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MST1 macrophage stimulating 1 [ Homo sapiens (human) ]

Gene ID: 4485, updated on 2-Nov-2024

Summary

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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
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Genomic context

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See MST1 in Genome Data Viewer
Location:
3p21.31
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (49683947..49689474, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (49713231..49718759, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (49721380..49726907, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14368 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14369 Neighboring gene BSN divergent transcript Neighboring gene bassoon presynaptic cytomatrix protein Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49675623-49676124 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49676125-49676624 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:49682435-49682618 Neighboring gene Sharpr-MPRA regulatory region 2684 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14370 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49723317-49724030 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49724031-49724744 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49726261-49726820 Neighboring gene acylaminoacyl-peptide hydrolase Neighboring gene Sharpr-MPRA regulatory region 3541 Neighboring gene ring finger protein 123 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49754537-49755037 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49756083-49756890 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19873 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:49758476-49758653 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19874 Neighboring gene adhesion molecule with Ig like domain 3 Neighboring gene GDP-mannose pyrophosphorylase B

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Goyette P, et al. Mucosal Immunol, 2008 Mar. PMID 19079170, Free PMC Article
  2. Mst1 overexpression inhibited the growth of human non-small cell lung cancer in vitro and in vivo. Xu CM, et al. Cancer Gene Ther, 2013 Aug. PMID 23928732
  3. Macrophage stimulating protein variation enhances the risk of sporadic extrahepatic cholangiocarcinoma. Krawczyk M, et al. Dig Liver Dis, 2013 Jul. PMID 23422030
  4. Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment. Sato S, et al. Clin Exp Metastasis, 2013 Mar. PMID 23011677
  5. The effects of macrophage-stimulating protein on the migration, proliferation, and collagen synthesis of skin fibroblasts in vitro and in vivo. Zhao J, et al. Tissue Eng Part A, 2015 Mar. PMID 25315688

See all (105) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Identify MST1/MSP as a mitogen for tracheal basal cells.
    Title: Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.
Submit: New GeneRIF Correction See all GeneRIFs (41)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 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

  1. NG_016454.1 RefSeqGene

    Range
    4290..9817
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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 ...

  6. 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

  1. NR_146060.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC099668

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    49683947..49689474 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047448159.1 → XP_047304115.1  hepatocyte growth factor-like protein isoform X3

  2. XM_017006460.3 → XP_016861949.1  hepatocyte growth factor-like protein isoform X1

  3. XM_047448158.1 → XP_047304114.1  hepatocyte growth factor-like protein isoform X2

  4. XM_047448160.1 → XP_047304116.1  hepatocyte growth factor-like protein isoform X4

  5. 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

  6. XM_047448161.1 → XP_047304117.1  hepatocyte growth factor-like protein isoform X6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    49713231..49718759 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054346578.1 → XP_054202553.1  hepatocyte growth factor-like protein isoform X3

  2. XM_054346577.1 → XP_054202552.1  hepatocyte growth factor-like protein isoform X8

  3. XM_054346575.1 → XP_054202550.1  hepatocyte growth factor-like protein isoform X7

  4. XM_054346574.1 → XP_054202549.1  hepatocyte growth factor-like protein isoform X1

  5. XM_054346576.1 → XP_054202551.1  hepatocyte growth factor-like protein isoform X2

  6. XM_054346583.1 → XP_054202558.1  hepatocyte growth factor-like protein isoform X11

  7. XM_054346579.1 → XP_054202554.1  hepatocyte growth factor-like protein isoform X9

  8. XM_054346581.1 → XP_054202556.1  hepatocyte growth factor-like protein isoform X4

  9. XM_054346580.1 → XP_054202555.1  hepatocyte growth factor-like protein isoform X10

  10. XM_054346582.1 → XP_054202557.1  hepatocyte growth factor-like protein isoform X11

  11. XM_054346584.1 → XP_054202559.1  hepatocyte growth factor-like protein isoform X5

  12. XM_054346585.1 → XP_054202560.1  hepatocyte growth factor-like protein isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P26927.2 GenPept UniProtKB/Swiss-Prot:P26927

Gene LinkOut

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