MSLN
Mesothelin
Also known as: CAK1, MPF, MSLN_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q13421
- Gene
- MSLN
- Ensembl
- ENSG00000102854
- Chromosome
- 16
- Canonical length
- 630 aa
- Protein class
- Cancer-related genes, Disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
- Subcellular location
- Vesicles,Plasma membrane
- Secretome location
- Intracellular and membrane
OverviewNCBI Gene
This gene encodes a preproprotein that is proteolytically processed to generate two protein products, megakaryocyte potentiating factor and mesothelin. Megakaryocyte potentiating factor functions as a cytokine that can stimulate colony formation of bone marrow megakaryocytes. Mesothelin is a glycosylphosphatidylinositol-anchored cell-surface protein that may function as a cell adhesion protein. This protein is overexpressed in epithelial mesotheliomas, ovarian cancers and in specific squamous cell carcinomas. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
Canonical amino-acid sequenceUniProt
630 residues, UniProt reviewed canonical sequence.
>Q13421|MSLN
1 MALPTARPLL GSCGTPALGS LLFLLFSLGW VQPSRTLAGE TGQEAAPLDG VLANPPNISS
61 LSPRQLLGFP CAEVSGLSTE RVRELAVALA QKNVKLSTEQ LRCLAHRLSE PPEDLDALPL
121 DLLLFLNPDA FSGPQACTRF FSRITKANVD LLPRGAPERQ RLLPAALACW GVRGSLLSEA
181 DVRALGGLAC DLPGRFVAES AEVLLPRLVS CPGPLDQDQQ EAARAALQGG GPPYGPPSTW
241 SVSTMDALRG LLPVLGQPII RSIPQGIVAA WRQRSSRDPS WRQPERTILR PRFRREVEKT
301 ACPSGKKARE IDESLIFYKK WELEACVDAA LLATQMDRVN AIPFTYEQLD VLKHKLDELY
361 PQGYPESVIQ HLGYLFLKMS PEDIRKWNVT SLETLKALLE VNKGHEMSPQ APRRPLPQVA
421 TLIDRFVKGR GQLDKDTLDT LTAFYPGYLC SLSPEELSSV PPSSIWAVRP QDLDTCDPRQ
481 LDVLYPKARL AFQNMNGSEY FVKIQSFLGG APTEDLKALS QQNVSMDLAT FMKLRTDAVL
541 PLTVAEVQKL LGPHVEGLKA EERHRPVRDW ILRQRQDDLD TLGLGLQGGI PNGYLVLDLS
601 MQEALSGTPC LLGPGPVLTV LALLLASTLALocalizationUniProt · AlphaFold · HPA
Whether an antibody against MSLN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.35
- Highest tissue expression
- 262 nTPM
Expression across tissuesHPA
Tissue
- fallopian tube: 262 nTPM
- adipose tissue: 89 nTPM
- lung: 68 nTPM
- salivary gland: 41 nTPM
- tonsil: 26 nTPM
- epididymis: 23 nTPM
Single-cell type
- conjunctival goblet cells: 998 nCPM
- fallopian secretory cells: 685 nCPM
- alveolar cells type 1: 376 nCPM
- mesothelial cells: 266 nCPM
- respiratory deuterosomal cells: 216 nCPM
- respiratory secretory cells: 215 nCPM
Immune cell
- myeloid DC: 5.9 nTPM
- non-classical monocyte: 1.8 nTPM
- intermediate monocyte: 1 nTPM
- total PBMC: 0.3 nTPM
- classical monocyte: 0.1 nTPM
- plasmacytoid DC: 0.1 nTPM
Brain region
- medulla oblongata: 3.4 nTPM
- cerebral cortex: 3 nTPM
- midbrain: 1.9 nTPM
- thalamus: 1.9 nTPM
- pons: 1.6 nTPM
- spinal cord: 1.5 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about MSLN.
Disease | ImmuneIEDB
Conditions an epitope on MSLN was assayed in.
- pancreatic ductal adenocarcinoma T cell
- pancreatic cancer T cell
- malignant pleural mesothelioma T cell
- pancreas disease T cell
- malignant mesothelioma T cell
- colorectal cancer T cell
ReferencesPubMed · IEDB
Publications for MSLN from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
3 publications
- SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other.
2008 · Adv Exp Med Biol · RCR 2 · 70 citations - The hen model of human ovarian cancer develops anti-mesothelin autoantibodies in response to mesothelin expressing tumors.
2011 · J Ovarian Res · RCR 0.2 · 8 citations - Autoantibodies to mesothelin in infertility.
2011 · Cancer Epidemiol Biomarkers Prev · RCR 0.2 · 7 citations
Reference: T cellIEDB
8 publications
- SARS-CoV-2-specific CD8+ T cell responses in convalescent COVID-19 individuals.
2021 · J Clin Invest · RCR 9.6 · 209 citations - Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.
2018 · Clin Cancer Res · RCR 2.2 · 77 citations - CD4 T cells target colorectal cancer antigens upregulated by oxaliplatin.
2019 · Int J Cancer · RCR 1.2 · 40 citations - Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells.
2024 · BMC Med · RCR 1.1 · 7 citations - Expansion of anti-mesothelin specific CD4+ and CD8+ T cell responses in patients with pancreatic carcinoma.
2014 · PLoS One · RCR 0.6 · 24 citations
Show 3 more
- Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS.
2018 · Front Immunol · RCR 0.4 · 12 citations - Identification of a novel HLA-A24-restricted cytotoxic T lymphocyte epitope peptide derived from mesothelin in pancreatic cancer.
2018 · Oncotarget · RCR 0.2 · 6 citations - Prediction of improved survival in patients with pancreatic cancer via IL-21 enhanced detection of mesothelin epitope-reactive T-cell responses.
2018 · Oncotarget · RCR 0.1 · 2 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.48
- gnomAD pLI
- 0
- gnomAD missense Z
- -1.04
- DepMap mean gene effect
- 0.07
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MSLN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads MSLN as an antibody target. Whether an autoantibody or antibody against MSLN could matter depends on whether native MSLN is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MSLN is annotated at the cell surface, where native MSLN is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label MSLN as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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