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A8E1C4

- DEN_MUHVK

UniProt

A8E1C4 - DEN_MUHVK

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Protein

Deneddylase

Gene

M48

Organism
Murid herpesvirus 1 (strain K181) (MuHV-1) (Mouse cytomegalovirus)
Status
Reviewed - Annotation score: 3 out of 5- Protein inferred from homologyi

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 CDKN1A/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
Sitei10 – 101Important for catalytic activityPROSITE-ProRule annotation
Active sitei23 – 231PROSITE-ProRule annotation
Active sitei156 – 1561PROSITE-ProRule annotation
Active sitei158 – 1581PROSITE-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.-)
Gene namesi
Name:M48
OrganismiMurid herpesvirus 1 (strain K181) (MuHV-1) (Mouse cytomegalovirus)
Taxonomic identifieri69156 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageHerpesviralesHerpesviridaeBetaherpesvirinaeMuromegalovirus
Virus hostiMus musculus (Mouse) [TaxID: 10090]

Subcellular locationi

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 21472147DeneddylasePRO_0000396954Add
BLAST

Interactioni

Subunit structurei

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

Protein-protein interaction databases

IntActiA8E1C4. 29 interactions.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 223221Peptidase C76PROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili649 – 68638Sequence AnalysisAdd
BLAST
Coiled coili937 – 96428Sequence AnalysisAdd
BLAST
Coiled coili1184 – 121936Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi296 – 3038Nuclear localization signalBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi233 – 2386Poly-Gly
Compositional biasi465 – 4684Poly-Thr
Compositional biasi536 – 5394Poly-Ala
Compositional biasi687 – 6904Poly-Ser
Compositional biasi691 – 6944Poly-Pro
Compositional biasi1567 – 15704Poly-Ser
Compositional biasi2046 – 20494Poly-Ser

Sequence similaritiesi

Belongs to the herpesviridae deneddylase family.Curated
Contains 1 peptidase C76 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

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.

