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 27-MAR-2024, entry version 185. 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 Q9NZJ0; P62258: YWHAE; NbExp=4; IntAct=EBI-1176075, EBI-356498; 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}; 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; 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; 120. DR ComplexPortal; CPX-2777; CRL4-CDT2 E3 ubiquitin ligase complex, CUL4B variant. DR ComplexPortal; CPX-2795; CRL4-CDT2 E3 ubiquitin ligase complex, CUL4A variant. DR CORUM; Q9NZJ0; -. DR ELM; Q9NZJ0; -. DR IntAct; Q9NZJ0; 24. 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; 9606-ENSP00000355958; -. DR PeptideAtlas; Q9NZJ0; -. DR ProteomicsDB; 83411; -. [Q9NZJ0-1] DR ProteomicsDB; 83412; -. [Q9NZJ0-2] DR Pumba; Q9NZJ0; -. DR Antibodypedia; 34605; 256 antibodies from 30 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 AGR; HGNC:30288; -. 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; PHSQFEK; -. DR OrthoDB; 196979at2759; -. 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; 811 hits in 1169 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 136 other cell types or tissues. DR ExpressionAtlas; Q9NZJ0; baseline and differential. 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:DNA damage response; 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 CDD; cd00200; WD40; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR22852:SF0; DENTICLELESS PROTEIN HOMOLOG; 1. DR PANTHER; PTHR22852; LETHAL 2 DENTICLELESS PROTEIN RETINOIC ACID-REGULATED NUCLEAR MATRIX-ASSOCIATED PROTEIN; 1. DR Pfam; PF00400; WD40; 5. DR SMART; SM00320; WD40; 6. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS00678; WD_REPEATS_1; 2. DR PROSITE; PS50082; WD_REPEATS_2; 5. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q9NZJ0; HS. 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 //