DTL_HUMAN
ID DTL_HUMAN Reviewed; 730 AA.
AC Q9NZJ0; A8K8H8; D3DT98; Q5VT77; Q96SN0; Q9NW03; Q9NW34; Q9NWM5;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 3.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Denticleless protein homolog;
DE AltName: Full=DDB1- and CUL4-associated factor 2;
DE AltName: Full=Lethal(2) denticleless protein homolog;
DE AltName: Full=Retinoic acid-regulated nuclear matrix-associated protein;
GN Name=DTL; Synonyms=CDT2, CDW1, DCAF2, L2DTL, RAMP;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND VARIANTS VAL-436 AND THR-694.
RX PubMed=11278750; DOI=10.1074/jbc.m010802200;
RA Cheung W.M., Chu A.H., Chu P.W., Ip N.Y.;
RT "Cloning and expression of a novel nuclear matrix-associated protein that
RT is regulated during the retinoic acid-induced neuronal differentiation.";
RL J. Biol. Chem. 276:17083-17091(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, IDENTIFICATION IN A DCX
RP (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, IDENTIFICATION BY
RP MASS SPECTROMETRY, AND VARIANTS VAL-436 AND THR-694.
RX PubMed=16861906; DOI=10.4161/cc.5.15.3149;
RA Higa L.A., Banks D., Wu M., Kobayashi R., Sun H., Zhang H.;
RT "L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates
RT CDT1 proteolysis in response to DNA damage.";
RL Cell Cycle 5:1675-1680(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-436 AND THR-694.
RA Mueller R., Ziegler B.L.;
RT "Identification of L2DTL, a human WD-40 repeat gene homolog of the
RT Drosophila lethal (2) denticleless heat shock gene [l(2)dtl].";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP VAL-436 AND THR-694.
RC TISSUE=Hepatoma, Teratocarcinoma, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-436.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-436
RP AND THR-694.
RC TISSUE=Lymph, and Testis;
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 [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND UBIQUITINATION.
RX PubMed=17106265; DOI=10.4161/cc.5.22.3500;
RA Pan H.W., Chou H.Y., Liu S.H., Peng S.Y., Liu C.L., Hsu H.C.;
RT "Role of L2DTL, cell cycle-regulated nuclear and centrosome protein, in
RT aggressive hepatocellular carcinoma.";
RL Cell Cycle 5:2676-2687(2006).
RN [9]
RP FUNCTION, AND IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3
RP UBIQUITIN-PROTEIN LIGASE COMPLEX.
RX PubMed=17085480; DOI=10.1101/gad.1482106;
RA Sansam C.L., Shepard J.L., Lai K., Ianari A., Danielian P.S., Amsterdam A.,
RA Hopkins N., Lees J.A.;
RT "DTL/CDT2 is essential for both CDT1 regulation and the early G2/M
RT checkpoint.";
RL Genes Dev. 20:3117-3129(2006).
RN [10]
RP FUNCTION, INTERACTION WITH DDB1, IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX)
RP E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, AND MUTAGENESIS OF ARG-246.
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 [11]
RP IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=17041588; DOI=10.1038/ncb1490;
RA Higa L.A., Wu M., Ye T., Kobayashi R., Sun H., Zhang H.;
RT "CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins
RT and regulates histone methylation.";
RL Nat. Cell Biol. 8:1277-1283(2006).
RN [12]
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 [13]
RP FUNCTION, AND IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3
RP UBIQUITIN-PROTEIN LIGASE COMPLEX.
RX PubMed=18794347; DOI=10.1101/gad.1676108;
RA Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.;
RT "PCNA-dependent regulation of p21 ubiquitylation and degradation via the
RT CRL4Cdt2 ubiquitin ligase complex.";
RL Genes Dev. 22:2496-2506(2008).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN A DCX (DDB1-CUL4-X-BOX) E3
RP UBIQUITIN-PROTEIN LIGASE COMPLEX.
