ID KDM5A_HUMAN Reviewed; 1690 AA. AC P29375; A8MV76; Q4LE72; Q86XZ1; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 02-SEP-2026, entry version 228. DE RecName: Full=Lysine-specific demethylase 5A; DE EC=1.14.11.67 {ECO:0000305|PubMed:17320160, ECO:0000305|PubMed:17320161, ECO:0000305|PubMed:17320163}; DE AltName: Full=Histone demethylase JARID1A; DE AltName: Full=Jumonji/ARID domain-containing protein 1A; DE AltName: Full=Retinoblastoma-binding protein 2; DE Short=RBBP-2; DE AltName: Full=[histone H3]-trimethyl-L-lysine(4) demethylase 5A {ECO:0000305}; GN Name=KDM5A {ECO:0000312|HGNC:HGNC:9886}; GN Synonyms=JARID1A, RBBP2, RBP2 {ECO:0000303|PubMed:18270511}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH RB1. RX PubMed=8414517; RA Fattaey A.R., Helin K., Dembski M.S., Dyson N., Harlow E., Vuocolo G.A., RA Hanobik M.G., Haskell K.M., Oliff A., Defeo-Jones D., Jones R.E.; RT "Characterization of the retinoblastoma binding proteins RBP1 and RBP2."; RL Oncogene 8:3149-3156(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., RA Okazaki N., Koga H., Nagase T., Ohara O.; RT "Preparation of a set of expression-ready clones of mammalian long cDNAs RT encoding large proteins by the ORF trap cloning method."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1099 (ISOFORMS 1/2). RC TISSUE=Eye, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1102-1564. RX PubMed=1857421; DOI=10.1038/352251a0; RA Defeo-Jones D., Huang P.S., Jones R.E., Haskell K.M., Vuocolo G.A., RA Hanobik M.G., Huber H.E., Oliff A.; RT "Cloning of cDNAs for cellular proteins that bind to the retinoblastoma RT gene product."; RL Nature 352:251-254(1991). RN [6] RP INTERACTION WITH RB1, AND SUBCELLULAR LOCATION. RX PubMed=7935440; DOI=10.1128/mcb.14.11.7256-7264.1994; RA Kim Y.W., Otterson G.A., Kratzke R.A., Coxon A.B., Kaye F.J.; RT "Differential specificity for binding of retinoblastoma binding protein 2 RT to RB, p107, and TATA-binding protein."; RL Mol. Cell. Biol. 14:7256-7264(1994). RN [7] RP INTERACTION WITH LMO2. RX PubMed=9129143; DOI=10.1038/sj.onc.1200988; RA Mao S., Neale G.A.M., Goorha R.M.; RT "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein RT 2."; RL Oncogene 14:1531-1539(1997). RN [8] RP FUNCTION, AND INTERACTION WITH ESR1. RX PubMed=11358960; DOI=10.1074/jbc.m100313200; RA Chan S.W., Hong W.; RT "Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone RT receptor-mediated transcription."; RL J. Biol. Chem. 276:28402-28412(2001). RN [9] RP SUBCELLULAR LOCATION, INTERACTION WITH RB1, AND FUNCTION. RX PubMed=15949438; DOI=10.1016/j.molcel.2005.05.012; RA Benevolenskaya E.V., Murray H.L., Branton P., Young R.A., Kaelin W.G. Jr.; RT "Binding of pRB to the PHD protein RBP2 promotes cellular RT differentiation."; RL Mol. Cell 18:623-635(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1603, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [11] RP FUNCTION. RX PubMed=17320163; DOI=10.1016/j.cell.2007.02.013; RA Klose R.J., Yan Q., Tothova Z., Yamane K., Erdjument-Bromage H., Tempst P., RA Gilliland D.G., Zhang Y., Kaelin W.G. Jr.; RT "The retinoblastoma binding protein RBP2 is an H3K4 demethylase."; RL Cell 128:889-900(2007). RN [12] RP FUNCTION. RX PubMed=17320161; DOI=10.1016/j.cell.2007.02.003; RA Christensen J., Agger K., Cloos P.A.C., Pasini D., Rose S., Sennels L., RA Rappsilber J., Hansen K.H., Salcini A.E., Helin K.; RT "RBP2 belongs to a family of demethylases, specific for tri-and RT dimethylated lysine 4 on histone 3."; RL Cell 128:1063-1076(2007). RN [13] RP FUNCTION. RX PubMed=17320160; DOI=10.1016/j.cell.2007.02.017; RA Iwase S., Lan F., Bayliss P., de la Torre-Ubieta L., Huarte M., Qi H.H., RA Whetstine J.R., Bonni A., Roberts T.M., Shi Y.; RT "The X-linked mental retardation gene SMCX/JARID1C defines a family of RT histone H3 lysine 4 demethylases."; RL Cell 128:1077-1088(2007). RN [14] RP INTERACTION WITH MYC AND MYCN. RX PubMed=17311883; DOI=10.1101/gad.1523007; RA Secombe J., Li L., Carlos L., Eisenman R.N.; RT "The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase RT required for dMyc-induced cell growth."; RL Genes Dev. 21:537-551(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111 AND SER-1331, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111, AND IDENTIFICATION BY RP 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 [18] RP INTERACTION WITH BMAL1 AND CLOCK. RX PubMed=21960634; DOI=10.1126/science.1206022; RA DiTacchio L., Le H.D., Vollmers C., Hatori M., Witcher M., Secombe J., RA Panda S.; RT "Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences RT the circadian clock."; RL Science 333:1881-1885(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204; SER-1330; SER-1438; RP SER-1488 AND SER-1666, 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1111, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-191 AND LYS-1007, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [22] RP STRUCTURE BY NMR OF 85-175, FUNCTION, DOMAIN, DNA-BINDING, AND MUTAGENESIS RP OF ARG-112; LYS-152; SER-156 AND LEU-157. RX PubMed=18270511; DOI=10.1038/nsmb.1400; RA Tu S., Teng Y.C., Yuan C., Wu Y.T., Chan M.Y., Cheng A.N., Lin P.H., RA Juan L.J., Tsai M.D.; RT "The ARID domain of the H3K4 demethylase RBP2 binds to a DNA CCGCCC RT motif."; RL Nat. Struct. Mol. Biol. 15:419-421(2008). RN [23] RP STRUCTURE BY NMR OF 1609-1659 IN COMPLEX WITH ZINC AND HISTONE H3, RP STRUCTURE BY X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1609-1659 IN COMPLEX RP WITH ZINC AND HISTONE H3, FUNCTION, INTERACTION WITH HISTONE H3, RP MUTAGENESIS OF VAL-1609; TRP-1625 AND 1634-GLU-TRP-1635, AND DOMAIN. RX PubMed=19430464; DOI=10.1038/nature08036; RA Wang G.G., Song J., Wang Z., Dormann H.L., Casadio F., Li H., Luo J.L., RA Patel D.J., Allis C.D.; RT "Haematopoietic malignancies caused by dysregulation of a chromatin-binding RT PHD finger."; RL Nature 459:847-851(2009). RN [24] RP X-RAY CRYSTALLOGRAPHY (3.18 ANGSTROMS) OF 12-797 IN COMPLEX WITH ZINC AND RP NICKEL. RX PubMed=27499454; DOI=10.1016/j.bmcl.2016.07.070; RA Labadie S.S., Dragovich P.S., Cummings R.T., Deshmukh G., Gustafson A., RA Han N., Harmange J.C., Kiefer J.R., Li Y., Liang J., Liederer B.M., Liu Y., RA Manieri W., Mao W., Murray L., Ortwine D.F., Trojer P., VanderPorten E., RA Vinogradova M., Wen L.; RT "Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors."; RL Bioorg. Med. Chem. Lett. 26:4492-4496(2016). RN [25] RP X-RAY CRYSTALLOGRAPHY (1.39 ANGSTROMS) OF 1-87 AND 348-588 IN COMPLEX WITH RP INHIBITORS; MANGANESE AND 2-OXOGLUTARATE, BIOPHYSICOCHEMICAL PROPERTIES, RP FUNCTION, AND MUTAGENESIS OF CYS-626 AND CYS-636. RX PubMed=27427228; DOI=10.1016/j.chembiol.2016.06.006; RA Horton J.R., Liu X., Gale M., Wu L., Shanks J.R., Zhang X., Webber P.J., RA Bell J.S., Kales S.C., Mott B.T., Rai G., Jansen D.J., Henderson M.J., RA Urban D.J., Hall M.D., Simeonov A., Maloney D.J., Johns M.A., Fu H., RA Jadhav A., Vertino P.M., Yan Q., Cheng X.; RT "Structural Basis for KDM5A Histone Lysine Demethylase Inhibition by RT Diverse Compounds."; RL Cell Chem. Biol. 23:769-781(2016). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1-87 AND 348-588 IN COMPLEX WITH RP MANGANESE AND 2-OXOGLUTARATE. RX PubMed=26645689; DOI=10.1074/jbc.m115.698449; RA Horton J.R., Engstrom A., Zoeller E.L., Liu X., Shanks J.R., Zhang X., RA Johns M.A., Vertino P.M., Fu H., Cheng X.; RT "Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of RT Histone H3 Lysine 4 Demethylases."; RL J. Biol. Chem. 291:2631-2646(2016). RN [27] RP X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) OF 12-797 IN COMPLEX WITH AN RP INHIBITOR ZINC AND NICKEL, AND ACTIVITY REGULATION. RX PubMed=27214401; DOI=10.1038/nchembio.2085; RA Vinogradova M., Gehling V.S., Gustafson A., Arora S., Tindell C.A., RA Wilson C., Williamson K.E., Guler G.D., Gangurde P., Manieri W., Busby J., RA Flynn E.M., Lan F., Kim H.J., Odate S., Cochran A.G., Liu Y., RA Wongchenko M., Yang Y., Cheung T.K., Maile T.M., Lau T., Costa M., RA Hegde G.V., Jackson E., Pitti R., Arnott D., Bailey C., Bellon S., RA Cummings R.T., Albrecht B.K., Harmange J.C., Kiefer J.R., Trojer P., RA Classon M.; RT "An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer RT cells."; RL Nat. Chem. Biol. 12:531-538(2016). RN [28] RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98. RX PubMed=16419055; DOI=10.1002/gcc.20308; RA van Zutven L.J., Onen E., Velthuizen S.C., van Drunen E., von Bergh A.R., RA van den Heuvel-Eibrink M.M., Veronese A., Mecucci C., Negrini M., RA de Greef G.E., Beverloo H.B.; RT "Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) RT as a new partner gene."; RL Genes Chromosomes Cancer 45:437-446(2006). RN [29] RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH NUP98. RX PubMed=23531517; DOI=10.1038/leu.2013.87; RA de Rooij J.D., Hollink I.H., Arentsen-Peters S.T., van Galen J.F., RA Berna Beverloo H., Baruchel A., Trka J., Reinhardt D., Sonneveld E., RA Zimmermann M., Alonzo T.A., Pieters R., Meshinchi S., RA van den Heuvel-Eibrink M.M., Zwaan C.M.; RT "NUP98/JARID1A is a novel recurrent abnormality in pediatric acute RT megakaryoblastic leukemia with a distinct HOX gene expression pattern."; RL Leukemia 27:2280-2288(2013). RN [30] RP INVOLVEMENT IN NEDEHC, VARIANT NEDEHC VAL-477, AND VARIANTS RP 1350-ARG--SER-1690 DEL AND LEU-1428. RX PubMed=33350388; DOI=10.7554/elife.56883; RA El Hayek L., Tuncay I.O., Nijem N., Russell J., Ludwig S., Kaur K., Li X., RA Anderton P., Tang M., Gerard A., Heinze A., Zacher P., Alsaif H.S., Rad A., RA Hassanpour K., Abbaszadegan M.R., Washington C., DuPont B.R., Louie R.J., RA Couse M., Faden M., Rogers R.C., Abou Jamra R., Elias E.R., Maroofian R., RA Houlden H., Lehman A., Beutler B., Chahrour M.H.; RT "KDM5A mutations identified in autism spectrum disorder using forward RT genetics."; RL Elife 9:0-0(2020). CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-4' of CC histone H3, thereby playing a central role in histone code. Does not CC demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' CC or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not CC monomethylated H3 'Lys-4'. Regulates specific gene transcription CC through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May CC stimulate transcription mediated by nuclear receptors. Involved in CC transcriptional regulation of Hox proteins during cell differentiation CC (PubMed:19430464). May participate in transcriptional repression of CC cytokines such as CXCL12. Plays a role in the regulation of the CC circadian rhythm and in maintaining the normal periodicity of the CC circadian clock. In a histone demethylase-independent manner, acts as a CC coactivator of the CLOCK-BMAL1-mediated transcriptional activation of CC PER1/2 and other clock-controlled genes and increases histone CC acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By CC similarity). Seems to act as a transcriptional corepressor for some CC genes such as MT1F and to favor the proliferation of cancer cells CC (PubMed:27427228). {ECO:0000250|UniProtKB:Q3UXZ9, CC ECO:0000269|PubMed:11358960, ECO:0000269|PubMed:15949438, CC ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17320161, CC ECO:0000269|PubMed:17320163, ECO:0000269|PubMed:18270511, CC ECO:0000269|PubMed:19430464, ECO:0000269|PubMed:27427228}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 2- CC oxoglutarate + 3 O2 = L-lysyl(4)-[histone H3] + 3 formaldehyde + 3 CC succinate + 3 CO2; Xref=Rhea:RHEA:60208, Rhea:RHEA-COMP:15537, CC Rhea:RHEA-COMP:15547, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61961; EC=1.14.11.67; CC Evidence={ECO:0000305|PubMed:17320160, ECO:0000305|PubMed:17320161, CC ECO:0000305|PubMed:17320163}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250}; CC -!- ACTIVITY REGULATION: The inhibitors KDOAM-25, CPI-455 and others CC inhibits its demethylase activity, resulting to cell growth arrest in CC cancer cells. {ECO:0000269|PubMed:27214401, CC ECO:0000269|PubMed:27427228}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=9 uM for 2-oxoglutarate {ECO:0000269|PubMed:27427228}; CC KM=2.9 uM for histone H3K4me3 {ECO:0000269|PubMed:27427228}; CC Note=kcat is 2.1 min(-1) and 1.9 min(-1) for 2-oxoglutarate and CC histone H3K4me3, respectively. {ECO:0000269|PubMed:27427228}; CC -!- SUBUNIT: Interacts with SUZ12; the interaction is direct (By CC similarity). Interacts with the viral protein-binding domain of RB1. CC Interacts with ESR1, MYC, MYCN and LMO2. Interacts with HDAC1; this CC interaction impairs histone deacetylation by HDAC1 (By similarity). CC Interacts with BMAL1 and CLOCK. Interacts (via PHD-type 1 zinc finger) CC with histone H3 unmodified at 'Lys-4' and (via PHD-type 3 zinc finger) CC with histone H3 di- and trimethylated at 'Lys-4' (PubMed:19430464). CC Interacts with FBXO39 (By similarity). {ECO:0000250|UniProtKB:Q3UXZ9, CC ECO:0000269|PubMed:11358960, ECO:0000269|PubMed:15949438, CC ECO:0000269|PubMed:17311883, ECO:0000269|PubMed:19430464, CC ECO:0000269|PubMed:21960634, ECO:0000269|PubMed:7935440, CC ECO:0000269|PubMed:8414517, ECO:0000269|PubMed:9129143}. CC -!- INTERACTION: CC P29375; P06400: RB1; NbExp=2; IntAct=EBI-1560836, EBI-491274; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:15949438, CC ECO:0000269|PubMed:7935440}. Nucleus {ECO:0000250|UniProtKB:Q3UXZ9}. CC Note=Occupies promoters of genes involved in RNA metabolism and CC mitochondrial function. {ECO:0000250|UniProtKB:Q3UXZ9}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P29375-1; Sequence=Displayed; CC Name=2; CC IsoId=P29375-2; Sequence=VSP_035746; CC -!- DOMAIN: The GSGFP motif is required for the interaction with SUZ12 (By CC similarity). The ARID domain specifically binds to the CCGCCC motif and CC is required for the lysine-specific histone demethylase activity CC (PubMed:18270511). The PHD-type 3 zinc finger is required for the CC interaction with histone H3 di- and trimethylated at 'Lys-4' CC (PubMed:19430464). {ECO:0000250|UniProtKB:Q3UXZ9, CC ECO:0000269|PubMed:18270511, ECO:0000269|PubMed:19430464}. CC -!- PTM: Ubiquitinated by the SCF(FBXO39) complex; leading to proteasomal CC degradation. {ECO:0000250|UniProtKB:Q3UXZ9}. CC -!- DISEASE: Note=A chromosomal aberration involving KDM5A has been found CC in M5 type acute myeloid leukemia. Translocation t(11;12)(p15;p13) with CC NUP98. {ECO:0000269|PubMed:23531517}. CC -!- DISEASE: Note=Chromosomal aberrations involving KDM5A have been found CC in M7 type childhood acute myeloid leukemia. Translocation CC t(11;12)(p15;p13) with NUP98. {ECO:0000269|PubMed:16419055, CC ECO:0000269|PubMed:23531517}. CC -!- DISEASE: El Hayek-Chahrour neurodevelopmental syndrome (NEDEHC) CC [MIM:620820]: An autosomal recessive neurodevelopmental disorder CC characterized by lack of speech, intellectual disability, autism, and CC developmental delay. {ECO:0000269|PubMed:33350388}. Note=The disease CC may be caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the JARID1 histone demethylase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB28544.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAE06081.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41033/JARID1A"; 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; S66431; AAB28544.1; ALT_FRAME; mRNA. DR EMBL; AB209999; BAE06081.1; ALT_INIT; mRNA. DR EMBL; AC005844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC007406; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC048307; AAH48307.1; ALT_TERM; mRNA. DR EMBL; BC053893; AAH53893.1; ALT_TERM; mRNA. DR EMBL; BC110916; AAI10917.1; ALT_TERM; mRNA. DR CCDS; CCDS41736.1; -. [P29375-1] DR PIR; I78879; I78879. DR RefSeq; NP_001036068.1; NM_001042603.3. [P29375-1] DR PDB; 2JXJ; NMR; -; A=85-175. DR PDB; 2KGG; NMR; -; A=1609-1659. DR PDB; 2KGI; NMR; -; A=1609-1659. DR PDB; 3GL6; X-ray; 1.90 A; A=1609-1659. DR PDB; 5C11; X-ray; 2.80 A; A=1609-1659. DR PDB; 5CEH; X-ray; 3.14 A; A=12-797. DR PDB; 5E6H; X-ray; 2.24 A; A=1-588. DR PDB; 5ISL; X-ray; 1.69 A; A=1-588. DR PDB; 5IVB; X-ray; 1.39 A; A=1-588. DR PDB; 5IVC; X-ray; 1.57 A; A=1-588. DR PDB; 5IVE; X-ray; 1.78 A; A=1-588. DR PDB; 5IVF; X-ray; 1.68 A; A=1-588. DR PDB; 5IVJ; X-ray; 1.57 A; A=1-588. DR PDB; 5IVV; X-ray; 1.85 A; A=1-588. DR PDB; 5IVY; X-ray; 1.45 A; A=1-588. DR PDB; 5IW0; X-ray; 1.63 A; A=1-588. DR PDB; 5IWF; X-ray; 2.29 A; A=1-588. DR PDB; 5K4L; X-ray; 3.18 A; A/B=12-797. DR PDB; 5V9P; X-ray; 3.00 A; A=12-797. DR PDB; 5V9T; X-ray; 3.05 A; A/B=12-797. DR PDB; 6BGU; X-ray; 1.68 A; A=1-588. DR PDB; 6BGV; X-ray; 1.59 A; A=1-588. DR PDB; 6BGW; X-ray; 1.64 A; A=1-588. DR PDB; 6BGX; X-ray; 1.88 A; A=1-588. DR PDB; 6BGY; X-ray; 1.22 A; A=1-588. DR PDB; 6BGZ; X-ray; 1.69 A; A=1-588. DR PDB; 6BH0; X-ray; 1.99 A; A=1-588. DR PDB; 6BH1; X-ray; 1.93 A; A=1-588. DR PDB; 6BH2; X-ray; 1.45 A; A=1-588. DR PDB; 6BH3; X-ray; 1.70 A; A=1-588. DR PDB; 6BH4; X-ray; 2.05 A; A=1-588. DR PDB; 6BH5; X-ray; 1.65 A; A=1-588. DR PDB; 6DQ4; X-ray; 1.39 A; A=1-588. DR PDB; 6DQ5; X-ray; 1.89 A; A=1-588. DR PDB; 6DQ6; X-ray; 1.59 A; A=1-588. DR PDB; 6DQ7; X-ray; 1.85 A; A=1-588. DR PDB; 6DQ8; X-ray; 1.46 A; A=1-588. DR PDB; 6DQ9; X-ray; 1.75 A; A=1-588. DR PDB; 6DQA; X-ray; 1.89 A; A=1-588. DR PDB; 6DQB; X-ray; 1.79 A; A=1-588. DR PDB; 6DQC; X-ray; 1.75 A; A=1-588. DR PDB; 6DQD; X-ray; 1.99 A; A=1-588. DR PDB; 6DQE; X-ray; 1.69 A; A=1-588. DR PDB; 6DQF; X-ray; 1.69 A; A=1-588. DR PDB; 7KLO; NMR; -; A=287-344. DR PDB; 7KLR; NMR; -; A=287-344. DR AlphaFoldDB; P29375; -. DR BMRB; P29375; -. DR MDposit; P29375; -. DR MDRepo; P29375; -. DR SMR; P29375; -. DR BioGRID; 111862; 77. DR DIP; DIP-472N; -. DR FunCoup; P29375; 4320. DR IntAct; P29375; 48. DR MINT; P29375; -. DR NDEx; IQUERY-CP-KDM5A; 3 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000382688; -. DR BindingDB; P29375; -. DR ChEMBL; CHEMBL2424504; -. DR DrugCentral; P29375; -. DR GuidetoPHARMACOLOGY; 2680; -. DR GlyGen; P29375; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P29375; -. DR PhosphoSitePlus; P29375; -. DR SwissPalm; P29375; -. DR BioMuta; KDM5A; -. DR DMDM; 215274124; -. DR jPOST; P29375; -. DR MassIVE; P29375; -. DR PaxDb; 9606-ENSP00000382688; -. DR PeptideAtlas; P29375; -. DR ProteomicsDB; 54559; -. [P29375-1] DR ProteomicsDB; 54560; -. [P29375-2] DR Pumba; P29375; -. DR Antibodypedia; 1751; 243 antibodies from 31 providers. DR DNASU; 5927; -. DR Ensembl; ENST00000399788.7; ENSP00000382688.2; ENSG00000073614.13. [P29375-1] DR GeneID; 5927; -. DR KEGG; hsa:5927; -. DR MANE-Select; ENST00000399788.7; ENSP00000382688.2; NM_001042603.3; NP_001036068.1. DR UCSC; uc001qif.3; human. [P29375-1] DR AGR; HGNC:9886; -. DR ClinPGx; PA34250; -. DR CTD; 5927; -. DR DisGeNET; 5927; -. DR GeneCards; KDM5A; -. DR HGNC; HGNC:9886; KDM5A. DR HPA; ENSG00000073614; Tissue enhanced (bone). DR MalaCards; KDM5A; -. DR MIM; 180202; gene. DR MIM; 620820; phenotype. DR OpenTargets; ENSG00000073614; -. DR VEuPathDB; HostDB:ENSG00000073614; -. DR eggNOG; KOG1246; Eukaryota. DR GeneTree; ENSGT00940000157170; -. DR HOGENOM; CLU_000991_2_0_1; -. DR InParanoid; P29375; -. DR OMA; GFDQVCK; -. DR OrthoDB; 1678912at2759; -. DR PAN-GO; P29375; 5 GO annotations based on evolutionary models. DR PhylomeDB; P29375; -. DR BioCyc; MetaCyc:ENSG00000073614-MONOMER; -. DR BRENDA; 1.14.11.67; 2681. DR PathwayCommons; P29375; -. DR Reactome; R-HSA-3214842; HDMs demethylate histones. DR Reactome; R-HSA-9821002; Chromatin modifications during the maternal to zygotic transition (MZT). DR SignaLink; P29375; -. DR SIGNOR; P29375; -. DR Agora; ENSG00000073614; -. DR BioGRID-ORCS; 5927; 19 hits in 1206 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; KDM5A; human. DR EvolutionaryTrace; P29375; -. DR GeneWiki; JARID1A; -. DR GenomeRNAi; 5927; -. DR Pharos; P29375; Tchem. DR PRO; PR:P29375; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P29375; protein. DR Bgee; ENSG00000073614; Expressed in colonic epithelium and 206 other cell types or tissues. DR ExpressionAtlas; P29375; baseline and differential. DR GO; GO:0000785; C:chromatin; IBA:GO_Central. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:CAFA. DR GO; GO:0032993; C:protein-DNA complex; IEA:Ensembl. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; IDA:GDB. DR GO; GO:0004857; F:enzyme inhibitor activity; ISS:UniProtKB. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0032452; F:histone demethylase activity; TAS:Reactome. DR GO; GO:0034647; F:histone H3K4me/H3K4me2/H3K4me3 demethylase activity; IDA:CAFA. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:CAFA. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0140718; P:facultative heterochromatin formation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IBA:GO_Central. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IMP:UniProtKB. DR CDD; cd16873; ARID_KDM5A; 1. DR CDD; cd15602; PHD1_KDM5A; 1. DR CDD; cd15606; PHD2_KDM5A; 1. DR CDD; cd15686; PHD3_KDM5A; 1. DR DisProt; DP02224; -. DR FunFam; 3.30.40.10:FF:000023; Lysine (K)-specific demethylase 5A; 1. DR FunFam; 3.30.40.10:FF:000368; Lysine demethylase 5A; 1. DR FunFam; 3.30.40.10:FF:000613; lysine-specific demethylase 5A; 1. DR FunFam; 2.60.120.650:FF:000035; PHD transcription factor Rum1; 1. DR FunFam; 1.10.150.60:FF:000001; Putative lysine-specific demethylase 5b; 1. DR FunFam; 2.60.120.650:FF:000001; Putative lysine-specific demethylase 5b; 1. DR Gene3D; 1.10.150.60; ARID DNA-binding domain; 1. DR Gene3D; 2.60.120.650; Cupin; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR InterPro; IPR001606; ARID_dom. DR InterPro; IPR036431; ARID_dom_sf. DR InterPro; IPR003347; JmjC_dom. DR InterPro; IPR003349; JmjN. DR InterPro; IPR048615; KDM5_C-hel. DR InterPro; IPR047974; KDM5A_ARID. DR InterPro; IPR047973; KDM5A_PHD1. DR InterPro; IPR047970; KDM5A_PHD2. DR InterPro; IPR047972; KDM5A_PHD3. DR InterPro; IPR013637; Lys_sp_deMease-like_dom. DR InterPro; IPR019786; Zinc_finger_PHD-type_CS. DR InterPro; IPR004198; Znf_C5HC2. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR10694; LYSINE-SPECIFIC DEMETHYLASE; 1. DR PANTHER; PTHR10694:SF17; LYSINE-SPECIFIC DEMETHYLASE 5A; 1. DR Pfam; PF01388; ARID; 1. DR Pfam; PF02373; JmjC; 1. DR Pfam; PF02375; JmjN; 1. DR Pfam; PF21323; KDM5_C-hel; 1. DR Pfam; PF00628; PHD; 2. DR Pfam; PF08429; PLU-1; 1. DR Pfam; PF02928; zf-C5HC2; 1. DR SMART; SM01014; ARID; 1. DR SMART; SM00501; BRIGHT; 1. DR SMART; SM00558; JmjC; 1. DR SMART; SM00545; JmjN; 1. DR SMART; SM00249; PHD; 3. DR SUPFAM; SSF46774; ARID-like; 1. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 3. DR PROSITE; PS51011; ARID; 1. DR PROSITE; PS51184; JMJC; 1. DR PROSITE; PS51183; JMJN; 1. DR PROSITE; PS01359; ZF_PHD_1; 2. DR PROSITE; PS50016; ZF_PHD_2; 3. DR PDBsum; 2JXJ; -. DR PDBsum; 2KGG; -. DR PDBsum; 2KGI; -. DR PDBsum; 3GL6; -. DR PDBsum; 5C11; -. DR PDBsum; 5CEH; -. DR PDBsum; 5E6H; -. DR PDBsum; 5ISL; -. DR PDBsum; 5IVB; -. DR PDBsum; 5IVC; -. DR PDBsum; 5IVE; -. DR PDBsum; 5IVF; -. DR PDBsum; 5IVJ; -. DR PDBsum; 5IVV; -. DR PDBsum; 5IVY; -. DR PDBsum; 5IW0; -. DR PDBsum; 5IWF; -. DR PDBsum; 5K4L; -. DR PDBsum; 5V9P; -. DR PDBsum; 5V9T; -. DR PDBsum; 6BGU; -. DR PDBsum; 6BGV; -. DR PDBsum; 6BGW; -. DR PDBsum; 6BGX; -. DR PDBsum; 6BGY; -. DR PDBsum; 6BGZ; -. DR PDBsum; 6BH0; -. DR PDBsum; 6BH1; -. DR PDBsum; 6BH2; -. DR PDBsum; 6BH3; -. DR PDBsum; 6BH4; -. DR PDBsum; 6BH5; -. DR PDBsum; 6DQ4; -. DR PDBsum; 6DQ5; -. DR PDBsum; 6DQ6; -. DR PDBsum; 6DQ7; -. DR PDBsum; 6DQ8; -. DR PDBsum; 6DQ9; -. DR PDBsum; 6DQA; -. DR PDBsum; 6DQB; -. DR PDBsum; 6DQC; -. DR PDBsum; 6DQD; -. DR PDBsum; 6DQE; -. DR PDBsum; 6DQF; -. DR PDBsum; 7KLO; -. DR PDBsum; 7KLR; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Autism; KW Autism spectrum disorder; Biological rhythms; Chromatin regulator; KW Chromosomal rearrangement; Developmental protein; Dioxygenase; KW Intellectual disability; Iron; Isopeptide bond; Metal-binding; Nucleus; KW Oxidoreductase; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..1690 FT /note="Lysine-specific demethylase 5A" FT /id="PRO_0000200584" FT DOMAIN 19..60 FT /note="JmjN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537" FT DOMAIN 84..174 FT /note="ARID" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00355" FT DOMAIN 437..603 FT /note="JmjC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538" FT ZN_FING 293..343 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 676..728 FT /note="C5HC2" FT /evidence="ECO:0000269|PubMed:27214401, FT ECO:0000269|PubMed:27499454, ECO:0007744|PDB:5CEH" FT ZN_FING 1161..1218 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1607..1661 FT /note="PHD-type 3" FT /evidence="ECO:0000269|PubMed:19430464" FT REGION 1327..1348 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1407..1433 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1490..1509 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1516..1543 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1623..1690 FT /note="Interaction with LMO2" FT /evidence="ECO:0000269|PubMed:9129143" FT MOTIF 419..423 FT /note="GSGFP motif" FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9" FT COMPBIAS 1337..1348 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1490..1503 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1520..1530 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 409 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:26645689, FT ECO:0000269|PubMed:27427228" FT BINDING 483 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, FT ECO:0000305|PubMed:26645689, ECO:0000305|PubMed:27214401, FT ECO:0000305|PubMed:27427228, ECO:0000305|PubMed:27499454" FT BINDING 485 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:26645689, FT ECO:0000305|PubMed:27214401, ECO:0000305|PubMed:27427228, FT ECO:0000305|PubMed:27499454" FT BINDING 491 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:26645689, FT ECO:0000269|PubMed:27427228" FT BINDING 493 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:26645689, FT ECO:0000269|PubMed:27427228" FT BINDING 501 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:26645689, FT ECO:0000269|PubMed:27427228" FT BINDING 571 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, FT ECO:0000305|PubMed:26645689, ECO:0000305|PubMed:27214401, FT ECO:0000305|PubMed:27427228, ECO:0000305|PubMed:27499454" FT SITE 1485..1486 FT /note="Breakpoint for translocation to form the NUP98-KDM5A FT fusion protein" FT /evidence="ECO:0000269|PubMed:16419055" FT MOD_RES 204 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1111 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1330 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1331 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1343 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9" FT MOD_RES 1345 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9" FT MOD_RES 1438 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1488 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1595 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q3UXZ9" FT MOD_RES 1598 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 1603 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES 1666 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 191 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1007 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1623..1690 FT /note="VDWVQCDGGCDEWFHQVCVGVSPEMAENEDYICINCAKKQGPVSPGPAPPPS FT FIMSYKLPMEDLKETS -> GVVFVTEEERDKKY (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8414517" FT /id="VSP_035746" FT VARIANT 477 FT /note="F -> V (in NEDEHC; uncertain significance; decreased FT protein expression levels)" FT /evidence="ECO:0000269|PubMed:33350388" FT /id="VAR_089688" FT VARIANT 865 FT /note="M -> T (in dbSNP:rs11062385)" FT /id="VAR_032984" FT VARIANT 1190 FT /note="P -> A (in dbSNP:rs2229353)" FT /id="VAR_032985" FT VARIANT 1350..1690 FT /note="Missing (found in a patient with severe intellectual FT disability, developmental delay, focal epilepsy, FT tetraspastic gait, ataxia and behavioral difficulties; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:33350388" FT /id="VAR_089689" FT VARIANT 1428 FT /note="R -> L (found in a patient diagnosed with an autism FT spectrum disorder, echolalia and intellectual disability; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:33350388" FT /id="VAR_089690" FT MUTAGEN 112 FT /note="R->E: Decreases DNA-binding." FT /evidence="ECO:0000269|PubMed:18270511" FT MUTAGEN 152 FT /note="K->E: Abolishes DNA-binding." FT /evidence="ECO:0000269|PubMed:18270511" FT MUTAGEN 156 FT /note="S->D: Decreases DNA-binding." FT /evidence="ECO:0000269|PubMed:18270511" FT MUTAGEN 157 FT /note="L->E: Decreases DNA-binding." FT /evidence="ECO:0000269|PubMed:18270511" FT MUTAGEN 626 FT /note="C->S: No effect on lysine-specific histone FT demethylase activity; when associated with S-636." FT /evidence="ECO:0000269|PubMed:27427228" FT MUTAGEN 636 FT /note="C->S: No effect on lysine-specific histone FT demethylase activity; when associated with S-626." FT /evidence="ECO:0000269|PubMed:27427228" FT MUTAGEN 1609 FT /note="V->G: No effect on interaction with histone H3 FT di- and trimethylated at 'Lys-4'." FT /evidence="ECO:0000269|PubMed:19430464" FT MUTAGEN 1625 FT /note="W->A: Abolishes interaction with histone H3 di- and FT trimethylated at 'Lys-4'." FT /evidence="ECO:0000269|PubMed:19430464" FT MUTAGEN 1634..1635 FT /note="EW->AA: Abolishes interaction with histone H3 FT di- and trimethylated at 'Lys-4'." FT /evidence="ECO:0000269|PubMed:19430464" FT CONFLICT 1411 FT /note="Q -> QVFFGK (in Ref. 1; AAB28544)" FT /evidence="ECO:0000305" FT CONFLICT 1547 FT /note="E -> K (in Ref. 1; AAB28544)" FT /evidence="ECO:0000305" FT CONFLICT 1612..1614 FT /note="AQN -> EPD (in Ref. 1; AAB28544)" FT /evidence="ECO:0000305" FT HELIX 15..17 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 28..30 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 32..43 FT /evidence="ECO:0007829|PDB:6BGY" FT TURN 44..46 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 47..51 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 52..54 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:6BGY" FT TURN 65..67 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:6BGY" FT TURN 77..82 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 85..100 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 117..126 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 130..136 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 139..145 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 154..161 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 162..166 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 167..173 FT /evidence="ECO:0007829|PDB:5V9P" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 198..201 FT /evidence="ECO:0007829|PDB:5V9T" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:7KLO" FT STRAND 301..304 FT /evidence="ECO:0007829|PDB:7KLR" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:7KLO" FT TURN 312..314 FT /evidence="ECO:0007829|PDB:7KLR" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:7KLO" FT STRAND 323..326 FT /evidence="ECO:0007829|PDB:7KLR" FT HELIX 338..342 FT /evidence="ECO:0007829|PDB:7KLO" FT TURN 350..353 FT /evidence="ECO:0007829|PDB:6DQ4" FT HELIX 356..358 FT /evidence="ECO:0007829|PDB:5IVB" FT HELIX 363..378 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 382..384 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 387..399 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:5E6H" FT STRAND 406..414 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 415..418 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 426..429 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 430..432 FT /evidence="ECO:0007829|PDB:5IVE" FT HELIX 433..435 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 436..440 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 445..447 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 448..450 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 451..453 FT /evidence="ECO:0007829|PDB:5IVY" FT HELIX 455..459 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 465..468 FT /evidence="ECO:0007829|PDB:5V9T" FT STRAND 470..474 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 479..483 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 486..488 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 490..499 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 501..506 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 508..510 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 511..521 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 524..526 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 531..534 FT /evidence="ECO:0007829|PDB:6BGY" FT TURN 535..537 FT /evidence="ECO:0007829|PDB:6BGV" FT HELIX 542..547 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 553..557 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 562..565 FT /evidence="ECO:0007829|PDB:6BGY" FT STRAND 570..586 FT /evidence="ECO:0007829|PDB:6BGY" FT HELIX 589..591 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 592..604 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 607..609 FT /evidence="ECO:0007829|PDB:5V9T" FT HELIX 613..621 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 629..655 FT /evidence="ECO:0007829|PDB:5V9P" FT STRAND 661..663 FT /evidence="ECO:0007829|PDB:5K4L" FT HELIX 666..668 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 671..673 FT /evidence="ECO:0007829|PDB:5V9P" FT STRAND 674..676 FT /evidence="ECO:0007829|PDB:5V9T" FT STRAND 685..688 FT /evidence="ECO:0007829|PDB:5V9P" FT STRAND 691..693 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 703..705 FT /evidence="ECO:0007829|PDB:5CEH" FT STRAND 711..713 FT /evidence="ECO:0007829|PDB:5CEH" FT STRAND 716..720 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 724..743 FT /evidence="ECO:0007829|PDB:5V9P" FT HELIX 766..772 FT /evidence="ECO:0007829|PDB:5V9P" FT TURN 780..784 FT /evidence="ECO:0007829|PDB:5V9P" FT STRAND 1620..1627 FT /evidence="ECO:0007829|PDB:3GL6" FT STRAND 1629..1632 FT /evidence="ECO:0007829|PDB:3GL6" FT STRAND 1635..1637 FT /evidence="ECO:0007829|PDB:3GL6" FT HELIX 1639..1641 FT /evidence="ECO:0007829|PDB:3GL6" FT HELIX 1645..1650 FT /evidence="ECO:0007829|PDB:3GL6" FT TURN 1656..1658 FT /evidence="ECO:0007829|PDB:3GL6" SQ SEQUENCE 1690 AA; 192095 MW; FCF6DC22DEF001DF CRC64; MAGVGPGGYA AEFVPPPECP VFEPSWEEFT DPLSFIGRIR PLAEKTGICK IRPPKDWQPP FACEVKSFRF TPRVQRLNEL EAMTRVRLDF LDQLAKFWEL QGSTLKIPVV ERKILDLYAL SKIVASKGGF EMVTKEKKWS KVGSRLGYLP GKGTGSLLKS HYERILYPYE LFQSGVSLMG VQMPNLDLKE KVEPEVLSTD TQTSPEPGTR MNILPKRTRR VKTQSESGDV SRNTELKKLQ IFGAGPKVVG LAMGTKDKED EVTRRRKVTN RSDAFNMQMR QRKGTLSVNF VDLYVCMFCG RGNNEDKLLL CDGCDDSYHT FCLIPPLPDV PKGDWRCPKC VAEECSKPRE AFGFEQAVRE YTLQSFGEMA DNFKSDYFNM PVHMVPTELV EKEFWRLVSS IEEDVIVEYG ADISSKDFGS GFPVKDGRRK ILPEEEEYAL SGWNLNNMPV LEQSVLAHIN VDISGMKVPW LYVGMCFSSF CWHIEDHWSY SINYLHWGEP KTWYGVPSHA AEQLEEVMRE LAPELFESQP DLLHQLVTIM NPNVLMEHGV PVYRTNQCAG EFVVTFPRAY HSGFNQGYNF AEAVNFCTAD WLPIGRQCVN HYRRLRRHCV FSHEELIFKM AADPECLDVG LAAMVCKELT LMTEEETRLR ESVVQMGVLM SEEEVFELVP DDERQCSACR TTCFLSALTC SCNPERLVCL YHPTDLCPCP MQKKCLRYRY PLEDLPSLLY GVKVRAQSYD TWVSRVTEAL SANFNHKKDL IELRVMLEDA EDRKYPENDL FRKLRDAVKE AETCASVAQL LLSKKQKHRQ SPDSGRTRTK LTVEELKAFV QQLFSLPCVI SQARQVKNLL DDVEEFHERA QEAMMDETPD SSKLQMLIDM GSSLYVELPE LPRLKQELQQ ARWLDEVRLT LSDPQQVTLD VMKKLIDSGV GLAPHHAVEK AMAELQELLT VSERWEEKAK VCLQARPRHS VASLESIVNE AKNIPAFLPN VLSLKEALQK AREWTAKVEA IQSGSNYAYL EQLESLSAKG RPIPVRLEAL PQVESQVAAA RAWRERTGRT FLKKNSSHTL LQVLSPRTDI GVYGSGKNRR KKVKELIEKE KEKDLDLEPL SDLEEGLEET RDTAMVVAVF KEREQKEIEA MHSLRAANLA KMTMVDRIEE VKFCICRKTA SGFMLQCELC KDWFHNSCVP LPKSSSQKKG SSWQAKEVKF LCPLCMRSRR PRLETILSLL VSLQKLPVRL PEGEALQCLT ERAMSWQDRA RQALATDELS SALAKLSVLS QRMVEQAARE KTEKIISAEL QKAAANPDLQ GHLPSFQQSA FNRVVSSVSS SPRQTMDYDD EETDSDEDIR ETYGYDMKDT ASVKSSSSLE PNLFCDEEIP IKSEEVVTHM WTAPSFCAEH AYSSASKSCS QGSSTPRKQP RKSPLVPRSL EPPVLELSPG AKAQLEELMM VGDLLEVSLD ETQHIWRILQ ATHPPSEDRF LHIMEDDSME EKPLKVKGKD SSEKKRKRKL EKVEQLFGEG KQKSKELKKM DKPRKKKLKL GADKSKELNK LAKKLAKEEE RKKKKEKAAA AKVELVKEST EKKREKKVLD IPSKYDWSGA EESDDENAVC AAQNCQRPCK DKVDWVQCDG GCDEWFHQVC VGVSPEMAEN EDYICINCAK KQGPVSPGPA PPPSFIMSYK LPMEDLKETS //