Homeobox protein NANOG

Function

Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal. 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.

Classification

Family (Pfam)

PF00046 Homeodomain

InterPro

Distal-less_Homeobox_TF, HD, Homeobox_CS, Homeodomain-like_sf

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 2

• 2VI6 X-ray 2.60A
• 8YDD X-ray 2.50A

A predicted model is available from AlphaFold.

Gene Ontology · 46

• GO:0000785 chromatin
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
• GO:0042802 identical protein binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0001010 RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity
• GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
• GO:0043565 sequence-specific DNA binding
• GO:1990837 sequence-specific double-stranded DNA binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0008134 transcription factor binding
• GO:0043697 cell dedifferentiation
• GO:0030154 cell differentiation
• GO:0036018 cellular response to erythropoietin
• GO:0072752 cellular response to rapamycin
• GO:0006351 DNA-templated transcription
• GO:0009880 embryonic pattern specification
• GO:0001714 endodermal cell fate specification
• GO:0010467 gene expression
• GO:0008406 gonad development
• GO:0001710 mesodermal cell fate commitment
• GO:0009825 multidimensional cell growth
• GO:0030514 negative regulation of BMP signaling pathway
• GO:0045596 negative regulation of cell differentiation
• GO:0010454 negative regulation of cell fate commitment
• GO:0042664 negative regulation of endodermal cell fate specification
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0008284 positive regulation of cell population proliferation
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0045931 positive regulation of mitotic cell cycle
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:2000035 regulation of stem cell division
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:1903925 response to bisphenol A
• GO:0032526 response to retinoic acid
• GO:0048863 stem cell differentiation
• GO:0017145 stem cell division
• GO:0019827 stem cell population maintenance
• GO:0042246 tissue regeneration

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Homeobox protein NANOG 1.00
• Homeobox protein NANOG 0.94
• Homeobox protein NANOG 0.93
• Homeobox protein NANOGP8 0.93
• Homeobox protein NANOG 0.93
• Homeobox protein NANOG 0.91
• Oocyte-specific homeobox protein 3 0.87
• Homeobox protein SEBOX 0.86
• Homeobox protein NOBOX 0.84
• Homeobox protein SEBOX 0.84
• Oocyte-specific homeobox protein 5 0.83
• Putative homeobox protein NANOG2 0.83

Co-cited proteins · studied together in the literature

• Zinc finger protein 281 2 shared papers
• Homeobox protein NANOG 5 shared papers
• Sal-like protein 4 2 shared papers
• Steroid hormone receptor ERR2 1 shared papers
• Homeobox protein NANOG 1 shared papers
• Homeobox protein NANOG 1 shared papers
• SMAD family member 1 1 shared papers
• Putative homeobox protein NANOG2 1 shared papers
• Putative ATP-dependent RNA helicase TDRD12 1 shared papers
• Putative ATP-dependent RNA helicase TDRD12 1 shared papers
• Sal-like protein 1 1 shared papers
• Histone-lysine N-methyltransferase NSD2 1 shared papers

Literature · 21 cited papers

• 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. · 2015
• Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Zfp281 functions as a transcriptional repressor for pluripotency of mouse embryonic stem cells. Stem Cells · 2011
• A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome. Nature · 2009
• Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells. J. Biol. Chem. · 2008
• Crystal structure and DNA binding of the homeodomain of the stem cell transcription factor Nanog. J. Mol. Biol. · 2008
• Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J. Biol. Chem. · 2006
• Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. · 2006
• Nanog promotes transfer of pluripotency after cell fusion. Nature · 2006
• A negative feedback loop of transcription factors that controls stem cell pluripotency and self-renewal. FASEB J. · 2006
• The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. · 2006
• The transcriptional landscape of the mammalian genome. Science · 2005
• … and 9 more in the literature graph