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Q9Y4B6 (VPRBP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein VPRBP
Alternative name(s):
DDB1- and CUL4-associated factor 1
HIV-1 Vpr-binding protein
Short name=VprBP
Serine/threonine-protein kinase VPRBP
EC=2.7.11.1
Vpr-interacting protein
Gene names
Name:VPRBP
Synonyms:DCAF1, KIAA0800, RIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1507 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (Ref.35). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: VPRBP is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (Ref.34). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (Ref.37). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (Ref.29). In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT. In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.24 Ref.25 Ref.29 Ref.30 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.37

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex. Interacts with DDB1; the interaction is direct. Also forms a ternary complex with DDA1 and DDB1. Interacts with NF2 (via FERM domain). Component of the EDVP complex, a E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and VPRBP. Interacts with DYRK2; the interaction is direct. Interacts with RAG1; the interaction is direct. Interacts with LLGL1 and LLGL2. Interacts with histone H3. Interact with HIV-1 virus Vpr protein and HIV-2 virus Vpx protein; the interaction is direct. Ref.5 Ref.7 Ref.9 Ref.13 Ref.14 Ref.20 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.34 Ref.36 Ref.38 Ref.39

Subcellular location

Cytoplasm. Nucleus. Note: Associated with chromatin in a DDB1-independent and cell cycle-dependent manner: recruited to chromatin as DNA is being replicated and is released from chromatin before mitosis. Ref.5 Ref.28

Tissue specificity

Ubiquitously expressed. Ref.5

Induction

Up-regulated in a number of cancer cell lines (at protein level). Ref.37

Domain

The protein kinase-like region mediates the threonine-protein kinase activity (Ref.37).

The DWD boxes are required for interaction with DDB1.

The chromo domain with a restricted pocket directly recognizes monomethylated substrates (Ref.35).

Sequence similarities

Belongs to the VPRBP/DCAF1 family.

Contains 1 chromo domain.

Contains 1 LisH domain.

Contains 5 WD repeats.

Sequence caution

The sequence BAA34520.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processHost-virus interaction
Transcription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
WD repeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

V(D)J recombination

Inferred from sequence or structural similarity. Source: UniProtKB

cell competition in a multicellular organism

Inferred from mutant phenotype Ref.29. Source: UniProtKB

histone H2A-T120 phosphorylation

Inferred from direct assay Ref.37. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.37. Source: UniProtKB

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.28. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

histone kinase activity (H2A-T120 specific)

Inferred from direct assay Ref.37. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.28. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DDB1Q165313EBI-1996353,EBI-350322
vprP125205EBI-1996353,EBI-6164519From a different organism.
vpxP180452EBI-1996353,EBI-6558105From a different organism.
vpxP195082EBI-1996353,EBI-6558117From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y4B6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9Y4B6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     87-87: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9Y4B6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     225-673: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15071507Protein VPRBP
PRO_0000287473

Regions

Domain562 – 59332Chromo
Domain846 – 87833LisH
Repeat1091 – 113040WD 1
Repeat1133 – 117442WD 2
Repeat1176 – 121338WD 3
Repeat1215 – 124733WD 4
Repeat1248 – 129043WD 5
Region141 – 500360Protein kinase-like
Region1091 – 1290200WD repeat-like region
Region1418 – 150790Interaction with NF2
Motif1242 – 12498DWD box 1
Motif1278 – 12858DWD box 2
Compositional bias1396 – 1500105Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue7011N6-acetyllysine By similarity
Modified residue8881Phosphothreonine Ref.23
Modified residue8951Phosphoserine Ref.19 Ref.23 Ref.27
Modified residue8981Phosphoserine Ref.23
Modified residue9791Phosphoserine Ref.33
Modified residue10001Phosphoserine Ref.8 Ref.31
Cross-link280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.16

Natural variations

Alternative sequence871Missing in isoform 2.
VSP_025498
Alternative sequence225 – 673449Missing in isoform 3.
VSP_025499
Natural variant2671N → D.
Corresponds to variant rs3749318 [ dbSNP | Ensembl ].
VAR_051486
Natural variant3781L → F Does not affect serine/threonine-protein kinase kinase activity. Ref.37
Corresponds to variant rs17712228 [ dbSNP | Ensembl ].
VAR_051487
Natural variant10311L → P.
Corresponds to variant rs9835229 [ dbSNP | Ensembl ].
VAR_051488

Experimental info

Mutagenesis1941K → R: Abolishes serine/threonine-protein kinase kinase activity. Ref.37
Mutagenesis3611D → A: Abolishes serine/threonine-protein kinase kinase activity. Ref.37
Mutagenesis3631K → A: Abolishes serine/threonine-protein kinase kinase activity. Ref.37

Secondary structure

............................................................................. 1507
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 15, 2007. Version 3.
Checksum: 7E71AB2CAC4962C5

FASTA1,507169,007
        10         20         30         40         50         60 
MTTVVVHVDS KAELTTLLEQ WEKEHGSGQD MVPILTRMSQ LIEKETEEYR KGDPDPFDDR 

        70         80         90        100        110        120 
HPGRADPECM LGHLLRILFK NDDFMNALVN AYVMTSREPP LNTAACRLLL DIMPGLETAV 

       130        140        150        160        170        180 
VFQEKEGIVE NLFKWAREAD QPLRTYSTGL LGGAMENQDI AANYRDENSQ LVAIVLRRLR 

       190        200        210        220        230        240 
ELQLQEVALR QENKRPSPRK LSSEPLLPLD EEAVDMDYGD MAVDVVDGDQ EEASGDMEIS 

       250        260        270        280        290        300 
FHLDSGHKTS SRVNSTTKPE DGGLKKNKSA KQGDRENFRK AKQKLGFSSS DPDRMFVELS 

       310        320        330        340        350        360 
NSSWSEMSPW VIGTNYTLYP MTPAIEQRLI LQYLTPLGEY QELLPIFMQL GSRELMMFYI 

       370        380        390        400        410        420 
DLKQTNDVLL TFEALKHLAS LLLHNKFATE FVAHGGVQKL LEIPRPSMAA TGVSMCLYYL 

       430        440        450        460        470        480 
SYNQDAMERV CMHPHNVLSD VVNYTLWLME CSHASGCCHA TMFFSICFSF RAVLELFDRY 

       490        500        510        520        530        540 
DGLRRLVNLI STLEILNLED QGALLSDDEI FASRQTGKHT CMALRKYFEA HLAIKLEQVK 

       550        560        570        580        590        600 
QSLQRTEGGI LVHPQPPYKA CSYTHEQIVE MMEFLIEYGP AQLYWEPAEV FLKLSCVQLL 

       610        620        630        640        650        660 
LQLISIACNW KTYYARNDTV RFALDVLAIL TVVPKIQLQL AESVDVLDEA GSTVSTVGIS 

       670        680        690        700        710        720 
IILGVAEGEF FIHDAEIQKS ALQIIINCVC GPDNRISSIG KFISGTPRRK LPQNPKSSEH 

       730        740        750        760        770        780 
TLAKMWNVVQ SNNGIKVLLS LLSIKMPITD ADQIRALACK ALVGLSRSST VRQIISKLPL 

       790        800        810        820        830        840 
FSSCQIQQLM KEPVLQDKRS DHVKFCKYAA ELIERVSGKP LLIGTDVSLA RLQKADVVAQ 

       850        860        870        880        890        900 
SRISFPEKEL LLLIRNHLIS KGLGETATVL TKEADLPMTA ASHSSAFTPV TAAASPVSLP 

       910        920        930        940        950        960 
RTPRIANGIA TRLGSHAAVG ASAPSAPTAH PQPRPPQGPL ALPGPSYAGN SPLIGRISFI 

       970        980        990       1000       1010       1020 
RERPSPCNGR KIRVLRQKSD HGAYSQSPAI KKQLDRHLPS PPTLDSIITE YLREQHARCK 

      1030       1040       1050       1060       1070       1080 
NPVATCPPFS LFTPHQCPEP KQRRQAPINF TSRLNRRASF PKYGGVDGGC FDRHLIFSRF 

      1090       1100       1110       1120       1130       1140 
RPISVFREAN EDESGFTCCA FSARERFLML GTCTGQLKLY NVFSGQEEAS YNCHNSAITH 

      1150       1160       1170       1180       1190       1200 
LEPSRDGSLL LTSATWSQPL SALWGMKSVF DMKHSFTEDH YVEFSKHSQD RVIGTKGDIA 

      1210       1220       1230       1240       1250       1260 
HIYDIQTGNK LLTLFNPDLA NNYKRNCATF NPTDDLVLND GVLWDVRSAQ AIHKFDKFNM 

      1270       1280       1290       1300       1310       1320 
NISGVFHPNG LEVIINTEIW DLRTFHLLHT VPALDQCRVV FNHTGTVMYG AMLQADDEDD 

      1330       1340       1350       1360       1370       1380 
LMEERMKSPF GSSFRTFNAT DYKPIATIDV KRNIFDLCTD TKDCYLAVIE NQGSMDALNM 

      1390       1400       1410       1420       1430       1440 
DTVCRLYEVG RQRLAEDEDE EEDQEEEEQE EEDDDEDDDD TDDLDELDTD QLLEAELEED 

      1450       1460       1470       1480       1490       1500 
DNNENAGEDG DNDFSPSDEE LANLLEEGED GEDEDSDADE EVELILGDTD SSDNSDLEDD 


IILSLNE 

« Hide

Isoform 2 [UniParc].

Checksum: 016CF082F1239B17
Show »

FASTA1,506168,936
Isoform 3 [UniParc].

Checksum: A5A53818C128F546
Show »

FASTA1,058118,235

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:277-286(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: B-cell and Skin.
[5]"Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein interaction with a novel human cytoplasmic protein VprBP."
Zhang S., Feng Y., Narayan O., Zhao L.-J.
Gene 263:131-140(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 107-1507, PROTEIN SEQUENCE OF 1174-1186 AND 1328-1343, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH HIV-1 VPR.
[6]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 375-1507.
Tissue: Testis.
[7]"Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein."
Zhao L.-J., Mukherjee S., Narayan O.
J. Biol. Chem. 269:15577-15582(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 VPR.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1000, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1."
Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.
Mol. Cell 23:709-721(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDB1.
[10]"Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery."
Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.
Nature 443:590-593(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase."
Le Rouzic E., Belaiedouni N., Estrabaud E., Morel M., Rain J.-C., Transy C., Margottin-Goguet F.
Cell Cycle 6:182-188(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor."
Wen X., Duus K.M., Friedrich T.D., de Noronha C.M.
J. Biol. Chem. 282:27046-27057(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr-induced G2 arrest."
Tan L., Ehrlich E., Yu X.F.
J. Virol. 81:10822-10830(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: COMPONENT OF E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, INTERACTION WITH HIV-1 VPR, FUNCTION.
[14]"HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4A[VPRBP] E3 ubiquitin ligase."
Belzile J.P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E.A.
PLoS Pathog. 3:E85-E85(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH HIV-1 VPR.
[15]"Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle."
Hrecka K., Gierszewska M., Srivastava S., Kozaczkiewicz L., Swanson S.K., Florens L., Washburn M.P., Skowronski J.
Proc. Natl. Acad. Sci. U.S.A. 104:11778-11783(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COMPONENT OF DDA1-DDB1-VRPBP/DCAF1 COMPLEX.
[16]"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-280.
Tissue: Mammary cancer.
[17]"HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system."
DeHart J.L., Zimmerman E.S., Ardon O., Monteiro-Filho C.M., Arganaraz E.R., Planelles V.
Virol. J. 4:57-57(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, COMPONENT OF THE CUL4A-RBX1-DDB1-VPRBP/DCAF1 COMPLEX, FUNCTION.
[18]"Assembly with the Cul4A-DDB1[DCAF1] ubiquitin ligase protects HIV-1 Vpr from proteasomal degradation."
Le Rouzic E., Morel M., Ayinde D., Belaidouni N., Letienne J., Transy C., Margottin-Goguet F.
J. Biol. Chem. 283:21686-21692(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-895, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development."
McCall C.M., Miliani de Marval P.L., Chastain P.D. II, Jackson S.C., He Y.J., Kotake Y., Cook J.G., Xiong Y.
Mol. Cell. Biol. 28:5621-5633(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDB1, COMPONENT OF THE CUL4A-RBX1-DDB1-VPRBP/DCAF1 COMPLEX, CHROMATIN ASSOCIATION.
[21]"VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation."
Huang J., Chen J.
Oncogene 27:4056-4064(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NF2.
[22]"Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for cullin 4 E3 ubiquitin ligase to enable macrophage infection."
Srivastava S., Swanson S.K., Manel N., Florens L., Washburn M.P., Skowronski J.
PLoS Pathog. 4:E1000059-E1000059(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HIV-2 VPX.
[23]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-888; SER-895 AND SER-898, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection."
Bergamaschi A., Ayinde D., David A., Le Rouzic E., Morel M., Collin G., Descamps D., Damond F., Brun-Vezinet F., Nisole S., Margottin-Goguet F., Pancino G., Transy C.
J. Virol. 83:4854-4860(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HIV-2 VPX.
[25]"Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase."
Maddika S., Chen J.
Nat. Cell Biol. 11:409-419(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE EDVP COMPLEX, FUNCTION.
[26]"Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions."
Jacquot G., Le Rouzic E., Maidou-Peindara P., Maizy M., Lefrere J.J., Daneluzzi V., Monteiro-Filho C.M., Hong D., Planelles V., Morand-Joubert L., Benichou S.
PLoS ONE 4:E7514-E7514(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 VPR.
[27]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-895, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[28]"Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus."
Li W., You L., Cooper J., Schiavon G., Pepe-Caprio A., Zhou L., Ishii R., Giovannini M., Hanemann C.O., Long S.B., Erdjument-Bromage H., Zhou P., Tempst P., Giancotti F.G.
Cell 140:477-490(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, INTERACTION WITH NF2.
[29]"Involvement of Lgl and Mahjong/VprBP in cell competition."
Tamori Y., Bialucha C.U., Tian A.G., Kajita M., Huang Y.C., Norman M., Harrison N., Poulton J., Ivanovitch K., Disch L., Liu T., Deng W.M., Fujita Y.
PLoS Biol. 8:E1000422-E1000422(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH LLGL1 AND LLGL2.
[30]"Evidence for an activation domain at the amino terminus of simian immunodeficiency virus Vpx."
Gramberg T., Sunseri N., Landau N.R.
J. Virol. 84:1387-1396(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[31]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1000, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[32]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-979, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation."
Jung H.Y., Wang X., Jun S., Park J.I.
J. Biol. Chem. 288:7252-7262(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TERT.
[35]"EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex."
Lee J.M., Lee J.S., Kim H., Kim K., Park H., Kim J.Y., Lee S.H., Kim I.S., Kim J., Lee M., Chung C.H., Seo S.B., Yoon J.B., Ko E., Noh D.Y., Kim K.I., Kim K.K., Baek S.H.
Mol. Cell 48:572-586(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[36]"Vpr-binding protein antagonizes p53-mediated transcription via direct interaction with H3 tail."
Kim K., Heo K., Choi J., Jackson S., Kim H., Xiong Y., An W.
Mol. Cell. Biol. 32:783-796(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HISTONE H3.
[37]"VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription."
Kim K., Kim J.M., Kim J.S., Choi J., Lee Y.S., Neamati N., Song J.S., Heo K., An W.
Mol. Cell 52:459-467(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INDUCTION, MUTAGENESIS OF LYS-194; ASP-361 AND LYS-363, CHARACTERIZATION OF VARIANT PHE-378.
[38]"HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP."
Maudet C., Sourisce A., Dragin L., Lahouassa H., Rain J.C., Bouaziz S., Ramirez B.C., Margottin-Goguet F.
PLoS ONE 8:E77320-E77320(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HIV-1 VPR.
[39]"Structural basis of lentiviral subversion of a cellular protein degradation pathway."
Schwefel D., Groom H.C., Boucherit V.C., Christodoulou E., Walker P.A., Stoye J.P., Bishop K.N., Taylor I.A.
Nature 505:234-238(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 1058-1396 IN COMPLEX WITH SAMHD1 AND IMMUNODEFICIENCY VIRUS PROTEIN VPX, FUNCTION, INTERACTION WITH SAMHD1 AND VIRAL VPX.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB018343 mRNA. Translation: BAA34520.2. Different initiation.
AC092037 Genomic DNA. No translation available.
BC022792 mRNA. Translation: AAH22792.1.
BC110371 mRNA. Translation: AAI10372.1.
AL080145 mRNA. Translation: CAB45738.1.
AF061935 mRNA. Translation: AAG27134.1.
PIRT12529.
RefSeqNP_001165375.1. NM_001171904.1. [Q9Y4B6-2]
NP_055518.1. NM_014703.2. [Q9Y4B6-1]
XP_005276808.1. XM_005276751.2. [Q9Y4B6-1]
XP_005276809.1. XM_005276752.2. [Q9Y4B6-1]
XP_005276810.1. XM_005276753.2. [Q9Y4B6-1]
XP_005276811.1. XM_005276754.2. [Q9Y4B6-1]
XP_005276812.1. XM_005276755.2. [Q9Y4B6-1]
XP_006713489.1. XM_006713426.1. [Q9Y4B6-1]
XP_006713490.1. XM_006713427.1. [Q9Y4B6-1]
UniGeneHs.716623.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4CC9X-ray2.47A1058-1396[»]
4P7IX-ray2.60C/D1447-1507[»]
4PXWX-ray1.72A/B1039-1401[»]
ProteinModelPortalQ9Y4B6.
SMRQ9Y4B6. Positions 1073-1392.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115079. 60 interactions.
DIPDIP-47048N.
IntActQ9Y4B6. 18 interactions.
MINTMINT-4947153.
STRING9606.ENSP00000273612.

