UniProtKB - Q80Z64 (NANOG_MOUSE)
Protein
Homeobox protein NANOG
Gene
Nanog
Organism
Mus musculus (Mouse)
Status
Functioni
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.By similarity10 Publications
Miscellaneous
'Nanog' is derived from 'Tir nan Og' the mythologic Celtic land of the ever young.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 96 – 155 | HomeoboxPROSITE-ProRule annotationAdd BLAST | 60 |
GO - Molecular functioni
- chromatin binding Source: MGI
- cis-regulatory region sequence-specific DNA binding Source: BHF-UCL
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: UniProtKB
- identical protein binding Source: IntAct
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity Source: UniProtKB
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: MGI
- sequence-specific DNA binding Source: BHF-UCL
- sequence-specific double-stranded DNA binding Source: MGI
- transcription factor binding Source: UniProtKB
- transcription regulatory region sequence-specific DNA binding Source: MGI
GO - Biological processi
- cell dedifferentiation Source: UniProtKB
- cellular response to erythropoietin Source: Ensembl
- cellular response to rapamycin Source: Ensembl
- embryonic pattern specification Source: HGNC-UCL
- endodermal cell fate specification Source: MGI
- gonad development Source: HGNC-UCL
- 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-UCL
- negative regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of cell population proliferation Source: MGI
- positive regulation of mitotic cell cycle Source: MGI
- positive regulation of stem cell proliferation Source: MGI
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- regulation of cell differentiation Source: MGI
- regulation of gene expression Source: MGI
- regulation of stem cell division Source: UniProtKB
- regulation of transcription, DNA-templated Source: MGI
- regulation of transcription by RNA polymerase II Source: GO_Central
- 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
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding, Repressor |
Biological process | Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Homeobox protein NANOGAlternative 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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1919200, Nanog |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation1 Publication
Nucleus
- nuclear chromatin Source: GO_Central
- nucleolus Source: MGI
- nucleoplasm Source: BHF-UCL
- nucleus Source: BHF-UCL
Keywords - Cellular componenti
NucleusPathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 101 | T → A: Decreased protein expression. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 103 | F → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 112 | K → E: Increases affinity for DNA and protein stability; when associated with R-147. 1 Publication | 1 | |
Mutagenesisi | 120 | Y → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 123 | L → A: Increased protein expression and stability. 1 Publication | 1 | |
Mutagenesisi | 125 | Q → A: Decreased protein expression. No effect on protein stability. 1 Publication | 1 | |
Mutagenesisi | 126 | M → A: No effect on protein stability. 1 Publication | 1 | |
Mutagenesisi | 126 | M → R: Increases affinity for DNA; when associated with E-137. 1 Publication | 1 | |
Mutagenesisi | 137 | Y → A: Increased protein expression. Decreased protein stability. 1 Publication | 1 | |
Mutagenesisi | 137 | Y → E: Increases affinity for DNA; when associated with R-126. 1 Publication | 1 | |
Mutagenesisi | 138 | K → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 138 | K → E: Reduced affinity for DNA. 1 Publication | 1 | |
Mutagenesisi | 141 | K → A: Decreased protein stability. 1 Publication | 1 | |
Mutagenesisi | 142 | T → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 142 | T → I: Slightly reduced affinity for DNA. 1 Publication | 1 | |
Mutagenesisi | 145 | Q → A: Increased protein expression. No effect on protein stability. 1 Publication | 1 | |
Mutagenesisi | 146 | N → A: No effect on protein stability. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 146 | N → E: Strongly reduced affinity for DNA. 1 Publication | 1 | |
Mutagenesisi | 147 | Q → R: Increases affinity for DNA and protein stability; when associated with E-112. 1 Publication | 1 | |
Mutagenesisi | 148 | R → A: Decreased protein stability. Decreased embryonic stem cell self-renewal. 1 Publication | 1 | |
Mutagenesisi | 149 | M → A: Increased protein expression. No effect on protein stability. 1 Publication | 1 | |
Mutagenesisi | 152 | K → A: Decreased protein expression and stability. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000261419 | 1 – 305 | Homeobox protein NANOGAdd BLAST | 305 |
Proteomic databases
PaxDbi | Q80Z64 |
PRIDEi | Q80Z64 |
PTM databases
iPTMneti | Q80Z64 |
PhosphoSitePlusi | Q80Z64 |
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
Bgeei | ENSMUSG00000012396, Expressed in embryonic stem cell and 46 other tissues |
ExpressionAtlasi | Q80Z64, baseline and differential |
Genevisiblei | Q80Z64, MM |
Interactioni
Subunit structurei
Interacts with SMAD1 (PubMed:16801560).
Interacts with SALL4 (PubMed:16840789).
Interacts with ZNF281/ZFP281 (PubMed:21915945, PubMed:22988117).
Interacts with PCGF1 (By similarity).
Interacts with ESRRB; reciprocally modulates their transcriptional activities (PubMed:18957414).
Interacts with NSD2 (PubMed:19483677).
By similarity6 PublicationsBinary interactionsi
Hide detailsQ80Z64
Nanog - isoform 1 [Q80Z64-1]
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-15699014,EBI-15699014 |
Ubc [P62991] | 3 | EBI-15699014,EBI-413074 |
PIN1 [Q13526] from Homo sapiens. | 2 | EBI-15699014,EBI-714158 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity Source: UniProtKB
- transcription factor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 215050, 288 interactors |
DIPi | DIP-29932N |
ELMi | Q80Z64 |
IntActi | Q80Z64, 154 interactors |
MINTi | Q80Z64 |
STRINGi | 10090.ENSMUSP00000012540 |
Miscellaneous databases
RNActi | Q80Z64, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q80Z64 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q80Z64 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 198 – 202 | 1 | 5 | |
Repeati | 203 – 207 | 2 | 5 | |
Repeati | 208 – 212 | 3 | 5 | |
Repeati | 213 – 217 | 4 | 5 | |
Repeati | 218 – 222 | 5 | 5 | |
Repeati | 223 – 227 | 6 | 5 | |
Repeati | 228 – 232 | 7 | 5 | |
Repeati | 233 – 237 | 8 | 5 | |
Repeati | 238 – 242 | 9 | 5 | |
Repeati | 243 – 247 | 10 | 5 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 96 – 155 | Sufficient for interaction with SALL41 PublicationAdd BLAST | 60 | |
Regioni | 123 – 152 | Required for DNA-bindingBy similarityAdd BLAST | 30 | |
Regioni | 198 – 247 | 10 X repeats starting with a Trp in each unitAdd BLAST | 50 | |
Regioni | 198 – 247 | Sufficient for transactivation activityAdd BLAST | 50 | |
Regioni | 248 – 305 | Sufficient for strong transactivation activityAdd BLAST | 58 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 198 – 243 | Trp-richAdd BLAST | 46 |
Sequence similaritiesi
Belongs to the Nanog homeobox family.Curated
Keywords - Domaini
Homeobox, RepeatPhylogenomic databases
eggNOGi | KOG0491, Eukaryota |
GeneTreei | ENSGT00670000098076 |
HOGENOMi | CLU_086240_0_0_1 |
InParanoidi | Q80Z64 |
PhylomeDBi | Q80Z64 |
TreeFami | TF337402 |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q80Z64-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 149 | M → V in BAC76998 (PubMed:12787504).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_021689 | 1 – 25 | Missing in isoform 2. 1 PublicationAdd BLAST | 25 |
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 |
CCDSi | CCDS39623.1 [Q80Z64-1] CCDS80607.1 [Q80Z64-2] |
RefSeqi | NP_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 |
Genome annotation databases
Ensembli | ENSMUST00000012540; ENSMUSP00000012540; ENSMUSG00000012396 [Q80Z64-1] ENSMUST00000112580; ENSMUSP00000108199; ENSMUSG00000012396 [Q80Z64-2] ENSMUST00000112581; ENSMUSP00000108200; ENSMUSG00000012396 [Q80Z64-2] |
GeneIDi | 71950 |
KEGGi | mmu:71950 |
UCSCi | uc009dpo.2, mouse [Q80Z64-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS39623.1 [Q80Z64-1] CCDS80607.1 [Q80Z64-2] |
RefSeqi | NP_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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2VI6 | X-ray | 2.60 | A/B/C/D/E/F/G/H | 96-155 | [»] | |
SMRi | Q80Z64 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 215050, 288 interactors |
DIPi | DIP-29932N |
ELMi | Q80Z64 |
IntActi | Q80Z64, 154 interactors |
MINTi | Q80Z64 |
STRINGi | 10090.ENSMUSP00000012540 |
PTM databases
iPTMneti | Q80Z64 |
PhosphoSitePlusi | Q80Z64 |
Proteomic databases
PaxDbi | Q80Z64 |
PRIDEi | Q80Z64 |
Genome annotation databases
Ensembli | ENSMUST00000012540; ENSMUSP00000012540; ENSMUSG00000012396 [Q80Z64-1] ENSMUST00000112580; ENSMUSP00000108199; ENSMUSG00000012396 [Q80Z64-2] ENSMUST00000112581; ENSMUSP00000108200; ENSMUSG00000012396 [Q80Z64-2] |
GeneIDi | 71950 |
KEGGi | mmu:71950 |
UCSCi | uc009dpo.2, mouse [Q80Z64-1] |
Organism-specific databases
CTDi | 79923 |
MGIi | MGI:1919200, Nanog |
Phylogenomic databases
eggNOGi | KOG0491, Eukaryota |
GeneTreei | ENSGT00670000098076 |
HOGENOMi | CLU_086240_0_0_1 |
InParanoidi | Q80Z64 |
PhylomeDBi | Q80Z64 |
TreeFami | TF337402 |
Miscellaneous databases
BioGRID-ORCSi | 71950, 3 hits in 18 CRISPR screens |
ChiTaRSi | Nanog, mouse |
EvolutionaryTracei | Q80Z64 |
PROi | PR:Q80Z64 |
RNActi | Q80Z64, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000012396, Expressed in embryonic stem cell and 46 other tissues |
ExpressionAtlasi | Q80Z64, baseline and differential |
Genevisiblei | Q80Z64, MM |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NANOG_MOUSE | |
Accessioni | Q80Z64Primary (citable) accession number: Q80Z64 Secondary accession number(s): Q6SMR1, Q7TN85 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 28, 2006 |
Last sequence update: | June 1, 2003 | |
Last modified: | February 10, 2021 | |
This is version 150 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families