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FLASH GENE

Symbol

HOXA10

contributors: mct - updated : 15-06-2016

HGNC name	homeobox A10
HGNC id	5100

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

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 Digestive intestine large intestine colon   highly   salivary gland       highly Reproductive female system uterus     highly   female system breast mammary gland   highly   male system prostate     highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective bone       Epithelial barrier/lining endometrium     Epithelial secretory glandular endocrine

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	developing uterus, expressed in the embryonic paramesonephric (Müllerian) ducts

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

helix-turn-helix, DNA binding domain

HOMOLOGY

interspecies

homolog to murine Hox-1.8

Homologene

FAMILY

ABD-B homeobox family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	may be regulating gene expression, morphogenesis, and differentiation
	playing a pivotal role in normal hematopoietic-lineage determination and regulation
	involved in regulating decidualization
	master regulator of postnatal hematopoietic development
	had an important role in induction of apoptosis by the Abl kinase inhibitors in chronic myelogenous leukemia cells
	transcription factor that is crucial for development and patterning of the uterus during embryogenesis
	required for uterine receptivity and implantation, and is a key regulator of decidualization )
	early activator of bone gene expression which functions by facilitating the remodeling of chromatin
	major differentiation factors of the NK-cell lineage, including HOXA9, HOXA10 and ID2, were (de)regulated via polycomb repressor complex 2 (PRC2) which therefore contributes to T-cell leukemogenesis
	facilitates myeloid progenitor expansion and impedes myeloid differentiation
	is a homeodomain transcription factor that is involved in maintenance of the myeloid progenitor population and implicated in myeloid leukemogenesis
	HOXA10 and HOXA13 are involved in the development of human genitalia
	role for HOXA10 in terminating emergency granulopoiesis, suggesting an important contribution by Hox proteins to the innate immune response
	HOXA10 and EMX2 are two transcription factors necessary for female Müllerian duct differentiation and development

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with SIRT2
	CAPN5 is a target of HOXA10 transcriptional regulation in endometrial cells
	target of PHGDH regulation in endometrial cells
	DUSP4 is a HOXA10 target gene
	interaction with PBX1 (acting to reduce HOXA10-mediated transcriptional activation at bone-specific promoters)
	TGFB2 is a HOXA10 target gene (HOXA10 activated TGFB2 transcription by interacting with tandem cis elements in the promoter)
	ARIH2 has E3 ubiquitin ligase activity, and HOXA10-overexpressing myeloid cells exhibited a ARIH2-dependent increase in protein ubiquitination
	CDX4 influenced transcription of HOXA10 target genes in a HOXA10-dependent manner
	HOXA10 activates ITGB3 transcription in myeloid progenitor cells and differentiating phagocytes
	FGF2 expression and secretion are regulated in a HOXA10-dependent manner in myeloid progenitor cells and differentiating phagocytes
	HOXA9, HOXA10 are direct transcriptional targets of SETBP1
	FGF2 and CDX4 are direct target genes of HOXA10 and HOXA10 is a CDX4 target gene
	CTNNB1 activates the HOXA10 and CDX4 genes in myeloid progenitor cells
	NKX2-5 mediates differential cardiac differentiation through interaction with HOXA10
	HOXA10-mediated expression of MMP26 promotes embryo adhesion during the process of embryonic implantation
	KMT2A collaborate with ESR1 to regulate HOXA10 expression in AML
	CDX4 activates transcription of the HOXA9 and HOXA10 genes, and HOXA10 activates CDX4 transcription
	HOXA10 actives transcription of the gene encoding ARIH2 during myeloid differentiation
	EMX2 gene is a known direct target of HOXA10 in the reproductive tract

cell & other

REGULATION

repressed by

progesterone in myometrium

Other	regulated by the testosterone
	regulated by 17ß-estradiol (E2) and progesterone

ASSOCIATED DISORDERS

corresponding disease(s)

HOXA10

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in polycystic ovary syndrome (PCOS), contributing to the diminished reproduction potential of women tumoral     --over   promoter hypomethylation is an important mechanism for high expression of HOXA10 in ovarian cancer and may be a potential prognostic factor in ovarian cancer tumoral     --over   in poor prognosis human AML(acute myeloid leukemia), and HOXA10 overexpression in myeloid progenitor cells increased TGFB2 production by the cells tumoral     --over   of HOXA9 and HOXA10 and their essential cofactor MEIS1 in cells with the t(4;11) chromosome translocation and MLL-AF4 in acute leukemia tumoral     --over   increases FGF2 mRNA expression and FGF2 protein secretion in U937 myeloid leukemia cells tumoral     --over   in prostate cancer cell lines and tissues compared to those in normal prostate epithelium

Susceptibility

to genital malformations

Variant & Polymorphism other	rare DNA sequence variations in the HOXA10 gene could contribute to the misdevelopment of female internal genitalia

Candidate gene	DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC
Marker
Therapy target

ANIMAL & CELL MODELS

mice with Hoxa10 gene disruption exhibited an overwhelming and fatal emergency granulopoiesis response that was characterized by tissue infiltration with granulocytes, but reversed by re-expression of Triad1 in the bone marrow