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FLASH GENE

Symbol

HGF

contributors: mct/npt - updated : 10-05-2017

HGNC name	hepatocyte growth factor (hepatopoietin A; scatter factor)
HGNC id	4893

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DFNB39 neurosensory deafness 39
Location	7q21.11      Physical location : 81.331.444 - 81.399.452
Synonym name	lung fibroblast-derived mitogen
	fibroblast-derived tumor cytotoxic factor
	hepatopoietin A
	scatter factor
	lung fibroblast-derived mitogen
Synonym symbol(s)	SF, HPTA, F-TCF, HGFB

DNA

TYPE	functioning gene
STRUCTURE	68.01 kb     21 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000601 18 splicing 2820 NP_000592 83 728 - Watanabe, Schultz (2009) lacking exon 8 containing exon 5b (medium exon) encoding for the longest product propeptide maturing in an alpha and a bêta chain product having a "Pan_Apple", a "Tryp_SPc" and four "KR" domains NM_001010931 (NK2) 8 splicing 1307 NP_001010931 33 290 - Watanabe, Schultz (2009) lacking exons 9 to 19 containing exon 5b (medium exon) encoding for a product having a "Pan_Apple" and a "KR" domain NM_001010932 18 splicing 2805 NP_001010932 73 723 - Watanabe, Schultz (2009) lacking exon 8 containing exon 5c (shorter than 5a & 5b) product having a "Pan_Apple", a "Tryp_SPc" and four "KR" domains NM_001010933 8 splicing 1292 NP_001010933 23 285 - Watanabe, Schultz (2009) lacking exons 9 to 19 containing exon 5c (shorter than 5a & 5b) product having a "Pan_Apple" and two "KR" domains NM_001010934 5 splicing 2079 NP_001010934 24 210 - Watanabe, Schultz (2009) lacking exon 6 to 19 containing exon 5a (longer than 5b & 5c) encoding for the shortest product product having a "Pan_Apple" and a "KR" domain

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 Cardiovascular heart       moderately Digestive intestine small intestine     moderately   liver       moderately Hearing/Equilibrium ear inner cochlea   highly Lymphoid/Immune lymph node       moderately   thymus       lowly Reproductive female system placenta     highly Respiratory lung       lowly   respiratory tract trachea     moderately Urinary kidney       lowly Visual eye retina     lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective         Muscular smooth     moderately

cells

System Cell Pubmed Species Stage Rna symbol   fibroblast Blood/Hematopoietic platelet Cardiovascular endothelial cell Digestive hepatocyte Lymphoid/Immune macrophage

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	tissue at a lowly level

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide (3,5 kDa)
	alpha and bêta chains mature peptide liked by a disulfide bound
	a Pan/Apple domain (Pan_Apple)
	four cysteine-rich kringle domains (KR)
	a trypsin-like serine protease domain (Tryp_SPc)

secondary structure

pyrrolidone carboxylic acid (post translationally modified by the cyclization of a N-terminal glutamine)

conjugated

GlycoP

mono polymer

heteromer , dimer

isoforms

Precursor

a 697 amino acids propetide (79,6 kda)

HOMOLOGY

interspecies	homolog to rattus Hgf (90,62 pc)
	homolog to murine Hgf (90,76 pc)

Homologene

FAMILY	peptidase family S1
	plasminogen subfamily

CATEGORY

signaling cytokine growth factor

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	required for normal embryonic development
	being a potent mitogen for mature parenchymal hepatocyte cells
	being an hepatotrophic factor
	acting as growth factor for a broad spectrum of tissues and cell types
	inducing Retinal Vascular Permeability (RVP) via MAP-Kinase and PI-3 Kinase without altering retinal hemodynamics
	plays a critical role in differentiation of hepatic stem cells
	implicated in branching morphogenesis and invasion, tumorigenesis, erythroid differentiation, neuronal survival, and wound healing (Schultz 2009)

CELLULAR PROCESS	cell life, proliferation/growth
	cell communication
	cell migration & motility

PHYSIOLOGICAL PROCESS

development , nervous system

text	axon guidance
	embryogenesis and morphogenesis
	control of cell proliferation

PATHWAY

metabolism

signaling

a component

dimer of an alpha chain and a beta chain linked by a disulfide bond

INTERACTION

DNA

RNA

small molecule

protein	with SOCS3 (regulating HGF-induced keratinocyte migration by inhibiting STAT3 phosphorylation)
	interacting with PRDM16 (in the central nervous system, appears to promote neural stem/progenitor cell function, partly by promoting HGF expression)
	HGF prevents XDH activation following hypoxia/reoxygenation (H/R) primarily by inhibiting the JAK2 signaling pathway and in turn, inhibiting the increase in cytosolic Ca2+

cell & other

REGULATION

repressed by

anti-tumor agent valproic acid (VPA), a histone deacetylase (HDAC) inhibitor

ASSOCIATED DISORDERS

corresponding disease(s)

DFNB39

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in hypopharyngeal squamous cell carcinoma tumoral     --over   with IL11, in polycythemia vera (PV)

Susceptibility

Variant & Polymorphism SNP	HGF is a potential locus associated with high myopia in the Han Chinese population

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   blocking the MET/HGF/IL11 pathways could be of interest as an additional therapeutic option in polycythemia vera

ANIMAL & CELL MODELS