RX PubMed=18794348; DOI=10.1101/gad.1703708;
RA Kim Y., Starostina N.G., Kipreos E.T.;
RT "The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to
RT control replication licensing.";
RL Genes Dev. 22:2507-2519(2008).
RN [15]
RP FUNCTION.
RX PubMed=18703516; DOI=10.1074/jbc.m806045200;
RA Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., Tsurimoto T.;
RT "CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-
RT coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation.";
RL J. Biol. Chem. 283:29045-29052(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-485; SER-490; SER-495;
RP SER-512; THR-516; SER-557; SER-676; SER-679 AND THR-684, AND IDENTIFICATION
RP 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 [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP FUNCTION.
RX PubMed=19332548; DOI=10.1074/jbc.m808810200;
RA Stuart S.A., Wang J.Y.;
RT "Ionizing radiation induces ATM-independent degradation of p21Cip1 in
RT transformed cells.";
RL J. Biol. Chem. 284:15061-15070(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512 AND THR-516, AND
RP IDENTIFICATION BY 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 [20]
RP FUNCTION.
RX PubMed=20129063; DOI=10.1016/j.molcel.2009.12.018;
RA Terai K., Abbas T., Jazaeri A.A., Dutta A.;
RT "CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote
RT translesion DNA synthesis.";
RL Mol. Cell 37:143-149(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-410; SER-490; SER-512 AND
RP THR-516, AND IDENTIFICATION BY 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 [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512 AND THR-516, AND
RP IDENTIFICATION BY 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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP INTERACTION WITH CDKN1A.
RX PubMed=23213251; DOI=10.1073/pnas.1214156110;
RA Zhang L., Mei Y., Fu N.Y., Guan L., Xie W., Liu H.H., Yu C.D., Yin Z.,
RA Yu V.C., You H.;
RT "TRIM39 regulates cell cycle progression and DNA damage responses via
RT stabilizing p21.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:20937-20942(2012).
RN [27]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=23892434; DOI=10.4161/cc.25314;
RA Abbas T., Keaton M., Dutta A.;
RT "Regulation of TGF-beta signaling, exit from the cell cycle, and cellular
RT migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-
RT Cdt2.";
RL Cell Cycle 12:2175-2182(2013).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-196; SER-410; SER-426;
RP SER-485; SER-490; THR-516; SER-557; SER-679; THR-702 AND SER-717, VARIANT
RP [LARGE SCALE ANALYSIS] THR-694, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE 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 [29]
RP FUNCTION, INTERACTION WITH DDB1 AND FBXO11, INDUCTION, UBIQUITINATION, AND
RP MUTAGENESIS OF ARG-246; ASP-457 AND SER-462.
RX PubMed=23478445; DOI=10.1016/j.molcel.2013.02.003;
RA Abbas T., Mueller A.C., Shibata E., Keaton M., Rossi M., Dutta A.;
RT "CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-
RT Set7/Set8-mediated cellular migration.";
RL Mol. Cell 49:1147-1158(2013).
RN [30]
RP FUNCTION, INTERACTION WITH FBXO11, IDENTIFICATION IN THE DCX(DTL) COMPLEX,
RP UBIQUITINATION, PHOSPHORYLATION AT THR-464 BY CDK1 AND CDK2, AND
RP MUTAGENESIS OF ASN-463; THR-464; PRO-465; THR-466; PHE-467; SER-468;
RP THR-471 AND SER-472.
RX PubMed=23478441; DOI=10.1016/j.molcel.2013.02.004;
RA Rossi M., Duan S., Jeong Y.T., Horn M., Saraf A., Florens L.,
RA Washburn M.P., Antebi A., Pagano M.;
RT "Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the
RT SCF(Fbxo11) ubiquitin ligase.";
RL Mol. Cell 49:1159-1166(2013).
RN [31]
RP FUNCTION.
RX PubMed=23677613; DOI=10.1093/nar/gkt397;
RA Bacquin A., Pouvelle C., Siaud N., Perderiset M., Salome-Desnoulez S.,
RA Tellier-Lebegue C., Lopez B., Charbonnier J.B., Kannouche P.L.;
RT "The helicase FBH1 is tightly regulated by PCNA via CRL4(Cdt2)-mediated
RT proteolysis in human cells.";
RL Nucleic Acids Res. 41:6501-6513(2013).
