ID NANOG_MOUSE Reviewed; 305 AA. AC Q80Z64; Q6SMR1; Q7TN85; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 27-MAR-2024, entry version 165. DE RecName: Full=Homeobox protein NANOG; DE AltName: Full=ES cell-associated protein 4; DE AltName: Full=Early embryo specific expression NK-type homeobox protein; DE AltName: Full=Homeobox transcription factor Nanog; GN Name=Nanog; Synonyms=Ecat4, Enk; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DNA-BINDING, RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=12787504; DOI=10.1016/s0092-8674(03)00393-3; RA Mitsui K., Tokuzawa Y., Itoh H., Segawa K., Murakami M., Takahashi K., RA Maruyama M., Maeda M., Yamanaka S.; RT "The homeoprotein Nanog is required for maintenance of pluripotency in RT mouse epiblast and ES cells."; RL Cell 113:631-642(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DEVELOPMENTAL STAGE, AND RP TISSUE SPECIFICITY. RC STRAIN=129/Ola; TISSUE=Embryonic stem cell; RX PubMed=12787505; DOI=10.1016/s0092-8674(03)00392-1; RA Chambers I., Colby D., Robertson M., Nichols J., Lee S., Tweedie S., RA Smith A.; RT "Functional expression cloning of Nanog, a pluripotency sustaining factor RT in embryonic stem cells."; RL Cell 113:643-655(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE. RC STRAIN=FVB/NJ; TISSUE=Embryonic stem cell; RX PubMed=12609610; DOI=10.1016/s1567-133x(03)00005-x; RA Wang S.-H., Tsai M.-S., Chiang M.-F., Li H.; RT "A novel NK-type homeobox gene, ENK (early embryo specific NK), RT preferentially expressed in embryonic stem cells."; RL Gene Expr. Patterns 3:99-103(2003). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), DEVELOPMENTAL STAGE, AND RP TISSUE SPECIFICITY. RC STRAIN=C57BL/6J; RX PubMed=15108323; DOI=10.1002/dvdy.20034; RA Hart A.H., Hartley L., Ibrahim M., Robb L.; RT "Identification, cloning and expression analysis of the pluripotency RT promoting Nanog genes in mouse and human."; RL Dev. Dyn. 230:187-198(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [6] RP FUNCTION. RX PubMed=14728807; DOI=10.1038/sj.cr.7290193; RA Pan G.J., Pei D.Q.; RT "Identification of two distinct transactivation domains in the pluripotency RT sustaining factor nanog."; RL Cell Res. 13:499-502(2003). RN [7] RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=15939376; DOI=10.1016/j.modgep.2005.03.001; RA Yamaguchi S., Kimura H., Tada M., Nakatsuji N., Tada T.; RT "Nanog expression in mouse germ cell development."; RL Gene Expr. Patterns 5:639-646(2005). RN [8] RP FUNCTION, AND DNA-BINDING. RX PubMed=15502159; DOI=10.1074/jbc.m407847200; RA Pan G., Pei D.; RT "The stem cell pluripotency factor NANOG activates transcription with two RT unusually potent subdomains at its C terminus."; RL J. Biol. Chem. 280:1401-1407(2005). RN [9] RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=15582778; DOI=10.1016/j.mod.2004.08.008; RA Hatano S.Y., Tada M., Kimura H., Yamaguchi S., Kono T., Nakano T., RA Suemori H., Nakatsuji N., Tada T.; RT "Pluripotential competence of cells associated with Nanog activity."; RL Mech. Dev. 122:67-79(2005). RN [10] RP INDUCTION. RX PubMed=15619621; DOI=10.1038/ncb1211; RA Lin T., Chao C., Saito S., Mazur S.J., Murphy M.E., Appella E., Xu Y.; RT "p53 induces differentiation of mouse embryonic stem cells by suppressing RT Nanog expression."; RL Nat. Cell Biol. 7:165-171(2005). RN [11] RP INDUCTION. RX PubMed=16790525; DOI=10.1096/fj.05-5543fje; RA Pan G., Li J., Zhou Y., Zheng H., Pei D.; RT "A negative feedback loop of transcription factors that controls stem cell RT pluripotency and self-renewal."; RL FASEB J. 20:1730-1732(2006). RN [12] RP INTERACTION WITH SALL4, AND DNA-BINDING. RX PubMed=16840789; DOI=10.1074/jbc.c600122200; RA Wu Q., Chen X., Zhang J., Loh Y.-H., Low T.-Y., Zhang W., Zhang W., RA Sze S.-K., Lim B., Ng H.-H.; RT "Sall4 interacts with Nanog and co-occupies Nanog genomic sites in RT embryonic stem cells."; RL J. Biol. Chem. 281:24090-24094(2006). RN [13] RP FUNCTION. RX PubMed=16791199; DOI=10.1038/nature04914; RA Silva J., Chambers I., Pollard S., Smith A.; RT "Nanog promotes transfer of pluripotency after cell fusion."; RL Nature 441:997-1001(2006). RN [14] RP FUNCTION, AND INDUCTION. RX PubMed=16518401; DOI=10.1038/ng1760; RA Loh Y.-H., Wu Q., Chew J.-L., Vega V.B., Zhang W., Chen X., Bourque G., RA George J., Leong B., Liu J., Wong K.-Y., Sung K.W., Lee C.W., Zhao X.-D., RA Chiu K.-P., Lipovich L., Kuznetsov V.A., Robson P., Stanton L.W., RA Wei C.-L., Ruan Y., Lim B., Ng H.-H.; RT "The Oct4 and Nanog transcription network regulates pluripotency in mouse RT embryonic stem cells."; RL Nat. Genet. 38:431-440(2006). RN [15] RP FUNCTION, INTERACTION WITH SMAD1, AND INDUCTION. RX PubMed=16801560; DOI=10.1073/pnas.0506945103; RA Suzuki A., Raya A., Kawakami Y., Morita M., Matsui T., Nakashima K., RA Gage F.H., Rodriguez-Esteban C., Izpisua Belmonte J.C.; RT "Nanog binds to Smad1 and blocks bone morphogenetic protein-induced RT differentiation of embryonic stem cells."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10294-10299(2006). RN [16] RP INTERACTION WITH ESRRB. RX PubMed=18957414; DOI=10.1074/jbc.m803481200; RA Zhang X., Zhang J., Wang T., Esteban M.A., Pei D.; RT "Esrrb activates Oct4 transcription and sustains self-renewal and RT pluripotency in embryonic stem cells."; RL J. Biol. Chem. 283:35825-35833(2008). RN [17] RP INTERACTION WITH NSD2. RX PubMed=19483677; DOI=10.1038/nature08086; RA Nimura K., Ura K., Shiratori H., Ikawa M., Okabe M., Schwartz R.J., RA Kaneda Y.; RT "A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf- RT Hirschhorn syndrome."; RL Nature 460:287-291(2009). RN [18] RP FUNCTION, AND INTERACTION WITH ZNF281. RX PubMed=21915945; DOI=10.1002/stem.736; RA Fidalgo M., Shekar P.C., Ang Y.S., Fujiwara Y., Orkin S.H., Wang J.; RT "Zfp281 functions as a transcriptional repressor for pluripotency of mouse RT embryonic stem cells."; RL Stem Cells 29:1705-1716(2011). RN [19] RP FUNCTION, INTERACTION WITH ZNF281, AND INDUCTION. RX PubMed=22988117; DOI=10.1073/pnas.1208533109; RA Fidalgo M., Faiola F., Pereira C.F., Ding J., Saunders A., Gingold J., RA Schaniel C., Lemischka I.R., Silva J.C., Wang J.; RT "Zfp281 mediates Nanog autorepression through recruitment of the NuRD RT complex and inhibits somatic cell reprogramming."; RL Proc. Natl. Acad. Sci. U.S.A. 109:16202-16207(2012). RN [20] RP FUNCTION, AND MUTAGENESIS OF THR-101; PHE-103; TYR-120; LEU-123; GLN-125; RP MET-126; TYR-137; LYS-138; LYS-141; THR-142; GLN-145; ASN-146; ARG-148; RP MET-149 AND LYS-152. RX PubMed=25825768; DOI=10.1073/pnas.1502855112; RA Hayashi Y., Caboni L., Das D., Yumoto F., Clayton T., Deller M.C., RA Nguyen P., Farr C.L., Chiu H.J., Miller M.D., Elsliger M.A., Deacon A.M., RA Godzik A., Lesley S.A., Tomoda K., Conklin B.R., Wilson I.A., Yamanaka S., RA Fletterick R.J.; RT "Structure-based discovery of NANOG variant with enhanced properties to RT promote self-renewal and reprogramming of pluripotent stem cells."; RL Proc. Natl. Acad. Sci. U.S.A. 112:4666-4671(2015). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 96-155, INTERACTION WITH DNA, RP PARTIAL PROTEIN SEQUENCE, AND MUTAGENESIS OF LYS-112; MET-126; TYR-137; RP LYS-138; THR-142; ASN-146 AND GLN-147. RX PubMed=18177668; DOI=10.1016/j.jmb.2007.11.091; RA Jauch R., Ng C.K.L., Saikatendu K.S., Stevens R.C., Kolatkar P.R.; RT "Crystal structure and DNA binding of the homeodomain of the stem cell RT transcription factor Nanog."; RL J. Mol. Biol. 376:758-770(2008). CC -!- FUNCTION: Transcription regulator involved in inner cell mass and CC embryonic stem (ES) cells proliferation and self-renewal CC (PubMed:25825768). Imposes pluripotency on ES cells and prevents their CC differentiation towards extraembryonic endoderm and trophectoderm CC lineages. Blocks bone morphogenetic protein-induced mesoderm CC differentiation of ES cells by physically interacting with SMAD1 and CC interfering with the recruitment of coactivators to the active SMAD CC transcriptional complexes. Acts as a transcriptional activator or CC repressor. Binds optimally to the DNA consensus sequence 5'- CC TAAT[GT][GT]-3' or 5'-[CG][GA][CG]C[GC]ATTAN[GC]-3'. Binds to the CC POU5F1/OCT4 promoter (By similarity). Able to autorepress its CC expression in differentiating (ES) cells: binds to its own promoter CC following interaction with ZNF281/ZFP281, leading to recruitment of the CC NuRD complex and subsequent repression of expression. When CC overexpressed, promotes cells to enter into S phase and proliferation. CC {ECO:0000250|UniProtKB:Q9H9S0, ECO:0000269|PubMed:12787504, CC ECO:0000269|PubMed:12787505, ECO:0000269|PubMed:14728807, CC ECO:0000269|PubMed:15502159, ECO:0000269|PubMed:16518401, CC ECO:0000269|PubMed:16791199, ECO:0000269|PubMed:16801560, CC ECO:0000269|PubMed:21915945, ECO:0000269|PubMed:22988117, CC ECO:0000269|PubMed:25825768}. CC -!- SUBUNIT: Interacts with SMAD1 (PubMed:16801560). Interacts with SALL4 CC (PubMed:16840789). Interacts with ZNF281/ZFP281 (PubMed:21915945, CC PubMed:22988117). Interacts with PCGF1 (By similarity). Interacts with CC ESRRB; reciprocally modulates their transcriptional activities CC (PubMed:18957414). Interacts with NSD2 (PubMed:19483677). CC {ECO:0000250|UniProtKB:Q9H9S0, ECO:0000269|PubMed:16801560, CC ECO:0000269|PubMed:16840789, ECO:0000269|PubMed:18957414, CC ECO:0000269|PubMed:19483677, ECO:0000269|PubMed:21915945, CC ECO:0000269|PubMed:22988117}. CC -!- INTERACTION: CC Q80Z64; Q61066: Nr0b1; NbExp=7; IntAct=EBI-2312517, EBI-2312665; CC Q80Z64; Q9QUR7: Pin1; NbExp=2; IntAct=EBI-2312517, EBI-2432975; CC Q80Z64; P20263: Pou5f1; NbExp=4; IntAct=EBI-2312517, EBI-1606219; CC Q80Z64; Q6PR54: Rif1; NbExp=5; IntAct=EBI-2312517, EBI-2312621; CC Q80Z64; P70414: Slc8a1; NbExp=9; IntAct=EBI-2312517, EBI-2312694; CC Q80Z64; P48432: Sox2; NbExp=10; IntAct=EBI-2312517, EBI-2313612; CC Q80Z64; Q99LI5: Znf281; NbExp=5; IntAct=EBI-2312517, EBI-2312719; CC Q80Z64-1; Q80Z64-1: Nanog; NbExp=2; IntAct=EBI-15699014, EBI-15699014; CC Q80Z64-1; P62991: Ubc; NbExp=3; IntAct=EBI-15699014, EBI-413074; CC Q80Z64-1; Q13526: PIN1; Xeno; NbExp=2; IntAct=EBI-15699014, EBI-714158; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, CC ECO:0000269|PubMed:15582778}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q80Z64-1; Sequence=Displayed; CC Name=2; Synonyms=Nanog1a, Nanog1b; CC IsoId=Q80Z64-2; Sequence=VSP_021689; CC -!- TISSUE SPECIFICITY: Not expressed in oocytes and spermatogonia (at CC protein level). Not expressed in many somatic organs, ovary, testis, CC fibroblast and hematopoietic cell lines. {ECO:0000269|PubMed:12787504, CC ECO:0000269|PubMed:12787505, ECO:0000269|PubMed:15108323, CC ECO:0000269|PubMed:15939376}. CC -!- DEVELOPMENTAL STAGE: Expressed in the central portion of the morula, CC the inner cell mass (ICM) of the blastocyst, in embryonic stem (ES) and CC embryonic germ (EG) cells, in the epiblast between 6.5 and 7.5 dpc, in CC primordial germ cells (PGCs) between 7.75 and 12.5 dpc (at protein CC level). The expression in PGCs decreases in female germ cells that CC entered meiosis at 13.5 dpc and in male germ cells that entered mitotic CC arrest at 14.5 dpc (at protein level). Not expressed in unfertilized CC eggs or 2- or 8-cell-stage embryos (at protein level). Expressed in the CC central portion of the morula, the inner cell mass (ICM) of the CC blastocyst, in ES and EG cells, in the epiblast at 6 dpc and in PGCs of CC genital ridges between 11.5 and 12.5 dpc. Expression decreases with ES CC differentiation. {ECO:0000269|PubMed:12609610, CC ECO:0000269|PubMed:12787504, ECO:0000269|PubMed:12787505, CC ECO:0000269|PubMed:15108323, ECO:0000269|PubMed:15582778, CC ECO:0000269|PubMed:15939376}. CC -!- INDUCTION: By the transcription factor POU5F1 in ES cells that acts as CC a direct biphasic regulator: a steady-state concentration of POU5F1 up- CC regulated its expression, while an elevated concentration of POU5F1 CC down-regulated its expression. Up-regulated by the transcription factor CC FOXD3. Up-regulated in ES cells by transcription factors T (Brachyury) CC and STAT3. Down-regulated by p53 in response to DNA damage induced by CC ultraviolet light (UV) or doxorubicin. Down-regulated upon ES CC differentiation by mediating autorepression through interaction with CC ZNF281/ZFP281. {ECO:0000269|PubMed:15619621, CC ECO:0000269|PubMed:16518401, ECO:0000269|PubMed:16790525, CC ECO:0000269|PubMed:16801560, ECO:0000269|PubMed:22988117}. CC -!- DISRUPTION PHENOTYPE: Loss of pluripotency in both ICM and ES cells and CC differentiated into extraembryonic (parietal and visceral) endoderm CC lineage. {ECO:0000269|PubMed:12787504}. CC -!- MISCELLANEOUS: 'Nanog' is derived from 'Tir nan Og' the mythologic CC Celtic land of the ever young. CC -!- SIMILARITY: Belongs to the Nanog homeobox family. {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; AB093574; BAC76998.1; -; mRNA. DR EMBL; AY278951; AAP92157.1; -; mRNA. DR EMBL; AF507043; AAO67362.1; -; mRNA. DR EMBL; AY455282; AAS57554.1; -; mRNA. DR EMBL; AY455285; AAS57556.1; -; mRNA. DR EMBL; AK010332; BAE43219.1; -; mRNA. DR CCDS; CCDS39623.1; -. [Q80Z64-1] DR CCDS; CCDS80607.1; -. [Q80Z64-2] DR RefSeq; NP_001276757.1; NM_001289828.1. DR RefSeq; NP_001276759.1; NM_001289830.1. [Q80Z64-2] DR RefSeq; NP_001276760.1; NM_001289831.1. [Q80Z64-2] DR RefSeq; NP_082292.1; NM_028016.3. [Q80Z64-1] DR RefSeq; XP_006506714.1; XM_006506651.2. DR PDB; 2VI6; X-ray; 2.60 A; A/B/C/D/E/F/G/H=96-155. DR PDBsum; 2VI6; -. DR AlphaFoldDB; Q80Z64; -. DR SMR; Q80Z64; -. DR BioGRID; 215050; 288. DR DIP; DIP-29932N; -. DR ELM; Q80Z64; -. DR IntAct; Q80Z64; 154. DR MINT; Q80Z64; -. DR STRING; 10090.ENSMUSP00000012540; -. DR GlyGen; Q80Z64; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q80Z64; -. DR PhosphoSitePlus; Q80Z64; -. DR PaxDb; 10090-ENSMUSP00000012540; -. DR Ensembl; ENSMUST00000012540.5; ENSMUSP00000012540.4; ENSMUSG00000012396.13. [Q80Z64-1] DR Ensembl; ENSMUST00000112580.8; ENSMUSP00000108199.2; ENSMUSG00000012396.13. [Q80Z64-2] DR Ensembl; ENSMUST00000112581.8; ENSMUSP00000108200.2; ENSMUSG00000012396.13. [Q80Z64-2] DR GeneID; 71950; -. DR KEGG; mmu:71950; -. DR UCSC; uc009dpo.2; mouse. [Q80Z64-1] DR AGR; MGI:1919200; -. DR CTD; 79923; -. DR MGI; MGI:1919200; Nanog. DR VEuPathDB; HostDB:ENSMUSG00000012396; -. DR eggNOG; KOG0491; Eukaryota. DR GeneTree; ENSGT00670000098076; -. DR HOGENOM; CLU_086240_0_0_1; -. DR InParanoid; Q80Z64; -. DR OMA; AWSNHSW; -. DR OrthoDB; 4050836at2759; -. DR PhylomeDB; Q80Z64; -. DR TreeFam; TF337402; -. DR BioGRID-ORCS; 71950; 5 hits in 80 CRISPR screens. DR ChiTaRS; Nanog; mouse. DR EvolutionaryTrace; Q80Z64; -. DR PRO; PR:Q80Z64; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q80Z64; Protein. DR Bgee; ENSMUSG00000012396; Expressed in embryonic cell in blastocyst and 24 other cell types or tissues. DR ExpressionAtlas; Q80Z64; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IMP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0070577; F:lysine-acetylated histone binding; IDA:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0001010; F:RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity; IDA:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI. DR GO; GO:0043697; P:cell dedifferentiation; IDA:UniProtKB. DR GO; GO:0009880; P:embryonic pattern specification; IEP:HGNC-UCL. DR GO; GO:0001714; P:endodermal cell fate specification; ISO:MGI. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0008406; P:gonad development; IEP:HGNC-UCL. DR GO; GO:0001710; P:mesodermal cell fate commitment; IDA:MGI. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:MGI. DR GO; GO:0010454; P:negative regulation of cell fate commitment; IDA:MGI. DR GO; GO:0042664; P:negative regulation of endodermal cell fate specification; TAS:HGNC-UCL. DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IDA:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:2000035; P:regulation of stem cell division; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0010033; P:response to organic substance; IDA:MGI. DR GO; GO:0032526; P:response to retinoic acid; IDA:MGI. DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:MGI. DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI. DR GO; GO:0017145; P:stem cell division; IDA:MGI. DR GO; GO:0019827; P:stem cell population maintenance; IMP:UniProtKB. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR PANTHER; PTHR24327; HOMEOBOX PROTEIN; 1. DR PANTHER; PTHR24327:SF72; HOMEOBOX PROTEIN NANOG2-RELATED; 1. DR Pfam; PF00046; Homeodomain; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR Genevisible; Q80Z64; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Developmental protein; KW Direct protein sequencing; DNA-binding; Homeobox; Nucleus; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1..305 FT /note="Homeobox protein NANOG" FT /id="PRO_0000261419" FT REPEAT 198..202 FT /note="1" FT REPEAT 203..207 FT /note="2" FT REPEAT 208..212 FT /note="3" FT REPEAT 213..217 FT /note="4" FT REPEAT 218..222 FT /note="5" FT REPEAT 223..227 FT /note="6" FT REPEAT 228..232 FT /note="7" FT REPEAT 233..237 FT /note="8" FT REPEAT 238..242 FT /note="9" FT REPEAT 243..247 FT /note="10" FT DNA_BIND 96..155 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 1..30 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 46..95 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 96..155 FT /note="Sufficient for interaction with SALL4" FT /evidence="ECO:0000269|PubMed:16840789" FT REGION 123..152 FT /note="Required for DNA-binding" FT /evidence="ECO:0000250|UniProtKB:Q9H9S0" FT REGION 198..247 FT /note="10 X repeats starting with a Trp in each unit" FT REGION 198..247 FT /note="Sufficient for transactivation activity" FT REGION 248..305 FT /note="Sufficient for strong transactivation activity" FT COMPBIAS 12..29 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 58..77 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 79..95 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..25 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15108323" FT /id="VSP_021689" FT MUTAGEN 101 FT /note="T->A: Decreased protein expression. Decreased FT embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 103 FT /note="F->A: Decreased protein expression and stability. FT Decreased embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 112 FT /note="K->E: Increases affinity for DNA and protein FT stability; when associated with R-147." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 120 FT /note="Y->A: Decreased protein expression and stability. FT Decreased embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 123 FT /note="L->A: Increased protein expression and stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 125 FT /note="Q->A: Decreased protein expression. No effect on FT protein stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 126 FT /note="M->A: No effect on protein stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 126 FT /note="M->R: Increases affinity for DNA; when associated FT with E-137." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 137 FT /note="Y->A: Increased protein expression. Decreased FT protein stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 137 FT /note="Y->E: Increases affinity for DNA; when associated FT with R-126." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 138 FT /note="K->A: Decreased protein expression and stability. FT Decreased embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 138 FT /note="K->E: Reduced affinity for DNA." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 141 FT /note="K->A: Decreased protein stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 142 FT /note="T->A: Decreased protein expression and stability. FT Decreased embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 142 FT /note="T->I: Slightly reduced affinity for DNA." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 145 FT /note="Q->A: Increased protein expression. No effect on FT protein stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 146 FT /note="N->A: No effect on protein stability. Decreased FT embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 146 FT /note="N->E: Strongly reduced affinity for DNA." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 147 FT /note="Q->R: Increases affinity for DNA and protein FT stability; when associated with E-112." FT /evidence="ECO:0000269|PubMed:18177668" FT MUTAGEN 148 FT /note="R->A: Decreased protein stability. Decreased FT embryonic stem cell self-renewal." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 149 FT /note="M->A: Increased protein expression. No effect on FT protein stability." FT /evidence="ECO:0000269|PubMed:25825768" FT MUTAGEN 152 FT /note="K->A: Decreased protein expression and stability." FT /evidence="ECO:0000269|PubMed:25825768" FT CONFLICT 149 FT /note="M -> V (in Ref. 1; BAC76998)" FT /evidence="ECO:0000305" FT HELIX 105..117 FT /evidence="ECO:0007829|PDB:2VI6" FT HELIX 123..133 FT /evidence="ECO:0007829|PDB:2VI6" FT HELIX 137..149 FT /evidence="ECO:0007829|PDB:2VI6" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:2VI6" SQ SEQUENCE 305 AA; 34240 MW; 4EF96408B767C79F CRC64; MSVGLPGPHS LPSSEEASNS GNASSMPAVF HPENYSCLQG SATEMLCTEA ASPRPSSEDL PLQGSPDSST SPKQKLSSPE ADKGPEEEEN KVLARKQKMR TVFSQAQLCA LKDRFQKQKY LSLQQMQELS SILNLSYKQV KTWFQNQRMK CKRWQKNQWL KTSNGLIQKG SAPVEYPSIH CSYPQGYLVN ASGSLSMWGS QTWTNPTWSS QTWTNPTWNN QTWTNPTWSS QAWTAQSWNG QPWNAAPLHN FGEDFLQPYV QLQQNFSASD LEVNLEATRE SHAHFSTPQA LELFLNYSVT PPGEI //