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Homeobox protein NANOG (ES cell-associated protein 4) (Early embryo specific expression NK-type homeobox protein) (Homeobox transcription factor Nanog)

 NANOG_MOUSE             Reviewed;         305 AA.
Q80Z64; Q6SMR1; Q7TN85;
28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
01-JUN-2003, sequence version 1.
22-NOV-2017, entry version 128.
RecName: Full=Homeobox protein NANOG;
AltName: Full=ES cell-associated protein 4;
AltName: Full=Early embryo specific expression NK-type homeobox protein;
AltName: Full=Homeobox transcription factor Nanog;
Name=Nanog; Synonyms=Ecat4, Enk;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DNA-BINDING,
DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
PubMed=12787504; DOI=10.1016/S0092-8674(03)00393-3;
Mitsui K., Tokuzawa Y., Itoh H., Segawa K., Murakami M., Takahashi K.,
Maruyama M., Maeda M., Yamanaka S.;
"The homeoprotein Nanog is required for maintenance of pluripotency in
mouse epiblast and ES cells.";
Cell 113:631-642(2003).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DEVELOPMENTAL STAGE,
AND TISSUE SPECIFICITY.
STRAIN=129/Ola; TISSUE=Embryonic stem cell;
PubMed=12787505; DOI=10.1016/S0092-8674(03)00392-1;
Chambers I., Colby D., Robertson M., Nichols J., Lee S., Tweedie S.,
Smith A.;
"Functional expression cloning of Nanog, a pluripotency sustaining
factor in embryonic stem cells.";
Cell 113:643-655(2003).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
STRAIN=FVB/NJ; TISSUE=Embryonic stem cell;
PubMed=12609610; DOI=10.1016/S1567-133X(03)00005-X;
Wang S.-H., Tsai M.-S., Chiang M.-F., Li H.;
"A novel NK-type homeobox gene, ENK (early embryo specific NK),
preferentially expressed in embryonic stem cells.";
Gene Expr. Patterns 3:99-103(2003).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), DEVELOPMENTAL STAGE,
AND TISSUE SPECIFICITY.
STRAIN=C57BL/6J;
PubMed=15108323; DOI=10.1002/dvdy.20034;
Hart A.H., Hartley L., Ibrahim M., Robb L.;
"Identification, cloning and expression analysis of the pluripotency
promoting Nanog genes in mouse and human.";
Dev. Dyn. 230:187-198(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[6]
FUNCTION.
PubMed=14728807; DOI=10.1038/sj.cr.7290193;
Pan G.J., Pei D.Q.;
"Identification of two distinct transactivation domains in the
pluripotency sustaining factor nanog.";
Cell Res. 13:499-502(2003).
[7]
DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
PubMed=15939376; DOI=10.1016/j.modgep.2005.03.001;
Yamaguchi S., Kimura H., Tada M., Nakatsuji N., Tada T.;
"Nanog expression in mouse germ cell development.";
Gene Expr. Patterns 5:639-646(2005).
[8]
FUNCTION, AND DNA-BINDING.
PubMed=15502159; DOI=10.1074/jbc.M407847200;
Pan G., Pei D.;
"The stem cell pluripotency factor NANOG activates transcription with
two unusually potent subdomains at its C terminus.";
J. Biol. Chem. 280:1401-1407(2005).
[9]
SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
PubMed=15582778; DOI=10.1016/j.mod.2004.08.008;
Hatano S.Y., Tada M., Kimura H., Yamaguchi S., Kono T., Nakano T.,
Suemori H., Nakatsuji N., Tada T.;
"Pluripotential competence of cells associated with Nanog activity.";
Mech. Dev. 122:67-79(2005).
[10]
INDUCTION.
PubMed=15619621; DOI=10.1038/ncb1211;
Lin T., Chao C., Saito S., Mazur S.J., Murphy M.E., Appella E., Xu Y.;
"p53 induces differentiation of mouse embryonic stem cells by
suppressing Nanog expression.";
Nat. Cell Biol. 7:165-171(2005).
[11]
INDUCTION.
PubMed=16790525; DOI=10.1096/fj.05-5543fje;
Pan G., Li J., Zhou Y., Zheng H., Pei D.;
"A negative feedback loop of transcription factors that controls stem
cell pluripotency and self-renewal.";
FASEB J. 20:1730-1732(2006).
[12]
INTERACTION WITH SALL4, AND DNA-BINDING.
PubMed=16840789; DOI=10.1074/jbc.C600122200;
Wu Q., Chen X., Zhang J., Loh Y.-H., Low T.-Y., Zhang W., Zhang W.,
Sze S.-K., Lim B., Ng H.-H.;
"Sall4 interacts with Nanog and co-occupies Nanog genomic sites in
embryonic stem cells.";
J. Biol. Chem. 281:24090-24094(2006).
[13]
FUNCTION.
PubMed=16791199; DOI=10.1038/nature04914;
Silva J., Chambers I., Pollard S., Smith A.;
"Nanog promotes transfer of pluripotency after cell fusion.";
Nature 441:997-1001(2006).
[14]
FUNCTION, AND INDUCTION.
PubMed=16518401; DOI=10.1038/ng1760;
Loh Y.-H., Wu Q., Chew J.-L., Vega V.B., Zhang W., Chen X.,
Bourque G., George J., Leong B., Liu J., Wong K.-Y., Sung K.W.,
Lee C.W., Zhao X.-D., Chiu K.-P., Lipovich L., Kuznetsov V.A.,
Robson P., Stanton L.W., Wei C.-L., Ruan Y., Lim B., Ng H.-H.;
"The Oct4 and Nanog transcription network regulates pluripotency in
mouse embryonic stem cells.";
Nat. Genet. 38:431-440(2006).
[15]
FUNCTION, INTERACTION WITH SMAD1, AND INDUCTION.
PubMed=16801560; DOI=10.1073/pnas.0506945103;
Suzuki A., Raya A., Kawakami Y., Morita M., Matsui T., Nakashima K.,
Gage F.H., Rodriguez-Esteban C., Izpisua Belmonte J.C.;
"Nanog binds to Smad1 and blocks bone morphogenetic protein-induced
differentiation of embryonic stem cells.";
Proc. Natl. Acad. Sci. U.S.A. 103:10294-10299(2006).
[16]
INTERACTION WITH ESRRB.
PubMed=18957414; DOI=10.1074/jbc.M803481200;
Zhang X., Zhang J., Wang T., Esteban M.A., Pei D.;
"Esrrb activates Oct4 transcription and sustains self-renewal and
pluripotency in embryonic stem cells.";
J. Biol. Chem. 283:35825-35833(2008).
[17]
FUNCTION, AND INTERACTION WITH ZNF281.
PubMed=21915945; DOI=10.1002/stem.736;
Fidalgo M., Shekar P.C., Ang Y.S., Fujiwara Y., Orkin S.H., Wang J.;
"Zfp281 functions as a transcriptional repressor for pluripotency of
mouse embryonic stem cells.";
Stem Cells 29:1705-1716(2011).
[18]
FUNCTION, INTERACTION WITH ZNF281, AND INDUCTION.
PubMed=22988117; DOI=10.1073/pnas.1208533109;
Fidalgo M., Faiola F., Pereira C.F., Ding J., Saunders A., Gingold J.,
Schaniel C., Lemischka I.R., Silva J.C., Wang J.;
"Zfp281 mediates Nanog autorepression through recruitment of the NuRD
complex and inhibits somatic cell reprogramming.";
Proc. Natl. Acad. Sci. U.S.A. 109:16202-16207(2012).
[19]
FUNCTION, AND MUTAGENESIS OF THR-101; PHE-103; TYR-120; LEU-123;
GLN-125; MET-126; TYR-137; LYS-138; LYS-141; THR-142; GLN-145;
ASN-146; ARG-148; MET-149 AND LYS-152.
PubMed=25825768; DOI=10.1073/pnas.1502855112;
Hayashi Y., Caboni L., Das D., Yumoto F., Clayton T., Deller M.C.,
Nguyen P., Farr C.L., Chiu H.J., Miller M.D., Elsliger M.A.,
Deacon A.M., Godzik A., Lesley S.A., Tomoda K., Conklin B.R.,
Wilson I.A., Yamanaka S., Fletterick R.J.;
"Structure-based discovery of NANOG variant with enhanced properties
to promote self-renewal and reprogramming of pluripotent stem cells.";
Proc. Natl. Acad. Sci. U.S.A. 112:4666-4671(2015).
[20]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 96-155, INTERACTION WITH DNA,
PARTIAL PROTEIN SEQUENCE, AND MUTAGENESIS OF LYS-112; MET-126;
TYR-137; LYS-138; THR-142; ASN-146 AND GLN-147.
PubMed=18177668; DOI=10.1016/j.jmb.2007.11.091;
Jauch R., Ng C.K.L., Saikatendu K.S., Stevens R.C., Kolatkar P.R.;
"Crystal structure and DNA binding of the homeodomain of the stem cell
transcription factor Nanog.";
J. Mol. Biol. 376:758-770(2008).
-!- FUNCTION: Transcription regulator involved in inner cell mass and
embryonic stem (ES) cells proliferation and self-renewal
(PubMed:25825768). Imposes pluripotency on ES cells and prevents
their differentiation towards extraembryonic endoderm and
trophectoderm lineages. Blocks bone morphogenetic protein-induced
mesoderm differentiation of ES cells by physically interacting
with SMAD1 and interfering with the recruitment of coactivators to
the active SMAD transcriptional complexes. Acts as a
transcriptional activator or repressor. Binds optimally to the DNA
consensus sequence 5'-TAAT[GT][GT]-3' or 5'-
[CG][GA][CG]C[GC]ATTAN[GC]-3'. Binds to the POU5F1/OCT4 promoter
(By similarity). Able to autorepress its expression in
differentiating (ES) cells: binds to its own promoter following
interaction with ZNF281/ZFP281, leading to recruitment of the NuRD
complex and subsequent repression of expression. When
overexpressed, promotes cells to enter into S phase and
proliferation. {ECO:0000250|UniProtKB:Q9H9S0,
ECO:0000269|PubMed:12787504, ECO:0000269|PubMed:12787505,
ECO:0000269|PubMed:14728807, ECO:0000269|PubMed:15502159,
ECO:0000269|PubMed:16518401, ECO:0000269|PubMed:16791199,
ECO:0000269|PubMed:16801560, ECO:0000269|PubMed:21915945,
ECO:0000269|PubMed:22988117, ECO:0000269|PubMed:25825768}.
-!- SUBUNIT: Interacts with SMAD1 and SALL4. Interacts with
ZNF281/ZFP281. Interacts with PCGF1 (By similarity). Interacts
with ESRRB; reciprocally modulates their transcriptional
activities (PubMed:18957414). {ECO:0000250|UniProtKB:Q9H9S0,
ECO:0000269|PubMed:16801560, ECO:0000269|PubMed:16840789,
ECO:0000269|PubMed:18177668, ECO:0000269|PubMed:18957414,
ECO:0000269|PubMed:21915945, ECO:0000269|PubMed:22988117}.
-!- INTERACTION:
Q61066:Nr0b1; NbExp=7; IntAct=EBI-2312517, EBI-2312665;
Q13526:PIN1 (xeno); NbExp=2; IntAct=EBI-15699014, EBI-714158;
Q9QUR7:Pin1; NbExp=2; IntAct=EBI-2312517, EBI-2432975;
P20263:Pou5f1; NbExp=4; IntAct=EBI-2312517, EBI-1606219;
Q6PR54:Rif1; NbExp=5; IntAct=EBI-2312517, EBI-2312621;
P70414:Slc8a1; NbExp=9; IntAct=EBI-2312517, EBI-2312694;
P48432:Sox2; NbExp=10; IntAct=EBI-2312517, EBI-2313612;
P62991:Ubc; NbExp=3; IntAct=EBI-15699014, EBI-413074;
Q99LI5:Znf281; NbExp=5; IntAct=EBI-2312517, EBI-2312719;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108, ECO:0000269|PubMed:15582778}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q80Z64-1; Sequence=Displayed;
Name=2; Synonyms=Nanog1a, Nanog1b;
IsoId=Q80Z64-2; Sequence=VSP_021689;
-!- TISSUE SPECIFICITY: Not expressed in oocytes and spermatogonia (at
protein level). Not expressed in many somatic organs, ovary,
testis, fibroblast and hematopoietic cell lines.
{ECO:0000269|PubMed:12787504, ECO:0000269|PubMed:12787505,
ECO:0000269|PubMed:15108323, ECO:0000269|PubMed:15939376}.
-!- DEVELOPMENTAL STAGE: Expressed in the central portion of the
morula, the inner cell mass (ICM) of the blastocyst, in embryonic
stem (ES) and embryonic germ (EG) cells, in the epiblast between
6.5 and 7.5 dpc, in primordial germ cells (PGCs) between 7.75 and
12.5 dpc (at protein level). The expression in PGCs decreases in
female germ cells that entered meiosis at 13.5 dpc and in male
germ cells that entered mitotic arrest at 14.5 dpc (at protein
level). Not expressed in unfertilized eggs or 2- or 8-cell-stage
embryos (at protein level). Expressed in the central portion of
the morula, the inner cell mass (ICM) of the blastocyst, in ES and
EG cells, in the epiblast at 6 dpc and in PGCs of genital ridges
between 11.5 and 12.5 dpc. Expression decreases with ES
differentiation. {ECO:0000269|PubMed:12609610,
ECO:0000269|PubMed:12787504, ECO:0000269|PubMed:12787505,
ECO:0000269|PubMed:15108323, ECO:0000269|PubMed:15582778,
ECO:0000269|PubMed:15939376}.
-!- INDUCTION: By the transcription factor POU5F1 in ES cells that
acts as a direct biphasic regulator: a steady-state concentration
of POU5F1 up-regulated its expression, while an elevated
concentration of POU5F1 down-regulated its expression. Up-
regulated by the transcription factor FOXD3. Up-regulated in ES
cells by transcription factors T (Brachyury) and STAT3. Down-
regulated by p53 in response to DNA damage induced by ultraviolet
light (UV) or doxorubicin. Down-regulated upon ES differentiation
by mediating autorepression through interaction with
ZNF281/ZFP281. {ECO:0000269|PubMed:15619621,
ECO:0000269|PubMed:16518401, ECO:0000269|PubMed:16790525,
ECO:0000269|PubMed:16801560, ECO:0000269|PubMed:22988117}.
-!- DISRUPTION PHENOTYPE: Loss of pluripotency in both ICM and ES
cells and differentiated into extraembryonic (parietal and
visceral) endoderm lineage. {ECO:0000269|PubMed:12787504}.
-!- MISCELLANEOUS: 'Nanog' is derived from 'Tir nan Og' the mythologic
Celtic land of the ever young.
-!- SIMILARITY: Belongs to the Nanog homeobox family. {ECO:0000305}.
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EMBL; AB093574; BAC76998.1; -; mRNA.
EMBL; AY278951; AAP92157.1; -; mRNA.
EMBL; AF507043; AAO67362.1; -; mRNA.
EMBL; AY455282; AAS57554.1; -; mRNA.
EMBL; AY455285; AAS57556.1; -; mRNA.
EMBL; AK010332; BAE43219.1; -; mRNA.
CCDS; CCDS39623.1; -. [Q80Z64-1]
CCDS; CCDS80607.1; -. [Q80Z64-2]
RefSeq; NP_001276757.1; NM_001289828.1.
RefSeq; NP_001276759.1; NM_001289830.1. [Q80Z64-2]
RefSeq; NP_001276760.1; NM_001289831.1. [Q80Z64-2]
RefSeq; NP_082292.1; NM_028016.3. [Q80Z64-1]
RefSeq; XP_006506714.1; XM_006506651.2. [Q80Z64-1]
UniGene; Mm.485537; -.
UniGene; Mm.491626; -.
UniGene; Mm.6047; -.
PDB; 2VI6; X-ray; 2.60 A; A/B/C/D/E/F/G/H=96-155.
PDBsum; 2VI6; -.
ProteinModelPortal; Q80Z64; -.
SMR; Q80Z64; -.
BioGrid; 215050; 282.
DIP; DIP-29932N; -.
ELM; Q80Z64; -.
IntAct; Q80Z64; 154.
STRING; 10090.ENSMUSP00000012540; -.
iPTMnet; Q80Z64; -.
PhosphoSitePlus; Q80Z64; -.
PaxDb; Q80Z64; -.
PRIDE; Q80Z64; -.
Ensembl; ENSMUST00000012540; ENSMUSP00000012540; ENSMUSG00000012396. [Q80Z64-1]
Ensembl; ENSMUST00000112580; ENSMUSP00000108199; ENSMUSG00000012396. [Q80Z64-2]
Ensembl; ENSMUST00000112581; ENSMUSP00000108200; ENSMUSG00000012396. [Q80Z64-2]
GeneID; 71950; -.
KEGG; mmu:71950; -.
UCSC; uc009dpo.2; mouse. [Q80Z64-1]
CTD; 79923; -.
MGI; MGI:1919200; Nanog.
eggNOG; KOG0491; Eukaryota.
eggNOG; ENOG4111UAT; LUCA.
GeneTree; ENSGT00670000098076; -.
HOGENOM; HOG000236291; -.
HOVERGEN; HBG058783; -.
InParanoid; Q80Z64; -.
KO; K10164; -.
OMA; SWNSQAW; -.
OrthoDB; EOG091G0JYT; -.
PhylomeDB; Q80Z64; -.
TreeFam; TF337402; -.
EvolutionaryTrace; Q80Z64; -.
PRO; PR:Q80Z64; -.
Proteomes; UP000000589; Chromosome 6.
Bgee; ENSMUSG00000012396; -.
ExpressionAtlas; Q80Z64; baseline and differential.
Genevisible; Q80Z64; MM.
GO; GO:0005730; C:nucleolus; ISO:MGI.
GO; GO:0005654; C:nucleoplasm; IDA:BHF-UCL.
GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0001158; F:enhancer sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0003714; F:transcription corepressor activity; IMP:UniProtKB.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IMP:UniProtKB.
GO; GO:0001010; F:transcription factor activity, sequence-specific DNA binding transcription factor recruiting; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:MGI.
GO; GO:0001205; F:transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:UniProtKB.
GO; GO:0043697; P:cell dedifferentiation; IDA:UniProtKB.
GO; GO:0008283; P:cell proliferation; ISO:MGI.
GO; GO:0036018; P:cellular response to erythropoietin; IEA:Ensembl.
GO; GO:0072752; P:cellular response to rapamycin; IEA:Ensembl.
GO; GO:0009880; P:embryonic pattern specification; IEP:HGNC.
GO; GO:0001714; P:endodermal cell fate specification; ISO:MGI.
GO; GO:0008406; P:gonad development; IEP:HGNC.
GO; GO:0001710; P:mesodermal cell fate commitment; IGI:MGI.
GO; GO:0009825; P:multidimensional cell growth; IEA:Ensembl.
GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:MGI.
GO; GO:0045596; P:negative regulation of cell differentiation; IDA:MGI.
GO; GO:0010454; P:negative regulation of cell fate commitment; IDA:MGI.
GO; GO:0042664; P:negative regulation of endodermal cell fate specification; TAS:HGNC.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:MGI.
GO; GO:0008284; P:positive regulation of cell proliferation; IDA:MGI.
GO; GO:0045931; P:positive regulation of mitotic cell cycle; IDA:MGI.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0045595; P:regulation of cell differentiation; ISO:MGI.
GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
GO; GO:2000035; P:regulation of stem cell division; IDA:UniProtKB.
GO; GO:2000036; P:regulation of stem cell population maintenance; IGI:MGI.
GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
GO; GO:0010033; P:response to organic substance; IDA:MGI.
GO; GO:0032526; P:response to retinoic acid; IDA:MGI.
GO; GO:0035019; P:somatic stem cell population maintenance; ISO:MGI.
GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
GO; GO:0017145; P:stem cell division; IDA:MGI.
GO; GO:0019827; P:stem cell population maintenance; IDA:MGI.
GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
Pfam; PF00046; Homeobox; 1.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
3D-structure; Activator; Alternative splicing; Complete proteome;
Developmental protein; Direct protein sequencing; DNA-binding;
Homeobox; Nucleus; Reference proteome; Repeat; Repressor;
Transcription; Transcription regulation.
