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Q13421 (MSLN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mesothelin
Alternative name(s):
CAK1 antigen
Pre-pro-megakaryocyte-potentiating factor

Cleaved into the following 2 chains:

  1. Megakaryocyte-potentiating factor
    Short name=MPF
  2. Mesothelin, cleaved form
Gene names
Name:MSLN
Synonyms:MPF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length630 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Membrane-anchored forms may play a role in cellular adhesion. Ref.9 Ref.11

Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro. Ref.9 Ref.11

Subunit structure

Interacts with MUC16. Ref.11

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor. Golgi apparatus Ref.2 Ref.14.

Megakaryocyte-potentiating factor: Secreted Ref.2 Ref.14.

Isoform 3: Secreted Ref.2 Ref.14.

Tissue specificity

Expressed in lung. Expressed at low levels in heart, placenta and kidney. Expressed in mesothelial cells. Highly expressed in mesotheliomas, ovarian cancers, and some squamous cell carcinomas (at protein level). Ref.1 Ref.12

Post-translational modification

Both MPF and the cleaved form of mesothelin are N-glycosylated. Ref.2 Ref.9 Ref.12

Proteolytically cleaved by a furin-like convertase to generate megakaryocyte-potentiating factor (MPF), and the cleaved form of mesothelin. Ref.2

Involvement in disease

Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer. Ref.4

Sequence similarities

Belongs to the mesothelin family.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13421-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Minor form.
Isoform 2 (identifier: Q13421-3)

The sequence of this isoform differs from the canonical sequence as follows:
     409-416: Missing.
Note: Major form.
Isoform 3 (identifier: Q13421-2)

Also known as: SMRP;

The sequence of this isoform differs from the canonical sequence as follows:
     409-416: Missing.
     601-630: MQEALSGTPCLLGPGPVLTVLALLLASTLA → VQGGRGGQAR...HPGLRAPLPC
Note: Soluble form found in the sera from patients with ovarian carcinoma.
Isoform 4 (identifier: Q13421-4)

The sequence of this isoform differs from the canonical sequence as follows:
     44-44: Missing.
     409-416: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3636 Ref.1 Ref.9
Chain37 – 606570Mesothelin
PRO_0000253559
Chain37 – 286250Megakaryocyte-potentiating factor
PRO_0000253560
Chain296 – 606311Mesothelin, cleaved form
PRO_0000253561
Propeptide607 – 63024Removed in mature form Potential
PRO_0000021769

Regions

Region262 – 28625Required for megakaryocyte-potentiating factor activity

Amino acid modifications

Lipidation6061GPI-anchor amidated serine Potential
Glycosylation571N-linked (GlcNAc...) Probable
Glycosylation3881N-linked (GlcNAc...) Potential
Glycosylation4961N-linked (GlcNAc...) Potential
Glycosylation5231N-linked (GlcNAc...) Potential
Disulfide bond302 ↔ 326 Ref.14

Natural variations

Alternative sequence441Missing in isoform 4.
VSP_021058
Alternative sequence409 – 4168Missing in isoform 2, isoform 3 and isoform 4.
VSP_021059
Alternative sequence601 – 63030MQEAL…ASTLA → VQGGRGGQARAGGRAGGVEV GALSHPSLCRGPLGDALPPR TWTCSHRPGTAPSLHPGLRA PLPC in isoform 3.
VSP_021060
Natural variant721A → V.
Corresponds to variant rs9927389 [ dbSNP | Ensembl ].
VAR_028381
Natural variant3091R → P. Ref.8
Corresponds to variant rs17850474 [ dbSNP | Ensembl ].
VAR_028382
Natural variant4971G → E.
Corresponds to variant rs35935235 [ dbSNP | Ensembl ].
VAR_054012
Natural variant6011M → V. Ref.1 Ref.2 Ref.4 Ref.7 Ref.8 Ref.10
Corresponds to variant rs1135210 [ dbSNP | Ensembl ].
VAR_028383

Experimental info

Sequence conflict4 – 118PTARPLLG → QRLDPCW in AAC50348. Ref.2
Sequence conflict15 – 184TPAL → DRP in AAC50348. Ref.2
Sequence conflict32 – 343QPS → HPA in AAC50348. Ref.2
Sequence conflict43 – 453QEA → TES in AAC50348. Ref.2
Sequence conflict491D → G in AAC50348. Ref.2
Sequence conflict53 – 564ANPP → TTPH in AAC50348. Ref.2
Sequence conflict1391R → H in AAV87530. Ref.4
Sequence conflict4021N → D in AAC50348. Ref.2
Sequence conflict6041A → T in AAC50348. Ref.2

