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Protein

Homeobox protein NANOG

Gene

NANOG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:25825768). 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.4 Publications

Miscellaneous

Exists an other tandem duplicated non-processed pseudogene (NANOGP1) and 10 other NANOG-related nucleotide sequences located on different chromosomes, all of which are processed pseudogenes lacking introns (NANOGP2 to NANOGP11); except NANOGP8 which is a retrogene.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi95 – 154HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: HGNC
  • cell proliferation Source: HGNC
  • endodermal cell fate specification Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of cell differentiation Source: HGNC
  • regulation of gene expression Source: UniProtKB
  • regulation of transcription, DNA-templated Source: HGNC
  • somatic stem cell population maintenance Source: UniProtKB
  • stem cell population maintenance Source: BHF-UCL

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Repressor
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2892245. POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation.
R-HSA-2892247. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
R-HSA-452723. Transcriptional regulation of pluripotent stem cells.
R-HSA-6785807. Interleukin-4 and 13 signaling.
SignaLinkiQ9H9S0.
SIGNORiQ9H9S0.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein NANOG
Alternative name(s):
Homeobox transcription factor Nanog
Short name:
hNanog
Gene namesi
Name:NANOG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111704.10.
HGNCiHGNC:20857. NANOG.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi102F → A: No effect on POU5F1 promoter DNA-binding. 1 Publication1
Mutagenesisi122L → A: Increased POU5F1 promoter DNA-binding and protein stability. 1 Publication1
Mutagenesisi124Q → A: Decreased POU5F1 promoter DNA-binding and protein stability. 1 Publication1
Mutagenesisi125M → A: Decreased POU5F1 promoter DNA-binding and protein stability. 1 Publication1
Mutagenesisi136Y → A: Decreased POU5F1 promoter DNA-binding and protein stability. 1 Publication1
Mutagenesisi137K → A: Inhibits POU5F1 promoter DNA-binding. 1 Publication1
Mutagenesisi140K → A: Decreased POU5F1 promoter DNA-binding and protein stability. 1 Publication1
Mutagenesisi141T → A: Inhibits POU5F1 promoter DNA-binding. 1 Publication1
Mutagenesisi144Q → A: No effect on POU5F1 promoter DNA-binding. Decreased protein stability. 1 Publication1
Mutagenesisi145N → A: Inhibits POU5F1 promoter DNA-binding. 1 Publication1
Mutagenesisi147R → A: Inhibits POU5F1 promoter DNA-binding. 1 Publication1
Mutagenesisi148M → A: No effect on POU5F1 promoter DNA-binding. Increased protein stability. 1 Publication1
Mutagenesisi151K → A: Decreased POU5F1 promoter DNA-binding and protein stability. 1 Publication1

Organism-specific databases

DisGeNETi79923.
OpenTargetsiENSG00000111704.
PharmGKBiPA134864904.

Chemistry databases

ChEMBLiCHEMBL3580527.

Polymorphism and mutation databases

BioMutaiNANOG.
DMDMi118573073.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002614181 – 305Homeobox protein NANOGAdd BLAST305

Proteomic databases

PaxDbiQ9H9S0.
PeptideAtlasiQ9H9S0.
PRIDEiQ9H9S0.

PTM databases

iPTMnetiQ9H9S0.
PhosphoSitePlusiQ9H9S0.

Expressioni

Tissue specificityi

Expressed in testicular carcinoma and derived germ cell tumors (at protein level). Expressed in fetal gonads, ovary and testis. Also expressed in ovary teratocarcinoma cell line and testicular embryonic carcinoma. Not expressed in many somatic organs and oocytes.5 Publications

Developmental stagei

Expressed in embryonic stem (ES) and carcinoma (EC) cells. Expressed in inner cell mass (ICM) of the blastocyst and gonocytes between 14 and 19 weeks of gestation (at protein level). Not expressed in oocytes, unfertilized oocytes, 2-16 cell embryos and early morula (at protein level). Expressed in embryonic stem cells (ES). Expression decreases with ES differentiation.5 Publications

Gene expression databases

BgeeiENSG00000111704.
CleanExiHS_NANOG.
ExpressionAtlasiQ9H9S0. baseline and differential.
GenevisibleiQ9H9S0. HS.

Organism-specific databases

HPAiCAB019380.

Interactioni

Subunit structurei

Interacts with SMAD1 and SALL4. Interacts with ZNF281/ZFP281 (By similarity). Interacts with PCGF1 (PubMed:26687479). Interacts with ESRRB; reciprocally modulates their transcriptional activities (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi123000. 225 interactors.
STRINGi9606.ENSP00000229307.

Structurei

Secondary structure

1305
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi104 – 116Combined sources13
Beta strandi117 – 119Combined sources3
Helixi122 – 131Combined sources10
Helixi136 – 148Combined sources13
Turni149 – 151Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KT0NMR-A75-157[»]
4RBOX-ray3.30A/D94-162[»]
ProteinModelPortaliQ9H9S0.
SMRiQ9H9S0.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H9S0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati196 – 20015
Repeati201 – 20525
Repeati206 – 21035
Repeati216 – 22045
Repeati221 – 22555
Repeati226 – 23065
Repeati231 – 23575
Repeati236 – 24085

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni122 – 151Required for DNA-binding1 PublicationAdd BLAST30
Regioni196 – 2408 X repeats starting with a Trp in each unitAdd BLAST45
Regioni196 – 240Sufficient for transactivation activityBy similarityAdd BLAST45
Regioni241 – 305Sufficient for strong transactivation activityBy similarityAdd BLAST65

Sequence similaritiesi

Belongs to the Nanog homeobox family.Curated

Keywords - Domaini

Homeobox, Repeat

Phylogenomic databases

eggNOGiKOG0491. Eukaryota.
ENOG4111UAT. LUCA.
GeneTreeiENSGT00670000098076.
HOGENOMiHOG000236291.
HOVERGENiHBG058783.
InParanoidiQ9H9S0.
KOiK10164.
OMAiSWNSQAW.
OrthoDBiEOG091G0JYT.
PhylomeDBiQ9H9S0.
TreeFamiTF337402.

Family and domain databases

CDDicd00086. homeodomain. 1 hit.
InterProiView protein in InterPro
IPR009057. Homeobox-like.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
PfamiView protein in Pfam
PF00046. Homeobox. 1 hit.
SMARTiView protein in SMART
SM00389. HOX. 1 hit.
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiView protein in PROSITE
PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H9S0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSVDPACPQS LPCFEASDCK ESSPMPVICG PEENYPSLQM SSAEMPHTET
60 70 80 90 100
VSPLPSSMDL LIQDSPDSST SPKGKQPTSA EKSVAKKEDK VPVKKQKTRT
110 120 130 140 150
VFSSTQLCVL NDRFQRQKYL SLQQMQELSN ILNLSYKQVK TWFQNQRMKS
160 170 180 190 200
KRWQKNNWPK NSNGVTQKAS APTYPSLYSS YHQGCLVNPT GNLPMWSNQT
210 220 230 240 250
WNNSTWSNQT QNIQSWSNHS WNTQTWCTQS WNNQAWNSPF YNCGEESLQS
260 270 280 290 300
CMQFQPNSPA SDLEAALEAA GEGLNVIQQT TRYFSTPQTM DLFLNYSMNM

QPEDV
Length:305
Mass (Da):34,620
Last modified:November 28, 2006 - v2
Checksum:iAC3B2E067C591773
GO
Isoform 2 (identifier: Q9H9S0-2) [UniParc]FASTAAdd to basket
Also known as: Nanog-delta 48

The sequence of this isoform differs from the canonical sequence as follows:
     168-183: Missing.

Show »
Length:289
Mass (Da):32,838
Checksum:i65FB4489711E7742
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02938482K → N4 PublicationsCorresponds to variant dbSNP:rs2889551Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021688168 – 183Missing in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB093576 mRNA. Translation: BAC76999.1.
AY230262 mRNA. Translation: AAP49529.1.
AY578089 mRNA. Translation: AAT81526.1.
AK022643 mRNA. Translation: BAB14151.1.
CH471116 Genomic DNA. Translation: EAW88649.1.
CH471116 Genomic DNA. Translation: EAW88651.1.
CCDSiCCDS31736.1. [Q9H9S0-1]
CCDS73436.1. [Q9H9S0-2]
RefSeqiNP_001284627.1. NM_001297698.1. [Q9H9S0-2]
NP_079141.2. NM_024865.3. [Q9H9S0-1]
UniGeneiHs.635882.

Genome annotation databases

EnsembliENST00000229307; ENSP00000229307; ENSG00000111704. [Q9H9S0-1]
ENST00000526286; ENSP00000435288; ENSG00000111704. [Q9H9S0-2]
GeneIDi79923.
KEGGihsa:79923.
UCSCiuc009zfy.2. human. [Q9H9S0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNANOG_HUMAN
AccessioniPrimary (citable) accession number: Q9H9S0
Secondary accession number(s): D3DUU4, Q2TTG0, Q6JZS5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 28, 2006
Last modified: September 27, 2017
This is version 144 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families