Reviewed, UniProtKB/Swiss-Prot Q9H9S0 (NANOG_HUMAN)

Names and origin

Protein names

Recommended name:
    Homeobox protein NANOG
Alternative name(s):
    Homeobox transcription factor Nanog
      Short name=hNanog

Gene names

Name:

NANOG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	305 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 By similarity. Acts as a transcriptional activator or repressor By similarity. Binds optimally to the DNA consensus sequence 5'-TAAT[GT][GT]-3' or 5'-[CG][GA][CG]C[GC]ATTAN[GC]-3' By similarity. When overexpressed, promotes cells to enter into S phase and proliferation By similarity.
Subunit structure	Interacts with SMAD1 and SALL4 By similarity.
Subcellular location	Nucleus. Ref.10
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.5 Ref.8
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.10 Ref.3 Ref.8 Ref.6 Ref.9
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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Homeobox Repeat
Ligand	DNA-binding
Molecular function	Activator Developmental protein Repressor
Gene Ontology (GO)
Biological process	cell differentiation Inferred from expression pattern. Source: HGNC cell proliferation Inferred from mutant phenotype. Source: HGNC embryonic development Ref.6 Inferred from expression pattern. Source: HGNC regulation of cell differentiation Inferred from mutant phenotype. Source: HGNC regulation of transcription, DNA-dependent Inferred from direct assay. Source: HGNC transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred by curator. Source: HGNC
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from direct assay. Source: HGNC
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 305	305	Homeobox protein NANOG		PRO_0000261418
Regions
	Repeat	196 – 200	5	1
	Repeat	201 – 205	5	2
	Repeat	206 – 210	5	3
	Repeat	216 – 220	5	4
	Repeat	221 – 225	5	5
	Repeat	226 – 230	5	6
	Repeat	231 – 235	5	7
	Repeat	236 – 240	5	8
	DNA binding	95 – 154	60	Homeobox Ref.3
	Region	196 – 240	45	8 X repeats starting with a Trp in each unit
	Region	196 – 240	45	Sufficient for transactivation activity By similarity
	Region	241 – 305	65	Sufficient for strong transactivation activity By similarity
Natural variations
	Alternative sequence	168 – 183	16	Missing in isoform 2.		VSP_021688
	Natural variant	82	1	K → N: dbSNP rs2889551. Ref.1 Ref.4 Ref.11		VAR_029384

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: AC3B2E067C591773	FASTA	305	34,620
	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
	Isoform 2 (Nanog-delta 48). Checksum: 65FB4489711E7742	FASTA	289	32,838
	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 NSNGVTQGCL VNPTGNLPMW 190 200 210 220 230 240 SNQTWNNSTW SNQTQNIQSW SNHSWNTQTW CTQSWNNQAW NSPFYNCGEE SLQSCMQFQP 250 260 270 280 NSPASDLEAA LEAAGEGLNV IQQTTRYFST PQTMDLFLNY SMNMQPEDV

References

	« Hide 'large scale' referencesShow '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: 12787504] [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: 14990856] [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: 16391521] [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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASN-82. Tissue: Teratocarcinoma.
[5]	"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: 12787505] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"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: 15108323] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[7]	"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: 16000880] [Abstract] Cited for: FUNCTION.
[8]	"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: 15982323] [Abstract] Cited for: DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[9]	"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: 15582778] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[10]	"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: 15983365] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[11]	"Eleven daughters of NANOG." Booth H.A., Holland P.W. Genomics 84:229-238(2004) [PubMed: 15233988] [Abstract] Cited for: VARIANT ASN-82.
+	Additional computationally mapped references.

Web resources

Wikipedia

Nanog entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB093576 mRNA. Translation: BAC76999.1. AY230262 mRNA. Translation: AAP49529.1. AY578089 mRNA. Translation: AAT81526.1. AK022643 mRNA. Translation: BAB14151.1.
IPI	IPI00434539. IPI00807368.
RefSeq	NP_079141.2.
UniGene	Hs.661360
3D structure databases
HSSP	HSSP built from PDB template 1IG7 based on UniProtKB P13297.
ModBase	Search...
Proteomic databases
PRIDE	Q9H9S0.
Genome annotation databases
Ensembl	ENSG00000111704. Homo sapiens. [Contig view]
GeneID	79923.
KEGG	hsa:79923.
Organism-specific databases
GeneCards	GC12P007833.
HGNC	HGNC:20857. NANOG.
HPA	CAB019380.
MIM	607937. gene.
PharmGKB	PA134864904.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9H9S0.
OMA	Q9H9S0. SWNSQAW.
Gene expression databases
Bgee	Q9H9S0.
CleanEx	HS_NANOG.
GermOnline	ENSG00000111704. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	69830.
SOURCE	Search...

Entry information

Entry name

NANOG_HUMAN

Accession

Primary (citable) accession number: Q9H9S0
Secondary accession number(s): Q2TTG0, Q6JZS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	November 28, 2006
Last modified:	June 16, 2009
This is version 61 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)