Secondary structure

........... 630
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: FA17E3609B6CC9CA

FASTA63068,986
        10         20         30         40         50         60 
MALPTARPLL GSCGTPALGS LLFLLFSLGW VQPSRTLAGE TGQEAAPLDG VLANPPNISS 

        70         80         90        100        110        120 
LSPRQLLGFP CAEVSGLSTE RVRELAVALA QKNVKLSTEQ LRCLAHRLSE PPEDLDALPL 

       130        140        150        160        170        180 
DLLLFLNPDA FSGPQACTRF FSRITKANVD LLPRGAPERQ RLLPAALACW GVRGSLLSEA 

       190        200        210        220        230        240 
DVRALGGLAC DLPGRFVAES AEVLLPRLVS CPGPLDQDQQ EAARAALQGG GPPYGPPSTW 

       250        260        270        280        290        300 
SVSTMDALRG LLPVLGQPII RSIPQGIVAA WRQRSSRDPS WRQPERTILR PRFRREVEKT 

       310        320        330        340        350        360 
ACPSGKKARE IDESLIFYKK WELEACVDAA LLATQMDRVN AIPFTYEQLD VLKHKLDELY 

       370        380        390        400        410        420 
PQGYPESVIQ HLGYLFLKMS PEDIRKWNVT SLETLKALLE VNKGHEMSPQ APRRPLPQVA 

       430        440        450        460        470        480 
TLIDRFVKGR GQLDKDTLDT LTAFYPGYLC SLSPEELSSV PPSSIWAVRP QDLDTCDPRQ 

       490        500        510        520        530        540 
LDVLYPKARL AFQNMNGSEY FVKIQSFLGG APTEDLKALS QQNVSMDLAT FMKLRTDAVL 

       550        560        570        580        590        600 
PLTVAEVQKL LGPHVEGLKA EERHRPVRDW ILRQRQDDLD TLGLGLQGGI PNGYLVLDLS 

       610        620        630 
MQEALSGTPC LLGPGPVLTV LALLLASTLA 

« Hide

Isoform 2 [UniParc].

Checksum: 1F0FE52883D0DDB8
Show »

FASTA62268,070
Isoform 3 (SMRP) [UniParc].

Checksum: C1B783689D5DC266
Show »

FASTA65671,492
Isoform 4 [UniParc].

Checksum: 1A736774094C28D0
Show »

