UHRF1_HUMAN
ID UHRF1_HUMAN Reviewed; 793 AA.
AC Q96T88; A0JBR2; A8K024; B2RBA9; Q2HIX7; Q8J022; Q9H6S6; Q9P115; Q9P1U7;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=E3 ubiquitin-protein ligase UHRF1;
DE EC=2.3.2.27;
DE AltName: Full=Inverted CCAAT box-binding protein of 90 kDa;
DE AltName: Full=Nuclear protein 95;
DE AltName: Full=Nuclear zinc finger protein Np95;
DE Short=HuNp95;
DE Short=hNp95;
DE AltName: Full=RING finger protein 106;
DE AltName: Full=RING-type E3 ubiquitin transferase UHRF1;
DE AltName: Full=Transcription factor ICBP90;
DE AltName: Full=Ubiquitin-like PHD and RING finger domain-containing protein 1;
DE Short=hUHRF1;
DE AltName: Full=Ubiquitin-like-containing PHD and RING finger domains protein 1;
GN Name=UHRF1; Synonyms=ICBP90, NP95, RNF106;
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, SUBCELLULAR LOCATION, DNA-BINDING, INDUCTION, AND FUNCTION.
RC TISSUE=Thymus;
RX PubMed=10646863;
RA Hopfner R., Mousli M., Jeltsch J.-M., Voulgaris A., Lutz Y., Marin C.,
RA Bellocq J.-P., Oudet P., Bronner C.;
RT "ICBP90, a novel human CCAAT binding protein, involved in the regulation of
RT topoisomerase IIa expression.";
RL Cancer Res. 60:121-128(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=17067204; DOI=10.1667/rr0459.1;
RA Muto M., Fujimori A., Nenoi M., Daino K., Matsuda Y., Kuroiwa A., Kubo E.,
RA Kanari Y., Utsuno M., Tsuji H., Ukai H., Mita K., Takahagi M., Tatsumi K.;
RT "Isolation and characterization of a novel human radiosusceptibility gene,
RT NP95.";
RL Radiat. Res. 166:723-733(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Davenport J.W., Fernandes E.R., Neale G.A.M., Goorha R.M.;
RT "LMO2-induced T cell leukemias overexpress Np95, a gene containing RING and
RT PHD zinc fingers and an ubiquitin-like domain.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LYS-379
RP AND THR-638.
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-240; LYS-379; THR-638;
RP MET-642 AND PHE-713.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [10]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=12838312; DOI=10.1038/sj.bjc.6601068;
RA Mousli M., Hopfner R., Abbady A.-Q., Monte D., Jeanblanc M., Oudet P.,
RA Louis B., Bronner C.;
RT "ICBP90 belongs to a new family of proteins with an expression that is
RT deregulated in cancer cells.";
RL Br. J. Cancer 89:120-127(2003).
RN [11]
RP PHOSPHORYLATION, PHOSPHORYLATION AT SER-298, AND MUTAGENESIS OF SER-298;
RP SER-651 AND SER-666.
RX PubMed=15178447; DOI=10.1016/j.bbrc.2004.05.028;
RA Trotzier M.-A., Bronner C., Bathami K., Mathieu E., Abbady A.-Q.,
RA Jeanblanc M., Muller C.D., Rochette-Egly C., Mousli M.;
RT "Phosphorylation of ICBP90 by protein kinase A enhances topoisomerase
RT IIalpha expression.";
RL Biochem. Biophys. Res. Commun. 319:590-595(2004).
RN [12]
RP INDUCTION, UBIQUITINATION, AND FUNCTION.
RX PubMed=15009091; DOI=10.1111/j.1356-9597.2004.00710.x;
RA Arima Y., Hirota T., Bronner C., Mousli M., Fujiwara T., Niwa S.,
RA Ishikawa H., Saya H.;
RT "Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent
RT DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S
RT transition.";
RL Genes Cells 9:131-142(2004).
RN [13]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, DNA-BINDING, AND INTERACTION WITH
RP HDAC1 AND UHRF1BP1.
RX PubMed=15361834; DOI=10.1038/sj.onc.1208053;
RA Unoki M., Nishidate T., Nakamura Y.;
RT "ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through
RT its SRA domain.";
RL Oncogene 23:7601-7610(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287 AND SER-639, AND
RP IDENTIFICATION BY 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-639, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DNMT1.
RX PubMed=17673620; DOI=10.1126/science.1147939;
RA Bostick M., Kim J.K., Esteve P.O., Clark A., Pradhan S., Jacobsen S.E.;
RT "UHRF1 plays a role in maintaining DNA methylation in mammalian cells.";
RL Science 317:1760-1764(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, 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 [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND AUTOUBIQUITINATION.
RX PubMed=17967883; DOI=10.1128/mcb.01598-07;
RA Karagianni P., Amazit L., Qin J., Wong J.;
RT "ICBP90, a novel methyl K9 H3 binding protein linking protein
RT ubiquitination with heterochromatin formation.";
RL Mol. Cell. Biol. 28:705-717(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-91 AND SER-707, 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 [20]
RP INVOLVEMENT IN CANCER.
RX PubMed=19491893; DOI=10.1038/sj.bjc.6605123;
RA Unoki M., Kelly J.D., Neal D.E., Ponder B.A., Nakamura Y., Hamamoto R.;
RT "UHRF1 is a novel molecular marker for diagnosis and the prognosis of
RT bladder cancer.";
RL Br. J. Cancer 101:98-105(2009).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EHMT2.
