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Protein

Protein VPRBP

Gene

Vprbp

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. 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. Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (By similarity). 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.By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • cell competition in a multicellular organism Source: UniProtKB
  • histone H2A-T120 phosphorylation Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein ubiquitination Source: UniProtKB-UniPathway
  • transcription, DNA-templated Source: UniProtKB-KW
  • V(D)J recombination Source: UniProtKB
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Host-virus interaction, Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein VPRBP
Alternative name(s):
DDB1- and CUL4-associated factor 1
Serine/threonine-protein kinase VPRBP (EC:2.7.11.1)
Gene namesi
Name:Vprbp
Synonyms:Dcaf1, Kiaa0800
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2445220. Vprbp.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • 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.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Early embryonic lethality. Conditional knockout in mouse embryonic fibroblasts results in severely defective progression through S phase and subsequent apoptosis (PubMed:18606781). Conditional knockout in B lineage-specific cells arrests B-cell development at the pro-B-to-pre-B cell transition: mice display modest reduction of D-J(H) rearrangement, while V(H)-DJ(H) and V(kappa)-J(kappa) rearrangements are severely impaired. D-J(H) coding joints show longer junctional nucleotide insertions and a higher mutation frequency in D and J segments than normal (PubMed:22157821).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002874741 – 1506Protein VPRBPAdd BLAST1506

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei202PhosphoserineBy similarity1
Modified residuei254PhosphoserineBy similarity1
Modified residuei700N6-acetyllysineCombined sources1
Modified residuei827PhosphoserineBy similarity1
Modified residuei887PhosphothreonineBy similarity1
Modified residuei894PhosphoserineBy similarity1
Modified residuei897PhosphoserineBy similarity1
Modified residuei978PhosphoserineBy similarity1
Modified residuei999PhosphoserineBy similarity1
Modified residuei1327PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ80TR8.
PeptideAtlasiQ80TR8.
PRIDEiQ80TR8.

PTM databases

iPTMnetiQ80TR8.
PhosphoSitePlusiQ80TR8.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000040325.
CleanExiMM_VPRBP.
ExpressionAtlasiQ80TR8. baseline and differential.
GenevisibleiQ80TR8. MM.

Interactioni

Subunit structurei

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 LLGL1 and LLGL2. Interacts with histone H3 (By similarity). Interacts with RAG1; the interaction is direct.By similarity

Protein-protein interaction databases

BioGridi236458. 1 interactor.
IntActiQ80TR8. 1 interactor.
STRINGi10090.ENSMUSP00000123865.

Structurei

3D structure databases

ProteinModelPortaliQ80TR8.
SMRiQ80TR8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini561 – 592ChromoAdd BLAST32
Domaini845 – 877LisHPROSITE-ProRule annotationAdd BLAST33
Repeati1090 – 1129WD 1Add BLAST40
Repeati1132 – 1173WD 2Add BLAST42
Repeati1175 – 1212WD 3Add BLAST38
Repeati1214 – 1246WD 4Add BLAST33
Repeati1247 – 1289WD 5Add BLAST43

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni141 – 499Protein kinase-likeBy similarityAdd BLAST359
Regioni1090 – 1289WD repeat-like regionAdd BLAST200
Regioni1417 – 1506Interaction with NF2By similarityAdd BLAST90

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1241 – 1248DWD box 18
Motifi1277 – 1284DWD box 28

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi923 – 944Pro-richAdd BLAST22
Compositional biasi1395 – 1499Asp/Glu-rich (acidic)Add BLAST105

Domaini

The protein kinase-like region mediates the threonine-protein kinase activity.By similarity
The DWD boxes are required for interaction with DDB1.By similarity
The chromo domain with a restricted pocket directly recognizes monomethylated substrates.By similarity

Sequence similaritiesi

Belongs to the VPRBP/DCAF1 family.Curated
Contains 1 chromo domain.Curated
Contains 1 LisH domain.PROSITE-ProRule annotation
Contains 5 WD repeats.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG1832. Eukaryota.
ENOG410XR8C. LUCA.
GeneTreeiENSGT00390000005874.
HOGENOMiHOG000007026.
HOVERGENiHBG108659.
InParanoidiQ80TR8.
KOiK11789.
OMAiGYESKQE.
OrthoDBiEOG091G0128.
PhylomeDBiQ80TR8.
TreeFamiTF314434.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
2.130.10.10. 2 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR006594. LisH.
IPR033270. VPRBP/DCAF1.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR13129. PTHR13129. 1 hit.
SMARTiSM00667. LisH. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
SSF50978. SSF50978. 2 hits.
PROSITEiPS50896. LISH. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q80TR8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MTTVVVHVDS KAELTTLLEQ WEKDHGSGQD MVPILTRMSE LIEKETEEYR
60 70 80 90 100
KGDPDPFDDR HPGRADPECM LGHLLRILFK NDDFMNALVN AYVMTSREPP
110 120 130 140 150
LNTAACRLLL DIMPGLETAV VFQEKEGIVE NLFKWAREAD QPLRTYSTGL
160 170 180 190 200
LGGAMENQDI AANYRDENSQ LVAIVLRRLR ELQLQEVALR QDSKRPSPRK
210 220 230 240 250
LSSEPLLPLD EEAVDMDYGD MAVDVVDGEQ ESSRDMEISF RLDSSHKTSS
260 270 280 290 300
RVNSATKPEE GGLKKNKSAK HGDRENFRKA KQKLGFSSSD PDRVFVELSN
310 320 330 340 350
SSWSEMSPWV IGTNYTLYPM TPAIEQRLIL QYLTPLGEYQ ELLPIFMQLG
360 370 380 390 400
SRELMMFYID LKQTNDVLLT FEALKHLASL LLHNKFATEF VAHGGVQKLL
410 420 430 440 450
EIPRPSMAAT GVSMCLYYLS YNQDAMERVC MHPHNVLSDV VNYTLWLMEC
460 470 480 490 500
SHASGCCHAT MFFSICFSFR AVLELFDRYD GLRRLVNLIS TLEILNLEDQ
510 520 530 540 550
GALLSDDEIF ASRQTGKHTC MALRKYFEAH LAIKLEQVKQ SLQRTEGGIL
560 570 580 590 600
VHPQPPYKAC SYTHEQIVEM MEFLIEYGPA QLYWEPAEVF LKLSCVQLLL
610 620 630 640 650
QLISIACNWK TYYARNDTVR FALDVLAILT VVPKIQLQLA ESVDVLDEAG
660 670 680 690 700
SAVSTVGISI ILGVAEGEFF IHDAEIQKSA LQIIINCVCG PDNRISSIGK
710 720 730 740 750
FISGTPRRKL SQTPKSSEHT LAKMWNVVQS NNGIKVLLSL LSIKMPITDA
760 770 780 790 800
DQIRALACKA LVGLSRSSTV RQIISKLPLF SSCQIQQLMK EPVLQDKRSD
810 820 830 840 850
HVKFCKYAAE LIERVSGKPL LIGTDVSLAR LQKADVVAQS RISFPEKELL
860 870 880 890 900
LLIRNHLISK GLGETATVLT READLPMTAA SHSSAFTPVT AAASPVSLPR
910 920 930 940 950
TPRIANGIAS RLGSHATVGA SAPSAPPAHP PPRPPQGSLP LPGPSYAGNS
960 970 980 990 1000
PLIGRISFIR ERPSPCNGRK IRVLRQKSDH GAYSQSPAIK KQLDRHLPSP
1010 1020 1030 1040 1050
PTLDSIITEY LREQHARCKN PVATCPPFSL FTPHQCPEPK QRRQAPINFT
1060 1070 1080 1090 1100
SRLNRRASFP KYGGVDGGCF DRHLIFSRFR PISVFREANE DESGFTCCAF
1110 1120 1130 1140 1150
SARERFLMLG TCTGQLKLYN VFSGQEEASY NCHNSAITHL EPSRDGSLLL
1160 1170 1180 1190 1200
TSATWSQPLS ALWGMKSVFD MKHSFTEDHY VEFSKHSQDR VIGTKGDIAH
1210 1220 1230 1240 1250
IYDIQTGNKL LTLFNPDLAN NYKRNCATFN PTDDLVLNDG VLWDVRSAQA
1260 1270 1280 1290 1300
IHKFDKFNMN ISGVFHPNGL EVIINTEIWD LRTFHLLHTV PALDQCRVVF
1310 1320 1330 1340 1350
NHTGTVMYGA MLQADDEDDL LEERMKSPFG SSFRTFNATD YKPIATIDVK
1360 1370 1380 1390 1400
RNIFDLCTDT KDCYLAVIEN QGSMDALNMD TVCRLYEVGR QRLAEDEDEE
1410 1420 1430 1440 1450
EDQEEEEQEE EDDDEDDDDT DDLDELDTDQ LLEAELEEDD NNENAGEDGD
1460 1470 1480 1490 1500
NDFSPSDEEL ANLLEEGEEG EDEDSDADEE VELILGDTDS SDNSDLEDDI

ILSLNE
Length:1,506
Mass (Da):168,931
Last modified:May 15, 2007 - v4
Checksum:i8E817B418BAC5FEA
GO
Isoform 2 (identifier: Q80TR8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1344-1344: I → IVMFYFS

Note: No experimental confirmation available.
Show »
Length:1,512
Mass (Da):169,706
Checksum:i553D5646E6B2C8C4
GO
Isoform 3 (identifier: Q80TR8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     952-977: LIGRISFIRERPSPCNGRKIRVLRQK → PPRKGIAFLKGKTNMSLGISQYIFFV
     978-1506: Missing.

Note: No experimental confirmation available.
Show »
Length:977
Mass (Da):108,775
Checksum:i5749EA4F9D879EFC
GO
Isoform 4 (identifier: Q80TR8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1404-1419: EEEEQEEEDDDEDDDD → QTARTTLIWKMTSSYL
     1420-1506: Missing.

Note: No experimental confirmation available.
Show »
Length:1,419
Mass (Da):159,284
Checksum:i24EEA355177BC23E
GO

Sequence cautioni

The sequence BAC65654 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1488T → S in BAC65654 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025500952 – 977LIGRI…VLRQK → PPRKGIAFLKGKTNMSLGIS QYIFFV in isoform 3. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_025501978 – 1506Missing in isoform 3. 1 PublicationAdd BLAST529
Alternative sequenceiVSP_0255021344I → IVMFYFS in isoform 2. 1 Publication1
Alternative sequenceiVSP_0255031404 – 1419EEEEQ…EDDDD → QTARTTLIWKMTSSYL in isoform 4. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_0255041420 – 1506Missing in isoform 4. 1 PublicationAdd BLAST87

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC065119 mRNA. Translation: AAH65119.1.
AK122372 Transcribed RNA. Translation: BAC65654.3. Different initiation.
AK029372 mRNA. Translation: BAC26425.1.
AK135721 mRNA. Translation: BAE22628.1.
CCDSiCCDS23485.1. [Q80TR8-4]
RefSeqiNP_001015507.1. NM_001015507.2. [Q80TR8-4]
XP_006511818.1. XM_006511755.3. [Q80TR8-1]
UniGeneiMm.440089.
Mm.491186.

Genome annotation databases

EnsembliENSMUST00000055009; ENSMUSP00000060025; ENSMUSG00000040325. [Q80TR8-1]
ENSMUST00000159645; ENSMUSP00000123865; ENSMUSG00000040325. [Q80TR8-4]
ENSMUST00000161758; ENSMUSP00000125730; ENSMUSG00000040325. [Q80TR8-2]
GeneIDi321006.
KEGGimmu:321006.
UCSCiuc009rkp.2. mouse. [Q80TR8-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC065119 mRNA. Translation: AAH65119.1.
AK122372 Transcribed RNA. Translation: BAC65654.3. Different initiation.
AK029372 mRNA. Translation: BAC26425.1.
AK135721 mRNA. Translation: BAE22628.1.
CCDSiCCDS23485.1. [Q80TR8-4]
RefSeqiNP_001015507.1. NM_001015507.2. [Q80TR8-4]
XP_006511818.1. XM_006511755.3. [Q80TR8-1]
UniGeneiMm.440089.
Mm.491186.

3D structure databases

ProteinModelPortaliQ80TR8.
SMRiQ80TR8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi236458. 1 interactor.
IntActiQ80TR8. 1 interactor.
STRINGi10090.ENSMUSP00000123865.

PTM databases

iPTMnetiQ80TR8.
PhosphoSitePlusiQ80TR8.

Proteomic databases

PaxDbiQ80TR8.
PeptideAtlasiQ80TR8.
PRIDEiQ80TR8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000055009; ENSMUSP00000060025; ENSMUSG00000040325. [Q80TR8-1]
ENSMUST00000159645; ENSMUSP00000123865; ENSMUSG00000040325. [Q80TR8-4]
ENSMUST00000161758; ENSMUSP00000125730; ENSMUSG00000040325. [Q80TR8-2]
GeneIDi321006.
KEGGimmu:321006.
UCSCiuc009rkp.2. mouse. [Q80TR8-4]

Organism-specific databases

CTDi321006.
MGIiMGI:2445220. Vprbp.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1832. Eukaryota.
ENOG410XR8C. LUCA.
GeneTreeiENSGT00390000005874.
HOGENOMiHOG000007026.
HOVERGENiHBG108659.
InParanoidiQ80TR8.
KOiK11789.
OMAiGYESKQE.
OrthoDBiEOG091G0128.
PhylomeDBiQ80TR8.
TreeFamiTF314434.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ80TR8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040325.
CleanExiMM_VPRBP.
ExpressionAtlasiQ80TR8. baseline and differential.
GenevisibleiQ80TR8. MM.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
2.130.10.10. 2 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR006594. LisH.
IPR033270. VPRBP/DCAF1.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR017986. WD40_repeat_dom.
[Graphical view]
PANTHERiPTHR13129. PTHR13129. 1 hit.
SMARTiSM00667. LisH. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
SSF50978. SSF50978. 2 hits.
PROSITEiPS50896. LISH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVPRBP_MOUSE
AccessioniPrimary (citable) accession number: Q80TR8
Secondary accession number(s): Q3UXD5, Q6P1E2, Q8CDY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: November 30, 2016
This is version 112 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.