RN [32]
RP FUNCTION, INTERACTION WITH CRY1, AND SUBCELLULAR LOCATION.
RX PubMed=26431207; DOI=10.1371/journal.pone.0139725;
RA Tong X., Zhang D., Guha A., Arthurs B., Cazares V., Gupta N., Yin L.;
RT "CUL4-DDB1-CDT2 E3 ligase regulates the molecular clock activity by
RT promoting ubiquitination-dependent degradation of the mammalian CRY1.";
RL PLoS ONE 10:E0139725-E0139725(2015).
RN [33]
RP FUNCTION.
RX PubMed=27906959; DOI=10.1371/journal.pgen.1006465;
RA Jo U., Cai W., Wang J., Kwon Y., D'Andrea A.D., Kim H.;
RT "PCNA-dependent cleavage and degradation of SDE2 regulates response to
RT replication stress.";
RL PLoS Genet. 12:E1006465-E1006465(2016).
CC -!- FUNCTION: Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex required for cell cycle control, DNA
CC damage response and translesion DNA synthesis. The DCX(DTL) complex,
CC also named CRL4(CDT2) complex, mediates the polyubiquitination and
CC subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2
CC (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480,
CC PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548,
CC PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613,
CC PubMed:27906959). CDT1 degradation in response to DNA damage is
CC necessary to ensure proper cell cycle regulation of DNA replication
CC (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1)
CC degradation during S phase or following UV irradiation is essential to
CC control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A
CC degradation is also important for a proper regulation of mechanisms
CC such as TGF-beta signaling, cell cycle progression, DNA repair and cell
CC migration (PubMed:23478445). Most substrates require their interaction
CC with PCNA for their polyubiquitination: substrates interact with PCNA
CC via their PIP-box, and those containing the 'K+4' motif in the PIP box,
CC recruit the DCX(DTL) complex, leading to their degradation. In
CC undamaged proliferating cells, the DCX(DTL) complex also promotes the
CC 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-
CC dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441,
CC PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex
CC regulates the circadian clock function by mediating the ubiquitination
CC and degradation of CRY1 (PubMed:26431207).
CC {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367,
CC ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480,
CC ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347,
CC ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548,
CC ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441,
CC ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613,
CC ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Component of the DCX(DTL) E3 ubiquitin ligase complex (also
CC called CRL4(CDT2)), at least composed of CUL4 (CUL4A or CUL4B), DDB1,
CC DTL/CDT2 and RBX1 (PubMed:16861906, PubMed:17085480, PubMed:16949367,
CC PubMed:17041588, PubMed:18794347, PubMed:18794348, PubMed:23478441).
CC Interacts with CDKN1A (PubMed:23213251). Interacts with DDB1
CC (PubMed:16949367, PubMed:23478445). Interacts with FBXO11; SCF(FBXWO11)
CC controls DTL stability but DCX(DTL) does not control FBXO11 stability
CC (PubMed:23478445, PubMed:23478441). Interacts with CRY1
CC (PubMed:26431207). {ECO:0000269|PubMed:16861906,
CC ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:17041588,
CC ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18794347,
CC ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:23213251,
CC ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445,
CC ECO:0000269|PubMed:26431207}.
CC -!- INTERACTION:
CC Q9NZJ0; Q16531: DDB1; NbExp=3; IntAct=EBI-1176075, EBI-350322;
CC Q9NZJ0; P40337-2: VHL; NbExp=3; IntAct=EBI-1176075, EBI-12157263;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26431207}. Nucleus
CC membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome. Chromosome.
