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FLASH GENE

Symbol

NKX2-1

contributors: mct - updated : 23-10-2015

HGNC name	NK2 homeobox 1
HGNC id	11825

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	like-sequence
SPECIAL FEATURE
text	duplicated form (with NKX2-8) of NKX2-2 on chromosome 20p
STRUCTURE	3.81 kb     2 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D14S1017 - NKX2-1 - D14S69 - D14S75 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003317 2 - 2352 NP_003308 38.6 371 - 2009 19336474 includes exons II and III NM_001079668 3 - 2183 NP_001073136 41 401 expressed differentially during mouse embryonic lung development 2009 19336474 includes three exons, reduced trancription activity

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Respiratory lung         Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous ependymal cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	embryonic striatum and brain, fetal gut

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	helix-turn-helix, DNA binding domain, a homeodomain, preferentially binding to thyroglobulin promoter
	a TN domain
	a NK2 specific domain
	two apparently redundant activation domains and is post-translationally modified by phosphorylation

HOMOLOGY

interspecies

homolog to murine Titf1

intraspecies

paralog to NKX2-4

Homologene

FAMILY

NK family of homeodomain containing transcritpion factor

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	activating the promoter of thyroid specific gene (thyroglobulin, thyroperoxidase) and controling the early events underlying the central activation of puberty
	playing a role in lung morphogenesis
	required for formation of the lung and differentiation of peripheral respiratory epithelial cells, and for morphogenesis of the fetal diencephalon
	plays a regulatory role in the transcription of growth hormone and prolactin genes and may regulate transdifferentiation of cells expressing these two hormones
	differential contribution of SHH-expressing and SHH-responding cells to medial amygdala neuronal diversity as well as the function of NKX2-1 in the development of this important limbic system structure
	functional role of phosphorylation in NKX2-1
	plays important roles in thyroglobulin (Tg) gene expression in chondrocytes
	transcriptionally regulates occludin, which represents another avenue of NKX2-1-mediated metastasis suppression
	GRHL2 and NKX2-1 form a regulatory loop that coordinates lung epithelial cell morphogenesis and differentiation
	expression of NKX2-1 is required to specify definitive endoderm to respiratory endoderm

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

text	lung morphogenesis

PATHWAY

metabolism

signaling

hormonal

thyroid

a component

INTERACTION

DNA	binding to thyroglobulin promoter

RNA

small molecule

protein	regulating SCGB3A2 expression
	interacting with RET promoter
	target of SLC26A4 (action is a prime factor in controlling thyroid differentiation)
	interacts physically and functionally with FOXA1(interaction is inhibitory and occurs through the NKX2.1 homeodomain in a DNA-independent manner)
	binds a highly conserved sequence in the LHX6 promoter, and this sequence appears to mediate the direct activation of LHX6 by NKX2.1
	HOXB5 binds to the promoter region 5prime upstream of the binding site of NKX2-1 and regulates RET expression
	MYBPH is a transcriptional target of NKX2-1, a master regulator of lung development that also plays a role as a lineage-survival oncogene in lung adenocarcinoma development
	transactivated the expression of the epithelial tight junction molecules occludin (OCLN) and CLDN1
	direct binding of Activin-A-responsive SMAD2 to the NKX2-1 promoter plays essential role during respiratory endoderm specification

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

TGDRD , BHC , DEL14QP

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in thyroid adenocarcinoma tumoral       gain of function coactivation of NKX2-1 and NKX2–8 pathways in non-small-cell lung cancer resistant to standard cisplatin therapy and with poor prognosis tumoral   amplification     and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer constitutional germinal mutation       in neuroendocrine cell hyperplasia of infancy (NEHI) tumoral     --other   ectopic expression of NKX2-1 in diffuse large B-cell lymphoma cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation

Susceptibility

to Hirschsprung disease (HSCR)

Variant & Polymorphism SNP	SNP repressing activation of transcription from HSCR-associated RET promoter haplotypes

Candidate gene	lung disease
Marker
Therapy target

ANIMAL & CELL MODELS