ID KDM4C_HUMAN Reviewed; 1056 AA. AC Q9H3R0; B4E1Y4; B7ZL46; F5H347; F5H7P0; O94877; Q2M3M0; Q5JUC9; Q5VYJ2; AC Q5VYJ3; DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 16-MAY-2006, sequence version 2. DT 24-JAN-2024, entry version 188. DE RecName: Full=Lysine-specific demethylase 4C; DE EC=1.14.11.66 {ECO:0000269|PubMed:16603238}; DE AltName: Full=Gene amplified in squamous cell carcinoma 1 protein; DE Short=GASC-1 protein; DE AltName: Full=JmjC domain-containing histone demethylation protein 3C; DE AltName: Full=Jumonji domain-containing protein 2C; DE AltName: Full=[histone H3]-trimethyl-L-lysine(9) demethylase 4C {ECO:0000305}; GN Name=KDM4C; Synonyms=GASC1, JHDM3C, JMJD2C, KIAA0780; 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 VARIANTS RP THR-492 AND ARG-772. RX PubMed=10987278; RA Yang Z.Q., Imoto I., Fukuda Y., Pimkhaokham A., Shimada Y., Imamura M., RA Sugano S., Nakamura Y., Inazawa J.; RT "Identification of a novel gene, GASC1, within an amplicon at 9p23-24 RT frequently detected in esophageal cancer cell lines."; RL Cancer Res. 60:4735-4739(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT THR-492. RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANT RP THR-492. RC TISSUE=Testis, 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 GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-1039. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, AND ENZYME ACTIVITY. RX PubMed=16603238; DOI=10.1016/j.cell.2006.03.028; RA Whetstine J.R., Nottke A., Lan F., Huarte M., Smolikov S., Chen Z., RA Spooner E., Li E., Zhang G., Colaiacovo M., Shi Y.; RT "Reversal of histone lysine trimethylation by the JMJD2 family of histone RT demethylases."; RL Cell 125:467-481(2006). RN [7] RP FUNCTION, AND MUTAGENESIS OF 190-HIS--GLU-192. 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). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 1-347 IN COMPLEX WITH ZINC AND RP NICKEL ION, COFACTOR, AND SUBSTRATE SPECIFICITY. RX PubMed=21914792; DOI=10.1074/jbc.m111.283689; RA Hillringhaus L., Yue W.W., Rose N.R., Ng S.S., Gileadi C., Loenarz C., RA Bello S.H., Bray J.E., Schofield C.J., Oppermann U.; RT "Structural and evolutionary basis for the dual substrate selectivity of RT human KDM4 histone demethylase family."; RL J. Biol. Chem. 286:41616-41625(2011). CC -!- FUNCTION: Histone demethylase that specifically demethylates 'Lys-9' CC and 'Lys-36' residues of histone H3, thereby playing a central role in CC histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor CC H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' CC residue, while it has no activity on mono- and dimethylated residues. CC Demethylation of Lys residue generates formaldehyde and succinate. CC {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 2-oxoglutarate + N(6),N(6),N(6)-trimethyl-L-lysyl(9)- CC [histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + N(6)-methyl-L- CC lysyl(9)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:60200, Rhea:RHEA- CC COMP:15538, Rhea:RHEA-COMP:15542, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:61929, ChEBI:CHEBI:61961; CC EC=1.14.11.66; Evidence={ECO:0000269|PubMed:16603238}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:21914792}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:21914792}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00537}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9H3R0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H3R0-2; Sequence=VSP_018311; CC Name=3; CC IsoId=Q9H3R0-3; Sequence=VSP_045462, VSP_045463; CC Name=4; CC IsoId=Q9H3R0-4; Sequence=VSP_046113, VSP_045462, VSP_045463; CC -!- TISSUE SPECIFICITY: Overexpressed in several esophageal squamous cell CC carcinomas (ESCs). {ECO:0000269|PubMed:10987278}. CC -!- DOMAIN: The 2 Tudor domains recognize and bind methylated histones. CC Double Tudor domain has an interdigitated structure and the unusual CC fold is required for its ability to bind methylated histone tails (By CC similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the JHDM3 histone demethylase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA34500.1; 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/432/GASC1"; 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; AB037901; BAB16102.1; -; mRNA. DR EMBL; AB018323; BAA34500.1; ALT_INIT; mRNA. DR EMBL; AK304032; BAG64946.1; -; mRNA. DR EMBL; AK310439; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL137020; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL161443; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL354707; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445592; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513412; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC104859; AAI04860.1; -; mRNA. DR EMBL; BC104861; AAI04862.1; -; mRNA. DR EMBL; BC143571; AAI43572.1; -; mRNA. DR CCDS; CCDS55285.1; -. [Q9H3R0-4] DR CCDS; CCDS55286.1; -. [Q9H3R0-3] DR CCDS; CCDS6471.1; -. [Q9H3R0-1] DR RefSeq; NP_001140167.1; NM_001146695.1. [Q9H3R0-3] DR RefSeq; NP_001140168.1; NM_001146696.1. [Q9H3R0-4] DR RefSeq; NP_055876.2; NM_015061.3. [Q9H3R0-1] DR PDB; 2XDP; X-ray; 1.56 A; A=875-995. DR PDB; 2XML; X-ray; 2.55 A; A/B=1-347. DR PDB; 4XDO; X-ray; 1.97 A; A/B=10-347. DR PDB; 4XDP; X-ray; 2.07 A; A/B=10-347. DR PDB; 5FJH; X-ray; 2.10 A; A/B=3-347. DR PDB; 5FJK; X-ray; 1.66 A; A=3-347. DR PDB; 5KR7; X-ray; 1.90 A; A/B=1-350. DR PDBsum; 2XDP; -. DR PDBsum; 2XML; -. DR PDBsum; 4XDO; -. DR PDBsum; 4XDP; -. DR PDBsum; 5FJH; -. DR PDBsum; 5FJK; -. DR PDBsum; 5KR7; -. DR AlphaFoldDB; Q9H3R0; -. DR SMR; Q9H3R0; -. DR BioGRID; 116712; 66. DR DIP; DIP-60098N; -. DR IntAct; Q9H3R0; 42. DR MINT; Q9H3R0; -. DR STRING; 9606.ENSP00000370710; -. DR BindingDB; Q9H3R0; -. DR ChEMBL; CHEMBL6175; -. DR GuidetoPHARMACOLOGY; 2677; -. DR iPTMnet; Q9H3R0; -. DR PhosphoSitePlus; Q9H3R0; -. DR BioMuta; KDM4C; -. DR DMDM; 97536525; -. DR EPD; Q9H3R0; -. DR jPOST; Q9H3R0; -. DR MassIVE; Q9H3R0; -. DR MaxQB; Q9H3R0; -. DR PaxDb; 9606-ENSP00000370710; -. DR PeptideAtlas; Q9H3R0; -. DR ProteomicsDB; 26163; -. DR ProteomicsDB; 27544; -. DR ProteomicsDB; 80741; -. [Q9H3R0-1] DR ProteomicsDB; 80742; -. [Q9H3R0-2] DR Pumba; Q9H3R0; -. DR Antibodypedia; 24299; 399 antibodies from 28 providers. DR DNASU; 23081; -. DR Ensembl; ENST00000381306.7; ENSP00000370707.3; ENSG00000107077.19. [Q9H3R0-2] DR Ensembl; ENST00000381309.8; ENSP00000370710.3; ENSG00000107077.19. [Q9H3R0-1] DR Ensembl; ENST00000536108.5; ENSP00000440656.3; ENSG00000107077.19. [Q9H3R0-4] DR Ensembl; ENST00000543771.5; ENSP00000445427.1; ENSG00000107077.19. [Q9H3R0-3] DR GeneID; 23081; -. DR KEGG; hsa:23081; -. DR MANE-Select; ENST00000381309.8; ENSP00000370710.3; NM_015061.6; NP_055876.2. DR UCSC; uc003zkg.4; human. [Q9H3R0-1] DR AGR; HGNC:17071; -. DR CTD; 23081; -. DR DisGeNET; 23081; -. DR GeneCards; KDM4C; -. DR HGNC; HGNC:17071; KDM4C. DR HPA; ENSG00000107077; Low tissue specificity. DR MIM; 605469; gene. DR neXtProt; NX_Q9H3R0; -. DR OpenTargets; ENSG00000107077; -. DR PharmGKB; PA164721503; -. DR VEuPathDB; HostDB:ENSG00000107077; -. DR eggNOG; KOG0958; Eukaryota. DR GeneTree; ENSGT00940000154930; -. DR HOGENOM; CLU_001442_0_0_1; -. DR InParanoid; Q9H3R0; -. DR OMA; VAKMEPH; -. DR OrthoDB; 48111at2759; -. DR PhylomeDB; Q9H3R0; -. DR TreeFam; TF106449; -. DR BioCyc; MetaCyc:ENSG00000107077-MONOMER; -. DR BRENDA; 1.14.11.27; 2681. DR BRENDA; 1.14.11.66; 2681. DR BRENDA; 1.14.11.69; 2681. DR PathwayCommons; Q9H3R0; -. DR Reactome; R-HSA-3214842; HDMs demethylate histones. DR Reactome; R-HSA-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3. DR SignaLink; Q9H3R0; -. DR SIGNOR; Q9H3R0; -. DR BioGRID-ORCS; 23081; 14 hits in 1173 CRISPR screens. DR ChiTaRS; KDM4C; human. DR EvolutionaryTrace; Q9H3R0; -. DR GeneWiki; JMJD2C; -. DR GenomeRNAi; 23081; -. DR Pharos; Q9H3R0; Tchem. DR PRO; PR:Q9H3R0; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9H3R0; Protein. DR Bgee; ENSG00000107077; Expressed in right hemisphere of cerebellum and 172 other cell types or tissues. DR ExpressionAtlas; Q9H3R0; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0062072; F:H3K9me3 modified histone binding; IMP:BHF-UCL. DR GO; GO:0032452; F:histone demethylase activity; EXP:Reactome. DR GO; GO:0051864; F:histone H3K36 demethylase activity; IDA:UniProtKB. DR GO; GO:0032454; F:histone H3K9 demethylase activity; IDA:UniProtKB. DR GO; GO:0140684; F:histone H3K9me2/H3K9me3 demethylase activity; IDA:UniProtKB. DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:BHF-UCL. DR GO; GO:0030374; F:nuclear receptor coactivator activity; IGI:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0030521; P:androgen receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; TAS:Reactome. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR GO; GO:2000736; P:regulation of stem cell differentiation; IEA:Ensembl. DR GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl. DR CDD; cd15715; ePHD_JMJD2C; 1. DR CDD; cd15577; PHD_JMJD2C; 1. DR CDD; cd20465; Tudor_JMJD2C_rpt1; 1. DR CDD; cd20468; Tudor_JMJD2C_rpt2; 1. DR Gene3D; 2.30.30.140; -; 1. DR Gene3D; 3.10.330.70; -; 1. DR Gene3D; 2.60.120.650; Cupin; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR034732; EPHD. DR InterPro; IPR003347; JmjC_dom. DR InterPro; IPR003349; JmjN. DR InterPro; IPR040477; KDM4-like_Tudor. DR InterPro; IPR002999; Tudor. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR10694; LYSINE-SPECIFIC DEMETHYLASE; 1. DR PANTHER; PTHR10694:SF104; LYSINE-SPECIFIC DEMETHYLASE 4C; 1. DR Pfam; PF02373; JmjC; 1. DR Pfam; PF02375; JmjN; 1. DR Pfam; PF13831; PHD_2; 1. DR Pfam; PF18104; Tudor_2; 2. DR Pfam; PF13832; zf-HC5HC2H_2; 1. DR SMART; SM00558; JmjC; 1. DR SMART; SM00545; JmjN; 1. DR SMART; SM00249; PHD; 2. DR SMART; SM00333; TUDOR; 2. DR SUPFAM; SSF51197; Clavaminate synthase-like; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR SUPFAM; SSF63748; Tudor/PWWP/MBT; 2. DR PROSITE; PS51805; EPHD; 1. DR PROSITE; PS51184; JMJC; 1. DR PROSITE; PS51183; JMJN; 1. DR Genevisible; Q9H3R0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; Dioxygenase; Iron; KW Metal-binding; Nucleus; Oxidoreductase; Reference proteome; Repeat; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1..1056 FT /note="Lysine-specific demethylase 4C" FT /id="PRO_0000183177" FT DOMAIN 16..58 FT /note="JmjN" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00537" FT DOMAIN 144..310 FT /note="JmjC" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538" FT DOMAIN 877..934 FT /note="Tudor 1" FT DOMAIN 935..991 FT /note="Tudor 2" FT ZN_FING 689..747 FT /note="PHD-type 1" FT ZN_FING 752..785 FT /note="C2HC pre-PHD-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT ZN_FING 808..865 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146" FT REGION 370..414 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 423..442 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 480..598 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 506..523 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 134 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:B2RXH2" FT BINDING 190 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT BINDING 192 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT BINDING 200 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250" FT BINDING 208 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:B2RXH2" FT BINDING 236 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21914792" FT BINDING 242 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21914792" FT BINDING 243 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000250|UniProtKB:B2RXH2" FT BINDING 278 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT BINDING 308 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21914792" FT BINDING 310 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21914792" FT VAR_SEQ 1 FT /note="M -> MKHYGLPWKRTEEAAADTALTIM (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046113" FT VAR_SEQ 809..813 FT /note="KCIFC -> GRLGI (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045462" FT VAR_SEQ 814..1056 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045463" FT VAR_SEQ 999..1056 FT /note="STASDMRFEDTFYGADIIQGERKRQRVLSSRFKNEYVADPVYRTFLKSSFQK FT KCQKRQ -> VSAGRCHLGTCQVNSLSSPHVSQAQQETYLGFWINSKKSQCNIFLSGTY FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9872452" FT /id="VSP_018311" FT VARIANT 206 FT /note="E -> D (in dbSNP:rs7864351)" FT /id="VAR_049660" FT VARIANT 396 FT /note="D -> N (in dbSNP:rs2296067)" FT /id="VAR_020340" FT VARIANT 492 FT /note="S -> T (in dbSNP:rs35826653)" FT /evidence="ECO:0000269|PubMed:10987278, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9872452" FT /id="VAR_049661" FT VARIANT 697 FT /note="N -> S (in dbSNP:rs35389625)" FT /id="VAR_049662" FT VARIANT 767 FT /note="Q -> E (in dbSNP:rs1407856)" FT /id="VAR_024681" FT VARIANT 772 FT /note="K -> R (in dbSNP:rs1417290)" FT /evidence="ECO:0000269|PubMed:10987278" FT /id="VAR_049663" FT VARIANT 1039 FT /note="V -> I (in dbSNP:rs913588)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_024682" FT MUTAGEN 190..192 FT /note="HTE->ATA: Abolishes lysine-specific histone FT demethylase activity." FT /evidence="ECO:0000269|PubMed:28262558" FT CONFLICT 155 FT /note="L -> I (in Ref. 1; BAB16102)" FT /evidence="ECO:0000305" FT CONFLICT 514 FT /note="C -> S (in Ref. 3; BAG64946)" FT /evidence="ECO:0000305" FT CONFLICT 807 FT /note="K -> R (in Ref. 3; BAG64946)" FT /evidence="ECO:0000305" FT STRAND 17..19 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 23..26 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 29..38 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 41..44 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 45..49 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 62..66 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 68..71 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 