MST1 macrophage stimulating 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MST1provided by HGNC
Official Full Name: macrophage stimulating 1provided by HGNC
Primary source: HGNC:HGNC:7380
See related: Ensembl:ENSG00000173531 MIM:142408; AllianceGenome:HGNC:7380
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MSP; HGFL; NF15S2; D3F15S2; DNF15S2
Summary: The protein encoded by this gene contains four kringle domains and a serine protease domain, similar to that found in hepatic growth factor. Despite the presence of the serine protease domain, the encoded protein may not have any proteolytic activity. The receptor for this protein is RON tyrosine kinase, which upon activation stimulates ciliary motility of ciliated epithelial lung cells. This protein is secreted and cleaved to form an alpha chain and a beta chain bridged by disulfide bonds. [provided by RefSeq, Jan 2010]
Annotation information: Note: MST1 (Gene ID: 4485) and STK4 (Gene ID: 6789) share the MST1 symbol/alias in common. MST1 is a widely used alternative name for serine/threonine kinase 4 (STK4), which can be confused with the official symbol for macrophage stimulating 1 (MST1). [01 Jun 2018]
Expression: Biased expression in liver (RPKM 45.2), duodenum (RPKM 24.6) and 13 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (49683947..49689474, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (49713231..49718759, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (49721380..49726907, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice.
Title: Mst1-mediated phosphorylation of Nur77 improves the endometrial receptivity in human and mice.
Macrophage-stimulating protein is decreased in severe preeclampsia and regulates the biological behavior of HTR-8/SVneo trophoblast cells.
Title: Macrophage-stimulating protein is decreased in severe preeclampsia and regulates the biological behavior of HTR-8/SVneo trophoblast cells.
circCRAMP1L is a novel biomarker of preeclampsia risk and may play a role in preeclampsia pathogenesis via regulation of the MSP/RON axis in trophoblasts.
Title: circCRAMP1L is a novel biomarker of preeclampsia risk and may play a role in preeclampsia pathogenesis via regulation of the MSP/RON axis in trophoblasts.
Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes.
Title: Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes.
Macrophage stimulating 1-induced inflammation response promotes aortic aneurysm formation through triggering endothelial cells death and activating the NF-kappaB signaling pathway.
Title: Macrophage stimulating 1-induced inflammation response promotes aortic aneurysm formation through triggering endothelial cells death and activating the NF-κB signaling pathway.
Comparative characterization of the HGF/Met and MSP/Ron systems in primary pancreatic adenocarcinoma.
Title: Comparative characterization of the HGF/Met and MSP/Ron systems in primary pancreatic adenocarcinoma.
Our analysis suggests that MST1 might interact with key susceptibility genes involved in autophagy and bacterial recognition. These findings provide insight into the genetic architecture of Crohn's disease in Chinese and may partially explain the disparity of genetic signals in Crohn's disease susceptibility across different ethnic populations by highlighting the contribution of gene-gene interactions.
Title: A novel susceptibility locus in MST1 and gene-gene interaction network for Crohn's disease in the Chinese population.
Mst1 overexpression inhibits mitophagy activity via suppressing the ERK-Mfn2 pathway, ultimately augmenting IL-24-inducd esophageal cancer death via enhanced mitochondrial stress.
Title: Overexpression of macrophage stimulating 1 enhances the anti-tumor effects of IL-24 in esophageal cancer via inhibiting ERK-Mfn2 signaling-dependent mitophagy.
Legionella pneumophila effector protein LegK7(lpg1924) hijacks the conserved Hippo signaling pathway by molecularly mimicking host Hippo kinase (MST1 in mammals), which is the key regulator of pathway activation.
Title: The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote Infection.
These data suggest that MSP is an effective inhibitor of inflammation and lipid accumulation in the stressed liver, thereby indicating that MSP has a key regulatory role in non-alcoholic steatohepatitis.
Title: MSP is a negative regulator of inflammation and lipogenesis in ex vivo models of non-alcoholic steatohepatitis.

Submit: New GeneRIF Correction See all GeneRIFs (42)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association identifies multiple ulcerative colitis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed
Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

APEH (e-PCR)
- UniSTS:253958

GDB:181206 (e-PCR)
- UniSTS:155174

GDB:512856 (e-PCR)
- UniSTS:157533

APEH (e-PCR)
- UniSTS:265936

GDB:180399 (e-PCR)
- UniSTS:155091

WI-16108 (e-PCR)
- UniSTS:2785

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT enables endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables receptor tyrosine kinase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in negative regulation of gluconeogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of cAMP-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of receptor signaling pathway via JAK-STAT	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: hepatocyte growth factor-like protein

Names: hepatocyte growth factor-like protein homolog; macrophage stimulating 1 (hepatocyte growth factor-like); macrophage-stimulating protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016454.1 RefSeqGene

Range

4290..9817

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001393581.1 → NP_001380510.1 hepatocyte growth factor-like protein isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC099668

Conserved Domains (5) summary

smart00130
Location:122 → 202

KR; Kringle domain

PHA03247
Location:234 → 457

PHA03247; large tegument protein UL36; Provisional

cd00190
Location:527 → 733

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd01099
Location:37 → 118

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...

cl00100
Location:202 → 241

KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
NM_001393582.1 → NP_001380511.1 hepatocyte growth factor-like protein isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AC099668

UniProtKB/Swiss-Prot

A6NLA3, A8MSX3, P26927, Q13350, Q14870, Q6GTN4

Conserved Domains (3) summary

smart00130
Location:382 → 464

KR; Kringle domain

cd00190
Location:498 → 702

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd01099
Location:37 → 118

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...
NM_001393583.1 → NP_001380512.1 hepatocyte growth factor-like protein isoform 4 precursor

Status: REVIEWED

Source sequence(s)

AC099668

Conserved Domains (4) summary

smart00130
Location:122 → 202

KR; Kringle domain

cd00190
Location:485 → 691

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd01099
Location:37 → 118

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...

cl00100
Location:202 → 241

KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...
NM_001393584.1 → NP_001380513.1 hepatocyte growth factor-like protein isoform 5 precursor

Status: REVIEWED

Source sequence(s)

AC099668

Conserved Domains (3) summary

smart00130
Location:338 → 419

KR; Kringle domain

cd00190
Location:453 → 676

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd01099
Location:37 → 118

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...
NM_001393585.1 → NP_001380514.1 hepatocyte growth factor-like protein isoform 6 precursor

Status: REVIEWED

Source sequence(s)

AC099668

UniProtKB/Swiss-Prot

A6NLA3, A8MSX3, P26927, Q13350, Q14870, Q6GTN4

Conserved Domains (3) summary

smart00130
Location:283 → 364

KR; Kringle domain

cd00190
Location:398 → 621

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

cd01099
Location:37 → 118

PAN_AP_HGF; Subfamily of PAN/APPLE-like domains; present in N-terminal (N) domains of plasminogen/hepatocyte growth factor proteins, and various proteins found in Bilateria, such as leech anti-platelet proteins. PAN/APPLE domains fulfill diverse biological functions ...
NM_020998.4 → NP_066278.3 hepatocyte growth factor-like protein isoform 1 precursor

See identical proteins and their annotated locations for NP_066278.3

Status: REVIEWED

Source sequence(s)

AC099668

Consensus CDS

CCDS33757.2

UniProtKB/Swiss-Prot

A6NLA3, A8MSX3, P26927, Q13350, Q14870, Q6GTN4

UniProtKB/TrEMBL

G3XAK1

Related

ENSP00000414287.2, ENST00000449682.3

Conserved Domains (5) summary

smart00020
Location:497 → 718

Tryp_SPc; Trypsin-like serine protease

smart00130
Location:382 → 464

KR; Kringle domain

cd00190
Location:498 → 721

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam00024
Location:39 → 117

PAN_1; PAN domain

pfam00051
Location:297 → 375

Kringle; Kringle domain

RNA

NR_146060.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC099668

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

49683947..49689474 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448159.1 → XP_047304115.1 hepatocyte growth factor-like protein isoform X3
XM_017006460.3 → XP_016861949.1 hepatocyte growth factor-like protein isoform X1
XM_047448158.1 → XP_047304114.1 hepatocyte growth factor-like protein isoform X2
XM_047448160.1 → XP_047304116.1 hepatocyte growth factor-like protein isoform X4
XM_011533738.4 → XP_011532040.1 hepatocyte growth factor-like protein isoform X5

UniProtKB/TrEMBL

Q13208

Conserved Domains (3) summary

smart00130
Location:382 → 464

KR; Kringle domain

pfam00024
Location:39 → 117

PAN_1; PAN domain

pfam00051
Location:297 → 375

Kringle; Kringle domain
XM_047448161.1 → XP_047304117.1 hepatocyte growth factor-like protein isoform X6

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

49713231..49718759 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346578.1 → XP_054202553.1 hepatocyte growth factor-like protein isoform X3
XM_054346577.1 → XP_054202552.1 hepatocyte growth factor-like protein isoform X8
XM_054346575.1 → XP_054202550.1 hepatocyte growth factor-like protein isoform X7
XM_054346574.1 → XP_054202549.1 hepatocyte growth factor-like protein isoform X1
XM_054346576.1 → XP_054202551.1 hepatocyte growth factor-like protein isoform X2
XM_054346583.1 → XP_054202558.1 hepatocyte growth factor-like protein isoform X11
XM_054346579.1 → XP_054202554.1 hepatocyte growth factor-like protein isoform X9
XM_054346581.1 → XP_054202556.1 hepatocyte growth factor-like protein isoform X4
XM_054346580.1 → XP_054202555.1 hepatocyte growth factor-like protein isoform X10
XM_054346582.1 → XP_054202557.1 hepatocyte growth factor-like protein isoform X11
XM_054346584.1 → XP_054202559.1 hepatocyte growth factor-like protein isoform X5
XM_054346585.1 → XP_054202560.1 hepatocyte growth factor-like protein isoform X6