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FLASH GENE

Symbol

HOXA9

contributors: mct/shn - updated : 09-03-2013

HGNC name	homeobox A9
HGNC id	5109

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	3.09 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D7S2538 - D7S2440 - HOXA9 - D7S2564 - D7S2441 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_152739 2 - 2076 NP_689952 - 272 - - NM_002142 - - 1903 - - - - HOXA10-HOXA9 readthrough, non-coding RNA

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 Reproductive female system uterus     highly Urinary kidney       highly

cell lineage	primitive hematopoietic cells
cell lines
fluid/secretion

at STAGE

Text	expressed throughout the forelimb bud at early stages

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

helix-turn-helix, DNA binding domain

HOMOLOGY

interspecies	ortholog to Hoxa9, Mus musculus
	ortholog to Hoxa9, Rattus norvegicus
	ortholog to HOXA9, pan troglodytes

intraspecies

homolog to hoxd9

Homologene

FAMILY

Abd-B homeobox family

CATEGORY

regulatory , DNA associated , transcription factor , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus

basic FUNCTION	transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities in the antero-posterior axis
	activating CYBB transcription in differentiated myeloid cells
	maintains endothelial cells in a quiescent state by negatively regulating NFKB1 activity
	important for normal hematopoiesis, modulating MEIS1 through CREB1 targeting
	overexpression of HOXA9 induces IGF1R expression and subsequently promotes leukemic cell growth
	acting as an obligate proinflammatory factor by mediating cytokine induction of E-selectin
	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
	an important regulatory role in cytokine induction of the EC-leukocyte adhesion molecules E-selectin and vascular cell adhesion molecule 1
	stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response
	HOXA9 and FLT3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

text	a key regulator of hematopoiesis and embryonic development

PATHWAY

metabolism

signaling

a component

HOXA9/MADH4 in response to TGFB stimulation to repress osteopontin gene transcription

INTERACTION

DNA

RNA

small molecule

protein	PBX2 and MEIS1
	Smad4
	CBP
	PIM1
	protein arginine methyltransferase 5, PRMT5
	HOXA9, HOXA10 are direct transcriptional targets of SETBP1
	DACH1 has a stronger transcription-promoting activity with HOXA9 than does PBX2 with HOXA9
	CDX4 activates transcription of the HOXA9 and HOXA10 genes, and HOXA10 activates CDX4 transcription
	SYNCRIP and MSI2 interact indirectly though shared mRNA targets (SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion)

cell & other

REGULATION

inhibited by

phosphorylation by PKC, impairing its DNA binding ability and inducing myeloid differentiation

Other	negatively regulated by miR-126 binding to the homeobox
	methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules
	stability of HOXA9 controled by CUL-4A ubiquitylation machinery

ASSOCIATED DISORDERS

corresponding disease(s)

AMLT2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       with NUP98 in translocation t(7;11),in acute myeloid leukemia (see AML2) tumoral       gain of function coactivated by MEIS1 in acute and chronic myelogenous leukemia and in infant acute lymphoid leukemia tumoral     --over   in acute monocytic leukemia tumoral     --over   of NUP98-HOXA9 represses myeloid-specific gene transcription, thereby contributing to differentiation block in leukemogenesis constitutional     --over   very high expression in haemopoietic cells in adults over sixty constitutional     --over   inhibits inflammatory cytokine dependent inducible expression of leukocyte adhesion molecules in endothelial cells tumoral   translocation     t(7;17)(p15;q23) with MSI2 may contribute to disease progression in chronic myeloid leukemia tumoral     --other   aberrant expression has been shown to be important to the development of leukemia 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

Susceptibility

Variant & Polymorphism

Candidate gene	hypermethylated target gene in ovarian carcinogenesis
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   is required for survival in human MLL-rearranged acute leukemias and targeting HOXA9 may be a novel therapeutic option

ANIMAL & CELL MODELS