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Protein

Mucin-1

Gene

Muc1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Names & Taxonomyi

Protein namesi
Recommended name:
Mucin-1
Short name:
MUC-1
Alternative name(s):
Episialin
CD_antigen: CD227
Cleaved into the following 2 chains:
Mucin-1 subunit alpha
Short name:
MUC1-NT
Short name:
MUC1-alpha
Mucin-1 subunit beta
Short name:
MUC1-beta
Alternative name(s):
MUC1-CT
Gene namesi
Name:Muc1
Synonyms:Muc-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:97231. Muc1.

Subcellular locationi

  • 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).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.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 535ExtracellularSequence analysisAdd BLAST515
Transmembranei536 – 556HelicalSequence analysisAdd BLAST21
Topological domaini557 – 630CytoplasmicSequence analysisAdd BLAST74

GO - Cellular componenti

  • apical plasma membrane Source: MGI
  • cell surface Source: MGI
  • cytoplasm Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Add BLAST20
ChainiPRO_000001928021 – 630Mucin-1Add BLAST610
ChainiPRO_000031745221 – 473Mucin-1 subunit alphaBy similarityAdd BLAST453
ChainiPRO_0000317453474 – 630Mucin-1 subunit betaBy similarityAdd BLAST157

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi43O-linked (GalNAc...)Sequence analysis1
Glycosylationi44O-linked (GalNAc...)Sequence analysis1
Glycosylationi45O-linked (GalNAc...)Sequence analysis1
Glycosylationi46O-linked (GalNAc...)Sequence analysis1
Glycosylationi50O-linked (GalNAc...)Sequence analysis1
Glycosylationi51O-linked (GalNAc...)Sequence analysis1
Glycosylationi53O-linked (GalNAc...)Sequence analysis1
Glycosylationi57O-linked (GalNAc...)Sequence analysis1
Glycosylationi125N-linked (GlcNAc...)Sequence analysis1
Glycosylationi275N-linked (GlcNAc...)Sequence analysis1
Glycosylationi302N-linked (GlcNAc...)Sequence analysis1
Glycosylationi335N-linked (GlcNAc...)Sequence analysis1
Glycosylationi355N-linked (GlcNAc...)Sequence analysis1
Glycosylationi366N-linked (GlcNAc...)Sequence analysis1
Glycosylationi408N-linked (GlcNAc...)Sequence analysis1
Glycosylationi432N-linked (GlcNAc...)Sequence analysis1
Glycosylationi449N-linked (GlcNAc...)Sequence analysis1
Glycosylationi508N-linked (GlcNAc...)Sequence analysis1
Lipidationi559S-palmitoyl cysteineBy similarity1
Lipidationi561S-palmitoyl cysteineBy similarity1
Modified residuei578Phosphotyrosine; by PDGFRBy similarity1
Modified residuei587PhosphotyrosineBy similarity1
Modified residuei593Phosphotyrosine; by PDGFRBy similarity1
Modified residuei599Phosphothreonine; by PKC/PRKCDBy similarity1
Modified residuei602Phosphoserine; by GSK3-betaBy similarity1
Modified residuei604Phosphotyrosine; by CSK, EGFR and SRCBy similarity1
Modified residuei618PhosphotyrosineBy similarity1

Post-translational modificationi

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).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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei473 – 474Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ02496.
PaxDbiQ02496.
PRIDEiQ02496.

PTM databases

iPTMnetiQ02496.
PhosphoSitePlusiQ02496.

Expressioni

Tissue specificityi

Expressed in a variety of epithelial tissues.

Gene expression databases

BgeeiENSMUSG00000042784.
CleanExiMM_MUC1.

Interactioni

Subunit structurei

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.By similarity1 Publication

Protein-protein interaction databases

BioGridi201606. 1 interactor.
STRINGi10090.ENSMUSP00000041963.

Structurei

3D structure databases

ProteinModelPortaliQ02496.
SMRiQ02496.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati42 – 611Add BLAST20
Repeati62 – 812Add BLAST20
Repeati82 – 1013Add BLAST20
Repeati102 – 1224; approximateAdd BLAST21
Repeati123 – 1435; approximateAdd BLAST21
Repeati144 – 1646; approximateAdd BLAST21
Repeati165 – 1847Add BLAST20
Repeati185 – 2048Add BLAST20
Repeati205 – 2259; approximateAdd BLAST21
Repeati226 – 24610; approximateAdd BLAST21
Repeati247 – 2561110
Repeati257 – 28612Add BLAST30
Repeati287 – 30613Add BLAST20
Repeati307 – 32614Add BLAST20
Repeati327 – 34615Add BLAST20
Repeati347 – 36616Add BLAST20
Domaini416 – 521SEAPROSITE-ProRule annotationAdd BLAST106

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni42 – 36616 X 20 AA approximate tandem repeatsAdd BLAST325
Regioni567 – 603Interaction with P531 PublicationAdd BLAST37
Regioni598 – 605Required for interaction with GSK3BBy similarity8
Regioni608 – 616Required for interaction with beta- and gamma-cateninsBy similarity9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi578 – 581Interaction with GRB2By similarity4
Motifi604 – 607Interaction with SRC and ESR1By similarity4
Motifi618 – 621Required for interaction with AP1S2By similarity4

Sequence similaritiesi

Contains 1 SEA domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IX6R. Eukaryota.
ENOG410ZQ7Z. LUCA.
HOVERGENiHBG003075.
InParanoidiQ02496.
KOiK06568.
PhylomeDBiQ02496.
TreeFamiTF336301.

Family and domain databases

Gene3Di3.30.70.960. 1 hit.
InterProiIPR023217. Mucin-1.
IPR000082. SEA_dom.
[Graphical view]
PANTHERiPTHR10006:SF8. PTHR10006:SF8. 1 hit.
PfamiPF01390. SEA. 1 hit.
[Graphical view]
SMARTiSM00200. SEA. 1 hit.
[Graphical view]
SUPFAMiSSF82671. SSF82671. 1 hit.
PROSITEiPS50024. SEA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q02496-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPGIRAPFF LLLLLASLKG FLALPSEENS VTSSQDTSSS LASTTTPVHS
60 70 80 90 100
SNSDPATRPP GDSTSSPVQS STSSPATRAP EDSTSTAVLS GTSSPATTAP
110 120 130 140 150
VNSASSPVAH GDTSSPATSL SKDSNSSPVV HSGTSSAATT APVDSTSSPV
160 170 180 190 200
VHGGTSSPAT SPPGDSTSSP DHSSTSSPAT RAPEDSTSTA VLSGTSSPAT
210 220 230 240 250
TAPVDSTSSP VAHDDTSSPA TSLSEDSASS PVAHGGTSSP ATSPLRDSTS
260 270 280 290 300
SPVHSSASIQ NIKTTSDLAS TPDHNGTSVT TTSSALGSAT SPDHSGTSTT
310 320 330 340 350
TNSSESVLAT TPVYSSMPFS TTKVTSGSAI IPDHNGSSVL PTSSVLGSAT
360 370 380 390 400
SLVYNTSAIA TTPVSNGTQP SVPSQYPVSP TMATTSSHST IASSSYYSTV
410 420 430 440 450
PFSTFSSNSS PQLSVGVSFF FLSFYIQNHP FNSSLEDPSS NYYQELKRNI
460 470 480 490 500
SGLFLQIFNG DFLGISSIKF RSGSVVVEST VVFREGTFSA SDVKSQLIQH
510 520 530 540 550
KKEADDYNLT ISEVKVNEMQ FPPSAQSRPG VPGWGIALLV LVCILVALAI
560 570 580 590 600
VYFLALAVCQ CRRKSYGQLD IFPTQDTYHP MSEYPTYHTH GRYVPPGSTK
610 620 630
RSPYEEVSAG NGSSSLSYTN PAVVTTSANL
Length:630
Mass (Da):64,539
Last modified:February 5, 2008 - v2
Checksum:iD9EC2A0815F65E8E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti120 – 121LS → PL in AAA39755 (PubMed:1714452).Curated2
Sequence conflicti138 – 139AT → PA (PubMed:1958179).Curated2
Sequence conflicti140T → TT (PubMed:1958179).Curated1
Sequence conflicti423S → F in AAA39755 (PubMed:1714452).Curated1
Sequence conflicti506D → S in AAA39755 (PubMed:1714452).Curated1
Sequence conflicti602S → Q in AAA39755 (PubMed:1714452).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M65132, M64928 Genomic DNA. Translation: AAA39755.1.
M84683 mRNA. Translation: AAA39756.1.
U16175 Genomic DNA. Translation: AAA98538.1.
M77226 Genomic DNA. Translation: AAA39754.1.
PIRiA39344.
I52257.
RefSeqiNP_038633.1. NM_013605.2.
UniGeneiMm.16193.

Genome annotation databases

GeneIDi17829.
KEGGimmu:17829.
UCSCiuc008pyh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M65132, M64928 Genomic DNA. Translation: AAA39755.1.
M84683 mRNA. Translation: AAA39756.1.
U16175 Genomic DNA. Translation: AAA98538.1.
M77226 Genomic DNA. Translation: AAA39754.1.
PIRiA39344.
I52257.
RefSeqiNP_038633.1. NM_013605.2.
UniGeneiMm.16193.

3D structure databases

ProteinModelPortaliQ02496.
SMRiQ02496.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201606. 1 interactor.
STRINGi10090.ENSMUSP00000041963.

PTM databases

iPTMnetiQ02496.
PhosphoSitePlusiQ02496.

Proteomic databases

MaxQBiQ02496.
PaxDbiQ02496.
PRIDEiQ02496.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi17829.
KEGGimmu:17829.
UCSCiuc008pyh.2. mouse.

Organism-specific databases

CTDi4582.
MGIiMGI:97231. Muc1.

Phylogenomic databases

eggNOGiENOG410IX6R. Eukaryota.
ENOG410ZQ7Z. LUCA.
HOVERGENiHBG003075.
InParanoidiQ02496.
KOiK06568.
PhylomeDBiQ02496.
TreeFamiTF336301.

Miscellaneous databases

PROiQ02496.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000042784.
CleanExiMM_MUC1.

Family and domain databases

Gene3Di3.30.70.960. 1 hit.
InterProiIPR023217. Mucin-1.
IPR000082. SEA_dom.
[Graphical view]
PANTHERiPTHR10006:SF8. PTHR10006:SF8. 1 hit.
PfamiPF01390. SEA. 1 hit.
[Graphical view]
SMARTiSM00200. SEA. 1 hit.
[Graphical view]
SUPFAMiSSF82671. SSF82671. 1 hit.
PROSITEiPS50024. SEA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMUC1_MOUSE
AccessioniPrimary (citable) accession number: Q02496
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 5, 2008
Last modified: November 2, 2016
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.