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Q02496 (MUC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mucin-1

Short name=MUC-1
Alternative name(s):
Episialin
CD_antigen=CD227

Cleaved into the following 2 chains:

  1. Mucin-1 subunit alpha
    Short name=MUC1-NT
    Short name=MUC1-alpha
  2. Mucin-1 subunit beta
    Short name=MUC1-beta
    Alternative name(s):
    MUC1-CT
Gene names
Name:Muc1
Synonyms:Muc-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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

The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.

The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, Src and NF-kappaB pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Regulates P53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of P53 and represses P53 activity.

Subunit structure

The alpha subunit forms a tight, non-covalent heterodimeric complex with the proteolytically-released beta-subunit. Binds directly the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several proteins such as SRC, CTNNB1 and ERBs. Interaction with the SH2 domain of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and, to a much lesser extent, the interaction with ERBB3 and ERBB4. Interacts with P53 in response to DNA damage. Interacts with KLF4. Interacts with estrogen receptor alpha/ESR1, through its DNA-binding domain, and stimulates its transcription activity. Binds ADAM17 By similarity. C.jejeuni adheres to gastric epithelial MUC1 and modulates its transcription. Ref.3

Subcellular location

Apical cell membrane; Single-pass type I membrane protein. Note: Exclusively located in the apical domain of the plasma membrane of highly polarized epithelial cells. After endocytosis, internalized and recycled to the cell membrane. Located to microvilli and to the tips of long filopodial protusions By similarity.

Mucin-1 subunit beta: Cell membrane. Cytoplasm. Nucleus. Note: On EGF and PDGFRB stimulation, transported to the nucleus through interaction with CTNNB1, a process which is stimulated by phosphorylation. On HRG stimulation, colocalizes with JUP/gamma-catenin at the nucleus By similarity. Some transportation to the nucleus when infected with C.jejeuni.

Tissue specificity

Expressed in a variety of epithelial tissues.

Post-translational modification

Probably both N- and extensively O-glycosylated (in repeat region).

Proteolytic cleavage in the SEA domain occurs in the endoplasmic reticulum by an autoproteolytic mechanism and requires the full-length SEA domain as well as requiring a Ser, Thr or Cys residue at the P + 1 site. Ectodomain shedding is mediated by ADAM17 in uterine epithelial cells By similarity.

Dual palmitoylation on cysteine residues in the CQC motif is required for recycling from endosomes back to the plasma membrane By similarity.

Phosphorylated on tyrosines and serine residues in the C-terminal. Phosphorylation on tyrosines in the C-terminal increases the nuclear location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation of the beta-catenin/E-cadherin complex. Src-mediated phosphorylation inhibits interaction with GSK3B. Csk- or Src- or EGFR-mediated phosphorylation on Tyr-604 increases binding to beta-catenin/CTNNB1. GSK3B-mediated phosphorylation on Ser-602 decreases this interaction but restores the formation of the beta-cadherin/E-cadherin complex. On T-cell receptor activation, phosphorylated by LCK. PDGFR-mediated phosphorylation increases nuclear colocalization of MUC1CT and CTNNB1 By similarity. Ref.3

Sequence similarities

Contains 1 SEA domain.

Caution

O-glycosylation sites are annotated in first sequence repeat only. Residues at similar position are probably glycosylated in all repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020
Chain21 – 630610Mucin-1
PRO_0000019280
Chain21 – 473453Mucin-1 subunit alpha By similarity
PRO_0000317452
Chain474 – 630157Mucin-1 subunit beta By similarity
PRO_0000317453

Regions

Topological domain21 – 535515Extracellular Potential
Transmembrane536 – 55621Helical; Potential
Topological domain557 – 63074Cytoplasmic Potential
Repeat42 – 61201
Repeat62 – 81202
Repeat82 – 101203
Repeat102 – 122214; approximate
Repeat123 – 143215; approximate
Repeat144 – 164216; approximate
Repeat165 – 184207
Repeat185 – 204208
Repeat205 – 225219; approximate
Repeat226 – 2462110; approximate
Repeat247 – 2561011
Repeat257 – 2863012
Repeat287 – 3062013
Repeat307 – 3262014
Repeat327 – 3462015
Repeat347 – 3662016
Domain416 – 521106SEA
Region42 – 36632516 X 20 AA approximate tandem repeats
Region567 – 60337Interaction with P53
Region598 – 6058Required for interaction with GSK3B By similarity
Region608 – 6169Required for interaction with beta- and gamma-catenins By similarity
Motif578 – 5814Interaction with GRB2 By similarity
Motif604 – 6074Interaction with SRC and ESR1 By similarity
Motif618 – 6214Required for interaction with AP1S2 By similarity

Sites

Site473 – 4742Cleavage; by autolysis By similarity

Amino acid modifications

Modified residue5661Phosphotyrosine By similarity
Modified residue5781Phosphotyrosine; by PDGFR By similarity
Modified residue5841Phosphotyrosine By similarity
Modified residue5871Phosphotyrosine By similarity
Modified residue5931Phosphotyrosine; by PDGFR By similarity
Modified residue5991Phosphothreonine; by PKC/PRKCD By similarity
Modified residue6021Phosphoserine; by GSK3-beta By similarity
Modified residue6041Phosphotyrosine; by CSK, EGFR and SRC By similarity
Modified residue6181Phosphotyrosine By similarity
Lipidation5591S-palmitoyl cysteine By similarity
Lipidation5611S-palmitoyl cysteine By similarity
Glycosylation431O-linked (GalNAc...) Potential
Glycosylation441O-linked (GalNAc...) Potential
Glycosylation451O-linked (GalNAc...) Potential
Glycosylation461O-linked (GalNAc...) Potential
Glycosylation501O-linked (GalNAc...) Potential
Glycosylation511O-linked (GalNAc...) Potential
Glycosylation531O-linked (GalNAc...) Potential
Glycosylation571O-linked (GalNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation2751N-linked (GlcNAc...) Potential
Glycosylation3021N-linked (GlcNAc...) Potential
Glycosylation3351N-linked (GlcNAc...) Potential
Glycosylation3551N-linked (GlcNAc...) Potential
Glycosylation3661N-linked (GlcNAc...) Potential
Glycosylation4081N-linked (GlcNAc...) Potential
Glycosylation4321N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Potential
Glycosylation5081N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict120 – 1212LS → PL in AAA39755. Ref.1
Sequence conflict138 – 1392AT → PA Ref.2
Sequence conflict1401T → TT Ref.2
Sequence conflict4231S → F in AAA39755. Ref.1
Sequence conflict5061D → S in AAA39755. Ref.1
Sequence conflict6021S → Q in AAA39755. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q02496 [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: D9EC2A0815F65E8E

FASTA63064,539
        10         20         30         40         50         60 
MTPGIRAPFF LLLLLASLKG FLALPSEENS VTSSQDTSSS LASTTTPVHS SNSDPATRPP 

        70         80         90        100        110        120 
GDSTSSPVQS STSSPATRAP EDSTSTAVLS GTSSPATTAP VNSASSPVAH GDTSSPATSL 

       130        140        150        160        170        180 
SKDSNSSPVV HSGTSSAATT APVDSTSSPV VHGGTSSPAT SPPGDSTSSP DHSSTSSPAT 

       190        200        210        220        230        240 
RAPEDSTSTA VLSGTSSPAT TAPVDSTSSP VAHDDTSSPA TSLSEDSASS PVAHGGTSSP 

       250        260        270        280        290        300 
ATSPLRDSTS SPVHSSASIQ NIKTTSDLAS TPDHNGTSVT TTSSALGSAT SPDHSGTSTT 

       310        320        330        340        350        360 
TNSSESVLAT TPVYSSMPFS TTKVTSGSAI IPDHNGSSVL PTSSVLGSAT SLVYNTSAIA 

