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Q9H9S0

- NANOG_HUMAN

UniProt

Q9H9S0 - NANOG_HUMAN

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Protein
Homeobox protein NANOG
Gene
NANOG
Organism
Homo sapiens (Human)
Status
Reviewed - 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.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi95 – 15460Homeobox1 Publication
Add
BLAST

GO - Molecular functioni

  1. DNA binding Source: UniProtKB
  2. chromatin binding Source: Ensembl
  3. enhancer sequence-specific DNA binding Source: Ensembl
  4. sequence-specific DNA binding transcription factor activity Source: HGNC
  5. transcription corepressor activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. cell differentiation Source: HGNC
  2. cell proliferation Source: HGNC
  3. embryo development Source: HGNC
  4. embryonic pattern specification Source: Ensembl
  5. endodermal cell fate specification Source: MGI
  6. gonad development Source: Ensembl
  7. mesodermal cell fate commitment Source: Ensembl
  8. negative regulation of BMP signaling pathway Source: Ensembl
  9. negative regulation of cell fate commitment Source: Ensembl
  10. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  11. positive regulation of cell proliferation Source: Ensembl
  12. positive regulation of mitotic cell cycle Source: Ensembl
  13. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  14. regulation of cell differentiation Source: HGNC
  15. regulation of gene expression Source: UniProtKB
  16. regulation of transcription, DNA-templated Source: HGNC
  17. response to retinoic acid Source: Ensembl
  18. somatic stem cell maintenance Source: UniProtKB
  19. stem cell division Source: Ensembl
  20. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_200670. POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation.
REACT_200759. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
REACT_200812. Transcriptional regulation of pluripotent stem cells.
SignaLinkiQ9H9S0.

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
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:20857. NANOG.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. nucleolus Source: BHF-UCL
  2. nucleoplasm Source: Ensembl
  3. nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134864904.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 305305Homeobox protein NANOG
PRO_0000261418Add
BLAST

Proteomic databases

PaxDbiQ9H9S0.
PRIDEiQ9H9S0.

PTM databases

PhosphoSiteiQ9H9S0.

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

BgeeiQ9H9S0.
CleanExiHS_NANOG.
GenevestigatoriQ9H9S0.

Organism-specific databases

HPAiCAB019380.

Interactioni

Subunit structurei

Interacts with SMAD1 and SALL4. Interacts with ZNF281/ZFP281 By similarity.

Protein-protein interaction databases

BioGridi123000. 6 interactions.
STRINGi9606.ENSP00000229307.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi104 – 11613
Beta strandi117 – 1193
Helixi122 – 13110
Helixi136 – 14813
Turni149 – 1513

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KT0NMR-A75-157[»]
ProteinModelPortaliQ9H9S0.
SMRiQ9H9S0. Positions 75-157.

Miscellaneous databases

EvolutionaryTraceiQ9H9S0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati196 – 20051
Repeati201 – 20552
Repeati206 – 21053
Repeati216 – 22054
Repeati221 – 22555
Repeati226 – 23056
Repeati231 – 23557
Repeati236 – 24058

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni196 – 240458 X repeats starting with a Trp in each unit
Add
BLAST
Regioni196 – 24045Sufficient for transactivation activity By similarity
Add
BLAST
Regioni241 – 30565Sufficient for strong transactivation activity By similarity
Add
BLAST

Sequence similaritiesi

Belongs to the Nanog homeobox family.

Keywords - Domaini

Homeobox, Repeat

Phylogenomic databases

eggNOGiNOG297592.
HOGENOMiHOG000236291.
HOVERGENiHBG058783.
InParanoidiQ9H9S0.
KOiK10164.
OMAiTWTNPTW.
PhylomeDBiQ9H9S0.
TreeFamiTF337402.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

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

MSVDPACPQS LPCFEASDCK ESSPMPVICG PEENYPSLQM SSAEMPHTET    50
VSPLPSSMDL LIQDSPDSST SPKGKQPTSA EKSVAKKEDK VPVKKQKTRT 100
VFSSTQLCVL NDRFQRQKYL SLQQMQELSN ILNLSYKQVK TWFQNQRMKS 150
KRWQKNNWPK NSNGVTQKAS APTYPSLYSS YHQGCLVNPT GNLPMWSNQT 200
WNNSTWSNQT QNIQSWSNHS WNTQTWCTQS WNNQAWNSPF YNCGEESLQS 250
CMQFQPNSPA SDLEAALEAA GEGLNVIQQT TRYFSTPQTM DLFLNYSMNM 300
QPEDV 305
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti82 – 821K → N.4 Publications
Corresponds to variant rs2889551 [ dbSNP | Ensembl ].
VAR_029384

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei168 – 18316Missing in isoform 2.
VSP_021688Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
RefSeqiNP_079141.2. NM_024865.2. [Q9H9S0-1]
XP_005253541.1. XM_005253484.2. [Q9H9S0-2]
UniGeneiHs.635882.

Genome annotation databases

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

Polymorphism databases

DMDMi118573073.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Nanog entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS31736.1. [Q9H9S0-1 ]
RefSeqi NP_079141.2. NM_024865.2. [Q9H9S0-1 ]
XP_005253541.1. XM_005253484.2. [Q9H9S0-2 ]
UniGenei Hs.635882.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2KT0 NMR - A 75-157 [» ]
ProteinModelPortali Q9H9S0.
SMRi Q9H9S0. Positions 75-157.
ModBasei Search...

Protein-protein interaction databases

BioGridi 123000. 6 interactions.
STRINGi 9606.ENSP00000229307.

PTM databases

PhosphoSitei Q9H9S0.

Polymorphism databases

DMDMi 118573073.

Proteomic databases

PaxDbi Q9H9S0.
PRIDEi Q9H9S0.

Protocols and materials databases

DNASUi 79923.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000229307 ; ENSP00000229307 ; ENSG00000111704 . [Q9H9S0-1 ]
ENST00000526286 ; ENSP00000435288 ; ENSG00000111704 . [Q9H9S0-2 ]
GeneIDi 79923.
KEGGi hsa:79923.
UCSCi uc009zfy.1. human. [Q9H9S0-1 ]

Organism-specific databases

CTDi 79923.
GeneCardsi GC12P007940.
H-InvDB HIX0010400.
HIX0038147.
HGNCi HGNC:20857. NANOG.
HPAi CAB019380.
MIMi 607937. gene.
neXtProti NX_Q9H9S0.
PharmGKBi PA134864904.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG297592.
HOGENOMi HOG000236291.
HOVERGENi HBG058783.
InParanoidi Q9H9S0.
KOi K10164.
OMAi TWTNPTW.
PhylomeDBi Q9H9S0.
TreeFami TF337402.

Enzyme and pathway databases

Reactomei REACT_200670. POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation.
REACT_200759. POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
REACT_200812. Transcriptional regulation of pluripotent stem cells.
SignaLinki Q9H9S0.

Miscellaneous databases

EvolutionaryTracei Q9H9S0.
GeneWikii Homeobox_protein_NANOG.
GenomeRNAii 79923.
NextBioi 69830.
PROi Q9H9S0.
SOURCEi Search...

Gene expression databases

Bgeei Q9H9S0.
CleanExi HS_NANOG.
Genevestigatori Q9H9S0.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
InterProi IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view ]
Pfami PF00046. Homeobox. 1 hit.
[Graphical view ]
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF46689. SSF46689. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells."
    Mitsui K., Tokuzawa Y., Itoh H., Segawa K., Murakami M., Takahashi K., Maruyama M., Maeda M., Yamanaka S.
    Cell 113:631-642(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASN-82, TISSUE SPECIFICITY.
    Tissue: Embryonic stem cell.
  2. "Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma."
    Clark A.T., Rodriguez R.T., Bodnar M.S., Abeyta M.J., Cedars M.I., Turek P.J., Firpo M.T., Reijo Pera R.A.
    Stem Cells 22:169-179(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Embryonic stem cell.
  3. "Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog."
    Kim J.S., Kim J., Kim B.S., Chung H.Y., Lee Y.Y., Park C.-S., Lee Y.S., Lee Y.H., Chung I.Y.
    Exp. Mol. Med. 37:601-607(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Tissue: Embryonic stem cell.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASN-82.
    Tissue: Teratocarcinoma.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASN-82.
  6. "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells."
    Chambers I., Colby D., Robertson M., Nichols J., Lee S., Tweedie S., Smith A.
    Cell 113:643-655(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  7. "Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human."
    Hart A.H., Hartley L., Ibrahim M., Robb L.
    Dev. Dyn. 230:187-198(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  8. "Identification of a putative transactivation domain in human Nanog."
    Oh J.-H., Do H.-J., Yang H.-M., Moon S.-Y., Cha K.-Y., Chung H.-M., Kim J.-H.
    Exp. Mol. Med. 37:250-254(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours."
    Hoei-Hansen C.E., Almstrup K., Nielsen J.E., Brask Sonne S., Graem N., Skakkebaek N.E., Leffers H., Rajpert-De Meyts E.
    Histopathology 47:48-56(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
  10. "Pluripotential competence of cells associated with Nanog activity."
    Hatano S.Y., Tada M., Kimura H., Yamaguchi S., Kono T., Nakano T., Suemori H., Nakatsuji N., Tada T.
    Mech. Dev. 122:67-79(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  11. "Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages."
    Hyslop L.A., Stojkovic M., Armstrong L., Walter T., Stojkovic P., Przyborski S., Herbert M., Murdoch A., Strachan T., Lako M.
    Stem Cells 23:1035-1043(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
  12. "Solution structure of human stem cell transcription factor NANOG."
    Center for eukaryotic structural genomics (CESG)
    Submitted (MAR-2010) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 75-157.
  13. Cited for: VARIANT ASN-82.

Entry informationi

Entry nameiNANOG_HUMAN
AccessioniPrimary (citable) accession number: Q9H9S0
Secondary accession number(s): D3DUU4, Q2TTG0, Q6JZS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 28, 2006
Last modified: September 3, 2014
This is version 117 of the entry and version 2 of the sequence. [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

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.

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

External Data

Dasty 3

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