FASTA62167,940

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of megakaryocyte potentiating factor cDNA."
Kojima T., Oh-Eda M., Hattori K., Taniguchi Y., Tamura M., Ochi N., Yamaguchi N.
J. Biol. Chem. 270:21984-21990(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 37-54 AND 90-117, TISSUE SPECIFICITY, VARIANT VAL-601.
Tissue: Pancreatic cancer.
[2]"Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers."
Chang K., Pastan I.
Proc. Natl. Acad. Sci. U.S.A. 93:136-140(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, GPI-ANCHOR, GLYCOSYLATION, CLEAVAGE, VARIANT VAL-601.
Tissue: Carcinoma.
[3]"Characterization of human mesothelin transcripts in ovarian and pancreatic cancer."
Muminova Z.E., Strong T.V., Shaw D.R.
BMC Cancer 4:19-19(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORMS 2 AND 3).
[4]"Humoral immune response to mesothelin in mesothelioma and ovarian cancer patients."
Ho M., Hassan R., Zhang J., Wang Q.-C., Onda M., Bera T., Pastan I.
Clin. Cancer Res. 11:3814-3820(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), DISEASE, VARIANT VAL-601.
Tissue: Lung and Spleen.
[5]"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16."
Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.
Hum. Mol. Genet. 10:339-352(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-601.
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), VARIANTS PRO-309 AND VAL-601.
Tissue: Pancreas and Placenta.
[9]"A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5."
Yamaguchi N., Hattori K., Oh-eda M., Kojima T., Imai N., Ochi N.
J. Biol. Chem. 269:805-808(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 37-54 (ISOFORMS 1/2/3), GLYCOSYLATION, FUNCTION.
Tissue: Pancreatic tumor.
[10]"Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma."
Scholler N., Fu N., Yang Y., Ye Z., Goodman G.E., Hellstroem K.E., Hellstroem I.
Proc. Natl. Acad. Sci. U.S.A. 96:11531-11536(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 297-630 (ISOFORM 3), PROTEIN SEQUENCE OF 296-314, VARIANT VAL-601.
[11]"Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion."
Rump A., Morikawa Y., Tanaka M., Minami S., Umesaki N., Takeuchi M., Miyajima A.
J. Biol. Chem. 279:9190-9198(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MUC16, FUNCTION.
[12]"Megakaryocyte potentiation factor cleaved from mesothelin precursor is a useful tumor marker in the serum of patients with mesothelioma."
Onda M., Nagata S., Ho M., Bera T.K., Hassan R., Alexander R.H., Pastan I.
Clin. Cancer Res. 12:4225-4231(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, TISSUE SPECIFICITY.
[13]"Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment."
Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N.
J. Proteome Res. 5:935-943(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Recognition of mesothelin by the therapeutic antibody MORAb-009: structural and mechanistic insights."
Ma J., Tang W.K., Esser L., Pastan I., Xia D.
J. Biol. Chem. 287:33123-33131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 302-359 IN COMPLEX WITH ANTOBODY, SUBCELLULAR LOCATION, DISULFIDE BOND.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D49441 mRNA. Translation: BAA08419.1.
U40434 mRNA. Translation: AAC50348.1.
AY743922 mRNA. Translation: AAV87530.1.
AE006464 Genomic DNA. Translation: AAK61253.1.
AL031258 Genomic DNA. Translation: CAC37289.1.
CH471112 Genomic DNA. Translation: EAW85719.1.
CH471112 Genomic DNA. Translation: EAW85720.1.
BC003512 mRNA. Translation: AAH03512.1.
BC009272 mRNA. Translation: AAH09272.1.
AF180951 mRNA. Translation: AAF01409.1.
RefSeqNP_001170826.1. NM_001177355.1.
NP_005814.2. NM_005823.5.
NP_037536.2. NM_013404.4.
XP_005255091.1. XM_005255034.2.
UniGeneHs.408488.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4F3FX-ray2.65C302-359[»]
ProteinModelPortalQ13421.
SMRQ13421. Positions 302-359.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115526. 12 interactions.
IntActQ13421. 1 interaction.

PTM databases

PhosphoSiteQ13421.

Polymorphism databases

DMDM116242654.

Proteomic databases

PaxDbQ13421.
PRIDEQ13421.

Protocols and materials databases

DNASU10232.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382862; ENSP00000372313; ENSG00000102854. [Q13421-1]
ENST00000545450; ENSP00000442965; ENSG00000102854. [Q13421-3]
ENST00000563941; ENSP00000456008; ENSG00000102854. [Q13421-3]
ENST00000566549; ENSP00000456702; ENSG00000102854. [Q13421-3]
GeneID10232.
KEGGhsa:10232.
UCSCuc002cjt.1. human. [Q13421-3]
uc002cjw.2. human. [Q13421-1]
uc010brd.1. human. [Q13421-4]

Organism-specific databases

CTD10232.
GeneCardsGC16P000810.
HGNCHGNC:7371. MSLN.
HPACAB002216.
HPA017172.
MIM601051. gene.
neXtProtNX_Q13421.
PharmGKBPA31176.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40535.
HOVERGENHBG081988.
InParanoidQ13421.
OMACDLPGRF.
OrthoDBEOG7M3HZW.
PhylomeDBQ13421.
TreeFamTF331713.

Gene expression databases

ArrayExpressQ13421.
BgeeQ13421.
GenevestigatorQ13421.

Family and domain databases

InterProIPR010335. Mesothelin.
IPR026664. Stereocilin_related.
[Graphical view]
PANTHERPTHR23412. PTHR23412. 1 hit.
PTHR23412:SF3. PTHR23412:SF3. 1 hit.
PfamPF06060. Mesothelin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMesothelin.
GenomeRNAi10232.
NextBio38744.
PROQ13421.
SOURCESearch...

Entry information

Entry nameMSLN_HUMAN
AccessionPrimary (citable) accession number: Q13421
Secondary accession number(s): D3DU65 expand/collapse secondary AC list , Q14859, Q4VQD5, Q96GR6, Q96KJ5, Q9BR17, Q9BTR2, Q9UCB2, Q9UK57
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM