Solution structure of human stem cell transcription factor Nanog homeodomain fragment
Structural highlights
2kt0 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NANOG_HUMAN 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'. Binds to the POU5F1/OCT4 promoter (PubMed:25825768). 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.[1][2][3][4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
↑ Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M. Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells. 2005 Sep;23(8):1035-43. doi: 10.1634/stemcells.2005-0080. Epub 2005 , Jun 27. PMID:15983365 doi:http://dx.doi.org/10.1634/stemcells.2005-0080
↑ Oh JH, Do HJ, Yang HM, Moon SY, Cha KY, Chung HM, Kim JH. Identification of a putative transactivation domain in human Nanog. Exp Mol Med. 2005 Jun 30;37(3):250-4. doi: 10.1038/emm.2005.33. PMID:16000880 doi:http://dx.doi.org/10.1038/emm.2005.33
↑ Kim JS, Kim J, Kim BS, Chung HY, Lee YY, Park CS, Lee YS, Lee YH, Chung IY. Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog. Exp Mol Med. 2005 Dec 31;37(6):601-7. doi: 10.1038/emm.2005.73. PMID:16391521 doi:http://dx.doi.org/10.1038/emm.2005.73
↑ Hayashi Y, Caboni L, Das D, Yumoto F, Clayton T, Deller MC, Nguyen P, Farr CL, Chiu HJ, Miller MD, Elsliger MA, Deacon AM, Godzik A, Lesley SA, Tomoda K, Conklin BR, Wilson IA, Yamanaka S, Fletterick RJ. Structure-based discovery of NANOG variant with enhanced properties to promote self-renewal and reprogramming of pluripotent stem cells. Proc Natl Acad Sci U S A. 2015 Mar 30. pii: 201502855. PMID:25825768 doi:http://dx.doi.org/10.1073/pnas.1502855112