       370        380        390        400        410        420 
TTPVSNGTQP SVPSQYPVSP TMATTSSHST IASSSYYSTV PFSTFSSNSS PQLSVGVSFF 

       430        440        450        460        470        480 
FLSFYIQNHP FNSSLEDPSS NYYQELKRNI SGLFLQIFNG DFLGISSIKF RSGSVVVEST 

       490        500        510        520        530        540 
VVFREGTFSA SDVKSQLIQH KKEADDYNLT ISEVKVNEMQ FPPSAQSRPG VPGWGIALLV 

       550        560        570        580        590        600 
LVCILVALAI VYFLALAVCQ CRRKSYGQLD IFPTQDTYHP MSEYPTYHTH GRYVPPGSTK 

       610        620        630 
RSPYEEVSAG NGSSSLSYTN PAVVTTSANL 

« Hide

References

[1]"Molecular cloning and analysis of the mouse homologue of the tumor-associated mucin, MUC1, reveals conservation of potential O-glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite-like polymorphism."
Spicer A.P., Parry G., Patton S., Gendler S.J.
J. Biol. Chem. 266:15099-15109(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The mouse episialin (Muc1) gene and its promoter: rapid evolution of the repetitive domain in the protein."
Vos H.L., Devries Y., Hilkens J.
Biochem. Biophys. Res. Commun. 181:121-130(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]"MUC1 cell surface mucin is a critical element of the mucosal barrier to infection."
McAuley J.L., Linden S.K., Png C.W., King R.M., Pennington H.L., Gendler S.J., Florin T.H., Hill G.R., Korolik V., McGuckin M.A.
J. Clin. Invest. 117:2313-2324(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CAMPYLOBACTER JEJUNI AND P53, INDUCTION, PHOSPHORYLATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M65132, M64928 Genomic DNA. Translation: AAA39755.1.
M84683 mRNA. Translation: AAA39756.1.
U16175 Genomic DNA. Translation: AAA98538.1.
M77226 Genomic DNA. Translation: AAA39754.1.
PIRA39344.
I52257.
RefSeqNP_038633.1. NM_013605.2.
UniGeneMm.16193.

3D structure databases

ProteinModelPortalQ02496.
SMRQ02496. Positions 418-519.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201606. 1 interaction.
STRING10090.ENSMUSP00000041963.

Protein family/group databases

MEROPSS71.001.

PTM databases

PhosphoSiteQ02496.

Proteomic databases

PaxDbQ02496.
PRIDEQ02496.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000041142; ENSMUSP00000041963; ENSMUSG00000042784.
GeneID17829.
KEGGmmu:17829.
UCSCuc008pyh.1. mouse.

Organism-specific databases

CTD4582.
MGIMGI:97231. Muc1.

Phylogenomic databases

eggNOGNOG77744.
GeneTreeENSGT00710000106874.
HOVERGENHBG003075.
InParanoidQ02496.
KOK06568.
OrthoDBEOG7S7SFP.
PhylomeDBQ02496.
TreeFamTF336301.

Gene expression databases

BgeeQ02496.
CleanExMM_MUC1.
GenevestigatorQ02496.

Family and domain databases

Gene3D3.30.70.960. 1 hit.
InterProIPR023217. Mucin-1.
IPR000082. SEA_dom.
[Graphical view]
PANTHERPTHR10006. PTHR10006. 1 hit.
PfamPF01390. SEA. 1 hit.
[Graphical view]
SMARTSM00200. SEA. 1 hit.
[Graphical view]
SUPFAMSSF82671. SSF82671. 1 hit.
PROSITEPS50024. SEA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio292529.
PROQ02496.
SOURCESearch...

Entry information

Entry nameMUC1_MOUSE
AccessionPrimary (citable) accession number: Q02496
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 5, 2008
Last modified: April 16, 2014
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot