NANOG_MOUSE
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 03-AUG-2022, entry version 156.
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}.
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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 iPTMnet; Q80Z64; -.
DR PhosphoSitePlus; Q80Z64; -.
DR PaxDb; Q80Z64; -.
DR PRIDE; Q80Z64; -.
DR Ensembl; ENSMUST00000012540; ENSMUSP00000012540; ENSMUSG00000012396. [Q80Z64-1]
DR Ensembl; ENSMUST00000112580; ENSMUSP00000108199; ENSMUSG00000012396. [Q80Z64-2]
DR Ensembl; ENSMUST00000112581; ENSMUSP00000108200; ENSMUSG00000012396. [Q80Z64-2]
DR GeneID; 71950; -.
DR KEGG; mmu:71950; -.
DR UCSC; uc009dpo.2; mouse. [Q80Z64-1]
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 PhylomeDB; Q80Z64; -.
DR TreeFam; TF337402; -.
DR BioGRID-ORCS; 71950; 5 hits in 75 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 epiblast (generic) and 22 other tissues.
DR ExpressionAtlas; Q80Z64; baseline and differential.
DR Genevisible; Q80Z64; MM.
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:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
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; IBA:GO_Central.
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:0036018; P:cellular response to erythropoietin; IEA:Ensembl.
DR GO; GO:0072752; P:cellular response to rapamycin; IEA:Ensembl.
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:0009825; P:multidimensional cell growth; IEA:Ensembl.
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: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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
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 GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR Pfam; PF00046; Homeodomain; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
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