RX PubMed=19056828; DOI=10.1093/nar/gkn961;
RA Kim J.K., Esteve P.O., Jacobsen S.E., Pradhan S.;
RT "UHRF1 binds G9a and participates in p21 transcriptional regulation in
RT mammalian cells.";
RL Nucleic Acids Res. 37:493-505(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, 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 [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-399 AND LYS-546, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP MUTAGENESIS OF TYR-188 AND TYR-191.
RX PubMed=20026581; DOI=10.1093/nar/gkp1152;
RA Rottach A., Frauer C., Pichler G., Bonapace I.M., Spada F., Leonhardt H.;
RT "The multi-domain protein Np95 connects DNA methylation and histone
RT modification.";
RL Nucleic Acids Res. 38:1796-1804(2010).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-287; SER-639 AND
RP SER-707, 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 [26]
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 [27]
RP FUNCTION, AUTOUBIQUITINATION, DEUBIQUITINATION BY USP7, AND INTERACTION
RP WITH USP7 AND DNMT1.
RX PubMed=21745816; DOI=10.1093/nar/gkr528;
RA Felle M., Joppien S., Nemeth A., Diermeier S., Thalhammer V., Dobner T.,
RA Kremmer E., Kappler R., Langst G.;
RT "The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1
RT and regulates the stability of UHRF1.";
RL Nucleic Acids Res. 39:8355-8365(2011).
RN [28]
RP HYDROXYMETHYLCYTOSINE-BINDING.
RX PubMed=21731699; DOI=10.1371/journal.pone.0021306;
RA Frauer C., Hoffmann T., Bultmann S., Casa V., Cardoso M.C., Antes I.,
RA Leonhardt H.;
RT "Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain.";
RL PLoS ONE 6:E21306-E21306(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287 AND SER-651, 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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; SER-91; SER-287; SER-368;
RP SER-639; SER-707 AND SER-709, 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 [31]
RP FUNCTION, INTERACTION WITH PML, AND MUTAGENESIS OF HIS-741.
RX PubMed=22945642; DOI=10.1038/onc.2012.406;
RA Guan D., Factor D., Liu Y., Wang Z., Kao H.Y.;
RT "The epigenetic regulator UHRF1 promotes ubiquitination-mediated
RT degradation of the tumor-suppressor protein promyelocytic leukemia
RT protein.";
RL Oncogene 32:3819-3828(2013).
RN [32]
RP INVOLVEMENT IN CANCER.
RX PubMed=22286757; DOI=10.1038/onc.2012.3;
RA Sabatino L., Fucci A., Pancione M., Carafa V., Nebbioso A., Pistore C.,
RA Babbio F., Votino C., Laudanna C., Ceccarelli M., Altucci L.,
RA Bonapace I.M., Colantuoni V.;
RT "UHRF1 coordinates peroxisome proliferator activated receptor gamma (PPARG)
RT epigenetic silencing and mediates colorectal cancer progression.";
RL Oncogene 31:5061-5072(2012).
RN [33]
RP INVOLVEMENT IN CANCER.
RX PubMed=22330138; DOI=10.1038/onc.2011.641;
RA Babbio F., Pistore C., Curti L., Castiglioni I., Kunderfranco P., Brino L.,
RA Oudet P., Seiler R., Thalman G.N., Roggero E., Sarti M., Pinton S.,
RA Mello-Grand M., Chiorino G., Catapano C.V., Carbone G.M., Bonapace I.M.;
RT "The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in
RT prostate cancer progression.";
RL Oncogene 31:4878-4887(2012).
RN [34]
RP AUTOUBIQUITINATION, DEUBIQUITINATION BY USP7, INTERACTION WITH USP7,
RP PHOSPHORYLATION AT SER-639, AND MUTAGENESIS OF SER-639.
RX PubMed=22411829; DOI=10.1073/pnas.1116349109;
RA Ma H., Chen H., Guo X., Wang Z., Sowa M.E., Zheng L., Hu S., Zeng P.,
RA Guo R., Diao J., Lan F., Harper J.W., Shi Y.G., Xu Y., Shi Y.;
RT "M phase phosphorylation of the epigenetic regulator UHRF1 regulates its
RT physical association with the deubiquitylase USP7 and stability.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:4828-4833(2012).
RN [35]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-385; LYS-546 AND LYS-670, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [36]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-279 AND LYS-670, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [37]
RP FUNCTION, INTERACTION WITH UHRF2 AND FANCD2, AND SUBCELLULAR LOCATION.
RX PubMed=30335751; DOI=10.1371/journal.pgen.1007643;
RA Motnenko A., Liang C.C., Yang D., Lopez-Martinez D., Yoshikawa Y., Zhan B.,
RA Ward K.E., Tian J., Haas W., Spingardi P., Kessler B.M., Kriaucionis S.,
RA Gygi S.P., Cohn M.A.;
RT "Identification of UHRF2 as a novel DNA interstrand crosslink sensor
RT protein.";
RL PLoS Genet. 14:e1007643-e1007643(2018).
RN [38]
RP INTERACTION WITH ZNF263.
RX PubMed=32051553; DOI=10.1038/s41388-020-1206-7;
RA Yu Z., Feng J., Wang W., Deng Z., Zhang Y., Xiao L., Wang Z., Liu C.,
RA Liu Q., Chen S., Wu M.;
RT "The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma
RT epigenetically.";
RL Oncogene 39:3163-3178(2020).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-76.
RG Structural genomics consortium (SGC);
RT "Ubiquitin-like domain of human nuclear zinc finger protein NP95.";
RL Submitted (JAN-2006) to the PDB data bank.
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 408-643.