73..80 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 83..90 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 96..103 FT /evidence="ECO:0007829|PDB:5FJK" FT TURN 106..108 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 116..126 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 133..139 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 158..166 FT /evidence="ECO:0007829|PDB:5FJK" FT TURN 171..174 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 177..181 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 186..190 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 197..206 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 208..213 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 215..217 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 218..228 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 230..235 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 239..242 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 245..247 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 249..255 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 260..264 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 269..272 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 277..282 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 284..293 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 299..304 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 309..311 FT /evidence="ECO:0007829|PDB:5FJH" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:4XDP" FT HELIX 320..326 FT /evidence="ECO:0007829|PDB:5FJK" FT TURN 328..330 FT /evidence="ECO:0007829|PDB:5FJK" FT HELIX 331..335 FT /evidence="ECO:0007829|PDB:5FJK" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:5KR7" FT STRAND 898..912 FT /evidence="ECO:0007829|PDB:2XDP" FT STRAND 917..921 FT /evidence="ECO:0007829|PDB:2XDP" FT HELIX 923..925 FT /evidence="ECO:0007829|PDB:2XDP" FT HELIX 931..934 FT /evidence="ECO:0007829|PDB:2XDP" FT STRAND 942..946 FT /evidence="ECO:0007829|PDB:2XDP" FT STRAND 952..969 FT /evidence="ECO:0007829|PDB:2XDP" FT STRAND 975..979 FT /evidence="ECO:0007829|PDB:2XDP" FT HELIX 980..982 FT /evidence="ECO:0007829|PDB:2XDP" FT STRAND 986..988 FT /evidence="ECO:0007829|PDB:2XDP" SQ SEQUENCE 1056 AA; 119982 MW; CBE871D4FAADD06D CRC64; MEVAEVESPL NPSCKIMTFR PSMEEFREFN KYLAYMESKG AHRAGLAKVI PPKEWKPRQC YDDIDNLLIP APIQQMVTGQ SGLFTQYNIQ KKAMTVKEFR QLANSGKYCT PRYLDYEDLE RKYWKNLTFV APIYGADING SIYDEGVDEW NIARLNTVLD VVEEECGISI EGVNTPYLYF GMWKTTFAWH TEDMDLYSIN YLHFGEPKSW YAIPPEHGKR LERLAQGFFP SSSQGCDAFL RHKMTLISPS VLKKYGIPFD KITQEAGEFM ITFPYGYHAG FNHGFNCAES TNFATVRWID YGKVAKLCTC RKDMVKISMD IFVRKFQPDR YQLWKQGKDI YTIDHTKPTP ASTPEVKAWL QRRRKVRKAS RSFQCARSTS KRPKADEEEE VSDEVDGAEV PNPDSVTDDL KVSEKSEAAV KLRNTEASSE EESSASRMQV EQNLSDHIKL SGNSCLSTSV TEDIKTEDDK AYAYRSVPSI SSEADDSIPL SSGYEKPEKS DPSELSWPKS PESCSSVAES NGVLTEGEES DVESHGNGLE PGEIPAVPSG ERNSFKVPSI AEGENKTSKS WRHPLSRPPA RSPMTLVKQQ APSDEELPEV LSIEEEVEET ESWAKPLIHL WQTKSPNFAA EQEYNATVAR MKPHCAICTL LMPYHKPDSS NEENDARWET KLDEVVTSEG KTKPLIPEMC FIYSEENIEY SPPNAFLEED GTSLLISCAK CCVRVHASCY GIPSHEICDG WLCARCKRNA WTAECCLCNL RGGALKQTKN NKWAHVMCAV AVPEVRFTNV PERTQIDVGR IPLQRLKLKC IFCRHRVKRV SGACIQCSYG RCPASFHVTC AHAAGVLMEP DDWPYVVNIT CFRHKVNPNV KSKACEKVIS VGQTVITKHR NTRYYSCRVM AVTSQTFYEV MFDDGSFSRD TFPEDIVSRD CLKLGPPAEG EVVQVKWPDG KLYGAKYFGS NIAHMYQVEF EDGSQIAMKR EDIYTLDEEL PKRVKARFST ASDMRFEDTF YGADIIQGER KRQRVLSSRF KNEYVADPVY RTFLKSSFQK KCQKRQ //