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Protein

Mesothelin

Gene

MSLN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Membrane-anchored forms may play a role in cellular adhesion.
Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.

GO - Biological processi

  • cell adhesion Source: UniProtKB
  • cell-matrix adhesion Source: GO_Central
  • pancreas development Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102854-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Mesothelin
Alternative name(s):
CAK1 antigen
Pre-pro-megakaryocyte-potentiating factor
Cleaved into the following 2 chains:
Gene namesi
Name:MSLN
Synonyms:MPF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:7371. MSLN.

Subcellular locationi

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • cell surface Source: GO_Central
  • extracellular space Source: Ensembl
  • Golgi apparatus Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

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

Organism-specific databases

DisGeNETi10232.
OpenTargetsiENSG00000102854.
PharmGKBiPA31176.

Polymorphism and mutation databases

BioMutaiMSLN.
DMDMi116242654.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 361 PublicationAdd BLAST36
ChainiPRO_000025355937 – 606MesothelinAdd BLAST570
ChainiPRO_000025356037 – 286Megakaryocyte-potentiating factorAdd BLAST250
ChainiPRO_0000253561296 – 606Mesothelin, cleaved formAdd BLAST311
PropeptideiPRO_0000021769607 – 630Removed in mature formSequence analysisAdd BLAST24

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi57N-linked (GlcNAc...)Curated1
Modified residuei200Phosphoserine; by FAM20C1 Publication1
Disulfide bondi302 ↔ 3261 Publication
Glycosylationi388N-linked (GlcNAc...)Sequence analysis1
Glycosylationi496N-linked (GlcNAc...)Sequence analysis1
Glycosylationi523N-linked (GlcNAc...)Sequence analysis1
Lipidationi606GPI-anchor amidated serineSequence analysis1

Post-translational modificationi

Both MPF and the cleaved form of mesothelin are N-glycosylated.3 Publications
Proteolytically cleaved by a furin-like convertase to generate megakaryocyte-potentiating factor (MPF), and the cleaved form of mesothelin.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Phosphoprotein

Proteomic databases

EPDiQ13421.
MaxQBiQ13421.
PaxDbiQ13421.
PeptideAtlasiQ13421.
PRIDEiQ13421.

PTM databases

iPTMnetiQ13421.
PhosphoSitePlusiQ13421.
SwissPalmiQ13421.

Expressioni

Tissue specificityi

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).2 Publications

Gene expression databases

BgeeiENSG00000102854.
ExpressionAtlasiQ13421. baseline and differential.
GenevisibleiQ13421. HS.

Organism-specific databases

HPAiCAB002216.
HPA017172.

Interactioni

Subunit structurei

Interacts with MUC16.2 Publications

Protein-protein interaction databases

BioGridi115526. 13 interactors.
IntActiQ13421. 2 interactors.
STRINGi9606.ENSP00000372313.

Structurei

Secondary structure

1630
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi313 – 317Combined sources5
Helixi320 – 326Combined sources7
Helixi329 – 334Combined sources6
Helixi336 – 341Combined sources6
Helixi346 – 358Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4F3FX-ray2.65C302-359[»]
ProteinModelPortaliQ13421.
SMRiQ13421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni262 – 286Required for megakaryocyte-potentiating factor activityAdd BLAST25

Sequence similaritiesi

Belongs to the mesothelin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IIJH. Eukaryota.
ENOG4111HFW. LUCA.
GeneTreeiENSGT00530000064019.
HOVERGENiHBG081988.
InParanoidiQ13421.
KOiK20733.
OMAiCDLPGRF.
OrthoDBiEOG091G04V4.
PhylomeDBiQ13421.
TreeFamiTF331713.