RX PubMed=18931436; DOI=10.1107/s1744309108027462;
RA Delagoutte B., Lallous N., Birck C., Oudet P., Samama J.P.;
RT "Expression, purification, crystallization and preliminary crystallographic
RT study of the SRA domain of the human UHRF1 protein.";
RL Acta Crystallogr. F 64:922-925(2008).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 414-617, AND MUTAGENESIS OF
RP ARG-433; ARG-443; TYR-466 AND ARG-491.
RX PubMed=18945682; DOI=10.1074/jbc.c800169200;
RA Qian C., Li S., Jakoncic J., Zeng L., Walsh M.J., Zhou M.M.;
RT "Structure and hemimethylated CpG binding of the SRA domain from human
RT UHRF1.";
RL J. Biol. Chem. 283:34490-34494(2008).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 414-617 IN COMPLEX WITH
RP HEMIMETHYLATED DNA, AND MUTAGENESIS OF GLY-448; ASP-469; ASN-489 AND
RP ARG-491.
RX PubMed=18772889; DOI=10.1038/nature07273;
RA Avvakumov G.V., Walker J.R., Xue S., Li Y., Duan S., Bronner C.,
RA Arrowsmith C.H., Dhe-Paganon S.;
RT "Structural basis for recognition of hemi-methylated DNA by the SRA domain
RT of human UHRF1.";
RL Nature 455:822-825(2008).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 298-366, AND MUTAGENESIS OF
RP ASP-334 AND ASP-337.
RX PubMed=21808300; DOI=10.1038/cr.2011.124;
RA Hu L., Li Z., Wang P., Lin Y., Xu Y.;
RT "Crystal structure of PHD domain of UHRF1 and insights into recognition of
RT unmodified histone H3 arginine residue 2.";
RL Cell Res. 21:1374-1378(2011).
RN [44]
RP STRUCTURE BY NMR OF 298-366, AND MUTAGENESIS OF ASP-334 AND ASP-337.
RX PubMed=21808299; DOI=10.1038/cr.2011.123;
RA Wang C., Shen J., Yang Z., Chen P., Zhao B., Hu W., Lan W., Tong X., Wu H.,
RA Li G., Cao C.;
RT "Structural basis for site-specific reading of unmodified R2 of histone H3
RT tail by UHRF1 PHD finger.";
RL Cell Res. 21:1379-1382(2011).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 126-285, STRUCTURE BY NMR OF
RP 126-285, AND MUTAGENESIS OF ASP-142; ASP-145; PHE-152; GLU-153; TYR-188 AND
RP ASP-190.
RX PubMed=21489993; DOI=10.1074/jbc.m111.234104;
RA Nady N., Lemak A., Walker J.R., Avvakumov G.V., Kareta M.S., Achour M.,
RA Xue S., Duan S., Allali-Hassani A., Zuo X., Wang Y.X., Bronner C.,
RA Chedin F., Arrowsmith C.H., Dhe-Paganon S.;
RT "Recognition of multivalent histone states associated with heterochromatin
RT by UHRF1 protein.";
RL J. Biol. Chem. 286:24300-24311(2011).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 298-367 IN COMPLEX WITH ZINC AND
RP HISTONE H3 PEPTIDE, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 334-ASP-GLU-335.
RX PubMed=21777816; DOI=10.1016/j.molcel.2011.07.006;
RA Rajakumara E., Wang Z., Ma H., Hu L., Chen H., Lin Y., Guo R., Wu F.,
RA Li H., Lan F., Shi Y.G., Xu Y., Patel D.J., Shi Y.;
RT "PHD finger recognition of unmodified histone H3R2 links UHRF1 to
RT regulation of euchromatic gene expression.";
RL Mol. Cell 43:275-284(2011).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 314-367, AND MUTAGENESIS OF
RP GLN-330; ASP-334 AND ASP-337.
RX PubMed=22096602; DOI=10.1371/journal.pone.0027599;
RA Lallous N., Legrand P., McEwen A.G., Ramon-Maiques S., Samama J.P.,
RA Birck C.;
RT "The PHD finger of human UHRF1 reveals a new subgroup of unmethylated
RT histone H3 tail readers.";
RL PLoS ONE 6:E27599-E27599(2011).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 299-364 IN COMPLEX WITH HISTONE
RP H3 PEPTIDE.
RX PubMed=22100450; DOI=10.1016/j.jmb.2011.11.012;
RA Xie S., Jakoncic J., Qian C.;
RT "UHRF1 double tudor domain and the adjacent PHD finger act together to
RT recognize K9me3-containing histone H3 tail.";
RL J. Mol. Biol. 415:318-328(2012).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 134-367 IN COMPLEX WITH ZINC AND
RP HISTONE H3 PEPTIDE, PHOSPHORYLATION AT SER-298, AND MUTAGENESIS OF
RP 295-ARG-ARG-296.
RX PubMed=22837395; DOI=10.1073/pnas.1203701109;
RA Arita K., Isogai S., Oda T., Unoki M., Sugita K., Sekiyama N., Kuwata K.,
RA Hamamoto R., Tochio H., Sato M., Ariyoshi M., Shirakawa M.;
RT "Recognition of modification status on a histone H3 tail by linked histone
RT reader modules of the epigenetic regulator UHRF1.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12950-12955(2012).
CC -!- FUNCTION: Multidomain protein that acts as a key epigenetic regulator
CC by bridging DNA methylation and chromatin modification. Specifically
CC recognizes and binds hemimethylated DNA at replication forks via its
CC YDG domain and recruits DNMT1 methyltransferase to ensure faithful
CC propagation of the DNA methylation patterns through DNA replication. In
CC addition to its role in maintenance of DNA methylation, also plays a
CC key role in chromatin modification: through its tudor-like regions and
CC PHD-type zinc fingers, specifically recognizes and binds histone H3
CC trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2'
CC (H3R2me0), respectively, and recruits chromatin proteins. Enriched in
CC pericentric heterochromatin where it recruits different chromatin
CC modifiers required for this chromatin replication. Also localizes to
CC euchromatic regions where it negatively regulates transcription
CC possibly by impacting DNA methylation and histone modifications. Has E3
CC ubiquitin-protein ligase activity by mediating the ubiquitination of
CC target proteins such as histone H3 and PML. It is still unclear how E3
CC ubiquitin-protein ligase activity is related to its role in chromatin
CC in vivo. Plays a role in DNA repair by cooperating with UHRF1 to ensure
CC recruitment of FANCD2 to interstrand cross-links (ICLs) leading to
CC FANCD2 activation. {ECO:0000269|PubMed:10646863,
CC ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834,
CC ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17967883,
CC ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:21745816,
CC ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:22945642,
CC ECO:0000269|PubMed:30335751}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with DNMT3A and DNMT3B (By similarity). Interacts
CC with DNMT1; the interaction is direct. Interacts with USP7; leading to
CC its deubiquitination. Interacts with histone H3. Interacts with HDAC1,
CC but not with HDAC2. Interacts with UHRF1BP1. Interacts with PML.
CC Interacts with EHMT2. Binds hemimethylated CpG containing
CC oligonucleotides. Interacts with ZNF263; recruited to the SIX3 promoter
CC along with other proteins involved in chromatin modification and
CC transcriptional corepression where it contributes to transcriptional
CC repression (PubMed:32051553). Interacts with UHRF2 (PubMed:30335751).
CC Interacts with FANCD2 (PubMed:30335751). {ECO:0000250,
CC ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17673620,
CC ECO:0000269|PubMed:18772889, ECO:0000269|PubMed:19056828,
CC ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:21777816,
CC ECO:0000269|PubMed:22100450, ECO:0000269|PubMed:22411829,
CC ECO:0000269|PubMed:22837395, ECO:0000269|PubMed:22945642,
CC ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:32051553}.
CC -!- INTERACTION:
CC Q96T88; P26358: DNMT1; NbExp=12; IntAct=EBI-1548946, EBI-719459;
CC Q96T88; Q9Y6K1: DNMT3A; NbExp=7; IntAct=EBI-1548946, EBI-923653;
CC Q96T88; Q9UBC3: DNMT3B; NbExp=7; IntAct=EBI-1548946, EBI-80125;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358,
CC ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:17673620,
CC ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:19056828,
CC ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:30335751}.
CC Note=Localizes to replication foci. Enriched in pericentric
CC heterochromatin. Also localizes to euchromatic regions.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96T88-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96T88-2; Sequence=VSP_044394;
CC -!- TISSUE SPECIFICITY: Expressed in thymus, bone marrow, testis, lung and
CC heart. Overexpressed in breast cancer. {ECO:0000269|PubMed:10646863,
CC ECO:0000269|PubMed:12838312, ECO:0000269|PubMed:15361834}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal thymus, liver and kidney.
CC {ECO:0000269|PubMed:10646863}.
CC -!- INDUCTION: Up-regulated in proliferating cells, and down-regulated in
CC quiescent cells. Down-regulated upon adriamycin-induced DNA damage, in
CC a p53/TP53 and CDKN1A-dependent way. Induced by E2F1 transcription
CC factor. {ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:12838312,
CC ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834}.
CC -!- DOMAIN: The tudor-like regions specifically recognize and bind histone
CC H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger
CC specifically recognizes and binds histone H3 trimethylated at 'Lys-9'
CC (H3K9me3). The tudor-like regions simultaneously recognizes H3K9me3
CC through a conserved aromatic cage in the first tudor-like subdomain and
CC unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains
CC (PubMed:21489993, PubMed:21777816 and PubMed:22100450). The linker
CC region plays a role in the formation of a histone H3-binding hole
CC between the reader modules formed by the tudor-like regions and the
CC PHD-type zinc finger by making extended contacts with the tandem tudor-
CC like regions (PubMed:22837395). {ECO:0000269|PubMed:22837395}.
CC -!- DOMAIN: The YDG domain (also named SRA domain) specifically recognizes
CC and binds hemimethylated DNA at replication forks (DNA that is only
CC methylated on the mother strand of replicating DNA) (PubMed:17673620).
CC It contains a binding pocket that accommodates the 5-methylcytosine
CC that is flipped out of the duplex DNA. 2 specialized loops reach
CC through the resulting gap in the DNA from both the major and the minor
CC grooves to read the other 3 bases of the CpG duplex. The major groove
CC loop confers both specificity for the CpG dinucleotide and
CC discrimination against methylation of deoxycytidine of the
CC complementary strand (PubMed:18772889). The YDG domain also recognizes
CC and binds 5-hydroxymethylcytosine (5hmC) (PubMed:21731699).
CC {ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:18772889,
CC ECO:0000269|PubMed:21731699}.
CC -!- DOMAIN: The RING finger is required for ubiquitin ligase activity.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-298 of the linker region decreases the
CC binding to H3K9me3. Phosphorylation at Ser-639 by CDK1 during M phase
CC impairs interaction with USP7, preventing deubiquitination and leading
CC to degradation by the proteasome. {ECO:0000269|PubMed:15178447,
CC ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22837395}.
CC -!- PTM: Ubiquitinated; which leads to proteasomal degradation.
CC Autoubiquitinated; interaction with USP7 leads to deubiquitination and
CC prevents degradation. Ubiquitination and degradation takes place during
CC M phase, when phosphorylation at Ser-639 prevents interaction with USP7
CC and subsequent deubiquitination. Polyubiquitination may be stimulated
CC by DNA damage. {ECO:0000269|PubMed:15009091,
CC ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:21745816,
CC ECO:0000269|PubMed:22411829}.
CC -!- DISEASE: Note=Defects in UHRF1 may be a cause of cancers. Overexpressed
CC in many different forms of human cancers, including bladder, breast,
CC cervical, colorectal and prostate cancers, as well as pancreatic
CC adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role
CC in the correlation of histone modification and gene silencing in cancer
CC progression. Expression is associated with a poor prognosis in patients
CC with various cancers, suggesting that it participates in cancer
CC progression.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15177.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/uhrf1/";
CC ---------------------------------------------------------------------------
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DR EMBL; AF129507; AAF28469.1; -; mRNA.
DR EMBL; AB177623; BAF36719.1; -; mRNA.
DR EMBL; AB177624; BAF36720.1; -; mRNA.
DR EMBL; AB075601; BAC20576.1; -; mRNA.
DR EMBL; AF274048; AAK55744.1; -; mRNA.
DR EMBL; EF560733; ABQ59043.1; -; mRNA.
DR EMBL; AK025578; BAB15177.1; ALT_INIT; mRNA.
DR EMBL; AK289389; BAF82078.1; -; mRNA.
DR EMBL; AK314579; BAG37156.1; -; mRNA.
DR EMBL; AY787925; AAV40831.1; -; Genomic_DNA.
DR EMBL; AC027319; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC053467; AAF64067.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69187.1; -; Genomic_DNA.
DR EMBL; BC113875; AAI13876.2; -; mRNA.
DR CCDS; CCDS74262.1; -. [Q96T88-2]
DR CCDS; CCDS74263.1; -. [Q96T88-1]
DR RefSeq; NP_001041666.1; NM_001048201.2. [Q96T88-1]
DR RefSeq; NP_001276979.1; NM_001290050.1. [Q96T88-1]
DR RefSeq; NP_001276980.1; NM_001290051.1. [Q96T88-1]
DR RefSeq; NP_001276981.1; NM_001290052.1. [Q96T88-1]
DR RefSeq; NP_037414.3; NM_013282.4.
DR PDB; 2FAZ; X-ray; 2.00 A; A/B=1-76.
DR PDB; 2L3R; NMR; -; A=126-285.
DR PDB; 2LGG; NMR; -; A=298-366.
DR PDB; 2LGK; NMR; -; A=298-366.
DR PDB; 2LGL; NMR; -; A=298-366.
DR PDB; 2PB7; X-ray; 1.90 A; A=408-643.
DR PDB; 3ASK; X-ray; 2.90 A; A/B/C/D=134-367.
DR PDB; 3ASL; X-ray; 1.41 A; A=298-367.
DR PDB; 3BI7; X-ray; 1.70 A; A=414-617.
DR PDB; 3CLZ; X-ray; 2.20 A; A/B/C/D=414-617.
DR PDB; 3DB3; X-ray; 2.40 A; A=126-285.
DR PDB; 3DB4; X-ray; 2.40 A; A=126-285.
DR PDB; 3DWH; X-ray; 1.95 A; A=414-617.
DR PDB; 3FL2; X-ray; 1.75 A; A=672-793.
DR PDB; 3SHB; X-ray; 1.80 A; A=298-366.
DR PDB; 3SOU; X-ray; 1.80 A; A/B=298-367.
DR PDB; 3SOW; X-ray; 1.95 A; A/B=298-367.
DR PDB; 3SOX; X-ray; 2.65 A; A/B=298-367.
DR PDB; 3T6R; X-ray; 1.95 A; A/B=299-364.
DR PDB; 3ZVY; X-ray; 1.95 A; A/B=296-367.
DR PDB; 3ZVZ; X-ray; 1.45 A; B=314-367.
DR PDB; 4GY5; X-ray; 2.96 A; A/B/C/D=134-366.
DR PDB; 4QQD; X-ray; 2.28 A; A/B=126-285.
DR PDB; 5C6D; X-ray; 2.29 A; C/D=634-665.
DR PDB; 5IAY; NMR; -; A=134-285, B=642-657.
DR PDB; 5XPI; X-ray; 2.20 A; A=127-283.
DR PDB; 5YY9; X-ray; 2.65 A; A/B=123-285.
DR PDB; 5YYA; X-ray; 1.70 A; A=123-285.
DR PDB; 6B9M; X-ray; 1.68 A; D=638-678.
DR PDB; 6IIW; X-ray; 1.70 A; A=299-366.
DR PDB; 6VCS; X-ray; 1.70 A; A/B/E=414-617.
DR PDB; 6VED; NMR; -; A=133-300.
DR PDB; 6VYJ; X-ray; 1.39 A; A=122-283.
DR PDB; 6W92; X-ray; 1.30 A; A=122-283.
DR PDB; 7FB7; X-ray; 1.45 A; A/B=123-285.
DR PDBsum; 2FAZ; -.
DR PDBsum; 2L3R; -.
DR PDBsum; 2LGG; -.
DR PDBsum; 2LGK; -.
DR PDBsum; 2LGL; -.
DR PDBsum; 2PB7; -.
DR PDBsum; 3ASK; -.
DR PDBsum; 3ASL; -.
DR PDBsum; 3BI7; -.
DR PDBsum; 3CLZ; -.
DR PDBsum; 3DB3; -.
DR PDBsum; 3DB4; -.
DR PDBsum; 3DWH; -.
DR PDBsum; 3FL2; -.
DR PDBsum; 3SHB; -.
DR PDBsum; 3SOU; -.
DR PDBsum; 3SOW; -.
DR PDBsum; 3SOX; -.
DR PDBsum; 3T6R; -.
DR PDBsum; 3ZVY; -.
DR PDBsum; 3ZVZ; -.
DR PDBsum; 4GY5; -.
DR PDBsum; 4QQD; -.
DR PDBsum; 5C6D; -.
DR PDBsum; 5IAY; -.
DR PDBsum; 5XPI; -.
DR PDBsum; 5YY9; -.
DR PDBsum; 5YYA; -.
DR PDBsum; 6B9M; -.
DR PDBsum; 6IIW; -.
DR PDBsum; 6VCS; -.
DR PDBsum; 6VED; -.
DR PDBsum; 6VYJ; -.
DR PDBsum; 6W92; -.
DR PDBsum; 7FB7; -.
DR AlphaFoldDB; Q96T88; -.
DR BMRB; Q96T88; -.
DR SASBDB; Q96T88; -.
DR SMR; Q96T88; -.
DR BioGRID; 118893; 177.
DR IntAct; Q96T88; 36.
DR MINT; Q96T88; -.
DR STRING; 9606.ENSP00000479617; -.
DR BindingDB; Q96T88; -.
DR ChEMBL; CHEMBL2424510; -.
DR GlyGen; Q96T88; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96T88; -.
DR PhosphoSitePlus; Q96T88; -.
DR SwissPalm; Q96T88; -.
DR BioMuta; UHRF1; -.
DR DMDM; 67462077; -.
DR EPD; Q96T88; -.
DR jPOST; Q96T88; -.
DR MassIVE; Q96T88; -.
DR MaxQB; Q96T88; -.
DR PeptideAtlas; Q96T88; -.
DR PRIDE; Q96T88; -.
DR ProteomicsDB; 78215; -. [Q96T88-1]
DR Antibodypedia; 72541; 413 antibodies from 34 providers.
DR DNASU; 29128; -.
DR Ensembl; ENST00000612630.4; ENSP00000484739.1; ENSG00000276043.5. [Q96T88-1]
DR Ensembl; ENST00000615884.4; ENSP00000478601.1; ENSG00000276043.5. [Q96T88-1]
DR Ensembl; ENST00000616255.1; ENSP00000478348.1; ENSG00000276043.5. [Q96T88-1]
DR Ensembl; ENST00000624301.3; ENSP00000485604.1; ENSG00000276043.5. [Q96T88-1]
DR Ensembl; ENST00000650932.1; ENSP00000498698.1; ENSG00000276043.5. [Q96T88-1]
DR GeneID; 29128; -.
DR KEGG; hsa:29128; -.
DR MANE-Select; ENST00000650932.1; ENSP00000498698.1; NM_001048201.3; NP_001041666.1.
DR UCSC; uc032hkj.2; human. [Q96T88-1]
DR CTD; 29128; -.
DR DisGeNET; 29128; -.
DR GeneCards; UHRF1; -.
DR HGNC; HGNC:12556; UHRF1.
DR HPA; ENSG00000276043; Group enriched (bone marrow, lymphoid tissue).
DR MIM; 607990; gene.
DR neXtProt; NX_Q96T88; -.
DR OpenTargets; ENSG00000276043; -.
DR PharmGKB; PA37196; -.
DR VEuPathDB; HostDB:ENSG00000276043; -.
DR eggNOG; ENOG502QRDQ; Eukaryota.
DR GeneTree; ENSGT00390000008296; -.
DR HOGENOM; CLU_022357_0_0_1; -.
DR InParanoid; Q96T88; -.
DR OrthoDB; 705927at2759; -.
DR PhylomeDB; Q96T88; -.
DR PathwayCommons; Q96T88; -.
DR Reactome; R-HSA-5334118; DNA methylation.
DR SignaLink; Q96T88; -.
DR SIGNOR; Q96T88; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 29128; 50 hits in 269 CRISPR screens.
DR ChiTaRS; UHRF1; human.
DR EvolutionaryTrace; Q96T88; -.
DR GeneWiki; UHRF1; -.
DR GenomeRNAi; 29128; -.
DR Pharos; Q96T88; Tbio.
DR PRO; PR:Q96T88; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96T88; protein.
DR Bgee; ENSG00000276043; Expressed in oocyte and 138 other tissues.
DR ExpressionAtlas; Q96T88; baseline and differential.
DR Genevisible; Q96T88; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0000791; C:euchromatin; IDA:UniProtKB.
DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; ISS:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:BHF-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0010390; P:histone monoubiquitination; ISS:BHF-UCL.
DR GO; GO:0016574; P:histone ubiquitination; IDA:UniProtKB.
DR GO; GO:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; IC:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IC:BHF-UCL.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR DisProt; DP01651; -.
DR Gene3D; 2.30.280.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00327; -.
DR InterPro; IPR015947; PUA-like_sf.
DR InterPro; IPR036987; SRA-YDG_sf.
DR InterPro; IPR003105; SRA_YDG.
DR InterPro; IPR021991; TTD_dom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR045134; UHRF1/2-like.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR14140; PTHR14140; 1.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF02182; SAD_SRA; 1.
DR Pfam; PF12148; TTD; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00249; PHD; 1.
DR SMART; SM00184; RING; 2.
DR SMART; SM00466; SRA; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF88697; SSF88697; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
DR PROSITE; PS51015; YDG; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle;
KW Chromatin regulator; DNA damage; DNA repair; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..793
FT /note="E3 ubiquitin-protein ligase UHRF1"
FT /id="PRO_0000056144"
FT DOMAIN 1..78
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 419..582
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 310..366
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 724..763
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 82..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 133..209
FT /note="Tudor-like 1"
FT REGION 216..283
FT /note="Tudor-like 2"
FT REGION 296..301
FT /note="Linker"
FT REGION 333..337
FT /note="Histone H3R2me0 binding"
FT REGION 353..355
FT /note="Histone H3R2me0 binding"
FT REGION 445..446
FT /note="Required to promote base flipping"
FT /evidence="ECO:0000250"
FT REGION 466..469
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT REGION 478..481
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT REGION 618..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 94..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 109..124
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 618..635
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 463..464
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT BINDING 469
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT SITE 316
FT /note="Histone H3K4me0 binding"
FT SITE 327
FT /note="Histone H3R2me0 binding"
FT SITE 330
FT /note="Histone H3R2me0 binding"
FT SITE 479
FT /note="Required to confer preferential recognition of
FT cytosine over thymine"
FT SITE 489
FT /note="Required to discriminate between hemimethylated DNA
FT versus symmetrically methylated DNA"
FT SITE 491
FT /note="Required for affinity and specificity for 5-mCpG
FT sequence"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPK1"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDF2"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 298
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:15178447,
FT ECO:0000269|PubMed:22837395"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 399
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 546
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 639
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:22411829,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 709
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 279
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 385
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 546
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 670
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1
FT /note="M -> MGVFAVPPLSSDTM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044394"
FT VARIANT 240
FT /note="D -> H (in dbSNP:rs17886098)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022554"
FT VARIANT 379
FT /note="E -> K (in dbSNP:rs17885791)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.6"
FT /id="VAR_022555"
FT VARIANT 638
FT /note="A -> T (in dbSNP:rs2307209)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.6"
FT /id="VAR_022556"
FT VARIANT 642
FT /note="T -> M (in dbSNP:rs17884843)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022557"
FT VARIANT 713
FT /note="L -> F (in dbSNP:rs17883563)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_022558"
FT MUTAGEN 142
FT /note="D->A: Impaired binding to histone H3 without
FT affecting the protein folding; when associated with A-153."
FT /evidence="ECO:0000269|PubMed:21489993"
FT MUTAGEN 145
FT /note="D->A: Impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:21489993"
FT MUTAGEN 152
FT /note="F->A: Impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:21489993"
FT MUTAGEN 153
FT /note="E->A: Impaired binding to histone H3 without
FT affecting the protein folding; when associated with A-142."
FT /evidence="ECO:0000269|PubMed:21489993"
FT MUTAGEN 188
FT /note="Y->A: Impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:20026581,
FT ECO:0000269|PubMed:21489993"
FT MUTAGEN 190
FT /note="D->A: Slightly impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:21489993"
FT MUTAGEN 191
FT /note="Y->A: Impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:20026581"
FT MUTAGEN 295..296
FT /note="RR->AA: Disrupts the simultaneous binding to H3R2me0
FT and H3K9me3."
FT /evidence="ECO:0000269|PubMed:22837395"
FT MUTAGEN 298
FT /note="S->A: Diminishes phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:15178447"
FT MUTAGEN 330
FT /note="Q->A,K: Does not affect ability to bind histone H3
FT peptide."
FT /evidence="ECO:0000269|PubMed:22096602"
FT MUTAGEN 334..335
FT /note="DE->AA: Abolishes binding to histone H3."
FT /evidence="ECO:0000269|PubMed:21777816"
FT MUTAGEN 334
FT /note="D->A: Impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:21808299,
FT ECO:0000269|PubMed:21808300, ECO:0000269|PubMed:22096602"
FT MUTAGEN 337
FT /note="D->A: Impaired binding to histone H3."
FT /evidence="ECO:0000269|PubMed:21808299,
FT ECO:0000269|PubMed:21808300, ECO:0000269|PubMed:22096602"
FT MUTAGEN 433
FT /note="R->A: Does not affect ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:18945682"
FT MUTAGEN 443
FT /note="R->A: Decreased ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:18945682"
FT MUTAGEN 448
FT /note="G->D: Decreased affinity for DNA."
FT /evidence="ECO:0000269|PubMed:18772889"
FT MUTAGEN 466
FT /note="Y->G: Decreased ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:18945682"
FT MUTAGEN 469
FT /note="D->G: Abolishes ability to bind hemimethylated DNA."
FT /evidence="ECO:0000269|PubMed:18772889"
FT MUTAGEN 489
FT /note="N->A: Abolishes specificity to hemimethylated DNA."
FT /evidence="ECO:0000269|PubMed:18772889"
FT MUTAGEN 491
FT /note="R->A: Decreased binding to methylated DNA but does
FT not affect ability to bind DNA."
FT /evidence="ECO:0000269|PubMed:18772889,
FT ECO:0000269|PubMed:18945682"
FT MUTAGEN 639
FT /note="S->A: Prevents phosphorylation by CDK1 during M
FT phase, leading to increased stability."
FT /evidence="ECO:0000269|PubMed:22411829"
FT MUTAGEN 639
FT /note="S->D: Mimics phosphorylation; impaired interaction
FT with USP7, leading to decreased stability."