PTM databases

PhosphoSiteQ9Y4B6.

Polymorphism databases

DMDM147742890.

Proteomic databases

MaxQBQ9Y4B6.
PaxDbQ9Y4B6.
PRIDEQ9Y4B6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000335891; ENSP00000338857; ENSG00000145041. [Q9Y4B6-3]
ENST00000563997; ENSP00000454540; ENSG00000260623. [Q9Y4B6-1]
ENST00000566027; ENSP00000456445; ENSG00000260623. [Q9Y4B6-1]
GeneID9730.
KEGGhsa:9730.
UCSCuc003dbe.2. human. [Q9Y4B6-1]
uc021wys.1. human. [Q9Y4B6-2]

Organism-specific databases

CTD9730.
GeneCardsGC03M051433.
HGNCHGNC:30911. VPRBP.
HPAHPA036142.
neXtProtNX_Q9Y4B6.
PharmGKBPA142670621.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG237621.
HOGENOMHOG000007026.
HOVERGENHBG108659.
InParanoidQ9Y4B6.
KOK11789.
OMADERIRSP.
PhylomeDBQ9Y4B6.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9Y4B6.
BgeeQ9Y4B6.
CleanExHS_VPRBP.
GenevestigatorQ9Y4B6.

Family and domain databases

Gene3D1.25.10.10. 2 hits.
2.130.10.10. 2 hits.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR006594. LisH_dimerisation.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR017986. WD40_repeat_dom.
[Graphical view]
SMARTSM00667. LisH. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 3 hits.
SSF50978. SSF50978. 2 hits.
PROSITEPS50896. LISH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiVPRBP.
GenomeRNAi9730.
NextBio36604.
PROQ9Y4B6.

Entry information

Entry nameVPRBP_HUMAN
AccessionPrimary (citable) accession number: Q9Y4B6
Secondary accession number(s): Q2YD74 expand/collapse secondary AC list , Q8TBD9, Q9HCA1, Q9UG37
Entry history
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: July 9, 2014
This is version 106 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM