Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NANOG contributors: mct/shn - updated : 06-01-2015
HGNC name Nanog homeobox
HGNC id 20857
Location 12p13.31      Physical location : 7.941.994 - 7.948.655
Synonym name
  • hNanog
  • homeobox protein NANOG
  • homeobox transcription factor Nanog
  • homeobox transcription factor Nanog-delta 48
  • Synonym symbol(s) FLJ12581, FLJ40451
    DNA
    TYPE functioning gene
    STRUCTURE 6.66 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU   other
    text structure
  • trp-rich repeats, in which trp-x-x-x is repeated 8 times
  • an Alu repetitive element in the 3-prime untranslated region
  • both TGFbeta- and BMP-responsive SMADs can bind with the NANOG proximal promoter, and this promoter activity is enhanced by TGFbeta/Activin and FGF signaling, is decreased by BMP signaling, and plays an essential role in sustaining embryonic stem cells self-renewal
  • MAPPING cloned Y linked N status provisional
    Map pter - D12S1623 - D12S1625 - NANOG - D12S1695 - D12S2205 - cen
    Physical map
    GRCC9 12p13.31 likely ortholog of mouse gene rich cluster, C9 gene B7 12p13 B7 gene ENO2 12p13.31 enolase 2, (gamma, neuronal) DRPLA 12p13.31 dentatorubral-pallidoluysian atrophy (atrophin-1) GRCC10 12p13.31 likely ortholog of mouse gene rich cluster, C10 gene PTPN6 12p13.31 protein tyrosine phosphatase, non-receptor type 6 REA 12p13.31 protein tyrosine phosphatase, non-receptor type 6 C2F 12p13 C2f protein LOC390285 12 similar to vav-1 interacting Kruppel-like protein isoform b C1S 12p13.31 complement component 1, s subcomponent C1R 12p13.31 complement component 1, r subcomponent C1RL 12p13.31 complement component 1, r subcomponent-like LOC283314 12p13.31 hypothetical protein LOC283314 RBP5 12p13.2 retinol binding protein 5, cellular CLSTN3 12p13.31 calsyntenin 3 PXR1 12p13.31 peroxisome receptor 1 LOC341392 12p13.31 similar to olfactory specific medium-chain acyl CoA synthetase M160 12p13.31 scavenger receptor cysteine-rich type 1 protein M160 CD163 12p13.3 CD163 antigen LOC390286 12 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) APOBEC1 12p13.2-p13.1 apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 GDF3 12p13.1 growth differentiation factor 3 LOC338759 12p13.31 STELLA CLECSF11 12p13.2-p12.3 C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 11 LOC360030 12p13.31 homeobox C14 NANOG 12p13.31 Nanog homeobox SLC2A14 12p13.3 solute carrier family 2 (facilitated glucose transporter), member 14 SLC2A3 12p13.3 solute carrier family 2 (facilitated glucose transporter), member 3 LOC283320 12p13.31 similar to 60 kDa heat shock protein, mitochondrial precursor (Hsp60) (60 kDa chaperonin) (CPN60) (Heat shock protein 60) (HSP-60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) (HuCHA60) FHX 12pter-p13.31 similar to 60 kDa heat shock protein, mitochondrial precursor (Hsp60) (60 kDa chaperonin) (CPN60) (Heat shock protein 60) (HSP-60) (Mitochondrial matrix protein P1) (P60 lymphocyte protein) (HuCHA60) C3AR1 12p13.3-p13.1 complement component 3a receptor 1 DKFZP566B183 12p13.31 DKFZP566B183 protein CLECSF6 12p13.1 C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 6 LOC283321 12p13.31 hypothetical LOC283321 LOC387828 12 LOC387828 FLJ10408 12p13.31 hypothetical protein FLJ10408 LOC387829 12 similar to Asparagine-linked glycosylation 1 homolog (yeast, beta-1,4-mannosyltransferase) LOC387830 12 similar to CG7889-PA LOC93320 12p13.31 similar to Alkaline sphingomyelinase LOC387831 12 hypothetical gene supported by AK074886 LOC390287 12 hypothetical gene supported by AK122996 LOC390288 12 similar to olfactory receptor GA_x6K02T2PVTD-14054886-14053957 LOC390289 12 similar to seven transmembrane helix receptor LOC341306 12p13.31 similar to 60S ribosomal protein L15 CLECSF8 12p13.31 C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 8 CLECSF9 12p13.32 C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 9 AICDA 12p13 activation-induced cytidine deaminase LOC94468 12p13.31 similar to 78 kDa gastrin-binding protein MAGP2 12p13.1-p12.2 similar to 78 kDa gastrin-binding protein KIAA1238 12p13.31 similar to 78 kDa gastrin-binding protein
    RNA
    TRANSCRIPTS type messenger
    text
  • two alternatively used first exons (1a and 1b/1b*) that both splice to the consecutive exons 2–6 (PMID: 20427424)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2098 34 305 - -
    - - 2055 - 289 - -
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon   Homo sapiens
     liver     Homo sapiens
    Endocrinepancreas     Homo sapiens
    Hearing/Equilibriumearinner   
     earmiddle   
    Lymphoid/Immunethymus     Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage pluripotent cells and developing germ cells, progenitor of mesodermal lineage (MPCs)
    cell lines testicular carcinoma and derived germ cell tumors, ovary teratocarcinoma cell line and testicular embryonic carcinoma, embryonic carcinoma cells
    fluid/secretion blood, amniotic fluid-derived stem cells (AFSc) seem to express NODAL, NANOG and DAZL and it speculated that the regulation of self-renewal in AFSc could be similar as in human embryonic stem cells
    at STAGE
    physiological period embryo
    Text embryonic pluripotent stem cells, fetal gonads, ovary and testis
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal domain (ND) rich in serine, threonine, and acidic residues
  • one homeobox domain, containing the DNA-binding motif
  • a leucine-rich nuclear export signal (NES) motif (125MQELSNILNL134) was found in the homeodomain (HD), exclusively localized to the nucleus, and may be functionally involved in CRM1-mediated nuclear export pathway
  • a nuclear localization signal (NLS) motif required for nuclear import
  • two basic NLS motifs are located at the N-terminus and C-terminus of the homeodomain and both motifs are required for complete nuclear localization
  • C-terminal domain (CD) containing two potent transactivation subdomains
  • conjugated PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to Nanog, Mus musculus
    ortholog to Nanog, Rattus norvegicus
    ortholog to Nanog, Rattus norvegicus
    Homologene
    FAMILY
  • homeobox family of DNA binding transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • originally found to be restricted to pluripotent stem cells
  • predominantly localizes in cytoplasm of colon cancer cells
  • basic FUNCTION
  • a central role in the transcription factor hierarchy that defines ES cell identity
  • homeobox-containing transcriptional factor required for maintaining the pluripotent state of stem cells
  • essential role in early development and required for the propagation of undifferentiated embryonic stem (ES) cells )
  • key pluripotency regulator and repressor of extraembryonic endoderm specification in ES cells
  • dispensible for expression of somatic pluripotency but specifically required for formation of germ cells
  • playing a central role in the transcription factor hierarchy that defines embryonic stem cell identity
  • may restrict the differentiation-inducing potential of POU5F1
  • involved in the regulation of cell differentiation
  • possessing an oncogenic potential that may be related to the role it plays in germ cell tumors and to its function in self renewal of ES cells
  • may act as a regulatory factor up-stream to POU5F1
  • have a central role in the maintenance of embryonic stem cells pluripotency
  • may function in concert with POU5F1 and SOX2 to establish ES cell identity
  • play fundamental roles in early development and stem cell pluripotency
  • upon overexpression, promotes cells to enter into S phase and proliferation
  • homeodomain transcription factor that is—in conjunction with POU5F1 and SOX2—responsible to establish a genetic circuit to maintain the stem cell compartment at the blastocyst stage of developing embryo
  • blocking BMP-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes
  • embryonic stem cells-specific homeodomain protein, is required for the self-renewal of ESCs (Embryonic stem cells)
  • essential for glioblastoma multiforme tumourigenicity in orthotopic xenografts and it is epistatic to HEDGEHOG-GLI activity
  • NANOG1, and NANOG2 (NANOGP1), activate a regulatory circuit that activates specific stem cell genes
  • master transcription factor associated with the maintenance of stem cell pluripotency
  • necessary and sufficient role of NANOG in inducing the transcription of KDR to regulate the angiogenic phenotypes of ECs (endothelial cells)
  • integral role for NANOG in neoplastic processes
  • homeodomain transcription factor, and an essential regulator for promotion of self-renewal of embryonic stem cells and inhibition of their differentiation
