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Protein

Homeobox protein NANOG

Gene

Nanog

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

GO - Molecular functioni

GO - Biological processi

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1919200 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

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
Mutagenesisi101T → A: Decreased protein expression. Decreased embryonic stem cell self-renewal. 1 Publication1
Mutagenesisi103F → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication1
Mutagenesisi112K → E: Increases affinity for DNA and protein stability; when associated with R-147. 1 Publication1
Mutagenesisi120Y → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication1
Mutagenesisi123L → A: Increased protein expression and stability. 1 Publication1
Mutagenesisi125Q → A: Decreased protein expression. No effect on protein stability. 1 Publication1
Mutagenesisi126M → A: No effect on protein stability. 1 Publication1
Mutagenesisi126M → R: Increases affinity for DNA; when associated with E-137. 1 Publication1
Mutagenesisi137Y → A: Increased protein expression. Decreased protein stability. 1 Publication1
Mutagenesisi137Y → E: Increases affinity for DNA; when associated with R-126. 1 Publication1
Mutagenesisi138K → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication1
Mutagenesisi138K → E: Reduced affinity for DNA. 1 Publication1
Mutagenesisi141K → A: Decreased protein stability. 1 Publication1
Mutagenesisi142T → A: Decreased protein expression and stability. Decreased embryonic stem cell self-renewal. 1 Publication1
Mutagenesisi142T → I: Slightly reduced affinity for DNA. 1 Publication1
Mutagenesisi145Q → A: Increased protein expression. No effect on protein stability. 1 Publication1
Mutagenesisi146N → A: No effect on protein stability. Decreased embryonic stem cell self-renewal. 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
Mutagenesisi148R → A: Decreased protein stability. Decreased embryonic stem cell self-renewal. 1 Publication1
Mutagenesisi149M → A: Increased protein expression. No effect on protein stability. 1 Publication1
Mutagenesisi152K → A: Decreased protein expression and stability. 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 Expressed in 22 organ(s), highest expression level in embryonic stem cell
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi215050, 282 interactors
DIPiDIP-29932N
ELMiQ80Z64
IntActiQ80Z64, 154 interactors
MINTiQ80Z64
STRINGi10090.ENSMUSP00000012540

Structurei

Secondary structure

1305
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
Regioni123 – 152Required for DNA-bindingBy similarityAdd BLAST30
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
OrthoDBiEOG091G0JYT
PhylomeDBiQ80Z64
TreeFamiTF337402

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
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

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
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

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...

Protein-protein interaction databases

BioGridi215050, 282 interactors
DIPiDIP-29932N
ELMiQ80Z64
IntActiQ80Z64, 154 interactors
MINTiQ80Z64
STRINGi10090.ENSMUSP00000012540

PTM databases

iPTMnetiQ80Z64
PhosphoSitePlusiQ80Z64

Proteomic databases

PaxDbiQ80Z64
PRIDEiQ80Z64

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi79923
MGIiMGI:1919200 Nanog

Phylogenomic databases

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

Miscellaneous databases

EvolutionaryTraceiQ80Z64
PROiPR:Q80Z64
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000012396 Expressed in 22 organ(s), highest expression level in embryonic stem cell
ExpressionAtlasiQ80Z64 baseline and differential
GenevisibleiQ80Z64 MM

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 135 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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