ID DCAF1_HUMAN Reviewed; 1507 AA. AC Q9Y4B6; Q2YD74; Q8TBD9; Q9HCA1; Q9UG37; DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 15-MAY-2007, sequence version 3. DT 27-MAR-2024, entry version 185. DE RecName: Full=DDB1- and CUL4-associated factor 1 {ECO:0000312|HGNC:HGNC:30911}; DE AltName: Full=HIV-1 Vpr-binding protein; DE Short=VprBP; DE AltName: Full=Serine/threonine-protein kinase VPRBP; DE EC=2.7.11.1; DE AltName: Full=Vpr-interacting protein; GN Name=DCAF1 {ECO:0000312|HGNC:HGNC:30911}; GN Synonyms=KIAA0800, RIP, VPRBP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [2] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=B-cell, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 107-1507, PROTEIN SEQUENCE OF 1174-1186 AND RP 1328-1343, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH RP HIV-1 VPR (MICROBIAL INFECTION). RX PubMed=11223251; DOI=10.1016/s0378-1119(00)00583-7; RA Zhang S., Feng Y., Narayan O., Zhao L.-J.; RT "Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein RT interaction with a novel human cytoplasmic protein VprBP."; RL Gene 263:131-140(2001). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 375-1507. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION). RX PubMed=8195203; DOI=10.1016/s0021-9258(17)40719-8; RA Zhao L.-J., Mukherjee S., Narayan O.; RT "Biochemical mechanism of HIV-I Vpr function. Specific interaction with a RT cellular protein."; RL J. Biol. Chem. 269:15577-15582(1994). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1000, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP INTERACTION WITH DDB1. RX PubMed=16949367; DOI=10.1016/j.molcel.2006.08.010; RA Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.; RT "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is RT required for S phase destruction of the replication factor Cdt1."; RL Mol. Cell 23:709-721(2006). RN [10] RP FUNCTION. RX PubMed=16964240; DOI=10.1038/nature05175; RA Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.; RT "Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase RT machinery."; RL Nature 443:590-593(2006). RN [11] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=17314515; DOI=10.4161/cc.6.2.3732; RA Le Rouzic E., Belaiedouni N., Estrabaud E., Morel M., Rain J.-C., RA Transy C., Margottin-Goguet F.; RT "HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of RT the Cul4-DDB1 ubiquitin ligase."; RL Cell Cycle 6:182-188(2007). RN [12] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=17620334; DOI=10.1074/jbc.m703955200; RA Wen X., Duus K.M., Friedrich T.D., de Noronha C.M.; RT "The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a RT DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as RT an adaptor."; RL J. Biol. Chem. 282:27046-27057(2007). RN [13] RP COMPONENT OF E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, INTERACTION WITH HIV-1 RP VPR (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL INFECTION). RX PubMed=17626091; DOI=10.1128/jvi.01380-07; RA Tan L., Ehrlich E., Yu X.F.; RT "DDB1 and Cul4A are required for human immunodeficiency virus type 1 Vpr- RT induced G2 arrest."; RL J. Virol. 81:10822-10830(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION (MICROBIAL INFECTION), AND RP INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION). RX PubMed=17630831; DOI=10.1371/journal.ppat.0030085; RA Belzile J.P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E.A.; RT "HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4A[VPRBP] E3 ubiquitin RT ligase."; RL PLoS Pathog. 3:E85-E85(2007). RN [15] RP FUNCTION (MICROBIAL INFECTION), AND COMPONENT OF DDA1-DDB1-VRPBP/DCAF1 RP COMPLEX. RX PubMed=17609381; DOI=10.1073/pnas.0702102104; RA Hrecka K., Gierszewska M., Srivastava S., Kozaczkiewicz L., Swanson S.K., RA Florens L., Washburn M.P., Skowronski J.; RT "Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate RT cell cycle."; RL Proc. Natl. Acad. Sci. U.S.A. 104:11778-11783(2007). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY, COMPONENT OF THE RP CUL4A-RBX1-DDB1-VPRBP/DCAF1 COMPLEX, AND FUNCTION (MICROBIAL INFECTION). RX PubMed=17559673; DOI=10.1186/1743-422x-4-57; RA DeHart J.L., Zimmerman E.S., Ardon O., Monteiro-Filho C.M., Arganaraz E.R., RA Planelles V.; RT "HIV-1 Vpr activates the G2 checkpoint through manipulation of the RT ubiquitin proteasome system."; RL Virol. J. 4:57-57(2007). RN [17] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=18524771; DOI=10.1074/jbc.m710298200; RA Le Rouzic E., Morel M., Ayinde D., Belaidouni N., Letienne J., Transy C., RA Margottin-Goguet F.; RT "Assembly with the Cul4A-DDB1[DCAF1] ubiquitin ligase protects HIV-1 Vpr RT from proteasomal degradation."; RL J. Biol. Chem. 283:21686-21692(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-895, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [19] RP FUNCTION, INTERACTION WITH DDB1, COMPONENT OF THE RP CUL4A-RBX1-DDB1-VPRBP/DCAF1 COMPLEX, AND CHROMATIN ASSOCIATION. RX PubMed=18606781; DOI=10.1128/mcb.00232-08; RA McCall C.M., Miliani de Marval P.L., Chastain P.D. II, Jackson S.C., RA He Y.J., Kotake Y., Cook J.G., Xiong Y.; RT "Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 RT protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for RT DNA replication and embryonic development."; RL Mol. Cell. Biol. 28:5621-5633(2008). RN [20] RP FUNCTION, AND INTERACTION WITH NF2. RX PubMed=18332868; DOI=10.1038/onc.2008.44; RA Huang J., Chen J.; RT "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for RT degradation."; RL Oncogene 27:4056-4064(2008). RN [21] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-2 VPX (MICROBIAL RP INFECTION). RX PubMed=18464893; DOI=10.1371/journal.ppat.1000059; RA Srivastava S., Swanson S.K., Manel N., Florens L., Washburn M.P., RA Skowronski J.; RT "Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor for RT cullin 4 E3 ubiquitin ligase to enable macrophage infection."; RL PLoS Pathog. 4:E1000059-E1000059(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-888; SER-895 AND SER-898, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [23] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-2 VPX (MICROBIAL RP INFECTION). RX PubMed=19264781; DOI=10.1128/jvi.00187-09; RA Bergamaschi A., Ayinde D., David A., Le Rouzic E., Morel M., Collin G., RA Descamps D., Damond F., Brun-Vezinet F., Nisole S., Margottin-Goguet F., RA Pancino G., Transy C.; RT "The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 RT DCAF1 ubiquitin ligase to overcome a postentry block in macrophage RT infection."; RL J. Virol. 83:4854-4860(2009). RN [24] RP IDENTIFICATION IN THE EDVP COMPLEX, AND FUNCTION. RX PubMed=19287380; DOI=10.1038/ncb1848; RA Maddika S., Chen J.; RT "Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 RT ligase."; RL Nat. Cell Biol. 11:409-419(2009). RN [25] RP INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION). RX PubMed=19838296; DOI=10.1371/journal.pone.0007514; RA Jacquot G., Le Rouzic E., Maidou-Peindara P., Maizy M., Lefrere J.J., RA Daneluzzi V., Monteiro-Filho C.M., Hong D., Planelles V., RA Morand-Joubert L., Benichou S.; RT "Characterization of the molecular determinants of primary HIV-1 Vpr RT proteins: impact of the Q65R and R77Q substitutions on Vpr functions."; RL PLoS ONE 4:E7514-E7514(2009). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-895, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND INTERACTION RP WITH NF2. RX PubMed=20178741; DOI=10.1016/j.cell.2010.01.029; RA Li W., You L., Cooper J., Schiavon G., Pepe-Caprio A., Zhou L., Ishii R., RA Giovannini M., Hanemann C.O., Long S.B., Erdjument-Bromage H., Zhou P., RA Tempst P., Giancotti F.G.; RT "Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase RT CRL4(DCAF1) in the nucleus."; RL Cell 140:477-490(2010). RN [28] RP FUNCTION, AND INTERACTION WITH LLGL1 AND LLGL2. RX PubMed=20644714; DOI=10.1371/journal.pbio.1000422; RA Tamori Y., Bialucha C.U., Tian A.G., Kajita M., Huang Y.C., Norman M., RA Harrison N., Poulton J., Ivanovitch K., Disch L., Liu T., Deng W.M., RA Fujita Y.; RT "Involvement of Lgl and Mahjong/VprBP in cell competition."; RL PLoS Biol. 8:E1000422-E1000422(2010). RN [29] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=19923175; DOI=10.1128/jvi.01437-09; RA Gramberg T., Sunseri N., Landau N.R.; RT "Evidence for an activation domain at the amino terminus of simian RT immunodeficiency virus Vpx."; RL J. Virol. 84:1387-1396(2010). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1000, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-979, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [33] RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL35 (MICROBIAL INFECTION). RX PubMed=22072767; DOI=10.1128/jvi.05442-11; RA Salsman J., Jagannathan M., Paladino P., Chan P.K., Dellaire G., Raught B., RA Frappier L.; RT "Proteomic profiling of the human cytomegalovirus UL35 gene products RT reveals a role for UL35 in the DNA repair response."; RL J. Virol. 86:806-820(2012). RN [34] RP FUNCTION, AND INTERACTION WITH TERT. RX PubMed=23362280; DOI=10.1074/jbc.m112.416792; RA Jung H.Y., Wang X., Jun S., Park J.I.; RT "Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT RT degradation."; RL J. Biol. Chem. 288:7252-7262(2013). RN [35] RP FUNCTION. RX PubMed=23063525; DOI=10.1016/j.molcel.2012.09.004; RA Lee J.M., Lee J.S., Kim H., Kim K., Park H., Kim J.Y., Lee S.H., Kim I.S., RA Kim J., Lee M., Chung C.H., Seo S.B., Yoon J.B., Ko E., Noh D.Y., Kim K.I., RA Kim K.K., Baek S.H.; RT "EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 RT E3 ubiquitin ligase complex."; RL Mol. Cell 48:572-586(2012). RN [36] RP FUNCTION, AND INTERACTION WITH HISTONE H3. RX PubMed=22184063; DOI=10.1128/mcb.06037-11; RA Kim K., Heo K., Choi J., Jackson S., Kim H., Xiong Y., An W.; RT "Vpr-binding protein antagonizes p53-mediated transcription via direct RT interaction with H3 tail."; RL Mol. Cell. Biol. 32:783-796(2012). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255; SER-828; SER-895; RP SER-979 AND SER-1328, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [38] RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, MUTAGENESIS OF LYS-194; ASP-361 RP AND LYS-363, AND CHARACTERIZATION OF VARIANT PHE-378. RX PubMed=24140421; DOI=10.1016/j.molcel.2013.09.017; RA Kim K., Kim J.M., Kim J.S., Choi J., Lee Y.S., Neamati N., Song J.S., RA Heo K., An W.; RT "VprBP has intrinsic kinase activity targeting histone H2A and represses RT gene transcription."; RL Mol. Cell 52:459-467(2013). RN [39] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 VPR (MICROBIAL RP INFECTION). RX PubMed=24116224; DOI=10.1371/journal.pone.0077320; RA Maudet C., Sourisce A., Dragin L., Lahouassa H., Rain J.C., Bouaziz S., RA Ramirez B.C., Margottin-Goguet F.; RT "HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD RT Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP."; RL PLoS ONE 8:E77320-E77320(2013). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-202 AND SER-1000, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [41] RP INTERACTION WITH DDB1; TET1; TET2 AND TET3, AND MUTAGENESIS OF ARG-1247 AND RP ARG-1283. RX PubMed=24357321; DOI=10.1126/science.1244587; RA Yu C., Zhang Y.L., Pan W.W., Li X.M., Wang Z.W., Ge Z.J., Zhou J.J., RA Cang Y., Tong C., Sun Q.Y., Fan H.Y.; RT "CRL4 complex regulates mammalian oocyte survival and reprogramming by RT activation of TET proteins."; RL Science 342:1518-1521(2013). RN [42] RP INTERACTION WITH TET1; TET2 AND TET3. RX PubMed=25557551; DOI=10.1016/j.molcel.2014.12.002; RA Nakagawa T., Lv L., Nakagawa M., Yu Y., Yu C., D'Alessio A.C., Nakayama K., RA Fan H.Y., Chen X., Xiong Y.; RT "CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of RT TET dioxygenases."; RL Mol. Cell 57:247-260(2015). RN [43] RP INTERACTION WITH ESR1 AND LATS1. RX PubMed=28068668; DOI=10.1038/nature20829; RA Britschgi A., Duss S., Kim S., Couto J.P., Brinkhaus H., Koren S., RA De Silva D., Mertz K.D., Kaup D., Varga Z., Voshol H., Vissieres A., RA Leroy C., Roloff T., Stadler M.B., Scheel C.H., Miraglia L.J., Orth A.P., RA Bonamy G.M., Reddy V.A., Bentires-Alj M.; RT "The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk RT with ERalpha."; RL Nature 541:541-545(2017). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) OF 1058-1396 IN COMPLEX WITH SAMHD1 RP AND IMMUNODEFICIENCY VIRUS PROTEIN VPX, FUNCTION (MICROBIAL INFECTION), AND RP INTERACTION WITH SAMHD1 AND VIRAL VPX (MICROBIAL INFECTION). RX PubMed=24336198; DOI=10.1038/nature12815; RA Schwefel D., Groom H.C., Boucherit V.C., Christodoulou E., Walker P.A., RA Stoye J.P., Bishop K.N., Taylor I.A.; RT "Structural basis of lentiviral subversion of a cellular protein RT degradation pathway."; RL Nature 505:234-238(2014). CC -!- FUNCTION: Acts both as a substrate recognition component of E3 CC ubiquitin-protein ligase complexes and as an atypical serine/threonine- CC protein kinase, playing key roles in various processes such as cell CC cycle, telomerase regulation and histone modification. Probable CC substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin- CC protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, CC which mediates ubiquitination and proteasome-dependent degradation of CC proteins such as NF2. Involved in the turnover of methylated proteins: CC recognizes and binds methylated proteins via its chromo domain, leading CC to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP CC complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is CC also involved in B-cell development: DCAF1 is recruited by RAG1 to CC ubiquitinate proteins, leading to limit error-prone repair during V(D)J CC recombination. Also part of the EDVP complex, an E3 ligase complex that CC mediates ubiquitination of proteins such as TERT, leading to TERT CC degradation and telomerase inhibition (PubMed:23362280). Also acts as CC an atypical serine/threonine-protein kinase that specifically mediates CC phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a CC nucleosomal context, thereby repressing transcription. H2AT120ph is CC present in the regulatory region of many tumor suppresor genes, down- CC regulates their transcription and is present at high level in a number CC of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during CC cell competition process via its interaction with LLGL1 and LLGL2 CC (PubMed:20644714). By acting on TET dioxygenses, essential for oocyte CC maintenance at the primordial follicle stage, hence essential for CC female fertility (By similarity). {ECO:0000250|UniProtKB:Q80TR8, CC ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17609381, CC ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18332868, CC ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:18606781, CC ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:20644714, CC ECO:0000269|PubMed:22184063, ECO:0000269|PubMed:23063525, CC ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:24140421}. CC -!- FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, it CC is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1- CC DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and CC also to protect the viral protein from proteasomal degradation by CC another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A- CC RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation CC of proteins such as TERT and ZIP/ZGPAT. {ECO:0000269|PubMed:17314515, CC ECO:0000269|PubMed:17559673, ECO:0000269|PubMed:17609381, CC ECO:0000269|PubMed:17620334, ECO:0000269|PubMed:17626091, CC ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18524771, CC ECO:0000269|PubMed:24116224}. CC -!- FUNCTION: (Microbial infection) In case of infection by HIV-2 virus, it CC is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1- CC DCAF1/VPRBP function leading to enhanced efficiency of macrophage CC infection and promotion of the replication of cognate primate CC lentiviruses in cells of monocyte/macrophage lineage. CC {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:18464893, CC ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:19923175, CC ECO:0000269|PubMed:24336198}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:24140421}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:24140421}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein CC ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex. Interacts CC with DDB1; the interaction is direct. Also forms a ternary complex with CC DDA1 and DDB1. Interacts with NF2 (via FERM domain). Component of the CC EDVP complex, a E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and CC DCAF1 (PubMed:24357321). Interacts with DYRK2; the interaction is CC direct. Interacts with RAG1; the interaction is direct. Interacts with CC LLGL1 and LLGL2. Interacts with histone H3. Interacts with ESR1 and CC LATS1; probably recruited by LATS1 to promote ESR1 ubiquitination and CC ubiquitin-mediated proteasomal degradation (PubMed:28068668). Directly CC interacts with TET1, TET2 and TET3 (via C-terminus) (PubMed:24357321, CC PubMed:25557551). {ECO:0000269|PubMed:16949367, CC ECO:0000269|PubMed:17559673, ECO:0000269|PubMed:17609381, CC ECO:0000269|PubMed:17626091, ECO:0000269|PubMed:18332868, CC ECO:0000269|PubMed:18606781, ECO:0000269|PubMed:19287380, CC ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:20644714, CC ECO:0000269|PubMed:22184063, ECO:0000269|PubMed:23362280, CC ECO:0000269|PubMed:24336198, ECO:0000269|PubMed:24357321, CC ECO:0000269|PubMed:25557551, ECO:0000269|PubMed:28068668}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 virus Vpr protein; CC the interaction is direct. {ECO:0000269|PubMed:11223251, CC ECO:0000269|PubMed:17626091, ECO:0000269|PubMed:17630831, CC ECO:0000269|PubMed:19838296, ECO:0000269|PubMed:24116224, CC ECO:0000269|PubMed:8195203}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-2 virus Vpx protein; CC the interaction is direct and the complex recruits SAMHD1 to promote CC its ubiquitin-dependent proteasomal degradation. CC {ECO:0000269|PubMed:18464893, ECO:0000269|PubMed:19264781, CC ECO:0000269|PubMed:24336198}. CC -!- SUBUNIT: (Microbial infection) Interacts (via C-terminus) with human CC cytomegalovirus protein UL35; this interaction induces the accumulation CC of cells in the G2 phase of the cell cycle. CC {ECO:0000269|PubMed:22072767}. CC -!- INTERACTION: CC Q9Y4B6; Q16531: DDB1; NbExp=3; IntAct=EBI-1996353, EBI-350322; CC Q9Y4B6; O95835: LATS1; NbExp=4; IntAct=EBI-1996353, EBI-444209; CC Q9Y4B6; Q9NRM7: LATS2; NbExp=2; IntAct=EBI-1996353, EBI-3506895; CC Q9Y4B6; A0A0H3LAC5: ERDMAN_2289; Xeno; NbExp=2; IntAct=EBI-1996353, EBI-25401874; CC Q9Y4B6; P12520: vpr; Xeno; NbExp=5; IntAct=EBI-1996353, EBI-6164519; CC Q9Y4B6; P18045: vpx; Xeno; NbExp=2; IntAct=EBI-1996353, EBI-6558105; CC Q9Y4B6; P19508: vpx; Xeno; NbExp=4; IntAct=EBI-1996353, EBI-6558117; CC Q9Y4B6-3; Q16531: DDB1; NbExp=2; IntAct=EBI-9915372, EBI-350322; CC Q9Y4B6-3; P60891: PRPS1; NbExp=3; IntAct=EBI-9915372, EBI-749195; CC Q9Y4B6-3; P05928: vpr; Xeno; NbExp=2; IntAct=EBI-9915372, EBI-9210238; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11223251}. Nucleus CC {ECO:0000269|PubMed:20178741}. Note=Associated with chromatin in a CC DDB1-independent and cell cycle-dependent manner: recruited to CC chromatin as DNA is being replicated and is released from chromatin CC before mitosis. Homogenous pancellular distribution is observed outside CC S-phase and a slight cytoplasmic-to-nuclear translocation from early to CC late S-phase. Colocalizes with TET1 and PCNA at replicating CC heterochromatin during late S phase (By similarity). More concentrated CC in nuclei than in cytoplasm in germinal vesicle (GV) stage oocytes, CC zygotes and the 2-cell stage, but distributed in the cytoplasm at the CC MII-stage oocytes (By similarity). {ECO:0000250|UniProtKB:Q80TR8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9Y4B6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y4B6-2; Sequence=VSP_025498; CC Name=3; CC IsoId=Q9Y4B6-3; Sequence=VSP_025499; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:11223251}. CC -!- INDUCTION: Up-regulated in a number of cancer cell lines (at protein CC level). {ECO:0000269|PubMed:24140421}. CC -!- DOMAIN: The protein kinase-like region mediates the threonine-protein CC kinase activity. {ECO:0000269|PubMed:24140421}. CC -!- DOMAIN: The DWD boxes are required for interaction with DDB1. CC -!- DOMAIN: The chromo domain with a restricted pocket directly recognizes CC monomethylated substrates. {ECO:0000269|PubMed:23063525}. CC -!- SIMILARITY: Belongs to the VPRBP/DCAF1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA34520.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB018343; BAA34520.2; ALT_INIT; mRNA. DR EMBL; AC092037; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022792; AAH22792.1; -; mRNA. DR EMBL; BC110371; AAI10372.1; -; mRNA. DR EMBL; AL080145; CAB45738.1; -; mRNA. DR EMBL; AF061935; AAG27134.1; -; mRNA. DR CCDS; CCDS74943.1; -. [Q9Y4B6-1] DR CCDS; CCDS74944.1; -. [Q9Y4B6-2] DR PIR; T12529; T12529. DR RefSeq; NP_001165375.1; NM_001171904.1. [Q9Y4B6-2] DR RefSeq; NP_055518.1; NM_014703.2. [Q9Y4B6-1] DR RefSeq; XP_005276810.1; XM_005276753.4. [Q9Y4B6-1] DR RefSeq; XP_005276812.1; XM_005276755.4. [Q9Y4B6-1] DR RefSeq; XP_011532575.1; XM_011534273.2. [Q9Y4B6-1] DR RefSeq; XP_011532576.1; XM_011534274.2. DR