PHF8_HUMAN
ID PHF8_HUMAN Reviewed; 1060 AA.
AC Q9UPP1; B3KMV4; B7Z911; Q5H9U5; Q5JPR9; Q5JPS0; Q5JPS2; Q5JPS3; Q5VUJ4;
AC Q7Z6D4; Q9HAH2;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Histone lysine demethylase PHF8;
DE EC=1.14.11.27 {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638};
DE EC=1.14.11.65 {ECO:0000269|PubMed:20208542};
DE AltName: Full=PHD finger protein 8;
DE AltName: Full=[histone H3]-dimethyl-L-lysine(36) demethylase PHF8 {ECO:0000305};
DE AltName: Full=[histone H3]-dimethyl-L-lysine(9) demethylase PHF8 {ECO:0000305};
GN Name=PHF8; Synonyms=KIAA1111, ZNF422;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 34-927 (ISOFORM 3), AND NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 515-1060 (ISOFORM 1).
RC TISSUE=Embryo, Teratocarcinoma, and Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Endometrial tumor;
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 GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5).
RC TISSUE=Brain, and Cervix;
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 [7]
RP INVOLVEMENT IN MRXSSD.
RX PubMed=16199551; DOI=10.1136/jmg.2004.029439;
RA Laumonnier F., Holbert S., Ronce N., Faravelli F., Lenzner S.,
RA Schwartz C.E., Lespinasse J., Van Esch H., Lacombe D., Goizet C.,
RA Phan-Dinh Tuy F., van Bokhoven H., Fryns J.-P., Chelly J., Ropers H.-H.,
RA Moraine C., Hamel B.C.J., Briault S.;
RT "Mutations in PHF8 are associated with X linked mental retardation and
RT cleft lip/cleft palate.";
RL J. Med. Genet. 42:780-786(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-857, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-705; THR-706; SER-854;
RP SER-857 AND SER-880, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-651; THR-705; THR-706;
RP SER-854 AND SER-857, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-283.
RX PubMed=20531378; DOI=10.1038/cr.2010.75;
RA Zhu Z., Wang Y., Li X., Wang Y., Xu L., Wang X., Sun T., Dong X., Chen L.,
RA Mao H., Yu Y., Li J., Chen P.A., Chen C.D.;
RT "PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis.";
RL Cell Res. 20:794-801(2010).
RN [13]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT MRXSSD SER-315.
RX PubMed=20548336; DOI=10.1038/cr.2010.81;
RA Qiu J., Shi G., Jia Y., Li J., Wu M., Li J., Dong S., Wong J.;
RT "The X-linked mental retardation gene PHF8 is a histone demethylase
RT involved in neuronal differentiation.";
RL Cell Res. 20:908-918(2010).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=19843542; DOI=10.1093/hmg/ddp480;
RA Loenarz C., Ge W., Coleman M.L., Rose N.R., Cooper C.D.O., Klose R.J.,
RA Ratcliffe P.J., Schofield C.J.;
RT "PHF8, a gene associated with cleft lip/palate and mental retardation,
RT encodes for an Nepsilon-dimethyl lysine demethylase.";
RL Hum. Mol. Genet. 19:217-222(2010).
RN [15]
RP FUNCTION, DOMAIN PHD-FINGER, INTERACTION WITH ZNF711, CHARACTERIZATION OF
RP VARIANT MRXSSD SER-315, AND MUTAGENESIS OF HIS-283.
RX PubMed=20346720; DOI=10.1016/j.molcel.2010.03.002;
RA Kleine-Kohlbrecher D., Christensen J., Vandamme J., Abarrategui I., Bak M.,
RA Tommerup N., Shi X., Gozani O., Rappsilber J., Salcini A.E., Helin K.;
RT "A functional link between the histone demethylase PHF8 and the
RT transcription factor ZNF711 in X-linked mental retardation.";
RL Mol. Cell 38:165-178(2010).
RN [16]
RP FUNCTION, DOMAIN PHD-FINGER, AND CHARACTERIZATION OF VARIANT MRXSSD
RP SER-315.