A8E1C4-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKIVRASRDQ SAPVYGPRAG SQCMSNCFTF LHTCYLMGID PVLDTTSLDA
60 70 80 90 100
VLDSGARLDA IADEKVKRQA LTDHPYRLGT EIPTVIETPA GITGHALSRP
110 120 130 140 150
FNGTAETQDL GGYKCLGILD FLTYARGKPL PVYIIVTVGV HTRGVIVARG
160 170 180 190 200
ATYVFDPHTT DLSAEAAVYV CDDFTEAISA LSFFGAMIGD FYYDAVLVYF
210 220 230 240 250
TRCRTTLISP SELLVQIMDQ YKDPDIDASV MSGSGGGGPS ISSSAASASA
260 270 280 290 300
SVSPLPSGAA SDGVTNGAGA QTSSKSGKKR RAPDVPPQQK GTAKTLRRSR
310 320 330 340 350
RPIRLPERLS EVIVEDVQTI EHFRTATQSL PVKPPQEWTM YCGEEPFYRQ
360 370 380 390 400
YFVDVGRQLL AHAIDTYVSL DKTTDESAVQ RFESLMGLSD ELDAVIAAAR
410 420 430 440 450
ATELSAPPLY KTYLSQRVSA SAVTRTDRLL ASKILALFEE GSATDFETVS
460 470 480 490 500
SWLRELLQQL PVENTTTTEA KIAAFVAQHP IPGERAFVCL RNSQVKSLGE
510 520 530 540 550
LLSVKRETLK VKYMENDATY RKILDAISKL GLASNAAAAI QSADTSHLDS
560 570 580 590 600
EQLASLAQAA EAYAQSAYES CQAKMTELLS TNHNRILTGS LPDSDIAAVL
610 620 630 640 650
AAFKAVSENV RALREVELLK SQVHVQLAQL TEDLLYLQTA EVKLEVTPSA
660 670 680 690 700
EIKKLRAEYE TARKQISDEE MRIKELIENM EDMITDSSSS PPPPEMLDML
710 720 730 740 750
RTQIEEVESM TVDEQDARRA DKVLGKLSTL DEAEAKATEF AQSLSTVNIP
760 770 780 790 800
SLNEIKGVKM LKSVLETNAD LRRAYVQAVT GMLENALKQL AEGNLPSDDM
810 820 830 840 850
MSRITALAEQ LPTGRQVRAD LLDSTDIVSQ MSRRLRYAAN QKNSTQSLED
860 870 880 890 900
VLNFFSENDD MIRKLLKTSW GKPVATVYRR VQVEYDRKME ELRESEWLKR
910 920 930 940 950
VKETDIDSPQ TLERLLKTAP NETILAKHAP DMHARLKKRM QSEAEKRTAD
960 970 980 990 1000
MKRLYEEMRK KVDTDLKVVS DSFSSQTPSM FSSIDLKSCG TSLVRLTKED
1010 1020 1030 1040 1050
RKAAIATFNA NLTKSLNSLL ASLVTVETAT IAAILKGADP EATSSTGSAG
1060 1070 1080 1090 1100
GGADRQKHTS TLENNISTLL GWQQKVLLPE TERDLLTIAH LLTALTHMRK
1110 1120 1130 1140 1150
NWRNPAAAFS STPHTAAYRN FAELANEIES RRTETLARYK SKYAELNASI
1160 1170 1180 1190 1200
HDNTKANDVT IKPEDTFTAA FRDTVKAMAA PFSTELQARL QARENELKDE
1210 1220 1230 1240 1250
LSDLNVKLKT KLERYLAKRS SQDARWRDLI TQHRIRLPEG LDVDTNRLRT
1260 1270 1280 1290 1300
DTVVTLNGII RSAATTLPYI TAKRGLEWTT EFILAAIEEK KDADPGMFAQ
1310 1320 1330 1340 1350
LATLLDNSQA IARKIEEKIV YNTKVEAEML ETAPEHTRES LSNLQLMLGQ
1360 1370 1380 1390 1400
LEAKRVVGGE ARYKILSDAI LTKQNKLAFA EDLEKLSARY FELARDIRSS
1410 1420 1430 1440 1450
KYGLDFDAQL LKTSLLKSEI GQHKKDPPST GEEVGLPEES TTAAKISISS
1460 1470 1480 1490 1500
LLLGIAALEK YIVAHRTLLD NFVSSQPLIS QAENIPALVG GPGEDDKPGQ
1510 1520 1530 1540 1550
EPFDWTRIDL SRLSACDVST ALYRGTDVFG ERRVMTARGI QLYLYATHGN
1560 1570 1580 1590 1600
FVFEAFSHVR GTKGLLSSSS GGGNGSGASS RQKDQQNATV TRRYRSVTVL
1610 1620 1630 1640 1650
ASIAATLQTF WSEISRYDIR ELLVESGRDP ESAADQRDRR LNTVMNLKLF
1660 1670 1680 1690 1700
VYVMTVAWSE ATPPVEPGSP EATHALEVSL LDFSTLMAAL HPEYVYAITT
1710 1720 1730 1740 1750
QPVDATLRGL IARLDRRTVD AAMNTQENPP PYDMRELKAF CLDTKQWTQE
1760 1770 1780 1790 1800
DIRPQMWMSD LVKQICTSHP RNRDASTSTK LFLYMLATKV LPRDILRCLW
1810 1820 1830 1840 1850
VQFRPAYASS IASLEELVSA LCDSFFKIYG TTSETVSARL KTGEKVERQV
1860 1870 1880 1890 1900
VLRHKPTMSL LDEFSQQEAV LDYILGSYVF AIPMTVGIHV TNIVNGRYRL
1910 1920 1930 1940 1950
IVRHLENLPS DPDFVKVVRS RDLSFDRFGW SYTVQNPVER SWFSLQEDRL
1960 1970 1980 1990 2000
RHLLTNPPQQ DRTPLVVYDS NTNYAVNAMM PPLKAPPATS RVHLTVKNPF
2010 2020 2030 2040 2050
STMRMIPHED EGDDAATSET PFTSLPINID FLRRDPPRLK RASGDSSSSV
2060 2070 2080 2090 2100
PAEDRDPDAR PQDSVPDQSL SEPLFSQTKV SSIVPKDAVT TLSNESISQT
2110 2120 2130 2140
FQIHPFRALS SAIMAAIEIL QETRLQLDTF ESDMCEAIRR IKILYLH
Length:2,147
Mass (Da):238,457
Last modified:November 13, 2007 - v1
Checksum:i4C5DB3F99EF1A63A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AM886412 Genomic DNA. Translation: CAP08095.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AM886412 Genomic DNA. Translation: CAP08095.1 .

3D structure databases

ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi A8E1C4. 29 interactions.

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. "Laboratory strains of murine cytomegalovirus are genetically similar to but phenotypically distinct from wild strains of virus."
    Smith L.M., McWhorter A.R., Masters L.L., Shellam G.R., Redwood A.J.
    J. Virol. 82:6689-6696(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K181.
  2. "Use of a murine cytomegalovirus K181-derived bacterial artificial chromosome as a vaccine vector for immunocontraception."
    Redwood A.J., Messerle M., Harvey N.L., Hardy C.M., Kozinowski U.H., Lawson M.A., Shellam G.R.
    J. Virol. 79:2998-3008(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K181.
  3. "A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases."
    Gastaldello S., Hildebrand S., Faridani O., Callegari S., Palmkvist M., Di Guglielmo C., Masucci M.G.
    Nat. Cell Biol. 12:351-361(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiDEN_MUHVK
AccessioniPrimary (citable) accession number: A8E1C4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 10, 2010
Last sequence update: November 13, 2007
Last modified: October 29, 2014
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

External Data

Dasty 3