CC Note=Nuclear matrix-associated protein. Translocates from the
CC interphase nucleus to the metaphase cytoplasm during mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NZJ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZJ0-2; Sequence=VSP_022879, VSP_022880, VSP_022881;
CC -!- TISSUE SPECIFICITY: Expressed in placenta and testis, very low
CC expression seen in skeletal muscle. Detected in all hematopoietic
CC tissues examined, with highest expression in thymus and bone marrow. A
CC low level detected in the spleen and lymph node, and barely detectable
CC level in the peripheral leukocytes. RA treatment down-regulated the
CC expression in NT2 cell. {ECO:0000269|PubMed:11278750,
CC ECO:0000269|PubMed:17106265}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all fetal tissues examined, included
CC brain, lung, liver, and kidney. Protein levels peak at G1 and decrease
CC through S-phase. {ECO:0000269|PubMed:11278750,
CC ECO:0000269|PubMed:23892434}.
CC -!- INDUCTION: Induced by TGF-beta, the up-regulation is immediate and
CC transient. {ECO:0000269|PubMed:23478445}.
CC -!- PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C).
CC Autoubiquitinated through 'Lys-48'-polyubiquitin chains in a PCNA-
CC independent reaction, allowing proteasomal turnover. Polyubiquitinated
CC by SCF(FBXO11) when not phosphorylated, leading to its degradation. A
CC tight regulation of the polyubiquitination by SCF(FBXO11) is involved
CC in the control of different processes such as TGF-beta signaling, cell
CC cycle progression and exit. {ECO:0000269|PubMed:17106265,
CC ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445}.
CC -!- PTM: Phosphorylated at Thr-464 by CDK1/Cyclin-B and CDK2/Cyclin-A but
CC not by CDK2/Cyclin-E, MAPK1 or PLK1. Phosphorylation at Thr-464
CC inhibits the interaction with FBXO11 and decreases upon cell cycle exit
CC induced by TGF-beta or serum starvation. {ECO:0000269|PubMed:23478441}.
CC -!- SIMILARITY: Belongs to the WD repeat cdt2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91552.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA91586.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF345896; AAK54706.1; -; mRNA.
DR EMBL; DQ641253; ABG23317.1; -; mRNA.
DR EMBL; AF195765; AAF35182.1; -; mRNA.
DR EMBL; AK000742; BAA91355.1; -; mRNA.
DR EMBL; AK001206; BAA91552.1; ALT_INIT; mRNA.
DR EMBL; AK001261; BAA91586.1; ALT_INIT; mRNA.
DR EMBL; AK027651; BAB55267.1; -; mRNA.
DR EMBL; AK292343; BAF85032.1; -; mRNA.
DR EMBL; AC092814; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592297; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL606468; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93395.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93397.1; -; Genomic_DNA.
DR EMBL; BC033540; AAH33540.1; -; mRNA.
DR EMBL; BC033297; AAH33297.1; -; mRNA.
DR CCDS; CCDS1502.1; -. [Q9NZJ0-1]
DR RefSeq; NP_001273158.1; NM_001286229.1.
DR RefSeq; NP_057532.3; NM_016448.3. [Q9NZJ0-1]
DR PDB; 6QC0; X-ray; 3.50 A; B/D/F=704-717.
DR PDBsum; 6QC0; -.
DR AlphaFoldDB; Q9NZJ0; -.
DR SMR; Q9NZJ0; -.
DR BioGRID; 119582; 107.
DR CORUM; Q9NZJ0; -.
DR ELM; Q9NZJ0; -.
DR IntAct; Q9NZJ0; 22.
DR STRING; 9606.ENSP00000355958; -.
DR GlyGen; Q9NZJ0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NZJ0; -.
DR PhosphoSitePlus; Q9NZJ0; -.
DR BioMuta; DTL; -.
DR DMDM; 302393825; -.
DR EPD; Q9NZJ0; -.
DR jPOST; Q9NZJ0; -.
DR MassIVE; Q9NZJ0; -.
DR MaxQB; Q9NZJ0; -.
DR PaxDb; Q9NZJ0; -.
DR PeptideAtlas; Q9NZJ0; -.
DR PRIDE; Q9NZJ0; -.
