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Q9H9S0 (NANOG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein NANOG
Alternative name(s):
Homeobox transcription factor Nanog
Short name=hNanog
Gene names
Name:NANOG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length305 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.8 Ref.11

Subunit structure

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

Subcellular location

Nucleus Ref.11.

Tissue specificity

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. Ref.1 Ref.2 Ref.3 Ref.6 Ref.9

Developmental stage

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. Ref.3 Ref.7 Ref.9 Ref.10 Ref.11

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.

Sequence similarities

Belongs to the Nanog homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainHomeobox
Repeat
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
Repressor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from expression pattern PubMed 16501172. Source: HGNC

cell proliferation

Inferred from mutant phenotype PubMed 16501172. Source: HGNC

embryo development

Inferred from expression pattern Ref.7. Source: HGNC

embryonic pattern specification

Inferred from electronic annotation. Source: Ensembl

endodermal cell fate specification

Inferred from direct assay PubMed 20713518. Source: MGI

gonad development

Inferred from electronic annotation. Source: Ensembl

mesodermal cell fate commitment

Inferred from electronic annotation. Source: Ensembl

negative regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell fate commitment

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20713518. Source: MGI

regulation of cell differentiation

Inferred from mutant phenotype PubMed 16501172. Source: HGNC

regulation of gene expression

Inferred from mutant phenotype PubMed 18388306. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 16153702. Source: HGNC

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

somatic stem cell maintenance

Inferred from mutant phenotype PubMed 18388306. Source: UniProtKB

stem cell division

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleolus

Inferred from direct assay PubMed 20458727. Source: BHF-UCL

nucleoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 18932205. Source: BHF-UCL

   Molecular_functionDNA binding

Inferred from direct assay PubMed 19427902. Source: UniProtKB

chromatin binding

Inferred from electronic annotation. Source: Ensembl

enhancer sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 16153702. Source: HGNC

transcription corepressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H9S0-1)

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.
Isoform 2 (identifier: Q9H9S0-2)

Also known as: Nanog-delta 48;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 305305Homeobox protein NANOG
PRO_0000261418

Regions

Repeat196 – 20051
Repeat201 – 20552
Repeat206 – 21053
Repeat216 – 22054
Repeat221 – 22555
Repeat226 – 23056
Repeat231 – 23557
Repeat236 – 24058
DNA binding95 – 15460Homeobox Ref.3
Region196 – 240458 X repeats starting with a Trp in each unit
Region196 – 24045Sufficient for transactivation activity By similarity
Region241 – 30565Sufficient for strong transactivation activity By similarity

Natural variations

Alternative sequence168 – 18316Missing in isoform 2.
VSP_021688
Natural variant821K → N. Ref.1 Ref.4 Ref.5 Ref.13
Corresponds to variant rs2889551 [ dbSNP | Ensembl ].
VAR_029384

Secondary structure

......... 305
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 28, 2006. Version 2.
Checksum: AC3B2E067C591773

FASTA30534,620
        10         20         30         40         50         60 
MSVDPACPQS LPCFEASDCK ESSPMPVICG PEENYPSLQM SSAEMPHTET VSPLPSSMDL 

        70         80         90        100        110        120 
LIQDSPDSST SPKGKQPTSA EKSVAKKEDK VPVKKQKTRT VFSSTQLCVL NDRFQRQKYL 

       130        140        150        160        170        180 
SLQQMQELSN ILNLSYKQVK TWFQNQRMKS KRWQKNNWPK NSNGVTQKAS APTYPSLYSS 

       190        200        210        220        230        240 
YHQGCLVNPT GNLPMWSNQT WNNSTWSNQT QNIQSWSNHS WNTQTWCTQS WNNQAWNSPF 

       250        260        270        280        290        300 
YNCGEESLQS CMQFQPNSPA SDLEAALEAA GEGLNVIQQT TRYFSTPQTM DLFLNYSMNM 


QPEDV 

« Hide

Isoform 2 (Nanog-delta 48) [UniParc].

Checksum: 65FB4489711E7742
Show »

FASTA28932,838

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Eleven daughters of NANOG."
Booth H.A., Holland P.W.
Genomics 84:229-238(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-82.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_079141.2. NM_024865.2.
XP_005253541.1. XM_005253484.2.
UniGeneHs.635882.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KT0NMR-A75-157[»]
ProteinModelPortalQ9H9S0.
SMRQ9H9S0. Positions 75-157.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123000. 6 interactions.
STRING9606.ENSP00000229307.

PTM databases

PhosphoSiteQ9H9S0.

Polymorphism databases

DMDM118573073.

Proteomic databases

PaxDbQ9H9S0.
PRIDEQ9H9S0.

Protocols and materials databases

DNASU79923.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229307; ENSP00000229307; ENSG00000111704. [Q9H9S0-1]
ENST00000526286; ENSP00000435288; ENSG00000111704. [Q9H9S0-2]
GeneID79923.
KEGGhsa:79923.
UCSCuc009zfy.1. human. [Q9H9S0-1]

Organism-specific databases

CTD79923.
GeneCardsGC12P007940.
H-InvDBHIX0010400.
HIX0038147.
HGNCHGNC:20857. NANOG.
HPACAB019380.
MIM607937. gene.
neXtProtNX_Q9H9S0.
PharmGKBPA134864904.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297592.
HOGENOMHOG000236291.
HOVERGENHBG058783.
InParanoidQ9H9S0.
KOK10164.
OMATWTNPTW.
PhylomeDBQ9H9S0.
TreeFamTF337402.

Enzyme and pathway databases

SignaLinkQ9H9S0.

Gene expression databases

BgeeQ9H9S0.
CleanExHS_NANOG.
GenevestigatorQ9H9S0.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9H9S0.
GeneWikiHomeobox_protein_NANOG.
GenomeRNAi79923.
NextBio69830.
PROQ9H9S0.
SOURCESearch...

Entry information

Entry nameNANOG_HUMAN
AccessionPrimary (citable) accession number: Q9H9S0
Secondary accession number(s): D3DUU4, Q2TTG0, Q6JZS5
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 28, 2006
Last modified: April 16, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM