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UniProtKB - Q80Z64 (NANOG_MOUSE)

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Protein

Homeobox protein NANOG

Gene

Nanog

Organism
Mus musculus (Mouse)
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'. 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.9 Publications

Miscellaneous

'Nanog' is derived from 'Tir nan Og' the mythologic Celtic land of the ever young.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi96 – 155HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • chromatin binding Source: MGI
  • DNA binding Source: MGI
  • enhancer sequence-specific DNA binding Source: BHF-UCL
  • sequence-specific DNA binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding transcription factor recruiting Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: MGI
Complete GO annotation...

GO - Biological processi

  • cell dedifferentiation Source: UniProtKB
  • cell proliferation Source: MGI
  • cellular response to erythropoietin Source: Ensembl
  • cellular response to rapamycin Source: Ensembl
  • embryonic pattern specification Source: HGNC
  • endodermal cell fate specification Source: MGI
  • gonad development Source: HGNC
  • mesodermal cell fate commitment Source: MGI
  • multidimensional cell growth Source: Ensembl
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of cell differentiation Source: MGI
  • negative regulation of cell fate commitment Source: MGI
  • negative regulation of endodermal cell fate specification Source: HGNC
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of mitotic cell cycle Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of cell differentiation Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of stem cell division Source: UniProtKB
  • regulation of stem cell population maintenance Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • response to organic substance Source: MGI
  • response to retinoic acid Source: MGI
  • somatic stem cell population maintenance Source: MGI
  • stem cell differentiation Source: MGI
  • stem cell division Source: MGI
  • stem cell population maintenance Source: MGI
  • tissue regeneration Source: Ensembl
Complete GO annotation...

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein NANOG
Alternative name(s):
ES cell-associated protein 4
Early embryo specific expression NK-type homeobox protein
Homeobox transcription factor Nanog
Gene namesi
Name:Nanog
Synonyms:Ecat4, Enk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1919200. Nanog.

Subcellular locationi

GO - Cellular componenti

  • nucleolus Source: MGI
  • nucleoplasm Source: BHF-UCL
  • nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Loss of pluripotency in both ICM and ES cells and differentiated into extraembryonic (parietal and visceral) endoderm lineage.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi112K → E: Increases affinity for DNA and protein stability; when associated with R-147. 1 Publication1
Mutagenesisi126M → R: Increases affinity for DNA; when associated with E-137. 1 Publication1
Mutagenesisi137Y → E: Increases affinity for DNA; when associated with R-126. 1 Publication1
Mutagenesisi138K → E: Reduced affinity for DNA. 1 Publication1
Mutagenesisi142T → I: Slightly reduced affinity for DNA. 1 Publication1
Mutagenesisi146N → E: Strongly reduced affinity for DNA. 1 Publication1
Mutagenesisi147Q → R: Increases affinity for DNA and protein stability; when associated with E-112. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002614191 – 305Homeobox protein NANOGAdd BLAST305

Proteomic databases

PaxDbiQ80Z64.
PRIDEiQ80Z64.

PTM databases

iPTMnetiQ80Z64.
PhosphoSitePlusiQ80Z64.

Expressioni

Tissue specificityi

Not expressed in oocytes and spermatogonia (at protein level). Not expressed in many somatic organs, ovary, testis, fibroblast and hematopoietic cell lines.4 Publications

Developmental stagei

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.6 Publications

Inductioni

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/ZFP281.5 Publications

Gene expression databases

BgeeiENSMUSG00000012396.
ExpressionAtlasiQ80Z64. baseline and differential.
GenevisibleiQ80Z64. MM.

Interactioni

Subunit structurei

Interacts with SMAD1 and SALL4. Interacts with ZNF281/ZFP281. Interacts with PCGF1 (By similarity). Interacts with ESRRB; reciprocally modulates their transcriptional activities (PubMed:18957414).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi215050. 282 interactors.
DIPiDIP-29932N.
IntActiQ80Z64. 150 interactors.
STRINGi10090.ENSMUSP00000012540.

Structurei

Secondary structure

1305
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi105 – 117Combined sources13
Helixi123 – 133Combined sources11
Helixi137 – 149Combined sources13
Helixi152 – 154Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VI6X-ray2.60A/B/C/D/E/F/G/H96-155[»]
ProteinModelPortaliQ80Z64.
SMRiQ80Z64.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ80Z64.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati198 – 20215
Repeati203 – 20725
Repeati208 – 21235
Repeati213 – 21745
Repeati218 – 22255
Repeati223 – 22765
Repeati228 – 23275
Repeati233 – 23785
Repeati238 – 24295
Repeati243 – 247105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni96 – 155Sufficient for interaction with SALL41 PublicationAdd BLAST60
Regioni198 – 24710 X repeats starting with a Trp in each unitAdd BLAST50
Regioni198 – 247Sufficient for transactivation activityAdd BLAST50
Regioni248 – 305Sufficient for strong transactivation activityAdd BLAST58

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi198 – 243Trp-richAdd BLAST46

Sequence similaritiesi

Belongs to the Nanog homeobox family.Curated

Keywords - Domaini

Homeobox, Repeat

Phylogenomic databases

eggNOGiKOG0491. Eukaryota.
ENOG4111UAT. LUCA.
GeneTreeiENSGT00670000098076.
HOGENOMiHOG000236291.
HOVERGENiHBG058783.
InParanoidiQ80Z64.
KOiK10164.
OMAiSWNSQAW.
OrthoDBiEOG091G0JYT.
PhylomeDBiQ80Z64.
TreeFamiTF337402.

Family and domain databases

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: Q80Z64-1) [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
MSVGLPGPHS LPSSEEASNS GNASSMPAVF HPENYSCLQG SATEMLCTEA 
        60         70         80         90        100
ASPRPSSEDL PLQGSPDSST SPKQKLSSPE ADKGPEEEEN KVLARKQKMR 
       110        120        130        140        150
TVFSQAQLCA LKDRFQKQKY LSLQQMQELS SILNLSYKQV KTWFQNQRMK 
       160        170        180        190        200
CKRWQKNQWL KTSNGLIQKG SAPVEYPSIH CSYPQGYLVN ASGSLSMWGS 
       210        220        230        240        250
QTWTNPTWSS QTWTNPTWNN QTWTNPTWSS QAWTAQSWNG QPWNAAPLHN 
       260        270        280        290        300
FGEDFLQPYV QLQQNFSASD LEVNLEATRE SHAHFSTPQA LELFLNYSVT 

PPGEI
Length:305
Mass (Da):34,240
Last modified:June 1, 2003 - v1
Checksum:i4EF96408B767C79F
GO
Isoform 2 (identifier: Q80Z64-2) [UniParc]FASTAAdd to basket
Also known as: Nanog1a, Nanog1b

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Show »
Length:280
Mass (Da):31,859
Checksum:i090B8AC6C26A37C6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti149M → V in BAC76998 (PubMed:12787504).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0216891 – 25Missing in isoform 2. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB093574 mRNA. Translation: BAC76998.1.
AY278951 mRNA. Translation: AAP92157.1.
AF507043 mRNA. Translation: AAO67362.1.
AY455282 mRNA. Translation: AAS57554.1.
AY455285 mRNA. Translation: AAS57556.1.
AK010332 mRNA. Translation: BAE43219.1.
CCDSiCCDS39623.1. [Q80Z64-1]
CCDS80607.1. [Q80Z64-2]
RefSeqiNP_001276757.1. NM_001289828.1.
NP_001276759.1. NM_001289830.1. [Q80Z64-2]
NP_001276760.1. NM_001289831.1. [Q80Z64-2]
NP_082292.1. NM_028016.3. [Q80Z64-1]
XP_006506714.1. XM_006506651.2. [Q80Z64-1]
UniGeneiMm.485537.
Mm.491626.
Mm.6047.

Genome annotation databases

EnsembliENSMUST00000012540; ENSMUSP00000012540; ENSMUSG00000012396. [Q80Z64-1]
ENSMUST00000112580; ENSMUSP00000108199; ENSMUSG00000012396. [Q80Z64-2]
ENSMUST00000112581; ENSMUSP00000108200; ENSMUSG00000012396. [Q80Z64-2]
GeneIDi71950.
KEGGimmu:71950.
UCSCiuc009dpo.2. mouse. [Q80Z64-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiNANOG_MOUSE
AccessioniPrimary (citable) accession number: Q80Z64
Secondary accession number(s): Q6SMR1, Q7TN85
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: June 1, 2003
Last modified: June 7, 2017
This is version 124 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families