RX PubMed=20421419; DOI=10.1128/mcb.01520-09;
RA Fortschegger K., de Graaf P., Outchkourov N.S., van Schaik F.M.,
RA Timmers H.T., Shiekhattar R.;
RT "PHF8 targets histone methylation and RNA polymerase II to activate
RT transcription.";
RL Mol. Cell. Biol. 30:3286-3298(2010).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH POLR1B
RP AND UBTF, CHARACTERIZATION OF VARIANT MRXSSD SER-315, AND MUTAGENESIS OF
RP TYR-43 AND 283-HIS--ASP-285.
RX PubMed=20208542; DOI=10.1038/nsmb.1778;
RA Feng W., Yonezawa M., Ye J., Jenuwein T., Grummt I.;
RT "PHF8 activates transcription of rRNA genes through H3K4me3 binding and
RT H3K9me1/2 demethylation.";
RL Nat. Struct. Mol. Biol. 17:445-450(2010).
RN [18]
RP FUNCTION, DOMAIN PHD-FINGER, CHARACTERIZATION OF VARIANT MRXSSD SER-315,
RP AND MUTAGENESIS OF TYR-43; TYR-50 AND TRP-65.
RX PubMed=20622853; DOI=10.1038/nature09261;
RA Qi H.H., Sarkissian M., Hu G.Q., Wang Z., Bhattacharjee A., Gordon D.B.,
RA Gonzales M., Lan F., Ongusaha P.P., Huarte M., Yaghi N.K., Lim H.,
RA Garcia B.A., Brizuela L., Zhao K., Roberts T.M., Shi Y.;
RT "Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and
RT craniofacial development.";
RL Nature 466:503-507(2010).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN PHD-FINGER, INTERACTION WITH SETD1A;
RP HCFC1 AND E2F1, CHARACTERIZATION OF VARIANT MRXSSD SER-315, PHOSPHORYLATION
RP AT SER-69 AND SER-120, AND MUTAGENESIS OF SER-69; SER-120 AND HIS-283.
RX PubMed=20622854; DOI=10.1038/nature09272;
RA Liu W., Tanasa B., Tyurina O.V., Zhou T.Y., Gassmann R., Liu W.T.,
RA Ohgi K.A., Benner C., Garcia-Bassets I., Aggarwal A.K., Desai A.,
RA Dorrestein P.C., Glass C.K., Rosenfeld M.G.;
RT "PHF8 mediates histone H4 lysine 20 demethylation events involved in cell
RT cycle progression.";
RL Nature 466:508-512(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-804; SER-857 AND SER-880, AND
RP 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-854; SER-857 AND SER-880, 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-722; SER-804;
RP SER-857 AND SER-880, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
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 [25]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 122-483 IN COMPLEX WITH IRON AND
RP ALPHA-KETOGLUTARATE, FUNCTION, AND CHARACTERIZATION OF VARIANT MRXSSD
RP SER-315.
RX PubMed=20101266; DOI=10.1038/cr.2010.8;
RA Yu L., Wang Y., Huang S., Wang J., Deng Z., Zhang Q., Wu W., Zhang X.,
RA Liu Z., Gong W., Chen Z.;
RT "Structural insights into a novel histone demethylase PHF8.";
RL Cell Res. 20:166-173(2010).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 115-483.
RX PubMed=20067792; DOI=10.1016/j.febslet.2009.12.055;
RA Yue W.W., Hozjan V., Ge W., Loenarz C., Cooper C.D., Schofield C.J.,
RA Kavanagh K.L., Oppermann U., McDonough M.A.;
RT "Crystal structure of the PHF8 Jumonji domain, an N(epsilon)-methyl lysine
RT demethylase.";
RL FEBS Lett. 584:825-830(2010).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-447 IN COMPLEX WITH IRON AND
RP N-OXALYLGLYCINE, ZINC-BINDING, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND DOMAIN LINKER AND PHD-FINGER.
RX PubMed=20023638; DOI=10.1038/nsmb.1753;
RA Horton J.R., Upadhyay A.K., Qi H.H., Zhang X., Shi Y., Cheng X.;
RT "Enzymatic and structural insights for substrate specificity of a family of
RT jumonji histone lysine demethylases.";
RL Nat. Struct. Mol. Biol. 17:38-43(2010).
RN [28]
RP VARIANT MRXSSD SER-315.
RX PubMed=17661819; DOI=10.1111/j.1399-0004.2007.00836.x;
RA Koivisto A.M., Ala-Mello S., Lemmelae S., Komu H.A., Rautio J.,
RA Jaervelae I.;
RT "Screening of mutations in the PHF8 gene and identification of a novel
RT mutation in a Finnish family with XLMR and cleft lip/cleft palate.";
RL Clin. Genet. 72:145-149(2007).
RN [29]
RP VARIANT SER-969 DEL.
RX PubMed=23092983; DOI=10.1038/tp.2012.102;
RA Nava C., Lamari F., Heron D., Mignot C., Rastetter A., Keren B., Cohen D.,
RA Faudet A., Bouteiller D., Gilleron M., Jacquette A., Whalen S., Afenjar A.,
RA Perisse D., Laurent C., Dupuits C., Gautier C., Gerard M., Huguet G.,
RA Caillet S., Leheup B., Leboyer M., Gillberg C., Delorme R., Bourgeron T.,
RA Brice A., Depienne C.;
RT "Analysis of the chromosome X exome in patients with autism spectrum
RT disorders identified novel candidate genes, including TMLHE.";
RL Transl. Psychiatry 2:E179-E179(2012).
CC -!- FUNCTION: Histone lysine demethylase with selectivity for the di- and
CC monomethyl states that plays a key role cell cycle progression, rDNA
CC transcription and brain development. Demethylates mono- and
CC dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2),
CC dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-
CC 20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1,
CC H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks.
CC Involved in cell cycle progression by being required to control G1-S
CC transition. Acts as a coactivator of rDNA transcription, by activating
CC polymerase I (pol I) mediated transcription of rRNA genes. Required for
CC brain development, probably by regulating expression of neuron-specific
CC genes. Only has activity toward H4K20Me1 when nucleosome is used as a
CC substrate and when not histone octamer is used as substrate. May also
CC have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however,
CC the relevance of this result remains unsure in vivo. Specifically binds
CC trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone
CC demethylase specificity: has weak activity toward H3K9Me2 in absence of
CC H3K4me3, while it has high activity toward H3K9me2 when binding
CC H3K4me3. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638,
CC ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542,
CC ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419,
CC ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336,
CC ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3]
CC + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(36)-[histone H3] + 2
CC succinate; Xref=Rhea:RHEA:42032, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:9787, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61976; EC=1.14.11.27;
CC Evidence={ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3]
CC + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(9)-[histone H3] + 2
CC succinate; Xref=Rhea:RHEA:60188, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15546, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61976; EC=1.14.11.65;
CC Evidence={ECO:0000269|PubMed:20208542};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000305|PubMed:19843542, ECO:0000305|PubMed:20023638};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:19843542,
CC ECO:0000305|PubMed:20023638};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=134 uM for histone H3 H3K9Me2 {ECO:0000269|PubMed:20023638};
CC KM=8 uM for histone H3 H3K4me3 and H3K9Me2
CC {ECO:0000269|PubMed:20023638};
CC -!- SUBUNIT: Interacts with POLR1B, UBTF, SETD1A, HCFC1, E2F1 and ZNF711.
CC Interacts with ZNF263; recruited to the SIX3 promoter along with other
CC proteins involved in chromatin modification and transcriptional
CC corepression where it contributes to transcriptional repression
CC (PubMed:32051553). {ECO:0000269|PubMed:20023638,
CC ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542,
CC ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20622854,
CC ECO:0000269|PubMed:32051553}.
CC -!- INTERACTION:
CC Q9UPP1; Q96QS3: ARX; NbExp=3; IntAct=EBI-1560800, EBI-11107474;
CC Q9UPP1; Q06330: RBPJ; NbExp=2; IntAct=EBI-1560800, EBI-632552;
CC Q9UPP1-2; P51610-1: HCFC1; NbExp=2; IntAct=EBI-6601215, EBI-396188;
CC Q9UPP1-2; Q15156: PML-RAR; NbExp=6; IntAct=EBI-6601215, EBI-867256;
CC Q9UPP1-2; P10276: RARA; NbExp=2; IntAct=EBI-6601215, EBI-413374;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19843542,
CC ECO:0000269|PubMed:20622854}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20531378}.
CC Note=Recruited to H3K4me3 sites on chromatin during interphase
CC (PubMed:20622854). Dissociates from chromatin when cells enter mitosis
CC (PubMed:20622854). {ECO:0000269|PubMed:20622854}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9UPP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UPP1-2; Sequence=VSP_014964;
CC Name=3;
CC IsoId=Q9UPP1-3; Sequence=VSP_014965;
CC Name=4;
CC IsoId=Q9UPP1-4; Sequence=VSP_014964, VSP_014965, VSP_043640;
CC Name=5;
CC IsoId=Q9UPP1-5; Sequence=VSP_014964, VSP_054019, VSP_054020,
CC VSP_054021;
CC -!- DOMAIN: The PHD-type zinc finger mediates the binding to H3K4me3.
CC Binding to H3K4me3 promotes its access to H3K9me2.
CC -!- DOMAIN: The linker region is a critical determinant of demethylase
CC specificity. It enables the active site of JmjC to reach the target
CC H3K9me2 when the PHD-type zinc finger binds to H3K4me3.
CC -!- PTM: Phosphorylation at Ser-69 and Ser-120 are required for
CC dissociation from chromatin and accumulation of H4K20Me1 levels during
CC prophase. {ECO:0000269|PubMed:20622854}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic,
CC Siderius type (MRXSSD) [MIM:300263]: A syndrome characterized by mild
CC to borderline intellectual disability with or without cleft lip/cleft
CC palate. {ECO:0000269|PubMed:16199551, ECO:0000269|PubMed:17661819,
CC ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542,
CC ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419,
CC ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853,
CC ECO:0000269|PubMed:20622854}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the JHDM1 histone demethylase family. JHDM1D
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83063.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB13877.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAI45929.1; Type=Erroneous termination; Note=Truncated C-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; AB029034; BAA83063.1; ALT_INIT; mRNA.
DR EMBL; CR933612; CAI45929.1; ALT_SEQ; mRNA.
DR EMBL; AK021696; BAB13877.1; ALT_INIT; mRNA.
DR EMBL; AK022788; BAG51116.1; -; mRNA.
DR EMBL; AK304272; BAH14147.1; -; mRNA.
DR EMBL; AL589872; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL732374; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z98051; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042108; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC053861; AAH53861.1; -; mRNA.
DR CCDS; CCDS14355.1; -. [Q9UPP1-2]
DR CCDS; CCDS55418.1; -. [Q9UPP1-4]
DR CCDS; CCDS55419.1; -. [Q9UPP1-5]
DR CCDS; CCDS55420.1; -. [Q9UPP1-1]
DR RefSeq; NP_001171825.1; NM_001184896.1. [Q9UPP1-1]
DR RefSeq; NP_001171826.1; NM_001184897.1. [Q9UPP1-4]
DR RefSeq; NP_055922.1; NM_015107.2. [Q9UPP1-2]
DR RefSeq; XP_016884851.1; XM_017029362.1. [Q9UPP1-2]
DR PDB; 2WWU; X-ray; 2.15 A; A=115-483.
DR PDB; 3K3N; X-ray; 2.40 A; A=122-483.
DR PDB; 3K3O; X-ray; 2.10 A; A=122-483.
DR PDB; 3KV4; X-ray; 2.19 A; A=37-483.
DR PDB; 4DO0; X-ray; 2.55 A; A=115-483.
DR PDB; 7CMZ; X-ray; 1.70 A; B=842-863.
DR PDBsum; 2WWU; -.
DR PDBsum; 3K3N; -.
DR PDBsum; 3K3O; -.
DR PDBsum; 3KV4; -.
DR PDBsum; 4DO0; -.
DR PDBsum; 7CMZ; -.
DR AlphaFoldDB; Q9UPP1; -.
DR SMR; Q9UPP1; -.
DR BioGRID; 116751; 159.
DR DIP; DIP-38913N; -.
DR IntAct; Q9UPP1; 51.
DR MINT; Q9UPP1; -.
DR STRING; 9606.ENSP00000350676; -.
DR BindingDB; Q9UPP1; -.
DR ChEMBL; CHEMBL1938212; -.
DR GuidetoPHARMACOLOGY; 2698; -.
DR GlyGen; Q9UPP1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UPP1; -.
DR PhosphoSitePlus; Q9UPP1; -.
DR SwissPalm; Q9UPP1; -.
DR BioMuta; PHF8; -.
DR DMDM; 73620986; -.
DR EPD; Q9UPP1; -.
DR jPOST; Q9UPP1; -.
DR MassIVE; Q9UPP1; -.
DR MaxQB; Q9UPP1; -.
DR PaxDb; Q9UPP1; -.
DR PeptideAtlas; Q9UPP1; -.
DR PRIDE; Q9UPP1; -.
DR ProteomicsDB; 85394; -. [Q9UPP1-1]
DR ProteomicsDB; 85395; -. [Q9UPP1-2]
DR ProteomicsDB; 85396; -. [Q9UPP1-3]
DR ProteomicsDB; 85397; -. [Q9UPP1-4]
DR ABCD; Q9UPP1; 1 sequenced antibody.
DR Antibodypedia; 26685; 130 antibodies from 25 providers.
DR DNASU; 23133; -.
DR Ensembl; ENST00000322659.12; ENSP00000319473.8; ENSG00000172943.21. [Q9UPP1-5]
DR Ensembl; ENST00000338154.11; ENSP00000338868.6; ENSG00000172943.21. [Q9UPP1-2]
DR Ensembl; ENST00000357988.9; ENSP00000350676.5; ENSG00000172943.21. [Q9UPP1-1]
DR GeneID; 23133; -.
DR KEGG; hsa:23133; -.
DR MANE-Select; ENST00000338154.11; ENSP00000338868.6; NM_015107.3; NP_055922.1. [Q9UPP1-2]
DR UCSC; uc004dst.4; human. [Q9UPP1-1]
DR CTD; 23133; -.
DR DisGeNET; 23133; -.
DR GeneCards; PHF8; -.
DR HGNC; HGNC:20672; PHF8.
DR HPA; ENSG00000172943; Tissue enhanced (epididymis).
DR MalaCards; PHF8; -.
DR MIM; 300263; phenotype.
DR MIM; 300560; gene.
DR neXtProt; NX_Q9UPP1; -.
DR OpenTargets; ENSG00000172943; -.
DR Orphanet; 85287; X-linked intellectual disability, Siderius type.
DR PharmGKB; PA134889361; -.
DR VEuPathDB; HostDB:ENSG00000172943; -.
DR eggNOG; KOG1633; Eukaryota.
DR GeneTree; ENSGT00940000157847; -.
DR HOGENOM; CLU_003540_2_0_1; -.
DR InParanoid; Q9UPP1; -.
DR OMA; DIFHQNI; -.
DR OrthoDB; 1384737at2759; -.
DR PhylomeDB; Q9UPP1; -.
DR TreeFam; TF106480; -.
DR BioCyc; MetaCyc:ENSG00000172943-MON; -.
DR BRENDA; 1.14.11.65; 2681.
DR BRENDA; 1.14.18.B1; 2681.
DR PathwayCommons; Q9UPP1; -.
DR Reactome; R-HSA-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-HSA-3214842; HDMs demethylate histones.
DR SignaLink; Q9UPP1; -.
DR BioGRID-ORCS; 23133; 23 hits in 722 CRISPR screens.
DR ChiTaRS; PHF8; human.
DR EvolutionaryTrace; Q9UPP1; -.
DR GeneWiki; PHF8; -.
DR GenomeRNAi; 23133; -.
DR Pharos; Q9UPP1; Tchem.
DR PRO; PR:Q9UPP1; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9UPP1; protein.
DR Bgee; ENSG00000172943; Expressed in right testis and 164 other tissues.
DR ExpressionAtlas; Q9UPP1; baseline and differential.
DR Genevisible; Q9UPP1; HS.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; IDA:UniProtKB.
DR GO; GO:0140680; F:histone H3-di/monomethyl-lysine-36 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0140683; F:histone H3-di/monomethyl-lysine-9 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0051864; F:histone H3-methyl-lysine-36 demethylase activity; IDA:UniProtKB.
DR GO; GO:0032454; F:histone H3-methyl-lysine-9 demethylase activity; IDA:UniProtKB.
DR GO; GO:0071558; F:histone H3-tri/di-methyl-lysine-27 demethylase activity; IDA:UniProtKB.
DR GO; GO:0035575; F:histone H4-methyl-lysine-20 demethylase activity; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0071557; P:histone H3-K27 demethylation; IDA:UniProtKB.
DR GO; GO:0070544; P:histone H3-K36 demethylation; IDA:UniProtKB.
DR GO; GO:0033169; P:histone H3-K9 demethylation; IDA:UniProtKB.
DR GO; GO:0035574; P:histone H4-K20 demethylation; IDA:UniProtKB.
DR GO; GO:0061188; P:negative regulation of ribosomal DNA heterochromatin assembly; IDA:UniProtKB.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006482; P:protein demethylation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR041070; JHD.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR Pfam; PF17811; JHD; 1.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF00628; PHD; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00249; PHD; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Cell cycle;
KW Chromatin regulator; Dioxygenase; Disease variant; Intellectual disability;
KW Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..1060
FT /note="Histone lysine demethylase PHF8"
FT /id="PRO_0000059295"
FT DOMAIN 231..387
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 41..92
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 100..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..115
FT /note="Linker"
FT REGION 508..534
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 768..840
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 852..902
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 915..1046
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..523
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 768..810
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 858..878
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 943..966
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 998..1032
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 280
FT /ligand="substrate"
FT BINDING 283
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266"
FT BINDING 285
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266"
FT BINDING 300
FT /ligand="substrate"
FT BINDING 355
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266"
FT MOD_RES 69
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:20622854"
FT MOD_RES 120
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:20622854,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 704
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q80TJ7"
FT MOD_RES 705
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 706
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 722
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 804
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 826
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TJ7"
FT MOD_RES 834
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TJ7"
FT MOD_RES 854
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT MOD_RES 857
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 880
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..36
FT /note="Missing (in isoform 2, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005"
FT /id="VSP_014964"
FT VAR_SEQ 478..578
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014965"
FT VAR_SEQ 717..746
FT /note="KLGNGSGAGGILDLLKASRQVGGPDYAALT -> YQTATPAPAQGAS (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054019"
FT VAR_SEQ 920..931
FT /note="ELQKAQKKKYIK -> VKKMKLSLTDSG (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054020"
FT VAR_SEQ 932..1060
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054021"
FT VAR_SEQ 1060
FT /note="L -> LRQVIVQAECRQAIHEPKLKRRDAHP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043640"
FT VARIANT 315
FT /note="F -> S (in MRXSSD; abolishes histone
FT methyltransferase activity; dbSNP:rs121918524)"
FT /evidence="ECO:0000269|PubMed:17661819,
FT ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542,
FT ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419,
FT ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853,
FT ECO:0000269|PubMed:20622854"
FT /id="VAR_062250"
FT VARIANT 969
FT /note="Missing (found in patients with autism spectrum
FT disorders; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23092983"
FT /id="VAR_076254"
FT MUTAGEN 43
FT /note="Y->A: Abolishes binding to H3K4me3; when associated
FT with A-50."
FT /evidence="ECO:0000269|PubMed:20208542,
FT ECO:0000269|PubMed:20622853"
FT MUTAGEN 50
FT /note="Y->A: Abolishes binding to H3K4me3; when associated
FT with A-43. Abolishes binding to H3K4me3; when associated
FT with A-65."
FT /evidence="ECO:0000269|PubMed:20622853"
FT MUTAGEN 65
FT /note="W->A: Abolishes binding to H3K4me3; when associated
FT with A-50."
FT /evidence="ECO:0000269|PubMed:20622853"
FT MUTAGEN 69
FT /note="S->A: Impairs phosphorylation by CDK1 and
FT dissociation from chromatin when cells enter mitosis; when
FT associated with A-120."
FT /evidence="ECO:0000269|PubMed:20622854"
FT MUTAGEN 120
FT /note="S->A: Impairs phosphorylation by CDK1 and
FT dissociation from chromatin when cells enter mitosis; when
FT associated with A-69."
FT /evidence="ECO:0000269|PubMed:20622854"
FT MUTAGEN 283..285
FT /note="HID->AAA: Abolishes histone methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:20208542"
FT MUTAGEN 283
FT /note="H->A: Abolishes histone methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20346720,
FT ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20622854"
FT CONFLICT 232
FT /note="S -> P (in Ref. 2; BAB13877)"
FT /evidence="ECO:0000305"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:3KV4"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:3KV4"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:3KV4"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3KV4"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:3KV4"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:3KV4"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:3KV4"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:3KV4"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:2WWU"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:3K3O"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 149..155
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 161..165
FT /evidence="ECO:0007829|PDB:3K3O"
FT TURN 167..170
FT /evidence="ECO:0007829|PDB:4DO0"
FT HELIX 180..187
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:3K3O"
FT TURN 198..201
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 208..215
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 224..230
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 235..238
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 244..249
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 251..255
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 270..274
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 290..305
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 309..319
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:3K3N"
FT STRAND 337..342
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 354..370
FT /evidence="ECO:0007829|PDB:3K3O"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:3K3N"
FT HELIX 376..389
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:3KV4"
FT HELIX 400..420
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 427..444
FT /evidence="ECO:0007829|PDB:3K3O"
FT TURN 446..448
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 449..451
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 462..477
FT /evidence="ECO:0007829|PDB:3K3O"
FT HELIX 844..847
FT /evidence="ECO:0007829|PDB:7CMZ"
SQ SEQUENCE 1060 AA; 117864 MW; 04C83D7C5E9E56B8 CRC64;
MNRSRAIVQR GRVLPPPAPL DTTNLAGRRT LQGRAKMASV PVYCLCRLPY DVTRFMIECD
MCQDWFHGSC VGVEEEKAAD IDLYHCPNCE VLHGPSIMKK RRGSSKGHDT HKGKPVKTGS
PTFVRELRSR TFDSSDEVIL KPTGNQLTVE FLEENSFSVP ILVLKKDGLG MTLPSPSFTV
RDVEHYVGSD KEIDVIDVTR QADCKMKLGD FVKYYYSGKR EKVLNVISLE FSDTRLSNLV
ETPKIVRKLS WVENLWPEEC VFERPNVQKY CLMSVRDSYT DFHIDFGGTS VWYHVLKGEK
IFYLIRPTNA NLTLFECWSS SSNQNEMFFG DQVDKCYKCS VKQGQTLFIP TGWIHAVLTP
VDCLAFGGNF LHSLNIEMQL KAYEIEKRLS TADLFRFPNF ETICWYVGKH ILDIFRGLRE
NRRHPASYLV HGGKALNLAF RAWTRKEALP DHEDEIPETV RTVQLIKDLA REIRLVEDIF
QQNVGKTSNI FGLQRIFPAG SIPLTRPAHS TSVSMSRLSL PSKNGSKKKG LKPKELFKKA
ERKGKESSAL GPAGQLSYNL MDTYSHQALK TGSFQKAKFN ITGACLNDSD DDSPDLDLDG
NESPLALLMS NGSTKRVKSL SKSRRTKIAK KVDKARLMAE QVMEDEFDLD SDDELQIDER
LGKEKATLII RPKFPRKLPR AKPCSDPNRV REPGEVEFDI EEDYTTDEDM VEGVEGKLGN
GSGAGGILDL LKASRQVGGP DYAALTEAPA SPSTQEAIQG MLCMANLQSS SSSPATSSLQ
AWWTGGQDRS SGSSSSGLGT VSNSPASQRT PGKRPIKRPA YWRTESEEEE ENASLDEQDS
LGACFKDAEY IYPSLESDDD DPALKSRPKK KKNSDDAPWS PKARVTPTLP KQDRPVREGT
RVASIETGLA AAAAKLAQQE LQKAQKKKYI KKKPLLKEVE QPRPQDSNLS LTVPAPTVAA
TPQLVTSSSP LPPPEPKQEA LSGSLADHEY TARPNAFGMA QANRSTTPMA PGVFLTQRRP
SVGSQSNQAG QGKRPKKGLA TAKQRLGRIL KIHRNGKLLL
