DCAF1_HUMAN
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 03-AUG-2022, entry version 176.
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}; 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 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 [42]
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). {ECO:0000269|PubMed:16964240,
CC ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17630831,
CC ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18524771,
CC ECO:0000269|PubMed:18606781, ECO:0000269|PubMed:19287380,
CC ECO:0000269|PubMed:20644714, ECO:0000269|PubMed:22184063,
CC ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:23362280,
CC 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. Interacts with DYRK2; the interaction is direct. Interacts with
CC RAG1; the interaction is direct. Interacts with LLGL1 and LLGL2.
CC Interacts with histone H3. Interacts with ESR1 and LATS1; probably
CC recruited by LATS1 to promote ESR1 ubiquitination and ubiquitin-
CC mediated proteasomal degradation (PubMed:28068668).
CC {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:17559673,
CC ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17626091,
CC ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18606781,
CC ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:20178741,
CC ECO:0000269|PubMed:20644714, ECO:0000269|PubMed:22184063,
CC ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:24336198,
CC 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. Nucleus. Note=Associated with
CC chromatin in a DDB1-independent and cell cycle-dependent manner:
CC recruited to chromatin as DNA is being replicated and is released from
CC chromatin before mitosis.
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 ---------------------------------------------------------------------------
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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. [Q9Y4B6-1]
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. [Q9Y4B6-1]
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 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 AlphaFoldDB; Q9Y4B6; -.
DR SMR; Q9Y4B6; -.
DR BioGRID; 115079; 206.
DR CORUM; Q9Y4B6; -.
DR DIP; DIP-47048N; -.
DR IntAct; Q9Y4B6; 79.
DR MINT; Q9Y4B6; -.
DR STRING; 9606.ENSP00000393183; -.
DR GlyGen; Q9Y4B6; 1 site, 1 O-linked glycan (1 site).
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; Q9Y4B6; -.
DR PeptideAtlas; Q9Y4B6; -.
DR PRIDE; Q9Y4B6; -.
DR ProteomicsDB; 86151; -. [Q9Y4B6-1]
DR ProteomicsDB; 86152; -. [Q9Y4B6-2]
DR ProteomicsDB; 86153; -. [Q9Y4B6-3]
DR Antibodypedia; 31017; 140 antibodies from 22 providers.
DR DNASU; 9730; -.
DR Ensembl; ENST00000335891.5; ENSP00000338857.5; ENSG00000145041.16. [Q9Y4B6-3]
DR Ensembl; ENST00000423656.5; ENSP00000393183.2; ENSG00000145041.16. [Q9Y4B6-1]
DR Ensembl; ENST00000504652.5; ENSP00000421724.2; ENSG00000145041.16. [Q9Y4B6-2]
DR Ensembl; ENST00000684031.1; ENSP00000506880.1; ENSG00000145041.16. [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 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; 105679at2759; -.
DR PhylomeDB; Q9Y4B6; -.
DR PathwayCommons; Q9Y4B6; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9Y4B6; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9730; 56 hits in 329 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 183 other tissues.
DR Genevisible; Q9Y4B6; HS.
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 kinase activity (H2A-T120 specific); 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:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0035212; P:cell competition in a multicellular organism; IMP:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:1990245; P:histone H2A-T120 phosphorylation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
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; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
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; PTHR13129; 1.
DR SMART; SM00667; LisH; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50896; LISH; 1.
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 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 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 TURN 1375..1378
FT /evidence="ECO:0007829|PDB:4CC9"
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
