ID IKZF1_HUMAN Reviewed; 519 AA. AC Q13422; A4D260; B4E0Z1; D3DVM5; O00598; Q53XL2; Q69BM4; Q8WVA3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 215. DE RecName: Full=DNA-binding protein Ikaros; DE AltName: Full=Ikaros family zinc finger protein 1; DE AltName: Full=Lymphoid transcription factor LyF-1; GN Name=IKZF1; Synonyms=IK1, IKAROS, LYF1, ZNFN1A1; 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], ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=8964602; DOI=10.1016/0165-2478(95)02479-4; RA Nietfeld W., Meyerhans A.; RT "Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of RT mouse Ikaros/LyF-1."; RL Immunol. Lett. 49:139-141(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=8543809; RA Molnar A., Wu P., Largespada D.A., Vortkamp A., Scherer S., Copeland N.G., RA Jenkins N.A., Bruns G., Georgopoulos K.; RT "The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA RT binding proteins, highly conserved in human and mouse."; RL J. Immunol. 156:585-592(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IKX). RA Sanchez-Tapia E.M., Rodriguez R.E., Gonzalez-Sarmiento R.; RT "Molecular misreading is involved in generation of Ikaros diversity."; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK2). RC TISSUE=Thymus; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK7). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK7). RC TISSUE=Lymph; 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 [10] RP IDENTIFICATION IN THE NURD COMPLEX, INTERACTION WITH SMARCA4 AND CHD4, AND RP FUNCTION. RX PubMed=10204490; DOI=10.1016/s1074-7613(00)80034-5; RA Kim J., Sif S., Jones B., Jackson A., Koipally J., Heller E., Winandy S., RA Viel A., Sawyer A., Ikeda T., Kingston R., Georgopoulos K.; RT "Ikaros DNA-binding proteins direct formation of chromatin remodeling RT complexes in lymphocytes."; RL Immunity 10:345-355(1999). RN [11] RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL TRANSLOCATION RP WITH BCL6. RX PubMed=10753856; RA Hosokawa Y., Maeda Y., Ichinohasama R., Miura I., Taniwaki M., Seto M.; RT "The Ikaros gene, a central regulator of lymphoid differentiation, fuses to RT the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient RT with diffuse large B-cell lymphoma."; RL Blood 95:2719-2721(2000). RN [12] RP INTERACTION WITH IKZF4 AND IKZF5. RX PubMed=10978333; DOI=10.1074/jbc.m005457200; RA Perdomo J., Holmes M., Chong B., Crossley M.; RT "Eos and pegasus, two members of the Ikaros family of proteins with RT distinct DNA binding activities."; RL J. Biol. Chem. 275:38347-38354(2000). RN [13] RP FUNCTION, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=17135265; DOI=10.1074/jbc.m605627200; RA Ronni T., Payne K.J., Ho S., Bradley M.N., Dorsam G., Dovat S.; RT "Human Ikaros function in activated T cells is regulated by coordinated RT expression of its largest isoforms."; RL J. Biol. Chem. 282:2538-2547(2007). RN [14] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=17934067; DOI=10.1182/blood-2007-07-098202; RA Dijon M., Bardin F., Murati A., Batoz M., Chabannon C., Tonnelle C.; RT "The role of Ikaros in human erythroid differentiation."; RL Blood 111:1138-1146(2008). RN [15] RP FUNCTION IN GAMMA SATELLITE DNA-BINDING. RX PubMed=19141594; DOI=10.1101/gr.086496.108; RA Kim J.-H., Ebersole T., Kouprina N., Noskov V.N., Ohzeki J.-I., RA Masumoto H., Mravinac B., Sullivan B.A., Pavlicek A., Dovat S., Pack S.D., RA Kwon Y.-W., Flanagan P.T., Loukinov D., Lobanenkov V., Larionov V.; RT "Human gamma-satellite DNA maintains open chromatin structure and protects RT a transgene from epigenetic silencing."; RL Genome Res. 19:533-544(2009). RN [16] RP INVOLVEMENT IN ACUTE LYMPHOBLASIC LEUKEMIA. RX PubMed=19129520; DOI=10.1056/nejmoa0808253; RA Mullighan C.G., Su X., Zhang J., Radtke I., Phillips L.A., Miller C.B., RA Ma J., Liu W., Cheng C., Schulman B.A., Harvey R.C., Chen I.-M., RA Clifford R.J., Carroll W.L., Reaman G., Bowman W.P., Devidas M., RA Gerhard D.S., Yang W., Relling M.V., Shurtleff S.A., Campana D., RA Borowitz M.J., Pui C.H., Smith M., Hunger S.P., Willman C.L., Downing J.R.; RT "Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia."; RL N. Engl. J. Med. 360:470-480(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63; SER-258; SER-361 AND RP SER-364, AND IDENTIFICATION BY 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION IN DNA-BINDING, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND RP ALTERNATIVE SPLICING. RX PubMed=22106042; DOI=10.1002/pbc.23406; RA Li Z., Song C., Ouyang H., Lai L., Payne K.J., Dovat S.; RT "Cell cycle-specific function of Ikaros in human leukemia."; RL Pediatr. Blood Cancer 59:69-76(2012). RN [20] RP PHOSPHORYLATION AT SER-361 AND SER-364 BY SYK, AND SUBCELLULAR LOCATION. RX PubMed=23071339; DOI=10.1073/pnas.1209828109; RA Uckun F.M., Ma H., Zhang J., Ozer Z., Dovat S., Mao C., Ishkhanian R., RA Goodman P., Qazi S.; RT "Serine phosphorylation by SYK is critical for nuclear localization and RT transcription factor function of Ikaros."; RL Proc. Natl. Acad. Sci. U.S.A. 109:18072-18077(2012). RN [21] RP INVOLVEMENT IN CVID13, VARIANT CVID13 CYS-210, CHARACTERIZATION OF VARIANT RP CVID13 CYS-210, AND SUBCELLULAR LOCATION. RX PubMed=21548011; DOI=10.1002/pbc.23160; RA Goldman F.D., Gurel Z., Al-Zubeidi D., Fried A.J., Icardi M., Song C., RA Dovat S.; RT "Congenital pancytopenia and absence of B lymphocytes in a neonate with a RT mutation in the Ikaros gene."; RL Pediatr. Blood Cancer 58:591-597(2012). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63; SER-261; SER-289; RP SER-298; SER-364; SER-368; SER-427 AND SER-445, AND IDENTIFICATION BY MASS RP 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 [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, 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 [24] RP VARIANTS CVID13 GLN-162; LEU-162; ARG-167 AND GLN-184, CHARACTERIZATION OF RP VARIANTS CVID13 GLN-162; LEU-162; ARG-167; GLN-184 AND CYS-210, AND RP MUTAGENESIS OF ASN-159 AND HIS-191. RX PubMed=26981933; DOI=10.1056/nejmoa1512234; RA Kuehn H.S., Boisson B., Cunningham-Rundles C., Reichenbach J., RA Stray-Pedersen A., Gelfand E.W., Maffucci P., Pierce K.R., Abbott J.K., RA Voelkerding K.V., South S.T., Augustine N.H., Bush J.S., Dolen W.K., RA Wray B.B., Itan Y., Cobat A., Sorte H.S., Ganesan S., Prader S., RA Martins T.B., Lawrence M.G., Orange J.S., Calvo K.R., Niemela J.E., RA Casanova J.L., Fleisher T.A., Hill H.R., Kumanovics A., Conley M.E., RA Rosenzweig S.D.; RT "Loss of B Cells in Patients with Heterozygous Mutations in IKAROS."; RL N. Engl. J. Med. 374:1032-1043(2016). CC -!- FUNCTION: Transcription regulator of hematopoietic cell differentiation CC (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, CC PubMed:19141594). Plays a role in the development of lymphocytes, CC B- and T-cells. Binds and activates the enhancer (delta-A element) of CC the CD3-delta gene. Repressor of the TDT (fikzfterminal CC deoxynucleotidyltransferase) gene during thymocyte differentiation. CC Regulates transcription through association with both HDAC-dependent CC and HDAC-independent complexes. Targets the 2 chromatin-remodeling CC complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), CC to the beta-globin locus in adult erythrocytes. Increases normal CC apoptosis in adult erythroid cells. Confers early temporal competence CC to retinal progenitor cells (RPCs) (By similarity). Function is CC isoform-specific and is modulated by dominant-negative inactive CC isoforms (PubMed:17135265, PubMed:17934067). CC {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, CC ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, CC ECO:0000269|PubMed:19141594}. CC -!- SUBUNIT: Heterodimer formed by the various isoforms; this modulates CC transcription regulator activity (PubMed:17135265, PubMed:17934067). CC Heterodimer with other IKAROS family members. Interacts with IKZF4 AND CC IKZF5 (PubMed:10978333). Component of the chromatin-remodeling NuRD CC repressor complex which includes at least HDAC1, HDAC2, RBBP4, RBBP7, CC IKZF1, MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4. Interacts directly with CC the CHD4 component of the NuRD complex. Interacts directly with CC SMARCA4; the interaction associates IKFZ1 with the BAF complex CC (PubMed:10204490). Interacts with SUMO1; the interaction sumoylates CC IKAROS, promoted by PIAS2 and PIAS3. Interacts with PIAS2 (isoform CC alpha); the interaction promotes sumoylation and reduces transcription CC repression. Interacts, to a lesser extent, with PIAS3. Interacts with CC PPP1CC; the interaction targets PPP1CC to pericentromeric CC heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it CC from degradation. Interacts with IKZF3 (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:10978333, CC ECO:0000305|PubMed:17135265, ECO:0000305|PubMed:17934067}. CC -!- INTERACTION: CC Q13422; Q8WTP8: AEN; NbExp=3; IntAct=EBI-745305, EBI-8637627; CC Q13422; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-745305, EBI-8643161; CC Q13422; Q96Q83: ALKBH3; NbExp=5; IntAct=EBI-745305, EBI-6658697; CC Q13422; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-745305, EBI-541426; CC Q13422; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-745305, EBI-742909; CC Q13422; Q7L5A3: ATOSB; NbExp=6; IntAct=EBI-745305, EBI-745689; CC Q13422; Q13895: BYSL; NbExp=5; IntAct=EBI-745305, EBI-358049; CC Q13422; Q8IYL3: C1orf174; NbExp=4; IntAct=EBI-745305, EBI-715898; CC Q13422; Q9H7E9: C8orf33; NbExp=3; IntAct=EBI-745305, EBI-715389; CC Q13422; Q9HC52: CBX8; NbExp=3; IntAct=EBI-745305, EBI-712912; CC Q13422; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-745305, EBI-10181988; CC Q13422; P61024: CKS1B; NbExp=3; IntAct=EBI-745305, EBI-456371; CC Q13422; Q13363-2: CTBP1; NbExp=3; IntAct=EBI-745305, EBI-10171858; CC Q13422; P56545: CTBP2; NbExp=5; IntAct=EBI-745305, EBI-741533; CC Q13422; P56545-3: CTBP2; NbExp=3; IntAct=EBI-745305, EBI-10171902; CC Q13422; O43602: DCX; NbExp=4; IntAct=EBI-745305, EBI-8646694; CC Q13422; P26196: DDX6; NbExp=3; IntAct=EBI-745305, EBI-351257; CC Q13422; Q92630: DYRK2; NbExp=3; IntAct=EBI-745305, EBI-749432; CC Q13422; Q3B820: FAM161A; NbExp=3; IntAct=EBI-745305, EBI-719941; CC Q13422; Q9Y247: FAM50B; NbExp=4; IntAct=EBI-745305, EBI-742802; CC Q13422; Q5TZK3: FAM74A6; NbExp=3; IntAct=EBI-745305, EBI-10247271; CC Q13422; P61328: FGF12; NbExp=3; IntAct=EBI-745305, EBI-6657662; CC Q13422; Q96NE9: FRMD6; NbExp=3; IntAct=EBI-745305, EBI-741729; CC Q13422; O76003: GLRX3; NbExp=3; IntAct=EBI-745305, EBI-374781; CC Q13422; Q8NEA9: GMCL2; NbExp=3; IntAct=EBI-745305, EBI-745707; CC Q13422; Q9H1K1: ISCU; NbExp=3; IntAct=EBI-745305, EBI-1047335; CC Q13422; Q8TAP4: LMO3; NbExp=3; IntAct=EBI-745305, EBI-742259; CC Q13422; Q9Y4Z0: LSM4; NbExp=3; IntAct=EBI-745305, EBI-372521; CC Q13422; Q9UI95: MAD2L2; NbExp=3; IntAct=EBI-745305, EBI-77889; CC Q13422; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-745305, EBI-348259; CC Q13422; Q9UBU8: MORF4L1; NbExp=3; IntAct=EBI-745305, EBI-399246; CC Q13422; Q15014: MORF4L2; NbExp=3; IntAct=EBI-745305, EBI-399257; CC Q13422; Q13330: MTA1; NbExp=3; IntAct=EBI-745305, EBI-714236; CC Q13422; Q9HC98: NEK6; NbExp=3; IntAct=EBI-745305, EBI-740364; CC Q13422; Q9BVI4: NOC4L; NbExp=3; IntAct=EBI-745305, EBI-395927; CC Q13422; Q13526: PIN1; NbExp=3; IntAct=EBI-745305, EBI-714158; CC Q13422; Q96T60: PNKP; NbExp=3; IntAct=EBI-745305, EBI-1045072; CC Q13422; O43741: PRKAB2; NbExp=3; IntAct=EBI-745305, EBI-1053424; CC Q13422; P25786: PSMA1; NbExp=3; IntAct=EBI-745305, EBI-359352; CC Q13422; P25789: PSMA4; NbExp=3; IntAct=EBI-745305, EBI-359310; CC Q13422; O75771: RAD51D; NbExp=5; IntAct=EBI-745305, EBI-1055693; CC Q13422; P57060: RWDD2B; NbExp=4; IntAct=EBI-745305, EBI-724442; CC Q13422; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-745305, EBI-748391; CC Q13422; O00560: SDCBP; NbExp=3; IntAct=EBI-745305, EBI-727004; CC Q13422; Q9H788: SH2D4A; NbExp=3; IntAct=EBI-745305, EBI-747035; CC Q13422; Q9NUL5: SHFL; NbExp=3; IntAct=EBI-745305, EBI-10313866; CC Q13422; P62306: SNRPF; NbExp=3; IntAct=EBI-745305, EBI-356900; CC Q13422; Q13573: SNW1; NbExp=3; IntAct=EBI-745305, EBI-632715; CC Q13422; Q9H0A9: SPATC1L; NbExp=3; IntAct=EBI-745305, EBI-372911; CC Q13422; Q9BSW7: SYT17; NbExp=3; IntAct=EBI-745305, EBI-745392; CC Q13422; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-745305, EBI-10180829; CC Q13422; Q15007: WTAP; NbExp=3; IntAct=EBI-745305, EBI-751647; CC Q13422; Q96NC0: ZMAT2; NbExp=3; IntAct=EBI-745305, EBI-2682299; CC Q13422; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-745305, EBI-740727; CC Q13422; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-745305, EBI-745520; CC Q13422; A8K932; NbExp=3; IntAct=EBI-745305, EBI-10174671; CC Q13422-7; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-11522367, EBI-8643161; CC Q13422-7; A1A5B0: ANKRD36; NbExp=3; IntAct=EBI-11522367, EBI-14100900; CC Q13422-7; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-11522367, EBI-541426; CC Q13422-7; Q7L5A3: ATOSB; NbExp=3; IntAct=EBI-11522367, EBI-745689; CC Q13422-7; Q99728: BARD1; NbExp=3; IntAct=EBI-11522367, EBI-473181; CC Q13422-7; Q13895: BYSL; NbExp=3; IntAct=EBI-11522367, EBI-358049; CC Q13422-7; Q8IYL3: C1orf174; NbExp=3; IntAct=EBI-11522367, EBI-715898; CC Q13422-7; Q9H7E9: C8orf33; NbExp=3; IntAct=EBI-11522367, EBI-715389; CC Q13422-7; Q9HC52: CBX8; NbExp=3; IntAct=EBI-11522367, EBI-712912; CC Q13422-7; Q8N715: CCDC185; NbExp=3; IntAct=EBI-11522367, EBI-740814; CC Q13422-7; O00311: CDC7; NbExp=3; IntAct=EBI-11522367, EBI-374980; CC Q13422-7; Q8IVW4: CDKL3; NbExp=3; IntAct=EBI-11522367, EBI-3919850; CC Q13422-7; P61024: CKS1B; NbExp=3; IntAct=EBI-11522367, EBI-456371; CC Q13422-7; Q96SW2-2: CRBN; NbExp=2; IntAct=EBI-11522367, EBI-10693561; CC Q13422-7; Q13363-2: CTBP1; NbExp=5; IntAct=EBI-11522367, EBI-10171858; CC Q13422-7; P56545-3: CTBP2; NbExp=3; IntAct=EBI-11522367, EBI-10171902; CC Q13422-7; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-11522367, EBI-5453285; CC Q13422-7; O43602-2: DCX; NbExp=3; IntAct=EBI-11522367, EBI-14148644; CC Q13422-7; P26196: DDX6; NbExp=3; IntAct=EBI-11522367, EBI-351257; CC Q13422-7; Q14192: FHL2; NbExp=3; IntAct=EBI-11522367, EBI-701903; CC Q13422-7; Q96NE9-2: FRMD6; NbExp=3; IntAct=EBI-11522367, EBI-13213391; CC Q13422-7; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-11522367, EBI-11522367; CC Q13422-7; A0A0S2Z5S9: LHX4; NbExp=3; IntAct=EBI-11522367, EBI-16429099; CC Q13422-7; P25800: LMO1; NbExp=3; IntAct=EBI-11522367, EBI-8639312; CC Q13422-7; P25791-3: LMO2; NbExp=3; IntAct=EBI-11522367, EBI-11959475; CC Q13422-7; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-11522367, EBI-11742507; CC Q13422-7; P61968: LMO4; NbExp=3; IntAct=EBI-11522367, EBI-2798728; CC Q13422-7; Q96A72: MAGOHB; NbExp=3; IntAct=EBI-11522367, EBI-746778; CC Q13422-7; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-11522367, EBI-726739; CC Q13422-7; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-11522367, EBI-348259; CC Q13422-7; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11522367, EBI-16439278; CC Q13422-7; P00540: MOS; NbExp=3; IntAct=EBI-11522367, EBI-1757866; CC Q13422-7; Q9Y5B8: NME7; NbExp=6; IntAct=EBI-11522367, EBI-744782; CC Q13422-7; O43809: NUDT21; NbExp=3; IntAct=EBI-11522367, EBI-355720; CC Q13422-7; O75928-2: PIAS2; NbExp=3; IntAct=EBI-11522367, EBI-348567; CC Q13422-7; Q13526: PIN1; NbExp=3; IntAct=EBI-11522367, EBI-714158; CC Q13422-7; Q96T60: PNKP; NbExp=3; IntAct=EBI-11522367, EBI-1045072; CC Q13422-7; O60437: PPL; NbExp=3; IntAct=EBI-11522367, EBI-368321; CC Q13422-7; P54646: PRKAA2; NbExp=3; IntAct=EBI-11522367, EBI-1383852; CC Q13422-7; Q99633: PRPF18; NbExp=3; IntAct=EBI-11522367, EBI-2798416; CC Q13422-7; P25789: PSMA4; NbExp=3; IntAct=EBI-11522367, EBI-359310; CC Q13422-7; P47897: QARS1; NbExp=3; IntAct=EBI-11522367, EBI-347462; CC Q13422-7; O75771: RAD51D; NbExp=3; IntAct=EBI-11522367, EBI-1055693; CC Q13422-7; Q6ZSC3: RBM43; NbExp=3; IntAct=EBI-11522367, EBI-2880658; CC Q13422-7; P78317: RNF4; NbExp=3; IntAct=EBI-11522367, EBI-2340927; CC Q13422-7; A0A0S2Z4G9: RNF6; NbExp=3; IntAct=EBI-11522367, EBI-16428950; CC Q13422-7; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-11522367, EBI-748391; CC Q13422-7; P09661: SNRPA1; NbExp=3; IntAct=EBI-11522367, EBI-876439; CC Q13422-7; P62306: SNRPF; NbExp=3; IntAct=EBI-11522367, EBI-356900; CC Q13422-7; Q15560: TCEA2; NbExp=3; IntAct=EBI-11522367, EBI-710310; CC Q13422-7; Q5T7W7: TSTD2; NbExp=3; IntAct=EBI-11522367, EBI-8994397; CC Q13422-7; P42681: TXK; NbExp=3; IntAct=EBI-11522367, EBI-7877438; CC Q13422-7; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-11522367, EBI-10180829; CC Q13422-7; Q15007: WTAP; NbExp=7; IntAct=EBI-11522367, EBI-751647; CC Q13422-7; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-11522367, EBI-740727; CC Q13422-7; Q9UK33: ZNF580; NbExp=3; IntAct=EBI-11522367, EBI-746277; CC Q13422-7; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-11522367, EBI-6427977; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17135265, CC ECO:0000269|PubMed:21548011, ECO:0000269|PubMed:22106042, CC ECO:0000269|PubMed:23071339}. Note=In resting lymphocytes, distributed CC diffusely throughout the nucleus. Localizes to pericentromeric CC heterochromatin in proliferating cells. This localization requires DNA CC binding which is regulated by phosphorylation / dephosphorylation CC events. {ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:22106042}. CC -!- SUBCELLULAR LOCATION: [Isoform Ik2]: Nucleus. Note=In resting CC lymphocytes, distributed diffusely throughout the nucleus. Localizes to CC pericentromeric heterochromatin in proliferating cells. This CC localization requires DNA binding which is regulated by phosphorylation CC / dephosphorylation events (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform Ik6]: Cytoplasm {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=Ik1; CC IsoId=Q13422-1; Sequence=Displayed; CC Name=Ik2; CC IsoId=Q13422-2; Sequence=VSP_006848; CC Name=Ik3; CC IsoId=Q13422-3; Sequence=VSP_006850; CC Name=Ik4; CC IsoId=Q13422-4; Sequence=VSP_006847, VSP_006850; CC Name=Ik5; CC IsoId=Q13422-5; Sequence=VSP_006852; CC Name=Ik6; CC IsoId=Q13422-6; Sequence=VSP_006849; CC Name=Ik7; CC IsoId=Q13422-7; Sequence=VSP_006851; CC Name=Ikx; CC IsoId=Q13422-8; Sequence=VSP_006851, VSP_053404, VSP_053405; CC -!- TISSUE SPECIFICITY: Abundantly expressed in thymus, spleen and CC peripheral blood Leukocytes and lymph nodes. Lower expression in bone CC marrow and small intestine. {ECO:0000269|PubMed:8543809, CC ECO:0000269|PubMed:8964602}. CC -!- DOMAIN: The N-terminal zinc-fingers 2 and 3 are required for DNA CC binding as well as for targeting IKFZ1 to pericentromeric CC heterochromatin. {ECO:0000250}. CC -!- DOMAIN: The C-terminal zinc-finger domain is required for dimerization. CC {ECO:0000250}. CC -!- PTM: Phosphorylation controls cell-cycle progression from late G(1) CC stage to S stage. Hyperphosphorylated during G2/M phase. CC Dephosphorylated state during late G(1) phase. Phosphorylation on Thr- CC 140 is required for DNA and pericentromeric location during mitosis. CC CK2 is the main kinase, in vitro. GSK3 and CDK may also contribute to CC phosphorylation of the C-terminal serine and threonine residues. CC Phosphorylation on these C-terminal residues reduces the DNA-binding CC ability. Phosphorylation/dephosphorylation events on Ser-13 and Ser-295 CC regulate TDT expression during thymocyte differentiation. CC Dephosphorylation by protein phosphatase 1 regulates stability and CC pericentromeric heterochromatin location. Phosphorylated in both CC lymphoid and non-lymphoid tissues (By similarity). Phosphorylation at CC Ser-361 and Ser-364 downstream of SYK induces nuclear translocation. CC {ECO:0000250, ECO:0000269|PubMed:22106042, CC ECO:0000269|PubMed:23071339}. CC -!- PTM: Sumoylated. Simultaneous sumoylation on the 2 sites results in a CC loss of both HDAC-dependent and HDAC-independent repression. Has no CC effect on pericentromeric heterochromatin location. Desumoylated by CC SENP1 (By similarity). {ECO:0000250}. CC -!- PTM: Polyubiquitinated. {ECO:0000250}. CC -!- DISEASE: Note=Defects in IKZF1 are frequent occurrences (28.6%) in CC acute lymphoblasic leukemia (ALL). Such alterations or deletions lead CC to poor prognosis for ALL. CC -!- DISEASE: Note=Chromosomal aberrations involving IKZF1 are a cause of B- CC cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;7)(q27;p12), CC with BCL6. CC -!- DISEASE: Immunodeficiency, common variable, 13 (CVID13) [MIM:616873]: A CC primary immunodeficiency characterized by antibody deficiency, CC hypogammaglobulinemia, recurrent bacterial infections and an inability CC to mount an antibody response to antigen. CVID13 is an autosomal CC dominant disease associated with a striking decrease in B-cell numbers. CC {ECO:0000269|PubMed:21548011, ECO:0000269|PubMed:26981933}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/258/Ikaros"; 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; U40462; AAC50459.1; -; mRNA. DR EMBL; S80876; AAB50683.1; -; mRNA. DR EMBL; AY377974; AAR84585.1; -; mRNA. DR EMBL; AK303586; BAG64603.1; -; mRNA. DR EMBL; BT009836; AAP88838.1; -; mRNA. DR EMBL; AC124014; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC233268; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471128; EAW60977.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60978.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60981.1; -; Genomic_DNA. DR EMBL; CH236955; EAL23900.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60979.1; -; Genomic_DNA. DR EMBL; BC018349; AAH18349.1; -; mRNA. DR CCDS; CCDS59055.1; -. [Q13422-7] DR CCDS; CCDS69299.1; -. [Q13422-5] DR CCDS; CCDS75596.1; -. [Q13422-1] DR CCDS; CCDS78233.1; -. [Q13422-2] DR RefSeq; NP_001207694.1; NM_001220765.2. [Q13422-7] DR RefSeq; NP_001207696.1; NM_001220767.2. DR RefSeq; NP_001207697.1; NM_001220768.2. [Q13422-3] DR RefSeq; NP_001207699.1; NM_001220770.2. DR RefSeq; NP_001207700.1; NM_001220771.2. [Q13422-5] DR RefSeq; NP_001278766.1; NM_001291837.1. [Q13422-7] DR RefSeq; NP_001278767.1; NM_001291838.1. [Q13422-2] DR RefSeq; NP_001278768.1; NM_001291839.1. DR RefSeq; NP_001278769.1; NM_001291840.1. [Q13422-6] DR RefSeq; NP_001278770.1; NM_001291841.1. DR RefSeq; NP_001278771.1; NM_001291842.1. DR RefSeq; NP_001278772.1; NM_001291843.1. DR RefSeq; NP_001278773.1; NM_001291844.1. DR RefSeq; NP_006051.1; NM_006060.5. [Q13422-1] DR RefSeq; XP_011513370.1; XM_011515068.2. DR RefSeq; XP_011513371.1; XM_011515069.2. DR RefSeq; XP_011513377.1; XM_011515075.2. DR RefSeq; XP_011513378.1; XM_011515076.2. DR RefSeq; XP_016867157.1; XM_017011668.1. [Q13422-2] DR PDB; 6H0F; X-ray; 3.25 A; C/F/I/L=141-174. DR PDB; 8D7Z; EM; 3.10 A; C=112-196. DR PDB; 8D80; EM; 3.60 A; C=112-196. DR PDBsum; 6H0F; -. DR PDBsum; 8D7Z; -. DR PDBsum; 8D80; -. DR AlphaFoldDB; Q13422; -. DR EMDB; EMD-27240; -. DR EMDB; EMD-27241; -. DR SMR; Q13422; -. DR BioGRID; 115604; 304. DR DIP; DIP-41110N; -. DR ELM; Q13422; -. DR IntAct; Q13422; 134. DR MINT; Q13422; -. DR STRING; 9606.ENSP00000331614; -. DR BindingDB; Q13422; -. DR ChEMBL; CHEMBL4739685; -. DR GlyCosmos; Q13422; 3 sites, 2 glycans. DR GlyGen; Q13422; 3 sites, 2 O-linked glycans (3 sites). DR iPTMnet; Q13422; -. DR MetOSite; Q13422; -. DR PhosphoSitePlus; Q13422; -. DR BioMuta; IKZF1; -. DR DMDM; 3913926; -. DR EPD; Q13422; -. DR jPOST; Q13422; -. DR MassIVE; Q13422; -. DR MaxQB; Q13422; -. DR PaxDb; 9606-ENSP00000331614; -. DR PeptideAtlas; Q13422; -. DR ProteomicsDB; 59401; -. [Q13422-1] DR ProteomicsDB; 59402; -. [Q13422-2] DR ProteomicsDB; 59403; -. [Q13422-3] DR ProteomicsDB; 59404; -. [Q13422-4] DR ProteomicsDB; 59405; -. [Q13422-5] DR ProteomicsDB; 59406; -. [Q13422-6] DR ProteomicsDB; 59407; -. [Q13422-7] DR ProteomicsDB; 66152; -. DR Pumba; Q13422; -. DR Antibodypedia; 3980; 667 antibodies from 47 providers. DR DNASU; 10320; -. DR Ensembl; ENST00000331340.8; ENSP00000331614.3; ENSG00000185811.21. [Q13422-1] DR Ensembl; ENST00000359197.9; ENSP00000352123.5; ENSG00000185811.21. [Q13422-7] DR Ensembl; ENST00000438033.5; ENSP00000396554.1; ENSG00000185811.21. [Q13422-2] DR Ensembl; ENST00000439701.2; ENSP00000413025.1; ENSG00000185811.21. [Q13422-7] DR Ensembl; ENST00000698575.1; ENSP00000513806.1; ENSG00000185811.21. [Q13422-5] DR GeneID; 10320; -. DR KEGG; hsa:10320; -. DR MANE-Select; ENST00000331340.8; ENSP00000331614.3; NM_006060.6; NP_006051.1. DR UCSC; uc003tow.5; human. [Q13422-1] DR AGR; HGNC:13176; -. DR CTD; 10320; -. DR DisGeNET; 10320; -. DR GeneCards; IKZF1; -. DR HGNC; HGNC:13176; IKZF1. DR HPA; ENSG00000185811; Group enriched (bone marrow, lymphoid tissue). DR MalaCards; IKZF1; -. DR MIM; 603023; gene. DR MIM; 616873; phenotype. DR neXtProt; NX_Q13422; -. DR OpenTargets; ENSG00000185811; -. DR Orphanet; 585909; B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2). DR Orphanet; 317473; Pancytopenia due to IKZF1 mutations. DR Orphanet; 36426; Stevens-Johnson syndrome. DR PharmGKB; PA37748; -. DR VEuPathDB; HostDB:ENSG00000185811; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000156782; -. DR HOGENOM; CLU_025502_2_0_1; -. DR InParanoid; Q13422; -. DR OMA; KAYKCEH; -. DR OrthoDB; 4179080at2759; -. DR PhylomeDB; Q13422; -. DR TreeFam; TF331189; -. DR PathwayCommons; Q13422; -. DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription. [Q13422-1] DR SignaLink; Q13422; -. DR SIGNOR; Q13422; -. DR BioGRID-ORCS; 10320; 38 hits in 1187 CRISPR screens. DR ChiTaRS; IKZF1; human. DR GeneWiki; IKZF1; -. DR GenomeRNAi; 10320; -. DR Pharos; Q13422; Tbio. DR PRO; PR:Q13422; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q13422; Protein. DR Bgee; ENSG00000185811; Expressed in leukocyte and 163 other cell types or tissues. DR ExpressionAtlas; Q13422; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005721; C:pericentric heterochromatin; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0019904; F:protein domain specific binding; IPI:CAFA. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:0030098; P:lymphocyte differentiation; IMP:UniProtKB. DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 5. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR24404:SF36; DNA-BINDING PROTEIN IKAROS; 1. DR PANTHER; PTHR24404; ZINC FINGER PROTEIN; 1. DR Pfam; PF00096; zf-C2H2; 3. DR SMART; SM00355; ZnF_C2H2; 6. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. DR Genevisible; Q13422; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cell cycle; KW Chromatin regulator; Chromosomal rearrangement; Cytoplasm; KW Developmental protein; Disease variant; DNA-binding; Isopeptide bond; KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1..519 FT /note="DNA-binding protein Ikaros" FT /id="PRO_0000047094" FT ZN_FING 117..139 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 145..167 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 173..195 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 201..224 FT /note="C2H2-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 462..484 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 490..514 FT /note="C2H2-type 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 1..72 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 154..163 FT /note="Required for both high-affinity DNA binding and FT pericentromeric heterochromatin localization" FT /evidence="ECO:0000250" FT REGION 180..195 FT /note="Required for both high-affinity DNA binding and FT pericentromeric heterochromatin localization" FT /evidence="ECO:0000250" FT REGION 381..406 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 468..471 FT /note="Required for binding PP1CC" FT /evidence="ECO:0000250" FT COMPBIAS 37..61 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 386..406 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 159 FT /note="Required for both pericentromeric heterochromatin FT localization and complete DNA binding" FT /evidence="ECO:0000250" FT SITE 162 FT /note="Required for both pericentromeric heterochromatin FT localization and complete DNA binding" FT /evidence="ECO:0000250" FT SITE 188 FT /note="Required for both pericentromeric heterochromatin FT localization and DNA binding" FT /evidence="ECO:0000250" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 23 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 63 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 101 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 140 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 168 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 196 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 258 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 261 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 289 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 295 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 298 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 361 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23071339, FT ECO:0007744|PubMed:19690332" FT MOD_RES 364 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23071339, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 368 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 389 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 391 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 397 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 398 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q03267" FT MOD_RES 427 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 445 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT CROSSLNK 58 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT CROSSLNK 241 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT VAR_SEQ 10..53 FT /note="Missing (in isoform Ik4)" FT /evidence="ECO:0000305" FT /id="VSP_006847" FT VAR_SEQ 54..283 FT /note="Missing (in isoform Ik6)" FT /evidence="ECO:0000305" FT /id="VSP_006849" FT VAR_SEQ 54..140 FT /note="Missing (in isoform Ik2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_006848" FT VAR_SEQ 141..283 FT /note="Missing (in isoform Ik5)" FT /evidence="ECO:0000305" FT /id="VSP_006852" FT VAR_SEQ 197..283 FT /note="Missing (in isoform Ik3 and isoform Ik4)" FT /evidence="ECO:0000305" FT /id="VSP_006850" FT VAR_SEQ 197..238 FT /note="Missing (in isoform Ik7 and isoform Ikx)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3, FT ECO:0000303|Ref.5" FT /id="VSP_006851" FT VAR_SEQ 260..268 FT /note="RSLVLDRLA -> ISRAGQTSK (in isoform Ikx)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_053404" FT VAR_SEQ 269..519 FT /note="Missing (in isoform Ikx)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_053405" FT VARIANT 162 FT /note="R -> L (in CVID13; abolishes binding to DNA; has FT diffuse nuclear localization; dbSNP:rs770551610)" FT /evidence="ECO:0000269|PubMed:26981933" FT /id="VAR_076401" FT VARIANT 162 FT /note="R -> Q (in CVID13; abolishes binding to DNA; has FT diffuse nuclear localization; dbSNP:rs770551610)" FT /evidence="ECO:0000269|PubMed:26981933" FT /id="VAR_076402" FT VARIANT 167 FT /note="H -> R (in CVID13; abolishes binding to DNA; has FT diffuse nuclear localization; dbSNP:rs869312884)" FT /evidence="ECO:0000269|PubMed:26981933" FT /id="VAR_076403" FT VARIANT 184 FT /note="R -> Q (in CVID13; abolishes binding to DNA; has FT diffuse nuclear localization; dbSNP:rs869312885)" FT /evidence="ECO:0000269|PubMed:26981933" FT /id="VAR_076404" FT VARIANT 210 FT /note="Y -> C (in CVID13; decreases binding to FT pericentromeric heterochromatin DNA; has diffuse nuclear FT localization; dbSNP:rs869312883)" FT /evidence="ECO:0000269|PubMed:21548011, FT ECO:0000269|PubMed:26981933" FT /id="VAR_076405" FT MUTAGEN 159 FT /note="N->A: Abolishes binding to DNA and has diffuse FT nuclear localization." FT /evidence="ECO:0000269|PubMed:26981933" FT MUTAGEN 191 FT /note="H->R: Abolishes binding to DNA and has diffuse FT nuclear localization." FT /evidence="ECO:0000269|PubMed:26981933" FT CONFLICT 11..12 FT /note="QV -> FS (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 214 FT /note="S -> T (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 245 FT /note="N -> K (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 296 FT /note="Missing (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 298 FT /note="S -> T (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 352..355 FT /note="KPLA -> RRS (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 372 FT /note="N -> Y (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT CONFLICT 420..426 FT /note="PHARNGL -> RRAQRV (in Ref. 2; AAB50683)" FT /evidence="ECO:0000305" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:8D7Z" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:8D7Z" FT HELIX 158..167 FT /evidence="ECO:0007829|PDB:8D7Z" SQ SEQUENCE 519 AA; 57528 MW; 7B0129C4E3FE41A8 CRC64; MDADEGQDMS QVSGKESPPV SDTPDEGDEP MPIPEDLSTT SGGQQSSKSD RVVASNVKVE TQSDEENGRA CEMNGEECAE DLRMLDASGE KMNGSHRDQG SSALSGVGGI RLPNGKLKCD ICGIICIGPN VLMVHKRSHT GERPFQCNQC GASFTQKGNL LRHIKLHSGE KPFKCHLCNY ACRRRDALTG HLRTHSVGKP HKCGYCGRSY KQRSSLEEHK ERCHNYLESM GLPGTLYPVI KEETNHSEMA EDLCKIGSER SLVLDRLASN VAKRKSSMPQ KFLGDKGLSD TPYDSSASYE KENEMMKSHV MDQAINNAIN YLGAESLRPL VQTPPGGSEV VPVISPMYQL HKPLAEGTPR SNHSAQDSAV ENLLLLSKAK LVPSEREASP SNSCQDSTDT ESNNEEQRSG LIYLTNHIAP HARNGLSLKE EHRAYDLLRA ASENSQDALR VVSTSGEQMK VYKCEHCRVL FLDHVMYTIH MGCHGFRDPF ECNMCGYHSQ DRYEFSSHIT RGEHRFHMS //