Family and domain databases

InterProiIPR010335. Mesothelin.
IPR026664. Stereocilin-rel.
[Graphical view]
PANTHERiPTHR23412. PTHR23412. 1 hit.
PfamiPF06060. Mesothelin. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13421-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MALPTARPLL GSCGTPALGS LLFLLFSLGW VQPSRTLAGE TGQEAAPLDG
60 70 80 90 100
VLANPPNISS LSPRQLLGFP CAEVSGLSTE RVRELAVALA QKNVKLSTEQ
110 120 130 140 150
LRCLAHRLSE PPEDLDALPL DLLLFLNPDA FSGPQACTRF FSRITKANVD
160 170 180 190 200
LLPRGAPERQ RLLPAALACW GVRGSLLSEA DVRALGGLAC DLPGRFVAES
210 220 230 240 250
AEVLLPRLVS CPGPLDQDQQ EAARAALQGG GPPYGPPSTW SVSTMDALRG
260 270 280 290 300
LLPVLGQPII RSIPQGIVAA WRQRSSRDPS WRQPERTILR PRFRREVEKT
310 320 330 340 350
ACPSGKKARE IDESLIFYKK WELEACVDAA LLATQMDRVN AIPFTYEQLD
360 370 380 390 400
VLKHKLDELY PQGYPESVIQ HLGYLFLKMS PEDIRKWNVT SLETLKALLE
410 420 430 440 450
VNKGHEMSPQ APRRPLPQVA TLIDRFVKGR GQLDKDTLDT LTAFYPGYLC
460 470 480 490 500
SLSPEELSSV PPSSIWAVRP QDLDTCDPRQ LDVLYPKARL AFQNMNGSEY
510 520 530 540 550
FVKIQSFLGG APTEDLKALS QQNVSMDLAT FMKLRTDAVL PLTVAEVQKL
560 570 580 590 600
LGPHVEGLKA EERHRPVRDW ILRQRQDDLD TLGLGLQGGI PNGYLVLDLS
610 620 630
MQEALSGTPC LLGPGPVLTV LALLLASTLA
Note: Minor form.
Length:630
Mass (Da):68,986
Last modified:October 17, 2006 - v2
Checksum:iFA17E3609B6CC9CA
GO
Isoform 2 (identifier: Q13421-3) [UniParc]FASTAAdd to basket

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

Note: Major form.
Show »
Length:622
Mass (Da):68,070
Checksum:i1F0FE52883D0DDB8
GO
Isoform 3 (identifier: Q13421-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:656
Mass (Da):71,492
Checksum:iC1B783689D5DC266
GO
Isoform 4 (identifier: Q13421-4) [UniParc]FASTAAdd to basket

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

Show »
Length:621
Mass (Da):67,940
Checksum:i1A736774094C28D0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4 – 11PTARPLLG → QRLDPCW in AAC50348 (PubMed:8552591).Curated8
Sequence conflicti15 – 18TPAL → DRP in AAC50348 (PubMed:8552591).Curated4
Sequence conflicti32 – 34QPS → HPA in AAC50348 (PubMed:8552591).Curated3
Sequence conflicti43 – 45QEA → TES in AAC50348 (PubMed:8552591).Curated3
Sequence conflicti49D → G in AAC50348 (PubMed:8552591).Curated1
Sequence conflicti53 – 56ANPP → TTPH in AAC50348 (PubMed:8552591).Curated4
Sequence conflicti139R → H in AAV87530 (PubMed:15897581).Curated1
Sequence conflicti402N → D in AAC50348 (PubMed:8552591).Curated1
Sequence conflicti604A → T in AAC50348 (PubMed:8552591).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02838172A → V.Corresponds to variant rs9927389dbSNPEnsembl.1
Natural variantiVAR_028382309R → P.1 PublicationCorresponds to variant rs17850474dbSNPEnsembl.1
Natural variantiVAR_054012497G → E.Corresponds to variant rs35935235dbSNPEnsembl.1
Natural variantiVAR_028383601M → V.6 PublicationsCorresponds to variant rs1135210dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02105844Missing in isoform 4. 1 Publication1
Alternative sequenceiVSP_021059409 – 416Missing in isoform 2, isoform 3 and isoform 4. 5 Publications8
Alternative sequenceiVSP_021060601 – 630MQEAL…ASTLA → VQGGRGGQARAGGRAGGVEV GALSHPSLCRGPLGDALPPR TWTCSHRPGTAPSLHPGLRA PLPC in isoform 3. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32356.1. [Q13421-1]
CCDS45370.1. [Q13421-3]
RefSeqiNP_001170826.1. NM_001177355.2. [Q13421-3]
NP_005814.2. NM_005823.5. [Q13421-3]
NP_037536.2. NM_013404.4. [Q13421-1]
XP_005255091.1. XM_005255034.4. [Q13421-4]
XP_011520650.1. XM_011522348.2. [Q13421-1]
XP_016878346.1. XM_017022857.1. [Q13421-1]
UniGeneiHs.408488.