FT /evidence="ECO:0000269|PubMed:22411829"
FT MUTAGEN 651
FT /note="S->A: No effect on in vitro phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:15178447"
FT MUTAGEN 666
FT /note="S->A: No effect on in vitro phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:15178447"
FT MUTAGEN 741
FT /note="H->A: Abolishes E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:22945642"
FT CONFLICT 383
FT /note="K -> E (in Ref. 5; BAF82078)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="K -> N (in Ref. 1; AAF28469)"
FT /evidence="ECO:0000305"
FT CONFLICT 457
FT /note="A -> S (in Ref. 1; AAF28469)"
FT /evidence="ECO:0000305"
FT CONFLICT 675
FT /note="S -> N (in Ref. 5; BAF82078)"
FT /evidence="ECO:0000305"
FT STRAND 1..7
FT /evidence="ECO:0007829|PDB:2FAZ"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:2FAZ"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:2FAZ"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2FAZ"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:2FAZ"
FT TURN 58..62
FT /evidence="ECO:0007829|PDB:2FAZ"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:2FAZ"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:7FB7"
FT STRAND 140..144
FT /evidence="ECO:0007829|PDB:6W92"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 151..162
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:2L3R"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:6W92"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:6W92"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:6W92"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:7FB7"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:2L3R"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 237..248
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 253..260
FT /evidence="ECO:0007829|PDB:6W92"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:6W92"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:2L3R"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2L3R"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:3ASK"
FT TURN 303..307
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:2LGG"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:3ASL"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:2LGL"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:3ASL"
FT TURN 334..336
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:3ASL"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:3ASL"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:3ASL"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:3DWH"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:3BI7"
FT HELIX 433..438
FT /evidence="ECO:0007829|PDB:3BI7"
FT TURN 439..442
FT /evidence="ECO:0007829|PDB:3DWH"
FT STRAND 448..452
FT /evidence="ECO:0007829|PDB:3BI7"
FT TURN 453..455
FT /evidence="ECO:0007829|PDB:3BI7"
FT STRAND 456..462
FT /evidence="ECO:0007829|PDB:3BI7"
FT STRAND 473..479
FT /evidence="ECO:0007829|PDB:3BI7"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:3CLZ"
FT HELIX 503..511
FT /evidence="ECO:0007829|PDB:3BI7"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:3BI7"
FT TURN 518..520
FT /evidence="ECO:0007829|PDB:3BI7"
FT HELIX 527..529
FT /evidence="ECO:0007829|PDB:3BI7"
FT STRAND 533..538
FT /evidence="ECO:0007829|PDB:3BI7"
FT HELIX 539..544
FT /evidence="ECO:0007829|PDB:3BI7"
FT STRAND 546..548
FT /evidence="ECO:0007829|PDB:3CLZ"
FT STRAND 550..568
FT /evidence="ECO:0007829|PDB:3BI7"
FT STRAND 572..582
FT /evidence="ECO:0007829|PDB:3BI7"
FT HELIX 592..601
FT /evidence="ECO:0007829|PDB:3BI7"
FT HELIX 611..617
FT /evidence="ECO:0007829|PDB:3BI7"
FT HELIX 678..686
FT /evidence="ECO:0007829|PDB:3FL2"
FT HELIX 688..690
FT /evidence="ECO:0007829|PDB:3FL2"
FT HELIX 691..699
FT /evidence="ECO:0007829|PDB:3FL2"
FT STRAND 706..708
FT /evidence="ECO:0007829|PDB:3FL2"
FT HELIX 710..721
FT /evidence="ECO:0007829|PDB:3FL2"
FT TURN 725..727
FT /evidence="ECO:0007829|PDB:3FL2"
FT STRAND 728..730
FT /evidence="ECO:0007829|PDB:3FL2"
FT STRAND 732..736
FT /evidence="ECO:0007829|PDB:3FL2"
FT STRAND 742..744
FT /evidence="ECO:0007829|PDB:3FL2"
FT HELIX 745..753
FT /evidence="ECO:0007829|PDB:3FL2"
FT TURN 760..762
FT /evidence="ECO:0007829|PDB:3FL2"
FT HELIX 776..785
FT /evidence="ECO:0007829|PDB:3FL2"
FT TURN 787..792
FT /evidence="ECO:0007829|PDB:3FL2"
SQ SEQUENCE 793 AA; 89814 MW; E65B15657525C89F CRC64;
MWIQVRTMDG RQTHTVDSLS RLTKVEELRR KIQELFHVEP GLQRLFYRGK QMEDGHTLFD
YEVRLNDTIQ LLVRQSLVLP HSTKERDSEL SDTDSGCCLG QSESDKSSTH GEAAAETDSR
PADEDMWDET ELGLYKVNEY VDARDTNMGA WFEAQVVRVT RKAPSRDEPC SSTSRPALEE
DVIYHVKYDD YPENGVVQMN SRDVRARART IIKWQDLEVG QVVMLNYNPD NPKERGFWYD
AEISRKRETR TARELYANVV LGDDSLNDCR IIFVDEVFKI ERPGEGSPMV DNPMRRKSGP
SCKHCKDDVN RLCRVCACHL CGGRQDPDKQ LMCDECDMAF HIYCLDPPLS SVPSEDEWYC
PECRNDASEV VLAGERLRES KKKAKMASAT SSSQRDWGKG MACVGRTKEC TIVPSNHYGP
IPGIPVGTMW RFRVQVSESG VHRPHVAGIH GRSNDGAYSL VLAGGYEDDV DHGNFFTYTG
SGGRDLSGNK RTAEQSCDQK LTNTNRALAL NCFAPINDQE GAEAKDWRSG KPVRVVRNVK
GGKNSKYAPA EGNRYDGIYK VVKYWPEKGK SGFLVWRYLL RRDDDEPGPW TKEGKDRIKK
LGLTMQYPEG YLEALANRER EKENSKREEE EQQEGGFASP RTGKGKWKRK SAGGGPSRAG
SPRRTSKKTK VEPYSLTAQQ SSLIREDKSN AKLWNEVLAS LKDRPASGSP FQLFLSKVEE
TFQCICCQEL VFRPITTVCQ HNVCKDCLDR SFRAQVFSCP ACRYDLGRSY AMQVNQPLQT
VLNQLFPGYG NGR