  • critical role in tumorigenesis, as well as in pluripotent stem cells
  • important roles of POU5F1 and NANOG in maintaining mesenchymal stem cells properties
  • NANOG plays an important role in embryonic stem cell (ESC) self-renewal and is essential for acquiring ground-state pluripotency during reprogramming
  • major transcription factor essential to the stem cell self-renewal and is associated with tumor malignancy
  • promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway
  • post-translational phosphorylation of NANOG is essential to regulate BMI1 and promote tumorigenesis
  • facilitates embryonic stem cell self-renewal and induced pluripotent stem cell generation during the final stage of reprogramming
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text gonad development
    PATHWAY
    metabolism
    signaling
    a component
  • Nanog-Nanog homodimerization is a critical aspect of its function promoting stem cell pluripotency
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • ZNF281 directly activate NANOG expression by binding to a site in the promoter in very close proximity to the POU5F1 and SOX2 binding sites
  • binds SATB1, and SATB2 (the NANOG locus and the balance of SATB1 and SATB2 contributes to the plasticity of NANOG expression and embryonic stem cell pluripotency)
  • interacting with SMAD1 and SALL4
  • phosphorylation promotes the interaction between NANOG and the prolyl isomerase PIN1, leading to NANOG stabilization by suppressing its ubiquitination
  • direct TET1 target and TET1 regulates NANOG expression by preventing the Nanog promoter from hypermethylation
  • important pathway for regulation of NANOG expression in pluripotent ESCs through direct activation by ZIC3
  • SALL1 is expressed in a differentiation-dependent manner and physically interacts with NANOG and SOX2, two components of the core pluripotency network
  • TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with HSP90AB1 and consequently regulates transcription of NANOG in embryonic stem cells
  • POU5F1, SOX2, and NANOG cooperate with a wide array of cofactors to orchestrate an embryonic stem (ES) cell-specific gene expression program that forms the molecular basis of pluripotency
  • NANOG binds the PTK2 promoter, up-regulates PTK2, and directly binds and is phosphorylated by PTK2 that regulates cell morphology, growth, and invasion
  • NANOG is subjected to a negative autoregulatory mechanism, i.e., autorepression, in ESCs, and such autorepression requires the coordinated action of the NANOG partner and transcriptional repressor ZNF281
  • binds directly to ESRRB, enhances binding of RNAPolII, and stimulates ESRRBb transcription
  • direct physical interaction between NANOG and SOX2 regulates embryonic stem cell self-renewal
  • DIDO1 could target to the loci of pluripotency factors such as NANOG and POU5F1 and positively regulate their expression
  • KLF4 expression resulted from the codependent and synergistic action of NANOG and STAT3 in embryonic stem cells and during initiation of reprogramming
  • SNAI1, but not SNAI2, is both a transcriptional target and protein partner of NANOG in reprogramming
  • ACTL6A could interact with NANOG and SOX2 and promote NANOG binding to pluripotency genes such as POU5F1 and SOX2
  • cell-cycle protein CDK6 could interact with NANOG in the spinal cord tissue
  • cell & other
    REGULATION
    activated by synergistic activation by POU5F1 and SOX2, that requires a multisubunit stem cell coactivator complex (SCC)
    inhibited by TP53 (TP53 directly suppresses the transcription of NANOG after DNA damage, contributing to the differentiation and elimination of DNA-damaged ESCs from the self-renewing pool)
    repressed by TCF3
    FGFR2, that induces rapid but reversible NANOG repression within ES cells
    Phosphorylated by PTK2, that binds and phosphorylates wild type NANOG protein but not the mutant NANOG with Y35F and Y174F mutations
    Other expression donw-regulated with ES differentiation
    regulated by KLF4
    regulated by HEDGEHOG-GLI (HH-GLI) signalling
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Deletion of Nanog causes early embryonic lethality, whereas constitutive expression enables autonomous self-renewal of embryonic stem cells