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Protein

Large tegument protein deneddylase

Gene

UL48

Organism
Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Large tegument protein that plays multiple roles in the viral cycle. During viral entry, remains associated with the capsid while most of the tegument is detached and participates in the capsid transport toward the host nucleus. Plays a role in the routing of the capsid at the nuclear pore complex and subsequent uncoating. Within the host nucleus, acts as a deneddylase and promotes the degradation of nuclear CRLs (cullin-RING ubiquitin ligases) and thereby stabilizes nuclear CRL substrates, while cytoplasmic CRLs remain unaffected. These modifications prevent host cell cycle S-phase progression and create a favorable environment allowing efficient viral genome replication. Participates later in the secondary envelopment of capsids. Indeed, plays a linker role for the association of the outer viral tegument to the capsids together with the inner tegument protein.UniRule annotation1 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).UniRule annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei24UniRule annotation1 Publication1
Active sitei160UniRule annotation1
Active sitei162UniRule annotation1 Publication1

GO - Molecular functioni

GO - Biological processi

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:
Large tegument protein deneddylaseUniRule annotation (EC:3.4.19.12UniRule annotation1 Publication, EC:3.4.22.-UniRule annotation1 Publication)
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 UniRule annotation
  • Host cytoplasm UniRule annotation
  • Host nucleus UniRule annotation

  • Note: Tightly associated with the capsid.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus, Virion, Virion tegument

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24C → S: Complete loss of DUB activity. 1 Publication1
Mutagenesisi162H → A: Complete loss of DUB activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004069131 – 2242Large tegument protein deneddylaseAdd BLAST2242

Interactioni

Subunit structurei

Interacts with host CUL1 and CUL4A; these interactions inhibit the E3 ligase activity of cullins. Interacts with inner tegument protein. Interacts with capsid vertex specific component CVC2. Interacts with the major capsid protein/MCP.UniRule annotation

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 226Peptidase C76UniRule annotationAdd BLAST223

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 238Deubiquitination activityUniRule annotationAdd BLAST238
Regioni328 – 332Interaction with inner tegument proteinUniRule annotation5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi244 – 247Poly-Thr4
Compositional biasi315 – 320Poly-Ser6
Compositional biasi326 – 329Poly-Ser4
Compositional biasi786 – 790Poly-Glu5
Compositional biasi1922 – 1931Poly-Thr10
Compositional biasi2134 – 2138Poly-Ala5

Sequence similaritiesi

Belongs to the herpesviridae large tegument protein family.UniRule annotation
Contains 1 peptidase C76 domain.UniRule annotation

Keywords - Domaini

Repeat

Family and domain databases

HAMAPiMF_04044. HSV_LTP. 1 hit.
InterProiIPR006928. htUSP.
[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:
EMBLi
GenBanki
DDBJi
Links Updated
GU980198 Genomic DNA. Translation: ADE88055.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
GU980198 Genomic DNA. Translation: ADE88055.1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

HAMAPiMF_04044. HSV_LTP. 1 hit.
InterProiIPR006928. htUSP.
[Graphical view]
PfamiPF04843. Herpes_teg_N. 1 hit.
[Graphical view]
PROSITEiPS51521. HTUSP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLTP_HCMVT
AccessioniPrimary (citable) accession number: D5LX59
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 5, 2011
Last sequence update: June 15, 2010
Last modified: November 30, 2016
This is version 17 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.