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FLASH GENE

Symbol

MST1

contributors: mct/npt/pgu - updated : 02-04-2020

HGNC name	macrophage stimulating 1 (hepatocyte growth factor-like)
HGNC id	7380

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	3.98 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	mutant TP53 associates with the promoter and represses its transcriptional activity, leading to a decrease in mRNA levels and a subsequent decrease in the levels of secreted protein

MAPPING

cloned

Y

linked

N

status

confirmed

Map	MST1 - APEH

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020998 12 - 2348 NP_066278 82 725 - 2008 18480548

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 liver       highly Reproductive male system testis     highly Urinary bladder       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal kinase domain
	four cysteine-rich kringle domains
	heterodimeric transmembrane glycoprotein (beta=150kD, alpha=35kD)
	two carboxy-terminal nuclear export signals (NES)

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to hippo

intraspecies

paralog to HGF

Homologene

FAMILY	peptidase S1 family
	plasminogen subfamily

CATEGORY

signaling cytokine growth factor

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	regulating macrophage migration, phagocytosis, and nitric oxide production
	involved in the regulation of peripheral macrophage activation
	has the potential to modulate inflammatory actions of microglia, which proposes novel aspects for the process of degeneration and/or regeneration of the brain
	protein regulating the innate immune responses to bacterial ligands and may have a role in the pathogenesis of inflammatory bowel diseases
	MST1/MST1R signaling seems to play at least some role in the pathogenesis of Merkel cell carcinoma
	may be one of the major determinants that affects the properties of tumor stroma and that produces a permissive microenvironment to promote cancer metastasis
	is a positive regulator of mammary gland ductal morphogenesis by controlling overall epithelial cell turnover, macrophage recruitment, and STAT3 activation in the developing mammary gland
	MST1/MST1R play important roles in inflammation, cell growth, migration, and epithelial to mesenchymal transition during tumor development
	appears to promote the migration of fibroblasts, enhances collagen synthesis and remodeling, and effectively improves wound healing
	hepatokine that potentially has a beneficial role in hepatic lipid and glucose metabolism via the activation of AMP-activated protein kinase (AMPK)
	is an effective inhibitor of inflammation and lipid accumulation in the stressed liver, thereby indicating that it has a key regulatory role in Non-alcoholic steatohepatitis (NASH)
	MST1 controlled inflammation response and mitochondrial function in endothelial cells
	MST1 is the primary factors responsible for endothelial cells dysfunction in aneurysms formation through inducing inflammation response, endothelial apoptosis, and NFKB1 signaling pathway activation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

MST1/MST1R system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response

INTERACTION

DNA

RNA

small molecule

protein	MST1R ligand
	interacting with RCC1 (RCC1 immobilization on the chromosomes at early stages of apoptosis is dependent on MST1 and its phosphorylation of histone H2B)
	major determinant of RASSF2 protein stability
	interacts strongly with RASSF5 but only weakly other components of the mammalian Hippo signaling pathway
	TMPRSS11D is likely important for MST1-MST1R signaling in the respiratory tract
	SAFB bound to AR and phosphorylated by MST1, previously shown to be an AR repressor, and MST1 localization to AR-dependent promoters was inhibited by SAFB depletion
	through binding to its receptor, RON or MST1R), it can activate epithelial cells and work as an inflammatory mediator

cell & other

REGULATION

Other

MST1 kinase activity is regulated by RASSF2 via RASSF2-MST1 protein complex formation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   reduced expression was observed in many types of cancer, including large-cell lung carcinoma tumoral   deletion     attenuated cerebral ischemia-reperfusion (IR) injury by improving mitochondrial function and reducing mitochondrial damage

Susceptibility

to Crohn disease

Variant & Polymorphism SNP	A>G at rs144982232 in MST1 showed the most significant association with Crohn's disease

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast potential target for the development of novel breast cancer therapies

ANIMAL & CELL MODELS