ID KDM5B_HUMAN Reviewed; 1544 AA. AC Q9UGL1; O95811; Q15752; Q9Y3Q5; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 27-MAR-2024, entry version 185. DE RecName: Full=Lysine-specific demethylase 5B; DE EC=1.14.11.67 {ECO:0000250|UniProtKB:Q80Y84}; DE AltName: Full=Cancer/testis antigen 31; DE Short=CT31; DE AltName: Full=Histone demethylase JARID1B; DE AltName: Full=Jumonji/ARID domain-containing protein 1B; DE AltName: Full=PLU-1; DE AltName: Full=Retinoblastoma-binding protein 2 homolog 1; DE Short=RBP2-H1; DE AltName: Full=[histone H3]-trimethyl-L-lysine(4) demethylase 5B {ECO:0000305}; GN Name=KDM5B; Synonyms=JARID1B, PLU1, RBBP2H1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RC TISSUE=Mammary cancer; RX PubMed=10336460; DOI=10.1074/jbc.274.22.15633; RA Lu P.J., Sundquist K., Baeckstrom D., Poulsom R., Hanby A., Meier-Ewert S., RA Jones T., Mitchell M., Pitha-Rowe P., Freemont P., Taylor-Papadimitriou J.; RT "A novel gene (PLU-1) containing highly conserved putative DNA/chromatin RT binding motifs is specifically up-regulated in breast cancer."; RL J. Biol. Chem. 274:15633-15645(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY. RC TISSUE=Teratocarcinoma; RX PubMed=10616211; RA Vogt T., Kroiss M., McClelland M., Gruss C., Becker B., Bosserhoff A.K., RA Rumpler G., Bogenrieder T., Landthaler M., Stolz W.; RT "Deficiency of a novel retinoblastoma binding protein 2-homolog is a RT consistent feature of sporadic human melanoma skin cancer."; RL Lab. Invest. 79:1615-1627(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=10878660; DOI=10.1038/sj.ejhg.5200474; RA Kashuba V., Protopopov A., Podowski R., Gizatullin R., Li J., Klein G., RA Wahlestedt C., Zabarovsky E.; RT "Isolation and chromosomal localization of a new human retinoblastoma RT binding protein 2 homologue 1a (RBBP2H1A)."; RL Eur. J. Hum. Genet. 8:407-413(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=12237901; DOI=10.1002/ijc.10644; RA Barrett A., Madsen B., Copier J., Lu P.J., Cooper L., Scibetta A.G., RA Burchell J., Taylor-Papadimitriou J.; RT "PLU-1 nuclear protein, which is upregulated in breast cancer, shows RT restricted expression in normal human adult tissues: a new cancer/testis RT antigen?"; RL Int. J. Cancer 101:581-588(2002). RN [6] RP FUNCTION, AND INTERACTION WITH FOXG1B AND PAX9. RX PubMed=12657635; DOI=10.1074/jbc.m301994200; RA Tan K., Shaw A.L., Madsen B., Jensen K., Taylor-Papadimitriou J., RA Freemont P.S.; RT "Human PLU-1 has transcriptional repression properties and interacts with RT the developmental transcription factors BF-1 and PAX9."; RL J. Biol. Chem. 278:20507-20513(2003). RN [7] RP TISSUE SPECIFICITY, AND INTERACTION WITH RB1. RX PubMed=15803180; DOI=10.1038/modpathol.3800413; RA Roesch A., Becker B., Meyer S., Wild P., Hafner C., Landthaler M., Vogt T.; RT "Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding RT protein downregulated in malignant melanomas."; RL Mod. Pathol. 18:1249-1257(2005). RN [8] RP FUNCTION, AND INTERACTION WITH RB1. RX PubMed=16645588; DOI=10.1038/sj.jid.5700324; RA Roesch A., Becker B., Schneider-Brachert W., Hagen I., Landthaler M., RA Vogt T.; RT "Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals RT tumor-suppressive functions in highly metastatic melanoma cells."; RL J. Invest. Dermatol. 126:1850-1859(2006). RN [9] 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 [10] 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 [11] RP INTERACTION WITH HDAC1; HDAC4; HDAC5 AND HDAC7, AND MUTAGENESIS OF HIS-335 RP AND HIS-1200. RX PubMed=17373667; DOI=10.1002/ijc.22673; RA Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., RA Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., Freemont P., RA Taylor-Papadimitriou J.; RT "Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts RT directly with histone deacetylases."; RL Int. J. Cancer 121:265-275(2007). RN [12] RP FUNCTION, AND MUTAGENESIS OF HIS-499. RX PubMed=17363312; DOI=10.1016/j.molcel.2007.03.001; RA Yamane K., Tateishi K., Klose R.J., Fang J., Fabrizio L.A., RA Erdjument-Bromage H., Taylor-Papadimitriou J., Tempst P., Zhang Y.; RT "PLU-1 is an H3K4 demethylase involved in transcriptional repression and RT breast cancer cell proliferation."; RL Mol. Cell 25:801-812(2007). RN [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-986; SER-1328 AND SER-1456, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [15] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-242 AND LYS-278, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [16] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-242; LYS-278 AND LYS-769, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [17] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. 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 [18] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-148; LYS-204; LYS-209; LYS-242; RP LYS-274; LYS-278; LYS-769 AND LYS-1450, AND IDENTIFICATION BY MASS RP 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 [19] RP INVOLVEMENT IN MRT65, AND VARIANTS MRT65 299-ARG--LYS-1544 DEL AND RP 1370-LEU--LYS-1544 DEL. RX PubMed=29276005; DOI=10.1016/j.ajhg.2017.11.013; RG Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) Study; RG Deciphering Developmental Disorders (DDD) Study; RA Faundes V., Newman W.G., Bernardini L., Canham N., Clayton-Smith J., RA Dallapiccola B., Davies S.J., Demos M.K., Goldman A., Gill H., Horton R., RA Kerr B., Kumar D., Lehman A., McKee S., Morton J., Parker M.J., Rankin J., RA Robertson L., Temple I.K., Banka S.; RT "Histone lysine methylases and demethylases in the landscape of human RT developmental disorders."; RL Am. J. Hum. Genet. 102:175-187(2018). RN [20] RP INVOLVEMENT IN MRT65. RX PubMed=30409806; DOI=10.1126/science.aar6731; RG Deciphering Developmental Disorders Study; RA Martin H.C., Jones W.D., McIntyre R., Sanchez-Andrade G., Sanderson M., RA Stephenson J.D., Jones C.P., Handsaker J., Gallone G., Bruntraeger M., RA McRae J.F., Prigmore E., Short P., Niemi M., Kaplanis J., Radford E.J., RA Akawi N., Balasubramanian M., Dean J., Horton R., Hulbert A., Johnson D.S., RA Johnson K., Kumar D., Lynch S.A., Mehta S.G., Morton J., Parker M.J., RA Splitt M., Turnpenny P.D., Vasudevan P.C., Wright M., Bassett A., RA Gerety S.S., Wright C.F., FitzPatrick D.R., Firth H.V., Hurles M.E., RA Barrett J.C.; RT "Quantifying the contribution of recessive coding variation to RT developmental disorders."; RL Science 362:1161-1164(2018). RN [21] RP STRUCTURE BY NMR OF 306-360 IN COMPLEX WITH ZINC AND HISTONE H3, FUNCTION, RP INTERACTION WITH HISTONE H3, AND MUTAGENESIS OF ASP-308; LEU-309; TYR-310; RP VAL-311; GLU-321; ASP-322; LEU-324; LEU-325; LEU-326; ASP-328; ASP-332; RP SER-333; TYR-334; ASP-345 AND TRP-351. RX PubMed=24952722; DOI=10.1007/s13238-014-0078-4; RA Zhang Y., Yang H., Guo X., Rong N., Song Y., Xu Y., Lan W., Zhang X., RA Liu M., Xu Y., Cao C.; RT "The PHD1 finger of KDM5B recognizes unmodified H3K4 during the RT demethylation of histone H3K4me2/3 by KDM5B."; RL Protein Cell 5:837-850(2014). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 26-101 AND 374-772 IN COMPLEX RP WITH ZINC; MANGANESE AND AN INHIBITOR, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=26741168; DOI=10.1021/acs.jmedchem.5b01635; RA Bavetsias V., Lanigan R.M., Ruda G.F., Atrash B., McLaughlin M.G., RA Tumber A., Mok N.Y., Le Bihan Y.V., Dempster S., Boxall K.J., RA Jeganathan F., Hatch S.B., Savitsky P., Velupillai S., Krojer T., RA England K.S., Sejberg J., Thai C., Donovan A., Pal A., Scozzafava G., RA Bennett J.M., Kawamura A., Johansson C., Szykowska A., Gileadi C., RA Burgess-Brown N.A., von Delft F., Oppermann U., Walters Z., Shipley J., RA Raynaud F.I., Westaway S.M., Prinjha R.K., Fedorov O., Burke R., RA Schofield C.J., Westwood I.M., Bountra C., Muller S., van Montfort R.L., RA Brennan P.E., Blagg J.; RT "8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell RT Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase RT Inhibitors."; RL J. Med. Chem. 59:1388-1409(2016). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 26-101 AND 374-772 IN COMPLEX RP WITH SEVERAL INHIBITORS; ZINC AND MANGANESE, DOMAIN, FUNCTION, AND ACTIVITY RP REGULATION. RX PubMed=27214403; DOI=10.1038/nchembio.2087; RA Johansson C., Velupillai S., Tumber A., Szykowska A., Hookway E.S., RA Nowak R.P., Strain-Damerell C., Gileadi C., Philpott M., Burgess-Brown N., RA Wu N., Kopec J., Nuzzi A., Steuber H., Egner U., Badock V., Munro S., RA LaThangue N.B., Westaway S., Brown J., Athanasou N., Prinjha R., RA Brennan P.E., Oppermann U.; RT "Structural analysis of human KDM5B guides histone demethylase inhibitor RT development."; RL Nat. Chem. Biol. 12:539-545(2016). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 26-100 AND 374-772 IN COMPLEX RP WITH INHIBITOR KDOAM-25; ZINC AND MANGANESE, FUNCTION, ACTIVITY REGULATION, RP AND MUTAGENESIS OF 499-HIS--GLU-501. RX PubMed=28262558; DOI=10.1016/j.chembiol.2017.02.006; RA Tumber A., Nuzzi A., Hookway E.S., Hatch S.B., Velupillai S., Johansson C., RA Kawamura A., Savitsky P., Yapp C., Szykowska A., Wu N., Bountra C., RA Strain-Damerell C., Burgess-Brown N.A., Ruda G.F., Fedorov O., Munro S., RA England K.S., Nowak R.P., Schofield C.J., La Thangue N.B., Pawlyn C., RA Davies F., Morgan G., Athanasou N., Muller S., Oppermann U., Brennan P.E.; RT "Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of RT H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma RT Cells."; RL Cell Chem. Biol. 24:371-380(2017). CC -!- FUNCTION: Histone demethylase that demethylates 'Lys-4' of histone H3, CC thereby playing a central role in histone code (PubMed:24952722, CC PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 CC 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and CC monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for CC FOXG1B and PAX9. Favors the proliferation of breast cancer cells by CC repressing tumor suppressor genes such as BRCA1 and HOXA5 CC (PubMed:24952722). In contrast, may act as a tumor suppressor for CC melanoma. Represses the CLOCK-BMAL1 heterodimer-mediated CC transcriptional activation of the core clock component PER2 (By CC similarity). {ECO:0000250|UniProtKB:Q80Y84, CC ECO:0000269|PubMed:12657635, ECO:0000269|PubMed:16645588, CC ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17363312, CC ECO:0000269|PubMed:24952722, ECO:0000269|PubMed:26645689, CC ECO:0000269|PubMed:26741168, ECO:0000269|PubMed:27214403, CC ECO:0000269|PubMed:28262558}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(4)- CC [histone H3] + 3 O2 = 3 CO2 + 3 formaldehyde + L-lysyl(4)-[histone CC H3] + 3 succinate; 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:0000250|UniProtKB:Q80Y84}; 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: Several specific inhibitors are being developed CC and tested (PubMed:27214403, PubMed:26741168). The inhibitor KDOAM-25 CC inhibits its demethylase activity, resulting to cell cycle arrest in CC myeloma cells (PubMed:28262558). {ECO:0000269|PubMed:26741168, CC ECO:0000269|PubMed:27214403, ECO:0000269|PubMed:28262558}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=9 uM for 2-oxoglutarate {ECO:0000269|PubMed:26645689}; CC KM=4 uM for histone H3K4me3 {ECO:0000269|PubMed:26645689}; CC Note=kcat is 1.9 min(-1) and 2.0 min(-1) for 2-oxoglutarate and CC histone H3K4me3, respectively. {ECO:0000269|PubMed:26645689}; CC -!- SUBUNIT: Interacts with FOXG1B, PAX9, MYC, MYCN and RB1. Interacts with CC HDAC1, HDAC4, HDAC5 and HDAC7. Interacts (via PHD-type 1 zinc finger) CC with histone H3 unmodified at 'Lys-4'; the interaction is inhibited CC when histone H3 is methylated at 'Arg-2' or 'Lys-4' (PubMed:24952722). CC {ECO:0000269|PubMed:12657635, ECO:0000269|PubMed:15803180, CC ECO:0000269|PubMed:16645588, ECO:0000269|PubMed:17311883, CC ECO:0000269|PubMed:17373667, ECO:0000269|PubMed:24952722}. CC -!- INTERACTION: CC Q9UGL1; P49711: CTCF; NbExp=8; IntAct=EBI-2514978, EBI-932887; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00355, CC ECO:0000255|PROSITE-ProRule:PRU00537, ECO:0000269|PubMed:10336460, CC ECO:0000269|PubMed:12237901}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UGL1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UGL1-2; Sequence=VSP_026408; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in CC testis. Down-regulated in melanoma and glioblastoma. Up-regulated in CC breast cancer (at protein level). {ECO:0000269|PubMed:10336460, CC ECO:0000269|PubMed:10616211, ECO:0000269|PubMed:10878660, CC ECO:0000269|PubMed:12237901, ECO:0000269|PubMed:15803180}. CC -!- DOMAIN: Both the JmjC domain and the JmjN domain are required for CC enzymatic activity. However ARID and PHD-type 1 domain are not required CC for activity per se but contributed to recognition of the H3(1-21)K4me2 CC substrate peptide. {ECO:0000269|PubMed:27214403}. CC -!- DOMAIN: The 2 first PHD-type zinc finger domains are required for CC transcription repression activity. CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 65 CC (MRT65) [MIM:618109]: A disorder characterized by significantly below CC average general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. MRT65 CC patients have moderate to severe intellectual disability, developmental CC delay, and facial dysmorphism. Camptodactyly is present in some CC patients. {ECO:0000269|PubMed:29276005, ECO:0000269|PubMed:30409806}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the JARID1 histone demethylase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAB63108.1; Type=Erroneous initiation; Note=Extended N-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; AJ132440; CAB43532.1; -; mRNA. DR EMBL; AF087481; AAD16061.1; -; mRNA. DR EMBL; AJ243706; CAB63108.1; ALT_INIT; mRNA. DR EMBL; AC098934; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104463; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS30974.1; -. [Q9UGL1-1] DR CCDS; CCDS81417.1; -. [Q9UGL1-2] DR RefSeq; NP_001300971.1; NM_001314042.1. [Q9UGL1-2] DR RefSeq; NP_006609.3; NM_006618.4. [Q9UGL1-1] DR PDB; 2MA5; NMR; -; A=1487-1544. DR PDB; 2MNY; NMR; -; A=306-360. DR PDB; 2MNZ; NMR; -; A=306-360. DR PDB; 5A1F; X-ray; 2.10 A; A=26-770. DR PDB; 5A3N; X-ray; 2.00 A; A=26-101, A=374-772. DR PDB; 5A3P; X-ray; 2.01 A; A=26-101, A=374-770. DR PDB; 5A3T; X-ray; 1.90 A; A=26-101, A=374-772. DR PDB; 5A3W; X-ray; 2.00 A; A=26-101, A=374-772. DR PDB; 5FPL; X-ray; 2.35 A; A=26-101, A=374-772. DR PDB; 5FPU; X-ray; 2.24 A; A=26-101, A=374-772. DR PDB; 5FUN; X-ray; 2.30 A; A=26-101, A=374-772. DR PDB; 5FUP; X-ray; 2.15 A; A=26-101, A=374-770. DR PDB; 5FV3; X-ray; 2.37 A; A=26-101, A=374-770. DR PDB; 5FY4; X-ray; 2.10 A; A=26-101, A=374-770. DR PDB; 5FY5; X-ray; 2.47 A; A=26-101, A=374-770. DR PDB; 5FY9; X-ray; 2.03 A; A=26-101, A=374-770. DR PDB; 5FYB; X-ray; 1.87 A; A=26-101, A=374-770. DR PDB; 5FYS; X-ray; 1.89 A; A=26-101, A=374-770. DR PDB; 5FYT; X-ray; 1.87 A; A=26-101, A=374-770. DR PDB; 5FYU; X-ray; 2.06 A; A=26-101, A=374-770. DR PDB; 5FYV; X-ray; 1.87 A; A=26-101, A=374-770. DR PDB; 5FYY; X-ray; 2.18 A; A=26-101, A=374-770. DR PDB; 5FYZ; X-ray; 1.75 A; A=26-101, A=374-770. DR PDB; 5FZ0; X-ray; 2.42 A; A=26-101, A=374-770. DR PDB; 5FZ1; X-ray; 2.39 A; A=26-101, A=374-770. DR PDB; 5FZ3; X-ray; 2.50 A; A=26-101, A=374-770. DR PDB; 5FZ4; X-ray; 2.07 A; A=26-101, A=374-770. DR PDB; 5FZ6; X-ray; 2.33 A; A=26-101, A=374-770. DR PDB; 5FZ7; X-ray; 2.30 A; A=26-101, A=374-770. DR PDB; 5FZ8; X-ray; 1.86 A; A=26-101, A=374-770. DR PDB; 5FZ9; X-ray; 2.06 A; A=26-101, A=374-770. DR PDB; 5FZA; X-ray; 2.10 A; A=26-101, A=374-770. DR PDB; 5FZB; X-ray; 2.18 A; A=26-101, A=374-770. DR PDB; 5FZC; X-ray; 2.05 A; A=26-101, A=374-770. DR PDB; 5FZD; X-ray; 2.05 A; A=26-101, A=374-770. DR PDB; 5FZE; X-ray; 2.02 A; A=26-101, A=374-770. DR PDB; 5FZF; X-ray; 1.97 A; A=26-101, A=374-770. DR PDB; 5FZG; X-ray; 1.96 A; A=26-101, A=374-770. DR PDB; 5FZH; X-ray; 2.09 A; A=26-101, A=374-442, A=444-770. DR PDB; 5FZI; X-ray; 1.95 A; A=26-101, A=374-770. DR PDB; 5FZK; X-ray; 2.05 A; A=26-101, A=374-770. DR PDB; 5FZL; X-ray; 2.55 A; A=26-101, A=374-770. DR PDB; 5FZM; X-ray; 2.49 A; A=26-101, A=376-770. DR PDB; 5LW9; X-ray; 2.30 A; A=26-99, A=374-772. DR PDB; 5LWB; X-ray; 2.39 A; A=26-101, A=374-772. DR PDB; 6EIN; X-ray; 2.11 A; A=26-101, A=374-772. DR PDB; 6EIU; X-ray; 1.88 A; A=26-100, A=374-754. DR PDB; 6EIY; X-ray; 2.15 A; A=26-100, A=374-754. DR PDB; 6EJ0; X-ray; 2.06 A; A=26-98, A=375-754. DR PDB; 6EJ1; X-ray; 2.07 A; A=26-98, A=375-754. DR PDB; 6EK6; X-ray; 2.05 A; A=347-754. DR PDB; 6H4Z; X-ray; 2.30 A; A=26-101, A=374-772. DR PDB; 6H50; X-ray; 2.19 A; A=26-101, A=374-772. DR PDB; 6H51; X-ray; 2.21 A; A=26-101, A=374-772. DR PDB; 6H52; X-ray; 2.14 A; A=26-101, A=374-772. DR PDB; 6RBI; X-ray; 2.21 A; A=26-101, A=374-772. DR PDBsum; 2MA5; -. DR PDBsum; 2MNY; -. DR PDBsum; 2MNZ; -. DR PDBsum; 5A1F; -. DR PDBsum; 5A3N; -. DR PDBsum; 5A3P; -. DR PDBsum; 5A3T; -. DR PDBsum; 5A3W; -. DR PDBsum; 5FPL; -. DR PDBsum; 5FPU; -. DR PDBsum; 5FUN; -. DR PDBsum; 5FUP; -. DR PDBsum; 5FV3; -. DR PDBsum; 5FY4; -. DR PDBsum; 5FY5; -. DR PDBsum; 5FY9; -. DR PDBsum; 5FYB; -. DR PDBsum; 5FYS; -. DR PDBsum; 5FYT; -. DR PDBsum; 5FYU; -. DR PDBsum; 5FYV; -. DR PDBsum; 5FYY; -. DR PDBsum; 5FYZ; -. DR PDBsum; 5FZ0; -. DR PDBsum; 5FZ1; -. DR PDBsum; 5FZ3; -. DR PDBsum; 5FZ4; -. DR PDBsum; 5FZ6; -. DR PDBsum; 5FZ7; -. DR PDBsum; 5FZ8; -. DR PDBsum; 5FZ9; -. DR PDBsum; 5FZA; -. DR PDBsum; 5FZB; -. DR PDBsum; 5FZC; -. DR PDBsum; 5FZD; -. DR PDBsum; 5FZE; -. DR PDBsum; 5FZF; -. DR PDBsum; 5FZG; -. DR PDBsum; 5FZH; -. DR PDBsum; 5FZI; -. DR PDBsum; 5FZK; -. DR PDBsum; 5FZL; -. DR PDBsum; 5FZM; -. DR PDBsum; 5LW9; -. DR PDBsum; 5LWB; -. DR PDBsum; 6EIN; -. DR PDBsum; 6EIU; -. DR PDBsum; 6EIY; -. DR PDBsum; 6EJ0; -. DR PDBsum; 6EJ1; -. DR PDBsum; 6EK6; -. DR PDBsum; 6H4Z; -. DR PDBsum; 6H50; -. DR PDBsum; 6H51; -. DR PDBsum; 6H52; -. DR PDBsum; 6RBI; -. DR AlphaFoldDB; Q9UGL1; -. DR BMRB; Q9UGL1; -. DR SASBDB; Q9UGL1; -. DR SMR; Q9UGL1; -. DR BioGRID; 115984; 92. DR CORUM; Q9UGL1; -. DR DIP; DIP-53652N; -. DR IntAct; Q9UGL1; 19. DR MINT; Q9UGL1; -. DR STRING; 9606.ENSP00000356233; -. DR BindingDB; Q9UGL1; -. DR ChEMBL; CHEMBL3774295; -. DR GuidetoPHARMACOLOGY; 2681; -. DR GlyGen; Q9UGL1; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9UGL1; -. DR PhosphoSitePlus; Q9UGL1; -. DR SwissPalm; Q9UGL1; -. DR BioMuta; KDM5B; -. DR DMDM; 296439317; -. DR EPD; Q9UGL1; -. DR jPOST; Q9UGL1; -. DR MassIVE; Q9UGL1; -. DR MaxQB; Q9UGL1; -. DR PaxDb; 9606-ENSP00000356234; -. DR PeptideAtlas; Q9UGL1; -. DR ProteomicsDB; 84231; -. [Q9UGL1-1] DR ProteomicsDB; 84232; -. [Q9UGL1-2] DR Pumba; Q9UGL1; -. DR ABCD; Q9UGL1; 1 sequenced antibody. DR Antibodypedia; 20655; 446 antibodies from 33 providers. DR DNASU; 10765; -. DR Ensembl; ENST00000367264.7; ENSP00000356233.2; ENSG00000117139.18. [Q9UGL1-2] DR Ensembl; ENST00000367265.9; ENSP00000356234.3; ENSG00000117139.18. [Q9UGL1-1] DR GeneID; 10765; -. DR KEGG; hsa:10765; -. DR MANE-Select; ENST00000367265.9; ENSP00000356234.3; NM_006618.5; NP_006609.3. DR UCSC; uc001gyf.4; human. [Q9UGL1-1] DR AGR; HGNC:18039; -. DR CTD; 10765; -. DR DisGeNET; 10765; -. DR GeneCards; KDM5B; -. DR HGNC; HGNC:18039; KDM5B. DR HPA; ENSG00000117139; Tissue enhanced (testis). DR MalaCards; KDM5B; -. DR MIM; 605393; gene. DR MIM; 618109; phenotype. DR neXtProt; NX_Q9UGL1; -. DR OpenTargets; ENSG00000117139; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR PharmGKB; PA164721626; -. DR VEuPathDB; HostDB:ENSG00000117139; -. DR eggNOG; KOG1246; Eukaryota. DR GeneTree; ENSGT00940000157076; -. DR HOGENOM; CLU_000991_2_2_1; -. DR InParanoid; Q9UGL1; -. DR OMA; TMMNPGR; -. DR OrthoDB; 48111at2759; -. DR PhylomeDB; Q9UGL1; -. DR TreeFam; TF106476; -. DR BioCyc; MetaCyc:ENSG00000117139-MONOMER; -. DR BRENDA; 1.14.11.67; 2681. DR PathwayCommons; Q9UGL1; -. DR Reactome; R-HSA-3214842; HDMs demethylate histones. DR Reactome; R-HSA-8866911; TFAP2 (AP-2) family regulates transcription of cell cycle factors. DR Reactome; R-HSA-9821002; Chromatin modifications during the maternal to zygotic transition (MZT). DR SignaLink; Q9UGL1; -. DR SIGNOR; Q9UGL1; -. DR BioGRID-ORCS; 10765; 32 hits in 1200 CRISPR screens. DR ChiTaRS; KDM5B; human. DR GeneWiki; JARID1B; -. DR GenomeRNAi; 10765; -. DR Pharos; Q9UGL1; Tchem. DR PRO; PR:Q9UGL1; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9UGL1; Protein. DR Bgee; ENSG00000117139; Expressed in sperm and 186 other cell types or tissues. DR ExpressionAtlas; Q9UGL1; baseline and differential. DR GO; GO:0000785; C:chromatin; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:CAFA. DR GO; GO:0003677; F:DNA binding; IDA:GDB. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0032452; F:histone demethylase activity; TAS:Reactome. DR GO; GO:0032453; F:histone H3K4 demethylase activity; IDA:CACAO. DR GO; GO:0034647; F:histone H3K4me/H3K4me2/H3K4me3 demethylase activity; IDA:UniProtKB. DR GO; GO:0003676; F:nucleic acid binding; IMP:DisProt. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IMP:CAFA. DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central. DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl. DR GO; GO:0060763; P:mammary duct terminal end bud growth; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:GDB. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0033601; P:positive regulation of mammary gland epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IBA:GO_Central. DR GO; GO:2000864; P:regulation of estradiol secretion; IEA:Ensembl. DR GO; GO:0060992; P:response to fungicide; IEA:Ensembl. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0007338; P:single fertilization; IEA:Ensembl. DR GO; GO:0061038; P:uterus morphogenesis; IEA:Ensembl. DR CDD; cd16874; ARID_KDM5B; 1. DR CDD; cd15603; PHD1_KDM5B; 1. DR CDD; cd15607; PHD2_KDM5B; 1. DR CDD; cd15687; PHD3_KDM5B; 1. DR DisProt; DP00712; -. 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); 2. 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; IPR047981; KDM5B_ARID. DR InterPro; IPR047978; KDM5B_PHD1. DR InterPro; IPR047979; KDM5B_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:SF3; LYSINE-SPECIFIC DEMETHYLASE 5B; 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; 3. 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 Genevisible; Q9UGL1; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms; KW Chromatin regulator; Dioxygenase; Disease variant; Intellectual disability; KW Iron; Isopeptide bond; Metal-binding; Nucleus; Oxidoreductase; KW Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..1544 FT /note="Lysine-specific demethylase 5B" FT /id="PRO_0000292412" FT DOMAIN 32..73 FT /note="JmjN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537" FT DOMAIN 97..187 FT /note="ARID" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00355" FT DOMAIN 453..619 FT /note="JmjC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538" FT ZN_FING 309..359 FT /note="PHD-type 1" FT /evidence="ECO:0000269|PubMed:24952722, FT ECO:0007744|PDB:2MNY" FT ZN_FING 692..744 FT /note="C5HC2" FT /evidence="ECO:0000269|PubMed:26741168, FT ECO:0000269|PubMed:27214403, ECO:0000269|PubMed:28262558" FT ZN_FING 1176..1224 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1484..1538 FT /note="PHD-type 3" FT /evidence="ECO:0007744|PDB:2MA5" FT REGION 201..230 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1374..1400 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1374..1390 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 425 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:P29375" FT BINDING 499 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:26741168, FT ECO:0000305|PubMed:27214403, ECO:0000305|PubMed:28262558" FT BINDING 501 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:26741168, FT ECO:0000305|PubMed:27214403, ECO:0000305|PubMed:28262558" FT BINDING 507 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:P29375" FT BINDING 509 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:P29375" FT BINDING 517 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:P29375" FT BINDING 587 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000305|PubMed:26741168, FT ECO:0000305|PubMed:27214403, ECO:0000305|PubMed:28262558" FT MOD_RES 832 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q80Y84" FT MOD_RES 986 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1456 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 148 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 204 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 209 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 242 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733" FT CROSSLNK 274 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 278 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733" FT CROSSLNK 769 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1450 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 237 FT /note="E -> ERQSLAVLPRLECSGAILAHCNLRLLDSSNSSASASQ (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:10616211" FT /id="VSP_026408" FT VARIANT 299..1544 FT /note="Missing (in MRT65)" FT /evidence="ECO:0000269|PubMed:29276005" FT /id="VAR_081276" FT VARIANT 1370..1544 FT /note="Missing (in MRT65)" FT /evidence="ECO:0000269|PubMed:29276005" FT /id="VAR_081277" FT MUTAGEN 308 FT /note="D->A: Slightly decreases interaction with histone FT H3. Decreases by 21% demethylase activity and repression of FT tumor suppressor genes expression." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 309 FT /note="L->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 310 FT /note="Y->A: Slightly decreases interaction with histone FT H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 310 FT /note="Y->F: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 311 FT /note="V->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 321 FT /note="E->A: Decreases interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 322 FT /note="D->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 324 FT /note="L->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 325 FT /note="L->A: Abolishes interaction with histone H3. FT Decreases by 44% demethylase activity and repression of FT tumor suppressor genes expression; when associated with FT A-328." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 326 FT /note="L->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 328 FT /note="D->A: Almost abolishes interaction with histone H3. FT Decreases by 44% demethylase activity and repression of FT tumor suppressor genes expression; when associated with FT A-325." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 332 FT /note="D->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 333 FT /note="S->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 334 FT /note="Y->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 335 FT /note="H->A: Slightly impairs transcription repression FT ability." FT /evidence="ECO:0000269|PubMed:17373667" FT MUTAGEN 345 FT /note="D->A: No effect on interaction with histone H3." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 351 FT /note="W->A: Abolishes interaction with histone H3. FT Decreases by 28% demethylase activity and repression of FT tumor suppressor genes expression." FT /evidence="ECO:0000269|PubMed:24952722" FT MUTAGEN 499..501 FT /note="HIE->AIA: Abolishes lysine-specific histone FT demethylase activity." FT /evidence="ECO:0000269|PubMed:28262558" FT MUTAGEN 499 FT /note="H->Y: Abolishes lysine-specific histone demethylase FT activity." FT /evidence="ECO:0000269|PubMed:17363312" FT MUTAGEN 1200 FT /note="H->A: Impairs transcription repression ability and FT interaction with HDAC4." FT /evidence="ECO:0000269|PubMed:17373667" FT CONFLICT 78 FT /note="V -> G (in Ref. 3; CAB63108)" FT /evidence="ECO:0000305" FT CONFLICT 585..589 FT /note="AYHSG -> VPQW (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT CONFLICT 708 FT /note="C -> W (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT CONFLICT 759 FT /note="A -> P (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT CONFLICT 771 FT /note="N -> T (in Ref. 2; AAD16061 and 3; CAB63108)" FT /evidence="ECO:0000305" FT CONFLICT 1182 FT /note="Q -> R (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT CONFLICT 1293 FT /note="A -> P (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT CONFLICT 1307 FT /note="P -> L (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT CONFLICT 1331 FT /note="S -> ST (in Ref. 2; AAD16061)" FT /evidence="ECO:0000305" FT HELIX 39..42 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 45..56 FT /evidence="ECO:0007829|PDB:5FYZ" FT TURN 57..59 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 60..64 FT /evidence="ECO:0007829|PDB:5FYZ" FT TURN 78..80 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 86..89 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:6EIU" FT STRAND 308..310 FT /evidence="ECO:0007829|PDB:2MNY" FT STRAND 313..315 FT /evidence="ECO:0007829|PDB:2MNZ" FT HELIX 319..323 FT /evidence="ECO:0007829|PDB:2MNY" FT STRAND 324..326 FT /evidence="ECO:0007829|PDB:2MNY" FT STRAND 328..331 FT /evidence="ECO:0007829|PDB:2MNY" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:2MNY" FT TURN 336..339 FT /evidence="ECO:0007829|PDB:2MNY" FT TURN 358..360 FT /evidence="ECO:0007829|PDB:6EK6" FT STRAND 363..366 FT /evidence="ECO:0007829|PDB:6EK6" FT HELIX 379..394 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 398..400 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 403..415 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 422..429 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:5FYT" FT STRAND 443..445 FT /evidence="ECO:0007829|PDB:5A3N" FT HELIX 449..454 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 458..460 FT /evidence="ECO:0007829|PDB:5FZ7" FT TURN 461..466 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 467..469 FT /evidence="ECO:0007829|PDB:5A3P" FT HELIX 472..474 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 480..483 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 486..490 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 495..499 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 502..504 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 506..515 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 517..521 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 524..526 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 527..537 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 539..542 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 548..550 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 552..554 FT /evidence="ECO:0007829|PDB:5FZG" FT HELIX 558..563 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 569..573 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 578..581 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 587..602 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 605..607 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 608..621 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 629..637 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 638..642 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 645..671 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 676..679 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 682..684 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 687..689 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 690..692 FT /evidence="ECO:0007829|PDB:5FYZ" FT TURN 693..695 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 701..706 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 719..721 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 727..729 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 730..735 FT /evidence="ECO:0007829|PDB:5FYZ" FT HELIX 738..752 FT /evidence="ECO:0007829|PDB:5FYZ" FT STRAND 1495..1500 FT /evidence="ECO:0007829|PDB:2MA5" FT STRAND 1502..1505 FT /evidence="ECO:0007829|PDB:2MA5" FT TURN 1506..1509 FT /evidence="ECO:0007829|PDB:2MA5" FT STRAND 1511..1514 FT /evidence="ECO:0007829|PDB:2MA5" FT HELIX 1515..1518 FT /evidence="ECO:0007829|PDB:2MA5" FT HELIX 1522..1526 FT /evidence="ECO:0007829|PDB:2MA5" FT HELIX 1533..1537 FT /evidence="ECO:0007829|PDB:2MA5" SQ SEQUENCE 1544 AA; 175658 MW; 70A0738D9A709F61 CRC64; MEAATTLHPG PRPALPLGGP GPLGEFLPPP ECPVFEPSWE EFADPFAFIH KIRPIAEQTG ICKVRPPPDW QPPFACDVDK LHFTPRIQRL NELEAQTRVK LNFLDQIAKY WELQGSTLKI PHVERKILDL FQLNKLVAEE GGFAVVCKDR KWTKIATKMG FAPGKAVGSH IRGHYERILN PYNLFLSGDS LRCLQKPNLT TDTKDKEYKP HDIPQRQSVQ PSETCPPARR AKRMRAEAMN IKIEPEETTE ARTHNLRRRM GCPTPKCENE KEMKSSIKQE PIERKDYIVE NEKEKPKSRS KKATNAVDLY VCLLCGSGND EDRLLLCDGC DDSYHTFCLI PPLHDVPKGD WRCPKCLAQE CSKPQEAFGF EQAARDYTLR TFGEMADAFK SDYFNMPVHM VPTELVEKEF WRLVSTIEED VTVEYGADIA SKEFGSGFPV RDGKIKLSPE EEEYLDSGWN LNNMPVMEQS VLAHITADIC GMKLPWLYVG MCFSSFCWHI EDHWSYSINY LHWGEPKTWY GVPGYAAEQL ENVMKKLAPE LFVSQPDLLH QLVTIMNPNT LMTHEVPVYR TNQCAGEFVI TFPRAYHSGF NQGFNFAEAV NFCTVDWLPL GRQCVEHYRL LHRYCVFSHD EMICKMASKA DVLDVVVAST VQKDMAIMIE DEKALRETVR KLGVIDSERM DFELLPDDER QCVKCKTTCF MSAISCSCKP GLLVCLHHVK ELCSCPPYKY KLRYRYTLDD LYPMMNALKL RAESYNEWAL NVNEALEAKI NKKKSLVSFK ALIEESEMKK FPDNDLLRHL RLVTQDAEKC ASVAQQLLNG KRQTRYRSGG GKSQNQLTVN ELRQFVTQLY ALPCVLSQTP LLKDLLNRVE DFQQHSQKLL SEETPSAAEL QDLLDVSFEF DVELPQLAEM RIRLEQARWL EEVQQACLDP SSLTLDDMRR LIDLGVGLAP YSAVEKAMAR LQELLTVSEH WDDKAKSLLK ARPRHSLNSL ATAVKEIEEI PAYLPNGAAL KDSVQRARDW LQDVEGLQAG GRVPVLDTLI ELVTRGRSIP VHLNSLPRLE TLVAEVQAWK ECAVNTFLTE NSPYSLLEVL CPRCDIGLLG LKRKQRKLKE PLPNGKKKST KLESLSDLER ALTESKETAS AMATLGEARL REMEALQSLR LANEGKLLSP LQDVDIKICL CQKAPAAPMI QCELCRDAFH TSCVAVPSIS QGLRIWLCPH CRRSEKPPLE KILPLLASLQ RIRVRLPEGD ALRYMIERTV NWQHRAQQLL SSGNLKFVQD RVGSGLLYSR WQASAGQVSD TNKVSQPPGT TSFSLPDDWD NRTSYLHSPF STGRSCIPLH GVSPEVNELL MEAQLLQVSL PEIQELYQTL LAKPSPAQQT DRSSPVRPSS EKNDCCRGKR DGINSLERKL KRRLEREGLS SERWERVKKM RTPKKKKIKL SHPKDMNNFK LERERSYELV RSAETHSLPS DTSYSEQEDS EDEDAICPAV SCLQPEGDEV DWVQCDGSCN QWFHQVCVGV SPEMAEKEDY ICVRCTVKDA PSRK //