MUC1

Protein identityUniProt · HPA

UniProt accession

P15941

Gene

MUC1

Ensembl

ENSG00000185499

Chromosome

1

Canonical length

1255 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Plasma membrane

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

1255 residues, UniProt reviewed canonical sequence.

>P15941|MUC1
     1  MTPGTQSPFF LLLLLTVLTV VTGSGHASST PGGEKETSAT QRSSVPSSTE KNAVSMTSSV
    61  LSSHSPGSGS STTQGQDVTL APATEPASGS AATWGQDVTS VPVTRPALGS TTPPAHDVTS
   121  APDNKPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   181  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   241  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   301  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   361  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   421  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   481  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   541  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   601  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   661  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   721  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   781  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   841  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS
   901  APDTRPAPGS TAPPAHGVTS APDTRPAPGS TAPPAHGVTS APDNRPALGS TAPPVHNVTS
   961  ASGSASGSAS TLVHNGTSAR ATTTPASKST PFSIPSHHSD TPTTLASHST KTDASSTHHS
  1021  SVPPLTSSNH STSPQLSTGV SFFFLSFHIS NLQFNSSLED PSTDYYQELQ RDISEMFLQI
  1081  YKQGGFLGLS NIKFRPGSVV VQLTLAFREG TINVHDVETQ FNQYKTEAAS RYNLTISDVS
  1141  VSDVPFPFSA QSGAGVPGWG IALLVLVCVL VALAIVYLIA LAVCQCRRKN YGQLDIFPAR
  1201  DTYHPMSEYP TYHTHGRYVP PSSTDRSPYE KVSAGNGGSS LSYTNPAVAA TSANL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MUC1 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

1

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

998 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MUC1.

Disease | AllUniProt

Conditions MUC1 is implicated in, by any mechanism.

• Tubulointerstitial kidney disease, autosomal dominant 2 (ADTKD2) MIM:174000

Disease | GeneticClinVar

9 pathogenic / likely-pathogenic of 160 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Tubulointerstitial kidney disease, autosomal dominant, 2

Disease | ImmuneIEDB

Conditions an epitope on MUC1 was assayed in.

• colon carcinoma T cell
• breast cancer B and T cell
• multiple myeloma T cell
• prostate cancer T cell
• pancreatic ductal adenocarcinoma T cell
• ovarian cancer T cell
• castration-resistant prostate carcinoma T cell
• lung adenocarcinoma T cell
• lung non-small cell carcinoma T cell
• breast carcinoma T cell
• adenoma B cell
• ovarian serous carcinoma T cell
• prostate adenocarcinoma B cell
• myeloid leukemia T cell
• ovary epithelial cancer T cell
• colorectal cancer T cell
• renal carcinoma T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against MUC1 are reported. Each links to that disease's full target list.

• Breast Neoplasms 9
• Lung Neoplasms 3
• Ovarian Neoplasms 3

Showing 3 of 4 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for MUC1 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.

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)

0.68

gnomAD pLI

0.02

gnomAD missense Z

-1.23

DepMap mean gene effect

-0.18

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA damage response, signal transduction by p53 class mediator
• mitotic G1 DNA damage checkpoint signaling
• negative regulation of cell adhesion mediated by integrin
• negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• negative regulation of transcription by competitive promoter binding
• positive regulation of transcription by RNA polymerase II

Molecular functions

• p53 binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• transcription coregulator activity

Cellular components

• apical plasma membrane
• chromatin
• extracellular exosome
• extracellular space
• Golgi lumen
• nucleus
• plasma membrane
• vesicle

Protein domainsUniProt · Pfam · InterPro

• SEA domain
• SEA domain superfamily
• SEA domain

KeywordsUniProt

• Autocatalytic cleavage
• Cell membrane
• Cytoplasm
• Disulfide bond
• Glycoprotein
• Lipoprotein
• Membrane
• Nucleus
• Palmitate
• Phosphoprotein
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Tumor suppressor

InteractionsUniProt · HPA

Protein binding partners of MUC1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CTNNB1
• KLF4
• P53
• JUP
• PRKCD
• ERBB3
• GSK3B
• EGFR
• ERBB4
• ADAM17
• ERBB2
• ICAM1
• ABL1
• SRC