CHAIN 1 305 Homeobox protein NANOG.
/FTId=PRO_0000261419.
REPEAT 198 202 1.
REPEAT 203 207 2.
REPEAT 208 212 3.
REPEAT 213 217 4.
REPEAT 218 222 5.
REPEAT 223 227 6.
REPEAT 228 232 7.
REPEAT 233 237 8.
REPEAT 238 242 9.
REPEAT 243 247 10.
DNA_BIND 96 155 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
REGION 96 155 Sufficient for interaction with SALL4.
{ECO:0000269|PubMed:16840789}.
REGION 123 152 Required for DNA-binding.
{ECO:0000250|UniProtKB:Q9H9S0}.
REGION 198 247 10 X repeats starting with a Trp in each
unit.
REGION 198 247 Sufficient for transactivation activity.
REGION 248 305 Sufficient for strong transactivation
activity.
COMPBIAS 198 243 Trp-rich.
VAR_SEQ 1 25 Missing (in isoform 2).
{ECO:0000303|PubMed:15108323}.
/FTId=VSP_021689.
MUTAGEN 101 101 T->A: Decreased protein expression.
Decreased embryonic stem cell self-
renewal. {ECO:0000269|PubMed:25825768}.
MUTAGEN 103 103 F->A: Decreased protein expression and
stability. Decreased embryonic stem cell
self-renewal.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 112 112 K->E: Increases affinity for DNA and
protein stability; when associated with
R-147. {ECO:0000269|PubMed:18177668}.
MUTAGEN 120 120 Y->A: Decreased protein expression and
stability. Decreased embryonic stem cell
self-renewal.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 123 123 L->A: Increased protein expression and
stability. {ECO:0000269|PubMed:25825768}.
MUTAGEN 125 125 Q->A: Decreased protein expression. No
effect on protein stability.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 126 126 M->A: No effect on protein stability.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 126 126 M->R: Increases affinity for DNA; when
associated with E-137.
{ECO:0000269|PubMed:18177668}.
MUTAGEN 137 137 Y->A: Increased protein expression.
Decreased protein stability.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 137 137 Y->E: Increases affinity for DNA; when
associated with R-126.
{ECO:0000269|PubMed:18177668}.
MUTAGEN 138 138 K->A: Decreased protein expression and
stability. Decreased embryonic stem cell
self-renewal.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 138 138 K->E: Reduced affinity for DNA.
{ECO:0000269|PubMed:18177668}.
MUTAGEN 141 141 K->A: Decreased protein stability.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 142 142 T->A: Decreased protein expression and
stability. Decreased embryonic stem cell
self-renewal.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 142 142 T->I: Slightly reduced affinity for DNA.
{ECO:0000269|PubMed:18177668}.
MUTAGEN 145 145 Q->A: Increased protein expression. No
effect on protein stability.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 146 146 N->A: No effect on protein stability.
Decreased embryonic stem cell self-
renewal. {ECO:0000269|PubMed:25825768}.
MUTAGEN 146 146 N->E: Strongly reduced affinity for DNA.
{ECO:0000269|PubMed:18177668}.
MUTAGEN 147 147 Q->R: Increases affinity for DNA and
protein stability; when associated with
E-112. {ECO:0000269|PubMed:18177668}.
MUTAGEN 148 148 R->A: Decreased protein stability.
Decreased embryonic stem cell self-
renewal. {ECO:0000269|PubMed:25825768}.
MUTAGEN 149 149 M->A: Increased protein expression. No
effect on protein stability.
{ECO:0000269|PubMed:25825768}.
MUTAGEN 152 152 K->A: Decreased protein expression and
stability. {ECO:0000269|PubMed:25825768}.
CONFLICT 149 149 M -> V (in Ref. 1; BAC76998).
{ECO:0000305}.
HELIX 105 117 {ECO:0000244|PDB:2VI6}.
HELIX 123 133 {ECO:0000244|PDB:2VI6}.
HELIX 137 149 {ECO:0000244|PDB:2VI6}.
HELIX 152 154 {ECO:0000244|PDB:2VI6}.
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


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