RefSeq; XP_011532577.1; XM_011534275.2. [Q9Y4B6-1] DR RefSeq; XP_011532578.1; XM_011534276.2. DR RefSeq; XP_011532579.1; XM_011534277.2. DR RefSeq; XP_016863035.1; XM_017007546.1. DR RefSeq; XP_016863036.1; XM_017007547.1. [Q9Y4B6-1] DR RefSeq; XP_016863037.1; XM_017007548.1. DR RefSeq; XP_016863038.1; XM_017007549.1. [Q9Y4B6-1] DR RefSeq; XP_016863039.1; XM_017007550.1. DR PDB; 3WA0; X-ray; 2.31 A; G/H=1418-1507. DR PDB; 4CC9; X-ray; 2.47 A; A=1058-1396. DR PDB; 4P7I; X-ray; 2.60 A; C/D=1447-1507. DR PDB; 4PXW; X-ray; 1.72 A; A/B=1039-1401. DR PDB; 4Z8L; X-ray; 2.60 A; A/D=1057-1396. DR PDB; 5AJA; X-ray; 2.65 A; A=1058-1396. DR PDB; 5JK7; X-ray; 3.49 A; C/E=1045-1396. DR PDB; 6N45; X-ray; 2.64 A; A/B=1475-1507. DR PDB; 6ZUE; X-ray; 3.09 A; B=1045-1396. DR PDB; 6ZX9; X-ray; 2.52 A; B=1045-1396. DR PDB; 7OKQ; EM; 8.40 A; B/F/J/N=2-1507. DR PDB; 7SSE; X-ray; 1.62 A; A/B=1077-1390. DR PDB; 7UFV; X-ray; 1.90 A; A/B=1077-1390. DR PDB; 7V7B; EM; 4.20 A; A/C=1-1507. DR PDB; 7V7C; EM; 3.70 A; A/E=1-1507. DR PDB; 8F8E; X-ray; 1.55 A; A/B=1077-1390. DR PDB; 8OG5; X-ray; 2.20 A; A=1039-1401. DR PDB; 8OG6; X-ray; 2.25 A; A=1039-1401. DR PDB; 8OG7; X-ray; 2.64 A; A=1039-1401. DR PDB; 8OG8; X-ray; 2.11 A; A=1039-1401. DR PDB; 8OG9; X-ray; 2.94 A; A=1039-1401. DR PDB; 8OGA; X-ray; 2.20 A; P=1079-1393. DR PDB; 8OGB; X-ray; 2.27 A; A=1039-1401. DR PDB; 8OGC; X-ray; 2.09 A; A=1039-1401. DR PDB; 8OO5; X-ray; 2.25 A; P=1079-1393. DR PDB; 8OOD; X-ray; 1.50 A; A=1039-1401. DR PDBsum; 3WA0; -. DR PDBsum; 4CC9; -. DR PDBsum; 4P7I; -. DR PDBsum; 4PXW; -. DR PDBsum; 4Z8L; -. DR PDBsum; 5AJA; -. DR PDBsum; 5JK7; -. DR PDBsum; 6N45; -. DR PDBsum; 6ZUE; -. DR PDBsum; 6ZX9; -. DR PDBsum; 7OKQ; -. DR PDBsum; 7SSE; -. DR PDBsum; 7UFV; -. DR PDBsum; 7V7B; -. DR PDBsum; 7V7C; -. DR PDBsum; 8F8E; -. DR PDBsum; 8OG5; -. DR PDBsum; 8OG6; -. DR PDBsum; 8OG7; -. DR PDBsum; 8OG8; -. DR PDBsum; 8OG9; -. DR PDBsum; 8OGA; -. DR PDBsum; 8OGB; -. DR PDBsum; 8OGC; -. DR PDBsum; 8OO5; -. DR PDBsum; 8OOD; -. DR AlphaFoldDB; Q9Y4B6; -. DR EMDB; EMD-12964; -. DR EMDB; EMD-31765; -. DR EMDB; EMD-31766; -. DR SMR; Q9Y4B6; -. DR BioGRID; 115079; 241. DR ComplexPortal; CPX-2769; CRL4-DCAF1 E3 ubiquitin ligase complex, CUL4A variant. DR ComplexPortal; CPX-2770; CRL4-DCAF1 E3 ubiquitin ligase complex, CUL4B variant. DR CORUM; Q9Y4B6; -. DR DIP; DIP-47048N; -. DR IntAct; Q9Y4B6; 79. DR MINT; Q9Y4B6; -. DR STRING; 9606.ENSP00000393183; -. DR GuidetoPHARMACOLOGY; 3244; -. DR GlyCosmos; Q9Y4B6; 1 site, 1 glycan. DR GlyGen; Q9Y4B6; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q9Y4B6; -. DR PhosphoSitePlus; Q9Y4B6; -. DR BioMuta; DCAF1; -. DR DMDM; 147742890; -. DR EPD; Q9Y4B6; -. DR jPOST; Q9Y4B6; -. DR MassIVE; Q9Y4B6; -. DR MaxQB; Q9Y4B6; -. DR PaxDb; 9606-ENSP00000393183; -. DR PeptideAtlas; Q9Y4B6; -. DR ProteomicsDB; 86151; -. [Q9Y4B6-1] DR ProteomicsDB; 86152; -. [Q9Y4B6-2] DR ProteomicsDB; 86153; -. [Q9Y4B6-3] DR Pumba; Q9Y4B6; -. DR Antibodypedia; 31017; 182 antibodies from 23 providers. DR DNASU; 9730; -. DR Ensembl; ENST00000423656.5; ENSP00000393183.2; ENSG00000145041.17. [Q9Y4B6-1] DR Ensembl; ENST00000504652.5; ENSP00000421724.2; ENSG00000145041.17. [Q9Y4B6-2] DR Ensembl; ENST00000684031.1; ENSP00000506880.1; ENSG00000145041.17. [Q9Y4B6-1] DR GeneID; 9730; -. DR KEGG; hsa:9730; -. DR MANE-Select; ENST00000684031.1; ENSP00000506880.1; NM_001387579.1; NP_001374508.1. DR UCSC; uc032rnn.1; human. [Q9Y4B6-1] DR AGR; HGNC:30911; -. DR CTD; 9730; -. DR DisGeNET; 9730; -. DR GeneCards; DCAF1; -. DR HGNC; HGNC:30911; DCAF1. DR HPA; ENSG00000145041; Tissue enhanced (testis). DR neXtProt; NX_Q9Y4B6; -. DR OpenTargets; ENSG00000145041; -. DR PharmGKB; PA142670621; -. DR VEuPathDB; HostDB:ENSG00000145041; -. DR eggNOG; KOG1832; Eukaryota. DR GeneTree; ENSGT00390000005874; -. DR HOGENOM; CLU_001785_1_0_1; -. DR InParanoid; Q9Y4B6; -. DR OMA; ECSQDQA; -. DR OrthoDB; 24025at2759; -. DR PhylomeDB; Q9Y4B6; -. DR PathwayCommons; Q9Y4B6; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9Y4B6; -. DR SIGNOR; Q9Y4B6; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 9730; 73 hits in 389 CRISPR screens. DR ChiTaRS; DCAF1; human. DR GeneWiki; VPRBP; -. DR GenomeRNAi; 9730; -. DR Pharos; Q9Y4B6; Tbio. DR PRO; PR:Q9Y4B6; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9Y4B6; Protein. DR Bgee; ENSG00000145041; Expressed in sperm and 185 other cell types or tissues. DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:1990244; F:histone H2AT120 kinase activity; IDA:UniProtKB. DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProt. DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB. DR GO; GO:0035212; P:cell competition in a multicellular organism; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:UniProt. DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0033151; P:V(D)J recombination; ISS:UniProtKB. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR IDEAL; IID00743; -. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR006594; LisH. DR InterPro; IPR033270; VPRBP/DCAF1. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR PANTHER; PTHR13129:SF4; DDB1- AND CUL4-ASSOCIATED FACTOR 1; 1. DR PANTHER; PTHR13129; VPRBP PROTEIN-RELATED; 1. DR SMART; SM00667; LisH; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50896; LISH; 1. DR Genevisible; Q9Y4B6; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Chromatin regulator; Cytoplasm; Direct protein sequencing; KW Host-virus interaction; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase; Ubl conjugation pathway; WD repeat. FT CHAIN 1..1507 FT /note="DDB1- and CUL4-associated factor 1" FT /id="PRO_0000287473" FT DOMAIN 562..593 FT /note="Chromo" FT DOMAIN 846..878 FT /note="LisH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126" FT REPEAT 1091..1130 FT /note="WD 1" FT REPEAT 1133..1174 FT /note="WD 2" FT REPEAT 1176..1213 FT /note="WD 3" FT REPEAT 1215..1247 FT /note="WD 4" FT REPEAT 1248..1290 FT /note="WD 5" FT REGION 141..500 FT /note="Protein kinase-like" FT REGION 242..288 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 917..947 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1091..1290 FT /note="WD repeat-like region" FT REGION 1393..1507 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1418..1507 FT /note="Interaction with NF2" FT MOTIF 1242..1249 FT /note="DWD box 1" FT MOTIF 1278..1285 FT /note="DWD box 2" FT COMPBIAS 259..282 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 928..942 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1395..1497 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 202 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 255 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 701 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q80TR8" FT MOD_RES 828 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 888 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 895 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 898 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 979 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1000 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569" FT MOD_RES 1328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 87 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_025498" FT VAR_SEQ 225..673 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_025499" FT VARIANT 267 FT /note="N -> D (in dbSNP:rs3749318)" FT /id="VAR_051486" FT VARIANT 378 FT /note="L -> F (does not affect serine/threonine-protein FT kinase kinase activity; dbSNP:rs17712228)" FT /evidence="ECO:0000269|PubMed:24140421" FT /id="VAR_051487" FT VARIANT 1031 FT /note="L -> P (in dbSNP:rs9835229)" FT /id="VAR_051488" FT MUTAGEN 194 FT /note="K->R: Abolishes serine/threonine-protein kinase FT kinase activity." FT /evidence="ECO:0000269|PubMed:24140421" FT MUTAGEN 361 FT /note="D->A: Abolishes serine/threonine-protein kinase FT kinase activity." FT /evidence="ECO:0000269|PubMed:24140421" FT MUTAGEN 363 FT /note="K->A: Abolishes serine/threonine-protein kinase FT kinase activity." FT /evidence="ECO:0000269|PubMed:24140421" FT MUTAGEN 1247 FT /note="R->A: Loss of interaction with DDB1, no effect on FT interaction with TET3; when associated with A-1283." FT /evidence="ECO:0000269|PubMed:24357321" FT MUTAGEN 1283 FT /note="R->A: Loss of interaction with DDB1, no effect on FT interaction with TET3; when associated with A-1247." FT /evidence="ECO:0000269|PubMed:24357321" FT HELIX 1050..1059 FT /evidence="ECO:0007829|PDB:6ZX9" FT STRAND 1062..1067 FT /evidence="ECO:0007829|PDB:5JK7" FT