Genome annotation databases

EnsembliENST00000382862; ENSP00000372313; ENSG00000102854. [Q13421-1]
ENST00000545450; ENSP00000442965; ENSG00000102854. [Q13421-3]
ENST00000563941; ENSP00000456008; ENSG00000102854. [Q13421-3]
ENST00000566549; ENSP00000456702; ENSG00000102854. [Q13421-3]
GeneIDi10232.
KEGGihsa:10232.
UCSCiuc002cjt.2. human. [Q13421-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32356.1. [Q13421-1]
CCDS45370.1. [Q13421-3]
RefSeqiNP_001170826.1. NM_001177355.2. [Q13421-3]
NP_005814.2. NM_005823.5. [Q13421-3]
NP_037536.2. NM_013404.4. [Q13421-1]
XP_005255091.1. XM_005255034.4. [Q13421-4]
XP_011520650.1. XM_011522348.2. [Q13421-1]
XP_016878346.1. XM_017022857.1. [Q13421-1]
UniGeneiHs.408488.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4F3FX-ray2.65C302-359[»]
ProteinModelPortaliQ13421.
SMRiQ13421.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115526. 13 interactors.
IntActiQ13421. 2 interactors.
STRINGi9606.ENSP00000372313.

PTM databases

iPTMnetiQ13421.
PhosphoSitePlusiQ13421.
SwissPalmiQ13421.

Polymorphism and mutation databases

BioMutaiMSLN.
DMDMi116242654.

Proteomic databases

EPDiQ13421.
MaxQBiQ13421.
PaxDbiQ13421.
PeptideAtlasiQ13421.
PRIDEiQ13421.

Protocols and materials databases

DNASUi10232.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382862; ENSP00000372313; ENSG00000102854. [Q13421-1]
ENST00000545450; ENSP00000442965; ENSG00000102854. [Q13421-3]
ENST00000563941; ENSP00000456008; ENSG00000102854. [Q13421-3]
ENST00000566549; ENSP00000456702; ENSG00000102854. [Q13421-3]
GeneIDi10232.
KEGGihsa:10232.
UCSCiuc002cjt.2. human. [Q13421-1]

Organism-specific databases

CTDi10232.
DisGeNETi10232.
GeneCardsiMSLN.
HGNCiHGNC:7371. MSLN.
HPAiCAB002216.
HPA017172.
MIMi601051. gene.
neXtProtiNX_Q13421.
OpenTargetsiENSG00000102854.
PharmGKBiPA31176.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIJH. Eukaryota.
ENOG4111HFW. LUCA.
GeneTreeiENSGT00530000064019.
HOVERGENiHBG081988.
InParanoidiQ13421.
KOiK20733.
OMAiCDLPGRF.
OrthoDBiEOG091G04V4.
PhylomeDBiQ13421.
TreeFamiTF331713.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000102854-MONOMER.

Miscellaneous databases

GeneWikiiMesothelin.
GenomeRNAii10232.
PROiQ13421.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102854.
ExpressionAtlasiQ13421. baseline and differential.
GenevisibleiQ13421. HS.

Family and domain databases

InterProiIPR010335. Mesothelin.
IPR026664. Stereocilin-rel.
[Graphical view]
PANTHERiPTHR23412. PTHR23412. 1 hit.
PfamiPF06060. Mesothelin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMSLN_HUMAN
AccessioniPrimary (citable) accession number: Q13421
Secondary accession number(s): D3DU65
, Q14859, Q4VQD5, Q96GR6, Q96KJ5, Q9BR17, Q9BTR2, Q9UCB2, Q9UK57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.