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 27-MAR-2024, entry version 188. 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 FUNCTION, CHARCTERIZATION OF VARIANT MRXSSD SER-315, AND MUTAGENESIS OF RP ARG-943. RX PubMed=31691806; DOI=10.1093/hmg/ddz254; RA Poeta L., Padula A., Attianese B., Valentino M., Verrillo L., Filosa S., RA Shoubridge C., Barra A., Schwartz C.E., Christensen J., van Bokhoven H., RA Helin K., Lioi M.B., Collombat P., Gecz J., Altucci L., Di Schiavi E., RA Miano M.G.; RT "Histone demethylase KDM5C is a SAHA-sensitive central hub at the RT crossroads of transcriptional axes involved in multiple neurodevelopmental RT disorders."; RL Hum. Mol. Genet. 28:4089-4102(2019). RN [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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. Positively modulates transcription of histone demethylase CC KDM5C, acting synergistically with transcription factor ARX; synergy CC may be related to enrichment of histone H3K4me3 in regulatory elements. CC {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 ECO:0000269|PubMed:31691806}. 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; Q9Y462: ZNF711; NbExp=7; IntAct=EBI-1560800, EBI-2849152; 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, ECO:0000269|PubMed:31691806}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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; 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. 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; 173. 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; 9606-ENSP00000350676; -. DR PeptideAtlas; Q9UPP1; -. DR ProteomicsDB; 85394; -. [Q9UPP1-1] DR ProteomicsDB; 85395; -. [Q9UPP1-2] DR ProteomicsDB; 85396; -. [Q9UPP1-3] DR ProteomicsDB; 85397; -. [Q9UPP1-4] DR Pumba; Q9UPP1; -. DR ABCD; Q9UPP1; 1 sequenced antibody. DR Antibodypedia; 26685; 174 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 AGR; HGNC:20672; -. DR CTD; 23133; -. DR DisGeNET; 23133; -. DR GeneCards; PHF8; -. DR HGNC; HGNC:20672; PHF8. DR HPA; ENSG00000172943; Low tissue specificity. 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; 2784357at2759; -. DR PhylomeDB; Q9UPP1; -. DR TreeFam; TF106480; -. DR BioCyc; MetaCyc:ENSG00000172943-MONOMER; -. 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 SABIO-RK; Q9UPP1; -. DR SignaLink; Q9UPP1; -. DR SIGNOR; Q9UPP1; -. DR BioGRID-ORCS; 23133; 27 hits in 797 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 166 other cell types or tissues. DR ExpressionAtlas; Q9UPP1; baseline and differential. 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:0071558; F:histone H3K27me2/H3K27me3 demethylase activity; IDA:UniProtKB. DR GO; GO:0051864; F:histone H3K36 demethylase activity; IDA:UniProtKB. DR GO; GO:0140680; F:histone H3K36me/H3K36me2 demethylase activity; IEA:UniProtKB-EC. DR GO; GO:0032454; F:histone H3K9 demethylase activity; IDA:UniProtKB. DR GO; GO:0140683; F:histone H3K9me/H3K9me2 demethylase activity; IEA:UniProtKB-EC. DR GO; GO:0035575; F:histone H4K20 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:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0061188; P:negative regulation of rDNA heterochromatin formation; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd15642; PHD_PHF8; 1. DR Gene3D; 1.20.58.1360; -; 1. DR Gene3D; 2.60.120.650; Cupin; 1. 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 PANTHER; PTHR23123:SF11; HISTONE LYSINE DEMETHYLASE PHF8; 1. DR PANTHER; PTHR23123; PHD/F-BOX CONTAINING PROTEIN; 1. 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; SSF51197; Clavaminate synthase-like; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR PROSITE; PS51184; JMJC; 1. DR PROSITE; PS01359; ZF_PHD_1; 1. DR PROSITE; PS50016; ZF_PHD_2; 1. DR Genevisible; Q9UPP1; HS. 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; reduces transcriptional FT activation 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, ECO:0000269|PubMed:31691806" FT /id="VAR_062250" FT VARIANT 969 FT /note="Missing (found in patients with autism spectrum FT disorders; uncertain 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 MUTAGEN 943 FT /note="R->H: Reduces transcriptional activation activity." FT /evidence="ECO:0000269|PubMed:31691806" 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 //