HELIX 1076..1078 FT /evidence="ECO:0007829|PDB:4CC9" FT STRAND 1081..1086 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1096..1101 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1107..1112 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1115..1121 FT /evidence="ECO:0007829|PDB:7SSE" FT TURN 1122..1124 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1127..1132 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1138..1143 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1147..1156 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1158..1165 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1167..1169 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1171..1176 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1180..1184 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1186..1188 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1191..1196 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1199..1204 FT /evidence="ECO:0007829|PDB:7SSE" FT TURN 1205..1207 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1210..1214 FT /evidence="ECO:0007829|PDB:7SSE" FT TURN 1217..1219 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1234..1239 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1242..1245 FT /evidence="ECO:0007829|PDB:7SSE" FT TURN 1246..1249 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1250..1254 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1259..1262 FT /evidence="ECO:0007829|PDB:4PXW" FT STRAND 1270..1275 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1278..1281 FT /evidence="ECO:0007829|PDB:7SSE" FT TURN 1282..1284 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1287..1290 FT /evidence="ECO:0007829|PDB:7SSE" FT HELIX 1292..1294 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1297..1301 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1305..1313 FT /evidence="ECO:0007829|PDB:7SSE" FT HELIX 1314..1316 FT /evidence="ECO:0007829|PDB:8OG5" FT STRAND 1329..1338 FT /evidence="ECO:0007829|PDB:7SSE" FT TURN 1339..1341 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1344..1349 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1354..1359 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1361..1363 FT /evidence="ECO:0007829|PDB:4CC9" FT STRAND 1365..1371 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1377..1379 FT /evidence="ECO:0007829|PDB:8OGC" FT STRAND 1382..1388 FT /evidence="ECO:0007829|PDB:7SSE" FT STRAND 1482..1485 FT /evidence="ECO:0007829|PDB:3WA0" FT STRAND 1501..1504 FT /evidence="ECO:0007829|PDB:3WA0" SQ SEQUENCE 1507 AA; 169007 MW; 7E71AB2CAC4962C5 CRC64; MTTVVVHVDS KAELTTLLEQ WEKEHGSGQD MVPILTRMSQ LIEKETEEYR KGDPDPFDDR HPGRADPECM LGHLLRILFK NDDFMNALVN AYVMTSREPP LNTAACRLLL DIMPGLETAV VFQEKEGIVE NLFKWAREAD QPLRTYSTGL LGGAMENQDI AANYRDENSQ LVAIVLRRLR ELQLQEVALR QENKRPSPRK LSSEPLLPLD EEAVDMDYGD MAVDVVDGDQ EEASGDMEIS FHLDSGHKTS SRVNSTTKPE DGGLKKNKSA KQGDRENFRK AKQKLGFSSS DPDRMFVELS NSSWSEMSPW VIGTNYTLYP MTPAIEQRLI LQYLTPLGEY QELLPIFMQL GSRELMMFYI DLKQTNDVLL TFEALKHLAS LLLHNKFATE FVAHGGVQKL LEIPRPSMAA TGVSMCLYYL SYNQDAMERV CMHPHNVLSD VVNYTLWLME CSHASGCCHA TMFFSICFSF RAVLELFDRY DGLRRLVNLI STLEILNLED QGALLSDDEI FASRQTGKHT CMALRKYFEA HLAIKLEQVK QSLQRTEGGI LVHPQPPYKA CSYTHEQIVE MMEFLIEYGP AQLYWEPAEV FLKLSCVQLL LQLISIACNW KTYYARNDTV RFALDVLAIL TVVPKIQLQL AESVDVLDEA GSTVSTVGIS IILGVAEGEF FIHDAEIQKS ALQIIINCVC GPDNRISSIG KFISGTPRRK LPQNPKSSEH TLAKMWNVVQ SNNGIKVLLS LLSIKMPITD ADQIRALACK ALVGLSRSST VRQIISKLPL FSSCQIQQLM KEPVLQDKRS DHVKFCKYAA ELIERVSGKP LLIGTDVSLA RLQKADVVAQ SRISFPEKEL LLLIRNHLIS KGLGETATVL TKEADLPMTA ASHSSAFTPV TAAASPVSLP RTPRIANGIA TRLGSHAAVG ASAPSAPTAH PQPRPPQGPL ALPGPSYAGN SPLIGRISFI RERPSPCNGR KIRVLRQKSD HGAYSQSPAI KKQLDRHLPS PPTLDSIITE YLREQHARCK NPVATCPPFS LFTPHQCPEP KQRRQAPINF TSRLNRRASF PKYGGVDGGC FDRHLIFSRF RPISVFREAN EDESGFTCCA FSARERFLML GTCTGQLKLY NVFSGQEEAS YNCHNSAITH LEPSRDGSLL LTSATWSQPL SALWGMKSVF DMKHSFTEDH YVEFSKHSQD RVIGTKGDIA HIYDIQTGNK LLTLFNPDLA NNYKRNCATF NPTDDLVLND GVLWDVRSAQ AIHKFDKFNM NISGVFHPNG LEVIINTEIW DLRTFHLLHT VPALDQCRVV FNHTGTVMYG AMLQADDEDD LMEERMKSPF GSSFRTFNAT DYKPIATIDV KRNIFDLCTD TKDCYLAVIE NQGSMDALNM DTVCRLYEVG RQRLAEDEDE EEDQEEEEQE EEDDDEDDDD TDDLDELDTD QLLEAELEED DNNENAGEDG DNDFSPSDEE LANLLEEGED GEDEDSDADE EVELILGDTD SSDNSDLEDD IILSLNE //