHQ VLMVLTGFGV QLSPAFYYEA
210 220 230 240 250
LFLYMLDVAT VPEAEIAARL VSTYRDRDID LTGVVRESAD TAATTTTAAP
260 270 280 290 300
SLPPLPDPIV DPGCPPGVAP SIPVYDPSSS PKKTPEKRRK DLSGSKHGGK
310 320 330 340 350
KKPPSTTSKT LATASSSSPS AIAAASSSSA VPPSYSCGEG ALPALGRYQQ
360 370 380 390 400
LVDEVEQELK ALTLPPLPAN TSAWTLHAAG TESGANAATA TAPSFDEAFL
410 420 430 440 450
TDRLQQLIIH AVNQRSCLRR PCGPQSAAQQ AVRAYLGLSK KLDAFLLNWL
460 470 480 490 500
HHGLDLRRMH DYLSHKTTKG TYSTLDRALL EKMQVVFDPY GRQHGPALIA
510 520 530 540 550
WVEEMLRYVE SKPTNELSQR LQRFVTKRPM PVSDSFVCLR PVDFQRLTQV
560 570 580 590 600
IEQRRRVLQR QREEYHGVYE HLAGLITSID IHDLDASDLN RREILKALQP
610 620 630 640 650
LDDNAKQELF RLGNAKMLEL QMDLDRLSTQ LLTRVHNHIL NGFLPVEDLK
660 670 680 690 700
QMERVVEQVL RLFYDLRDLK LCDGSYEEGF VVIREQLSYL MTGTVRDNVP
710 720 730 740 750
LLQEILQLRH AYQQATQQNE GRLTQIHDLL HVIETLVRDP GSRGSALTLA
760 770 780 790 800
LVQEQLAQLE ALGGLQLPEV QQRLQNAQLA LSRLYEEEEE TQRFLDGLSY
810 820 830 840 850
DDPPTEQTIK RHPQLREMLR RDEQTRLRLI NAVLSMFHTL VMRLARDESP
860 870 880 890 900
RPTFFDAVSL LLQQLPPDSH EREDLRAANA TYAQMVKKLE QIEKAGTGAS
910 920 930 940 950
EKRFQALREL VYFFRNHEYF FQHMVGRLGV GPQVTELYER YQHEMEEQHL
960 970 980 990 1000
ERLEREWQEE AGKLTVTSVE DVQRVLARAP SHRVMHQMQQ TLTTKMQDFL
1010 1020 1030 1040 1050
DKEKRKQEEQ QRQLLDGYQK KVQQDLQRVV DAVKGEMLST IPHQPLEATL
1060 1070 1080 1090 1100
ELLLGLDQRA QPLLDKFNQD LLSALQQLSK KLDGRINECL HGVLTGDVER
1110 1120 1130 1140 1150
RCHPHREAAM QTQASLNHLD QVLGPQLLIH ETQQALQHAV HQAQFIEKCQ
1160 1170 1180 1190 1200
QGDPTTAITG SEFESDFARY RSSQQKMEGQ LQETRQQMTE TSERLDRSLR
1210 1220 1230 1240 1250
QDPGSSSVTR VPEKPFKGQE LAGRITPPPV DFQRPVFKTL LDQQADAARK
1260 1270 1280 1290 1300
ALSDEADLLN QKVQTQLRQR DEQLSTAQNL WTDLVTRHKM SGGLDVTTPD
1310 1320 1330 1340 1350
AKALMEKPLE TLRELLGKAT QQLPYLSAER TVRWMLAFLE EALAQITADP
1360 1370 1380 1390 1400
THPHHGSRTH YRNLQQQAVE SAVTLAHQIE QNAACENFIA QHQEATANGA
1410 1420 1430 1440 1450
STPRVDMVQA VEAVWQRLEP GRVAGGAARH QKVQELLQRL GQTLGDLELQ
1460 1470 1480 1490 1500
ETLATEYFAL LHGIQTFSYG LDFRSQLEKI RDLRTRFAEL AKRRGTRLSN
1510 1520 1530 1540 1550
EGALPNPRKP QATTSLGAFT RGLNALERHV QLGHQYLLNK LNGSSLVYRL
1560 1570 1580 1590 1600
EDIPSVLPPT HETDPALIMR DRLRRLCFAR HHDTFLEVVD VFGMRQIVTQ
1610 1620 1630 1640 1650
AGEPIHLVTD YGNVAFKYLA LRDDGRPLAW RRRCSGGGLK NVVTTRYKAI
1660 1670 1680 1690 1700
TVAVAVCQTL RTFWPQISQY DLRPYLTQHQ SHTHPAETHT LHNLKLFCYL
1710 1720 1730 1740 1750
VSTAWHQRID TQQELTAADR VGSGEGGDVG EQRPGRGTVL RLSLQEFCVL
1760 1770 1780 1790 1800
IAALYPEYIY TVLKYPVQMS LPSLTAHLHQ DVIHAVVNNT HKMPPDHLPE
1810 1820 1830 1840 1850
QVKAFCITPT QWPAMQLNKL FWENKLVQQL CQVGPQKSTP PLGKLWLYAM
1860 1870 1880 1890 1900
ATLVFPQDML QCLWLELKPQ YAETYASVSE LVQTLFQIFT QQCEMVTEGY
1910 1920 1930 1940 1950
TQPQLPTGEP VLQMIRVRRQ DTTTTDTNTT TEPGLLDVFI QTETALDYAL
1960 1970 1980 1990 2000
GSWLFGIPVC LGVHVADLLK GQRVLVARHL EYTSRDRDFL RIQRSRDLNL
2010 2020 2030 2040 2050
SQLLQDTWTE TPLEHCWLQA QIRRLRDYLR FPTRLEFIPL VIYNAQDHTV
2060 2070 2080 2090 2100
VRVLRPPSTF EQDHSRLVLD EAFPIFPLYD QDDNSSADNV AASGAAPTPP
2110 2120 2130 2140 2150
VPFNRVPVNI QFLRENPPPI ARVQQPPRRH RHRAAAAADD DGQIDHVQDD
2160 2170 2180 2190 2200
TSRTADSALV STAFGGSVFQ ENRLGETPLC RDELVAVAPG AASTSFASPP
2210 2220 2230 2240
ITVLTQNVLS ALEILRLVRL NLRQLAQSVQ DTIQHMRFLY LL
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: October 29, 2014
This is version 12 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