DR ProteomicsDB; 83411; -. [Q9NZJ0-1]
DR ProteomicsDB; 83412; -. [Q9NZJ0-2]
DR Antibodypedia; 34605; 227 antibodies from 29 providers.
DR DNASU; 51514; -.
DR Ensembl; ENST00000366991.5; ENSP00000355958.4; ENSG00000143476.18. [Q9NZJ0-1]
DR GeneID; 51514; -.
DR KEGG; hsa:51514; -.
DR MANE-Select; ENST00000366991.5; ENSP00000355958.4; NM_016448.4; NP_057532.4.
DR UCSC; uc009xdc.5; human. [Q9NZJ0-1]
DR CTD; 51514; -.
DR DisGeNET; 51514; -.
DR GeneCards; DTL; -.
DR HGNC; HGNC:30288; DTL.
DR HPA; ENSG00000143476; Group enriched (bone marrow, intestine, lymphoid tissue, placenta, testis).
DR MIM; 610617; gene.
DR neXtProt; NX_Q9NZJ0; -.
DR OpenTargets; ENSG00000143476; -.
DR PharmGKB; PA142671941; -.
DR VEuPathDB; HostDB:ENSG00000143476; -.
DR eggNOG; KOG0321; Eukaryota.
DR GeneTree; ENSGT00530000064210; -.
DR HOGENOM; CLU_023407_0_0_1; -.
DR InParanoid; Q9NZJ0; -.
DR OMA; VSMRKIC; -.
DR OrthoDB; 1288134at2759; -.
DR PhylomeDB; Q9NZJ0; -.
DR TreeFam; TF324483; -.
DR PathwayCommons; Q9NZJ0; -.
DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q9NZJ0; -.
DR SIGNOR; Q9NZJ0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51514; 779 hits in 1091 CRISPR screens.
DR ChiTaRS; DTL; human.
DR GeneWiki; DTL_(gene); -.
DR GenomeRNAi; 51514; -.
DR Pharos; Q9NZJ0; Tbio.
DR PRO; PR:Q9NZJ0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NZJ0; protein.
DR Bgee; ENSG00000143476; Expressed in secondary oocyte and 135 other tissues.
DR ExpressionAtlas; Q9NZJ0; baseline and differential.
DR Genevisible; Q9NZJ0; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IMP:UniProtKB.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031465; C:Cul4B-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0019985; P:translesion synthesis; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00400; WD40; 5.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Chromosome; Cytoplasm; Cytoskeleton; DNA damage; DNA replication; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..730
FT /note="Denticleless protein homolog"
FT /id="PRO_0000274867"
FT REPEAT 47..89
FT /note="WD 1"
FT REPEAT 96..135
FT /note="WD 2"
FT REPEAT 138..178
FT /note="WD 3"
FT REPEAT 214..253
FT /note="WD 4"
FT REPEAT 267..308
FT /note="WD 5"
FT REPEAT 313..354
FT /note="WD 6"
FT REPEAT 358..398
FT /note="WD 7"
FT REGION 188..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 399..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 465..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 599..631
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 644..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 168..171
FT /note="DDB1-binding motif"
FT MOTIF 197..203
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 243..246
FT /note="DDB1-binding motif"
FT COMPBIAS 417..443
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 481..498
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 599..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 675..703
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 196
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 464
FT /note="Phosphothreonine; by CDK1 and CDK2"
FT /evidence="ECO:0000269|PubMed:23478441"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 516
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 676
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 679
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 684
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 702
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 717
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 18..59
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022879"
FT VAR_SEQ 240..253
FT /note="IKVWDLRKNYTAYR -> FKSDFGFHWLYFIC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022880"
FT VAR_SEQ 254..730
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022881"
FT VARIANT 425
FT /note="S -> N (in dbSNP:rs35137676)"
FT /id="VAR_062095"
FT VARIANT 436
FT /note="A -> V (in dbSNP:rs3135474)"
FT /evidence="ECO:0000269|PubMed:11278750,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16861906, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.6"
FT /id="VAR_030353"
FT VARIANT 694
FT /note="K -> T (in dbSNP:rs6540718)"
FT /evidence="ECO:0000269|PubMed:11278750,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16861906, ECO:0000269|Ref.3,
FT ECO:0007744|PubMed:23186163"
FT /id="VAR_030354"
FT MUTAGEN 246
FT /note="R->A: Blocks association with DDB1 and
FT ubiquitination by DCX(DTL). No effect on ubiquitination by
FT SCF(FBXO11)."
FT /evidence="ECO:0000269|PubMed:16949367,
FT ECO:0000269|PubMed:23478445"
FT MUTAGEN 457
FT /note="D->A: Increases protein stability, but no effect on
FT interaction with FBXO11 and polyubiquitination. Delays cell
FT migration."
FT /evidence="ECO:0000269|PubMed:23478445"
FT MUTAGEN 462
FT /note="S->A: Blocks interaction with FBXO11 and
FT ubiquitination, increasing protein stability. Delays cell
FT migration."
FT /evidence="ECO:0000269|PubMed:23478445"
FT MUTAGEN 463
FT /note="N->A: No effect on interaction with FBXO11.
FT Increases protein stability."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 464
FT /note="T->A: Blocks interaction with FBXO11 and increases
FT protein stability. Not phosphorylated by CDK1 or CDK2."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 464
FT /note="T->D: Blocks interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 465
FT /note="P->A: Inhibits phosphorylation on T-464. No effect
FT on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 466
FT /note="T->A: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 466
FT /note="T->D: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 467
FT /note="F->A: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 468
FT /note="S->A: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 468
FT /note="S->D: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 471
FT /note="T->A: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 471
FT /note="T->D: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 472
FT /note="S->A: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT MUTAGEN 472
FT /note="S->D: No effect on interaction with FBXO11."
FT /evidence="ECO:0000269|PubMed:23478441"
FT CONFLICT 83
FT /note="S -> P (in Ref. 4; BAA91355)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="L -> F (in Ref. 4; BAF85032)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="I -> T (in Ref. 4; BAA91552)"
FT /evidence="ECO:0000305"
FT TURN 709..712
FT /evidence="ECO:0007829|PDB:6QC0"
SQ SEQUENCE 730 AA; 79468 MW; CE8D54234D44F002 CRC64;
MLFNSVLRQP QLGVLRNGWS SQYPLQSLLT GYQCSGNDEH TSYGETGVPV PPFGCTFSSA
PNMEHVLAVA NEEGFVRLYN TESQSFRKKC FKEWMAHWNA VFDLAWVPGE LKLVTAAGDQ
TAKFWDVKAG ELIGTCKGHQ CSLKSVAFSK FEKAVFCTGG RDGNIMVWDT RCNKKDGFYR
QVNQISGAHN TSDKQTPSKP KKKQNSKGLA PSVDFQQSVT VVLFQDENTL VSAGAVDGII
KVWDLRKNYT AYRQEPIASK SFLYPGSSTR KLGYSSLILD STGSTLFANC TDDNIYMFNM
TGLKTSPVAI FNGHQNSTFY VKSSLSPDDQ FLVSGSSDEA AYIWKVSTPW QPPTVLLGHS
QEVTSVCWCP SDFTKIATCS DDNTLKIWRL NRGLEEKPGG DKLSTVGWAS QKKKESRPGL
VTVTSSQSTP AKAPRAKCNP SNSSPSSAAC APSCAGDLPL PSNTPTFSIK TSPAKARSPI
NRRGSVSSVS PKPPSSFKMS IRNWVTRTPS SSPPITPPAS ETKIMSPRKA LIPVSQKSSQ
AEACSESRNR VKRRLDSSCL ESVKQKCVKS CNCVTELDGQ VENLHLDLCC LAGNQEDLSK
DSLGPTKSSK IEGAGTSISE PPSPISPYAS ESCGTLPLPL RPCGEGSEMV GKENSSPENK
NWLLAMAAKR KAENPSPRSP SSQTPNSRRQ SGKKLPSPVT ITPSSMRKIC TYFHRKSQED
FCGPEHSTEL
