Q9H9S0 (NANOG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	305 AA.
Sequence status	Complete.
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. 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 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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Inferred from mutant phenotype PubMed 16501172. Source: HGNC endodermal cell fate specification Inferred from direct assay PubMed 20713518. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20713518. Source: MGI somatic stem cell maintenance Inferred from mutant phenotype PubMed 18388306. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleolus Inferred from direct assay PubMed 20458727. Source: BHF-UCL
Molecular_function	DNA binding Inferred from direct assay PubMed 19427902. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro 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 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. Ref.1 Ref.4 Ref.5 Ref.13
Corresponds to variant rs2889551 [ dbSNP | Ensembl ].

VAR_029384

Secondary structure

1

.

.

.

.

.

.

.

.

.

305

Helix Strand Turn

Details...

Helix

104 – 116

13

Beta strand

117 – 119

3

Helix

122 – 131

10

Helix

136 – 148

13

Turn

149 – 151

3

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) [UniParc]. 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] [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]	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. , 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.

Web resources

Wikipedia

Nanog entry

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.

IPI

IPI00434539.
IPI00807368.

RefSeq

NP_079141.2. NM_024865.2.

UniGene

Hs.635882.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KT0	NMR	-	A	75-157	[»]

ProteinModelPortal

Q9H9S0.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000229307.

PTM databases

PhosphoSite

Q9H9S0.

Polymorphism databases

DMDM

118573073.

Proteomic databases

PaxDb

Q9H9S0.

PRIDE

Q9H9S0.

Protocols and materials databases

DNASU

79923.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000229307; ENSP00000229307; ENSG00000111704.
ENST00000526286; ENSP00000435288; ENSG00000111704.

GeneID

79923.

KEGG

hsa:79923.

UCSC

uc009zfy.1. human.

Organism-specific databases

CTD

79923.

GeneCards

GC12P007940.

H-InvDB

HIX0010400.
HIX0038147.

HGNC

HGNC:20857. NANOG.

HPA

CAB019380.

MIM

607937. gene.

neXtProt

NX_Q9H9S0.

PharmGKB

PA134864904.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG297592.

HOGENOM

HOG000236291.

HOVERGEN

HBG058783.

InParanoid

Q9H9S0.

KO

K10164.

OMA

TWTNPTW.

OrthoDB

EOG40VVQM.

PhylomeDB

Q9H9S0.

Gene expression databases

ArrayExpress

Q9H9S0.

Bgee

Q9H9S0.

CleanEx

HS_NANOG.

Genevestigator

Q9H9S0.

GermOnline

ENSG00000111704. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR017970. Homeobox_CS.
IPR001356. Homeodomain.
IPR009057. Homeodomain-like.
[Graphical view]

Pfam

PF00046. Homeobox. 1 hit.
[Graphical view]

SMART

SM00389. HOX. 1 hit.
[Graphical view]

SUPFAM

SSF46689. Homeodomain_like. 1 hit.

PROSITE

PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9H9S0.

GenomeRNAi

79923.

NextBio

69830.

SOURCE

Search...

Entry information

Entry name

NANOG_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 104 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.