UHRF1_MOUSE
ID UHRF1_MOUSE Reviewed; 782 AA.
AC Q8VDF2; Q3U9D7; Q3U9P2; Q3UI74; Q3UIE6; Q3ULF2; Q3ULQ0; Q8C6F1; Q8VIA1;
AC Q9Z1H6;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=E3 ubiquitin-protein ligase UHRF1;
DE EC=2.3.2.27;
DE AltName: Full=Nuclear protein 95;
DE AltName: Full=Nuclear zinc finger protein Np95;
DE AltName: Full=RING-type E3 ubiquitin transferase UHRF1;
DE AltName: Full=Ubiquitin-like PHD and RING finger domain-containing protein 1;
DE Short=mUhrf1;
DE AltName: Full=Ubiquitin-like-containing PHD and RING finger domains protein 1;
GN Name=Uhrf1; Synonyms=Np95;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=T lymphoblast;
RX PubMed=9880673; DOI=10.1007/s003359900920;
RA Fujimori A., Matsuda Y., Takemoto Y., Hashimoto Y., Kubo E., Araki R.,
RA Fukumura R., Mita K., Tatsumi K., Muto M.;
RT "Cloning and mapping of Np95 gene which encodes a novel nuclear protein
RT associated with cell proliferation.";
RL Mamm. Genome 9:1032-1035(1998).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J;
RC TISSUE=Bone marrow, Heart, Small intestine, Spleen, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-474, FUNCTION IN DNA REPAIR, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=12084726; DOI=10.1074/jbc.m205189200;
RA Muto M., Kanari Y., Kubo E., Takabe T., Kurihara T., Fujimori A.,
RA Tatsumi K.;
RT "Targeted disruption of Np95 gene renders murine embryonic stem cells
RT hypersensitive to DNA damaging agents and DNA replication blocks.";
RL J. Biol. Chem. 277:34549-34555(2002).
RN [7]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=8634372; DOI=10.1111/j.1365-2184.1995.tb00051.x;
RA Muto M., Utsuyama M., Horiguchi T., Kubo E., Sado T., Hirokawa K.;
RT "The characterization of the monoclonal antibody Th-10a, specific for a
RT nuclear protein appearing in the S phase of the cell cycle in normal
RT thymocytes and its unregulated expression in lymphoma cell lines.";
RL Cell Prolif. 28:645-657(1995).
RN [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10984098; DOI=10.1247/csf.25.149;
RA Uemura T., Kubo E., Kanari Y., Ikemura T., Tatsumi K., Muto M.;
RT "Temporal and spatial localization of novel nuclear protein NP95 in mitotic
RT and meiotic cells.";
RL Cell Struct. Funct. 25:149-159(2000).
RN [9]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=11161719; DOI=10.1006/excr.2000.5115;
RA Miura M., Watanabe H., Sasaki T., Tatsumi K., Muto M.;
RT "Dynamic changes in subnuclear NP95 location during the cell cycle and its
RT spatial relationship with DNA replication foci.";
RL Exp. Cell Res. 263:202-208(2001).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=12058012; DOI=10.1083/jcb.200201025;
RA Bonapace I.M., Latella L., Papait R., Nicassio F., Sacco A., Muto M.,
RA Crescenzi M., Di Fiore P.P.;
RT "Np95 is regulated by E1A during mitotic reactivation of terminally
RT differentiated cells and is essential for S phase entry.";
RL J. Cell Biol. 157:909-914(2002).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-730.
RX PubMed=14993289; DOI=10.1128/mcb.24.6.2526-2535.2004;
RA Citterio E., Papait R., Nicassio F., Vecchi M., Gomiero P., Mantovani R.,
RA Di Fiore P.P., Bonapace I.M.;
RT "Np95 is a histone-binding protein endowed with ubiquitin ligase
RT activity.";
RL Mol. Cell. Biol. 24:2526-2535(2004).
RN [12]
RP FUNCTION, AND INTERACTION WITH HDAC1.
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 [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DNMT1.
RX PubMed=17994007; DOI=10.1038/nature06397;
RA Sharif J., Muto M., Takebayashi S., Suetake I., Iwamatsu A., Endo T.A.,
RA Shinga J., Mizutani-Koseki Y., Toyoda T., Okamura K., Tajima S.,
RA Mitsuya K., Okano M., Koseki H.;
RT "The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1
RT to methylated DNA.";
RL Nature 450:908-912(2007).
RN [14]
RP FUNCTION.
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 [15]
RP INTERACTION WITH DNMT3A AND DNMT3B.
RX PubMed=19798101; DOI=10.1038/embor.2009.201;
RA Meilinger D., Fellinger K., Bultmann S., Rothbauer U., Bonapace I.M.,
RA Klinkert W.E., Spada F., Leonhardt H.;
RT "Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and
RT mediates epigenetic silencing of the viral CMV promoter in embryonic stem
RT cells.";
RL EMBO Rep. 10:1259-1264(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-656, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [17]
RP 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-161 AND SER-519, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP DNA-BINDING.
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 [20]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-148.
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 [21]
RP FUNCTION, AUTOUBIQUITINATION, DEUBIQUITINATION BY USP7, AND INTERACTION
RP WITH USP7 AND DNMT1.
RX PubMed=21268065; DOI=10.1002/jcb.22998;
RA Qin W., Leonhardt H., Spada F.;
RT "Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA
RT methyltransferase Dnmt1.";
RL J. Cell. Biochem. 112:439-444(2011).
RN [22]
RP INTERACTION WITH PRAMEL7.
RX PubMed=28604677; DOI=10.1038/ncb3554;
RA Graf U., Casanova E.A., Wyck S., Dalcher D., Gatti M., Vollenweider E.,
RA Okoniewski M.J., Weber F.A., Patel S.S., Schmid M.W., Li J., Sharif J.,
RA Wanner G.A., Koseki H., Wong J., Pelczar P., Penengo L., Santoro R.,
RA Cinelli P.;
RT "Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic
RT combined pathways.";
RL Nat. Cell Biol. 19:763-773(2017).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 405-613 IN COMPLEX WITH
RP HEMIMETHYLATED DNA.
RX PubMed=18772891; DOI=10.1038/nature07249;
RA Arita K., Ariyoshi M., Tochio H., Nakamura Y., Shirakawa M.;
RT "Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-
RT flipping mechanism.";
RL Nature 455:818-821(2008).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 419-628 IN COMPLEX WITH
RP HEMIMETHYLATED DNA.
RX PubMed=18772888; DOI=10.1038/nature07280;
RA Hashimoto H., Horton J.R., Zhang X., Bostick M., Jacobsen S.E., Cheng X.;
RT "The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix.";
RL Nature 455:826-829(2008).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 417-628.
RX PubMed=19077538; DOI=10.4161/epi.4.1.7370;
RA Hashimoto H., Horton J.R., Zhang X., Cheng X.;
RT "UHRF1, a modular multi-domain protein, regulates replication-coupled
RT crosstalk between DNA methylation and histone modifications.";
RL Epigenetics 4:8-14(2009).
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:0000250|UniProtKB:Q96T88,
CC ECO:0000269|PubMed:12058012, ECO:0000269|PubMed:12084726,
CC ECO:0000269|PubMed:14993289, ECO:0000269|PubMed:15361834,
CC ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17994007,
CC ECO:0000269|PubMed:21268065, ECO:0000269|PubMed:21489993}.
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. Interacts with DNMT1; the
CC interaction is direct. Interacts with USP7; leading to its
CC deubiquitination. Interacts with HDAC1, but not with HDAC2. Interacts
CC with UHRF1BP1. Interacts with PML. Interacts with EHMT2. Binds
CC hemimethylated CpG containing oligonucleotides (PubMed:15361834,
CC PubMed:17994007, PubMed:18772888, PubMed:18772891, PubMed:19056828,
CC PubMed:19798101, PubMed:21268065). Interacts with PRAMEL7
CC (PubMed:28604677). Interacts with ZNF263; recruited to the SIX3
CC promoter along with other proteins involved in chromatin modification
CC and transcriptional corepression where it contributes to
CC transcriptional repression (By similarity). Interacts with UHRF2 (By
CC similarity). Interacts with FANCD2 (By similarity).
CC {ECO:0000250|UniProtKB:Q96T88, ECO:0000269|PubMed:14993289,
CC ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17994007,
CC ECO:0000269|PubMed:18772888, ECO:0000269|PubMed:18772891,
CC ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:19798101,
CC ECO:0000269|PubMed:21268065, ECO:0000269|PubMed:28604677}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00358,
CC ECO:0000269|PubMed:10984098, ECO:0000269|PubMed:11161719,
CC ECO:0000269|PubMed:14993289, ECO:0000269|PubMed:17994007,
CC ECO:0000269|PubMed:21489993, ECO:0000269|PubMed:8634372}.
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=Q8VDF2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VDF2-2; Sequence=VSP_044395;
CC -!- TISSUE SPECIFICITY: Expressed in thymus, testis, spleen and lung.
CC Within testis, expressed in almost all cells except elongated
CC spermatids. {ECO:0000269|PubMed:10984098, ECO:0000269|PubMed:9880673}.
CC -!- INDUCTION: Up-regulated in proliferating cells, and down-regulated in
CC quiescent or differentiated cells. Early induced by E1A in postmitotic
CC cells. Down-regulated by aphidicolin. {ECO:0000269|PubMed:10984098,
CC ECO:0000269|PubMed:11161719, ECO:0000269|PubMed:12058012,
CC ECO:0000269|PubMed:8634372}.
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). The linker region plays a role in the formation of a
CC histone H3-binding hole between the reader modules formed by the tudor-
CC like regions and the PHD-type zinc finger by making extended contacts
CC with the tandem tudor-like regions. {ECO:0000269|PubMed:21489993}.
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:17994007).
CC The YDG domain contains a binding pocket that accommodates the 5-
CC methylcytosine that is flipped out of the duplex DNA. 2 specialized
CC loops reach through the resulting gap in the DNA from both the major
CC and the minor grooves to read the other 3 bases of the CpG duplex. The
CC major groove loop confers both specificity for the CpG dinucleotide and
CC discrimination against methylation of deoxycytidine of the
CC complementary strand (PubMed:18772888). The YDG domain also recognizes
CC and binds 5-hydroxymethylcytosine (5hmC). {ECO:0000269|PubMed:17994007,
CC ECO:0000269|PubMed:18772888}.
CC -!- DOMAIN: The RING finger is required for ubiquitin ligase activity.
CC -!- PTM: Phosphorylation at Ser-303 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 (By similarity). {ECO:0000250}.
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:21268065}.
CC -!- DISRUPTION PHENOTYPE: Mice display a sensitization to DNA damage and
CC replication block, and die in mid-gestation.
CC {ECO:0000269|PubMed:12084726}.
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DR EMBL; D87908; BAA74579.1; -; mRNA.
DR EMBL; AF274046; AAK55743.1; -; mRNA.
DR EMBL; AK075819; BAC35985.1; -; mRNA.
DR EMBL; AK143688; BAE25499.1; -; mRNA.
DR EMBL; AK145376; BAE26398.1; -; mRNA.
DR EMBL; AK145543; BAE26496.1; -; mRNA.
DR EMBL; AK146951; BAE27560.1; -; mRNA.
DR EMBL; AK147046; BAE27632.1; -; mRNA.
DR EMBL; AK150489; BAE29605.1; -; mRNA.
DR EMBL; AK151701; BAE30624.1; -; mRNA.
DR EMBL; AK151837; BAE30730.1; -; mRNA.
DR EMBL; AK152930; BAE31605.1; -; mRNA.
DR EMBL; AK153083; BAE31708.1; -; mRNA.
DR EMBL; AC026385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022167; AAH22167.1; -; mRNA.
DR EMBL; AB066246; BAB79496.1; -; Genomic_DNA.
DR CCDS; CCDS28903.1; -. [Q8VDF2-1]
DR CCDS; CCDS50151.1; -. [Q8VDF2-2]
DR RefSeq; NP_001104548.1; NM_001111078.1. [Q8VDF2-1]
DR RefSeq; NP_001104549.1; NM_001111079.1. [Q8VDF2-2]
DR RefSeq; NP_001104550.1; NM_001111080.1. [Q8VDF2-2]
DR RefSeq; NP_035061.3; NM_010931.3. [Q8VDF2-1]
DR PDB; 2ZKD; X-ray; 1.60 A; A/B=404-613.
DR PDB; 2ZKE; X-ray; 2.60 A; A=404-613.
DR PDB; 2ZKF; X-ray; 2.55 A; A=404-613.
DR PDB; 2ZKG; X-ray; 1.77 A; A/B/C/D=404-613.
DR PDB; 2ZO0; X-ray; 2.19 A; B=419-628.
DR PDB; 2ZO1; X-ray; 1.96 A; B=419-628.
DR PDB; 2ZO2; X-ray; 3.09 A; B=419-628.
DR PDB; 3F8I; X-ray; 2.29 A; A/B=419-628.
DR PDB; 3F8J; X-ray; 1.99 A; B=417-628.
DR PDB; 3FDE; X-ray; 1.41 A; A/B=419-628.
DR PDB; 6M2V; X-ray; 3.00 A; A/B=417-628.
DR PDB; 6VEE; NMR; -; A=122-305.
DR PDB; 6VFO; NMR; -; A=303-380.
DR PDBsum; 2ZKD; -.
DR PDBsum; 2ZKE; -.
DR PDBsum; 2ZKF; -.
DR PDBsum; 2ZKG; -.
DR PDBsum; 2ZO0; -.
DR PDBsum; 2ZO1; -.
DR PDBsum; 2ZO2; -.
DR PDBsum; 3F8I; -.
DR PDBsum; 3F8J; -.
DR PDBsum; 3FDE; -.
DR PDBsum; 6M2V; -.
DR PDBsum; 6VEE; -.
DR PDBsum; 6VFO; -.
DR AlphaFoldDB; Q8VDF2; -.
DR SMR; Q8VDF2; -.
DR BioGRID; 201816; 33.
DR MINT; Q8VDF2; -.
DR STRING; 10090.ENSMUSP00000001258; -.
DR iPTMnet; Q8VDF2; -.
DR PhosphoSitePlus; Q8VDF2; -.
DR SwissPalm; Q8VDF2; -.
DR REPRODUCTION-2DPAGE; Q8VDF2; -.
DR EPD; Q8VDF2; -.
DR jPOST; Q8VDF2; -.
DR MaxQB; Q8VDF2; -.
DR PaxDb; Q8VDF2; -.
DR PeptideAtlas; Q8VDF2; -.
DR PRIDE; Q8VDF2; -.
DR ProteomicsDB; 298473; -. [Q8VDF2-1]
DR ProteomicsDB; 298474; -. [Q8VDF2-2]
DR Antibodypedia; 72541; 413 antibodies from 34 providers.
DR DNASU; 18140; -.
DR Ensembl; ENSMUST00000001258; ENSMUSP00000001258; ENSMUSG00000001228. [Q8VDF2-1]
DR Ensembl; ENSMUST00000113035; ENSMUSP00000108658; ENSMUSG00000001228. [Q8VDF2-2]
DR Ensembl; ENSMUST00000113038; ENSMUSP00000108661; ENSMUSG00000001228. [Q8VDF2-2]
DR Ensembl; ENSMUST00000113039; ENSMUSP00000108662; ENSMUSG00000001228. [Q8VDF2-1]
DR GeneID; 18140; -.
DR KEGG; mmu:18140; -.
DR UCSC; uc008dbp.2; mouse. [Q8VDF2-1]
DR UCSC; uc008dbq.2; mouse. [Q8VDF2-2]
DR CTD; 29128; -.
DR MGI; MGI:1338889; Uhrf1.
DR VEuPathDB; HostDB:ENSMUSG00000001228; -.
DR eggNOG; ENOG502QRDQ; Eukaryota.
DR GeneTree; ENSGT00390000008296; -.
DR HOGENOM; CLU_022357_0_0_1; -.
DR InParanoid; Q8VDF2; -.
DR OMA; WYDAEIC; -.
DR OrthoDB; 705927at2759; -.
DR PhylomeDB; Q8VDF2; -.
DR TreeFam; TF106434; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 18140; 34 hits in 115 CRISPR screens.
DR ChiTaRS; Uhrf1; mouse.
DR EvolutionaryTrace; Q8VDF2; -.
DR PRO; PR:Q8VDF2; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8VDF2; protein.
DR Bgee; ENSMUSG00000001228; Expressed in metanephric ureteric bud and 217 other tissues.
DR ExpressionAtlas; Q8VDF2; baseline and differential.
DR Genevisible; Q8VDF2; MM.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR GO; GO:0008327; F:methyl-CpG binding; ISO:MGI.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:BHF-UCL.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS: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; IDA:BHF-UCL.
DR GO; GO:0016574; P:histone ubiquitination; ISS: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:0051247; P:positive regulation of protein metabolic process; ISO:MGI.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:BHF-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 2.30.280.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
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..782
FT /note="E3 ubiquitin-protein ligase UHRF1"
FT /id="PRO_0000056145"
FT DOMAIN 1..78
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 424..586
FT /note="YDG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00358"
FT ZN_FING 304..371
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 713..752
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 83..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..205
FT /note="Tudor-like 1"
FT REGION 212..280
FT /note="Tudor-like 2"
FT REGION 293..306
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 338..342
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 358..360
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT REGION 450..451
FT /note="Required to promote base flipping"
FT REGION 471..474
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT REGION 483..486
FT /note="Required for formation of a 5-methylcytosine-binding
FT pocket"
FT REGION 623..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 105..119
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 635..666
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 468..469
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT /evidence="ECO:0000250"
FT BINDING 474
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_part="5-methylcytosine group"
FT /ligand_part_id="ChEBI:CHEBI:65274"
FT /evidence="ECO:0000250"
FT SITE 321
FT /note="Histone H3K4me0 binding"
FT /evidence="ECO:0000250"
FT SITE 332
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 335
FT /note="Histone H3R2me0 binding"
FT /evidence="ECO:0000250"
FT SITE 484
FT /note="Required to confer preferential recognition of
FT cytosine over thymine"
FT /evidence="ECO:0000250"
FT SITE 494
FT /note="Required to discriminate between hemimethylated DNA
FT versus symmetrically methylated DNA"
FT SITE 496
FT /note="Required for affinity and specificity for 5-mCpG
FT sequence"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPK1"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPK1"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 303
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 404
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 550
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 639
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT MOD_RES 656
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 759
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPK1"
FT CROSSLNK 390
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT CROSSLNK 550
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT CROSSLNK 664
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96T88"
FT VAR_SEQ 293..301
FT /note="PPPALRNTG -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_044395"
FT MUTAGEN 148
FT /note="F->A: Abolishes binding to histone H3K9me3 and
FT ability to repress transcription of target genes."
FT /evidence="ECO:0000269|PubMed:21489993"
FT MUTAGEN 730
FT /note="H->A: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:14993289"
FT CONFLICT 104
FT /note="S -> P (in Ref. 3; BAE30624)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="D -> G (in Ref. 3; BAE31708/BAE31605/BAE30730/
FT BAE29605)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="E -> K (in Ref. 6; BAB79496)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="P -> L (in Ref. 6; BAB79496)"
FT /evidence="ECO:0000305"
FT CONFLICT 455..456
FT /note="HG -> PW (in Ref. 6; BAB79496)"
FT /evidence="ECO:0000305"
FT CONFLICT 471
FT /note="Y -> H (in Ref. 3; BAE27560)"
FT /evidence="ECO:0000305"
FT CONFLICT 637
FT /note="P -> A (in Ref. 3; BAE26398)"
FT /evidence="ECO:0000305"
FT CONFLICT 702
FT /note="I -> V (in Ref. 3; BAE31708/BAE31605/BAE30730/
FT BAE29605)"
FT /evidence="ECO:0000305"
FT CONFLICT 753
FT /note="F -> Y (in Ref. 5; AAH22167)"
FT /evidence="ECO:0000305"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 147..156
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 179..186
FT /evidence="ECO:0007829|PDB:6VEE"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:6VEE"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:6VEE"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 218..223
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 233..245
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 248..257
FT /evidence="ECO:0007829|PDB:6VEE"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 261..267
FT /evidence="ECO:0007829|PDB:6VEE"
FT TURN 271..273
FT /evidence="ECO:0007829|PDB:6VEE"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:6VEE"
FT TURN 308..312
FT /evidence="ECO:0007829|PDB:6VFO"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:6VFO"
FT TURN 324..327
FT /evidence="ECO:0007829|PDB:6VFO"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:6VFO"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:6VFO"
FT TURN 339..342
FT /evidence="ECO:0007829|PDB:6VFO"
FT STRAND 343..346
FT /evidence="ECO:0007829|PDB:6VFO"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:6VFO"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:6VFO"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:6VFO"
FT TURN 405..408
FT /evidence="ECO:0007829|PDB:2ZKD"
FT STRAND 434..437
FT /evidence="ECO:0007829|PDB:3FDE"
FT HELIX 438..443
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 453..457
FT /evidence="ECO:0007829|PDB:3FDE"
FT TURN 458..460
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 461..467
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:2ZO1"
FT STRAND 478..484
FT /evidence="ECO:0007829|PDB:3FDE"
FT TURN 492..494
FT /evidence="ECO:0007829|PDB:3FDE"
FT HELIX 508..515
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:3FDE"
FT HELIX 531..533
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 537..543
FT /evidence="ECO:0007829|PDB:3FDE"
FT TURN 546..548
FT /evidence="ECO:0007829|PDB:2ZO2"
FT STRAND 550..552
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 554..572
FT /evidence="ECO:0007829|PDB:3FDE"
FT STRAND 576..586
FT /evidence="ECO:0007829|PDB:3FDE"
FT HELIX 596..605
FT /evidence="ECO:0007829|PDB:3FDE"
FT HELIX 615..622
FT /evidence="ECO:0007829|PDB:3FDE"
SQ SEQUENCE 782 AA; 88304 MW; DC5EEDFCDF69619B CRC64;
MWIQVRTMDG KETHTVNSLS RLTKVQELRK KIEEVFHVEP QLQRLFYRGK QMEDGHTLFD
YDVRLNDTIQ LLVRQSLALP LSTKERDSEL SDSDSGYGVG HSESDKSSTH GEGAAEADDK
TVWEDTDLGL YKVNEYVDVR DNIFGAWFEA QVVQVQKRAL SEDEPCSSSA VKTSEDDIMY
HVKYDDYPEH GVDIVKAKNV RARARTVIPW ENLEVGQVVM ANYNVDYPRK RGFWYDVEIC
RKRQTRTARE LYGNIRLLND SQLNNCRIMF VDEVLMIELP KERRPLIASP SQPPPALRNT
GKSGPSCRFC KDDENKPCRK CACHVCGGRE APEKQLLCDE CDMAFHLYCL KPPLTSVPPE
PEWYCPSCRT DSSEVVQAGE KLKESKKKAK MASATSSSRR DWGKGMACVG RTTECTIVPA
NHFGPIPGVP VGTMWRFRVQ VSESGVHRPH VAGIHGRSND GAYSLVLAGG YEDDVDNGNY
FTYTGSGGRD LSGNKRTAGQ SSDQKLTNNN RALALNCHSP INEKGAEAED WRQGKPVRVV
RNMKGGKHSK YAPAEGNRYD GIYKVVKYWP ERGKSGFLVW RYLLRRDDTE PEPWTREGKD
RTRQLGLTMQ YPEGYLEALA NKEKSRKRPA KALEQGPSSS KTGKSKQKST GPTLSSPRAS
KKSKLEPYTL SEQQANLIKE DKGNAKLWDD VLTSLQDGPY QIFLSKVKEA FQCICCQELV
FRPVTTVCQH NVCKDCLDRS FRAQVFSCPA CRFELDHSSP TRVNQPLQTI LNQLFPGYGS
GR
