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FLASH GENE

Symbol

HAX1

contributors: mct/pgu - updated : 23-12-2020

HGNC name	HCLS1 associated protein X-1
HGNC id	16915

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	SCNP3 severe congenital neutropenia 3
Location	1q21.3      Physical location : 154.245.038 - 154.248.349
Synonym name	interleukin 1 alpha N terminal binding protein
	HS1 binding protein
	Hematopoietic cell specific Lyn Substrate 1 (HS1)-binding protein
	HCLS1 (and PKD2) associated protein
Synonym symbol(s)	HS1BP1, HAX-1, HCLSBP1, SCN3, FLJ17042, FLJ18492, FLJ93803, FLJ17042

DNA

TYPE	functioning gene
STRUCTURE	3.31 kb     7 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006118 7 splicing 1196 NP_006109 35 279 - 2008 18611981 isoform a NM_001018837 7 splicing 1052 NP_001018238 26 231 - 2008 18611981 using an alternate in-frame splice site compared to variant 1 isoform b having the same N- and C-termini

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart         Homo sapiens Digestive salivary gland       highly Endocrine neuroendocrine pituitary     highly   pancreas         Nervous brain         Skin/Tegument skin       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte Skin/Tegument melanocyte

cell lineage
cell lines	meningioma and synovial sarcoma cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	SH3 domain containing protein
	putative consensus binding motif
	a BH-domain
	C-terminal region, termed the Hax1 homology domain (HD1), essential for association with HTRA2, to facilitate its mitochondrial processing

HOMOLOGY

interspecies

ortholog to murine Hax1

Homologene

FAMILY

Bcl-2-family-related protein

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria,inner
	intracellular,cytoplasm,organelle,mitochondria,interspace
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus
	intracellular,nuclear envelope
text	localizes to sarcoplasmic reticulum (SR) in the heart

basic FUNCTION	a major regulator of myeloid homeostasis
	functioning in promoting cell survival
	playing a role in motility and/or adhesion of cells
	required to suppress apoptosis in lymphocytes and neurons
	functions in signal transduction and cytoskeletal control
	regulator of contractility and calcium cycling in the heart
	represents a regulatory mechanism in cardiac calcium cycling and its responses to sympathetic stimulation, implicating its importance in calcium homeostasis and cell survival
	represents an additional regulator of sarcoplasmic reticulum calcium transport and contractility in the heart
	negative regulator of integrin-mediated adhesion and chemotaxis through RHOA, and a novel regulator of neutrophil uropod detachment and chemotaxis through RHOA
	role of HAX1 in the non-canonical NFKB1 pathway
	HAX1 is involved in mRNA processing as an element of P-body interaction network
	HAX1 could protect endothelial precursor cells (EPCs) from apoptosis in oxidative stress
	HAX1 promotes hepatocellular carcinoma HCC metastasis by epithelial-mesenchymal transition (EMT) through activating the NFKB1 pathway

CELLULAR PROCESS	cell life, antiapoptosis
	cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

UCP3-HAX1 complex may regulate mitochondrial functional changes caused by mitochondrial Ca(2+)

INTERACTION

DNA

RNA

small molecule

protein	PKD2
	cortactin
	interaction with the mitochondrial proteases PARL (presenilin-associated, rhomboid-like) and HTRA2, to suppress apoptosis in lymphocytes and neurons
	associates with PARL on the inner mitochondrial membrane
	interacting with caspase-9
	interacting with XIAP, suppressing its polyubiquitination and thus inhibiting apoptosis
	PELO interacts with HAX1, EIF3G and SRPX proteins and that this interaction occurs at the cytoskeleton
	binding partner of SAV1 (SAV1 attenuates its protective role against apoptosis in MCF-7 breast cancer cells)
	molecular interaction between human TPCN1/TPCN2 and the anti-apoptotic protein HAX1 (HCLS-associated X-1)and the observed binding of HAX1 to TPCs may represent a conserved mechanism by which these endolysosomal ion channels are regulated
	anti-apoptotic protein HAX1 interacting with RNF217
	MAPRE2 association with HAX1 plays a significant role in focal adhesion turnover and epidermal migration
	UCP3 interacted with HAX1, an anti-apoptotic protein that was localized in the mitochondria, and is involved in cellular responses to Ca(2+)
	HAX1 is required for KDM4B-mediated mitochondrial apoptosis
	HAX1 is likely a major mediator of PLN inhibitory activity and a critical gatekeeper of sarcoplasmic reticulum calcium cycling and contractility in the heart
	HAX1 protein levels are indeed regulated through FXN modulation

cell & other

REGULATION

activated by

directly by KDM4B

ASSOCIATED DISORDERS

corresponding disease(s)

SCNP3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in lesional psoriatic skin constitutional     --over   protects cardiac myocytes from apoptosis through caspase-9 inhibition constitutional     --over   reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and leading to depressed myocyte calcium kinetics and mechanics tumoral     --over   in hepatocellular carcinoma (HCC)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	HAX1 can be a novel molecular marker for HCC
	HAX1 could be considered as a potential biomarker of cardiac disease in FRDA
Therapy target
	System Type Disorder Pubmed cancer     is a potential therapeutic target for the treatment of cancer cancer digestive liver could be a potential therapeutic target for HCC treatment

ANIMAL & CELL MODELS

murine Hax1(-/-) B cells show a significantly reduced expression of CXCR4, which might have an influence on the observed defects in B-cell development