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FLASH GENE

Symbol

MUC1

contributors: mct - updated : 17-06-2017

HGNC name	mucin 1, cell surface associated
HGNC id	7508

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MCKD1 medullary cystic kidney disease 1
Location	1q22      Physical location : 155.158.301 - 155.162.700
Synonym name	mucin 1, transmembrane
	peanut lectin binding, episialin
	polymorphic epithelial mucin
	breast carcinoma-associated antigen DF3
	tumor-associated epithelial membrane antigen
	peanut-reactive urinary mucin
	polymorphic epithelial mucin
	H23 antigen
	DF3 antigen
	episialin
	CD227 antigen
Synonym symbol(s)	PUM, CD227, EMA, PEM, H23AG, MAM6, PEMT, KL-6, MUC-1/SEC, MUC1/ZD

DNA

TYPE	functioning gene
STRUCTURE	4.40 kb     8 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

motif	repetitive sequence
text structure	tandem repeat

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002456 8 splicing 1209 NP_002447 - 273 in tissues as an oligomeric complex composed of monomers linked by disulfide bonds contributed by MUC1/ZD cysteine AAs 2012 23193156 also called MUC-1/ZD mucin short variant C-terminal 43AAs are novel and result from a reading frameshift engendered by a splicing event that forms MUC1/ZD generated by an alternative splicing event that both deletes the tandem-repeat array and leads to a C-terminal reading frameshift NM_001018016 8 splicing 1182 NP_001018016 - 264 - 2012 23193156 also called MUC1/Y or short variant Y NM_001018017 8 - 1155 NP_001018017 - 255 - 2012 23193156 NM_001044393 7 - 973 NP_001037858 - 158 - 2012 23193156 NM_001044392 5 - 873 NP_001037857 - 159 - 2012 23193156 NM_001044391 5 - 846 NP_001037856 - 150 - 2012 23193156 NM_001044390 7 - 1005 NP_001037855 - 203 - 2012 23193156 NM_001204294 7 - 1091 - 230 - 2012 23193156 NM_001204293 7 - 1098 NP_001191222 - 198 - 2012 23193156 NM_001204285 8 - 1826 NP_001191214 - 475 - 2012 23193156 NM_001204289 7 - 1115 NP_001191218 - 238 - 2012 23193156 NM_001204291 7 - 1124 NP_001191220 - 241 - 2012 23193156 NM_001204292 7 - 1118 NP_001191221 - 239 - 2012 23193156 NM_001204296 7 - 1037 NP_001191225 - 212 - 2012 23193156 NM_001204295 6 - 968 NP_001191224 - 189 - 2012 23193156 NM_001204288 8 - 1161 NP_001191217 - 219 - 2012 23193156 NM_001204297 5 - 932 NP_001191226 - 177 - 2012 23193156 NM_001204287 8 - 1247 NP_001191216 - 282 - 2012 23193156 NM_001204286 8 - 1853 NP_001191215 - 484 - 2012 23193156 NM_001204290 - - 1052 NP_001191219 - 217 - 2012 23193156

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine pancreas         Reproductive female system breast         male system prostate       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining uroepithelium     Epithelial secretory glandular endocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	the metanephric blastema and throughout fetal life in the ureteric buds, distal convoluted tubules, and collecting ducts

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal subunit is a large extracellular subunit (>250 kDa) consisting of variable numbers of 20-AA tandem repeats that are extensively linked hundreds of O-glycans
	one SEA domain
	a heavily O-glycosylated mucin-like domain with a variable number of nearly perfect tandem repeats and adjacent imperfect repeats, that constitute an apical targeting signal
	MUC1 extracellular subunit (MUC1-N) is located in nuclear speckles (interchromatin granule clusters) and closely associates with the spliceosome protein U2AF65
	a cytoplasmic domain (MUC1-CD), the minimal functional unit of MUC1, contributing to the malignant phenotype in cells by binding directly to beta-catenin, and having a critical role in the development of mammary gland preneoplasia and tumorigenesis
	C-terminal receptor subunit (MUC1-C), cytoplasmic domain, promoting STAT3 activation and MUC1-C and STAT3 function in an autoinductive loop that may play a role in cancer cell survival , C-terminal transmembrane subunit consists of a 58 AA extracellular domain, a 28 AA transmembrane domain, and a 72 AA cytoplasmic domain (CD)

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY

mucin family

CATEGORY

secretory , protooncogene

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
	intracellular,nucleus,chromatin/chromosome
	intracellular,nucleus,nucleolus
text	transmembrane mucin glycoprotein
	MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and MUC1-N and MUC1-C have dissimilar intranuclear distribution patterns
	normally expressed on the apical borders of secretory epithelial cells

basic FUNCTION	may be playing a role in adhesive functions and in cell-cell interactions, metastasis and signaling
	inducing cellular transformation
	involved in in renal morphogenesis processes
	playing a critical role in embryo implantation, protection of mucosal epithelia from microbial and enzymic attack and various aspects of tumour progression
	stabilizes Bcr-Abl and contributes to the pathogenesis of chronic myelogenous leukemia cells by promoting self renewal and inhibiting differentiation and apoptosis
	activates the beta-catenin and NF-kappaB pathways in multiple myeloma cells and contributes to their growth and survival
	cooperating oncoprotein with multiple oncogenic tyrosine kinase pathways
	direct activator of RELA and an inhibitor of MUC1 function is effective in blocking activation of the NF-kappaB pathway
	regulates nuclear localization and function of the epidermal growth factor receptor
	direct role of the MUC1 in initiating epithelial to mesenchymal transition during pancreatic cancer
	may be involved in human nephrogenesis and may play a relevant role in mesenchymal-epithelial transition from the cap mesenchyme to the renal vesicle, changing the fate of renal stem/progenitor cells
	is an immunoregulatory protein of T cells capable of giving a positive or negative stimulus
	acts as a master regulator of the metabolic program in pancreatic cancer
	pivotal role of MUC1 in controlling the hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors in pancreatic cancer
	inhibit apoptosis induced by genotoxic agents
	can inhibit apoptosis via activating MAPK8 pathway in response to genotoxic anticancer agents

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

protein constituent of membrane

INTERACTION

DNA

RNA

small molecule

protein	binding of the MUC1 C-Terminus to CAMLG in human epithelial cells, and possible biological significance of the MUC1-CAMLG interaction
	interacting with STAT3 (constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis)
	substrate for gamma-secretase
	MUC1 and EGFR interact in the nucleus of breast cancer cells, which promotes the accumulation of chromatin-bound EGFR
	dynamic interplay among cytokine-activated transcription factors, progesterone receptor isoforms and transcriptional coregulators in modulating MUC1 expression
	LGALS3-dependent regulation of MUC1/EGFR functions may represent an interesting mechanism modulating the EGFR-stimulated cell growth of pancreatic cancer cells
	association of MUC1 with PDGFA and MUC1 regulates the expression and secretion of PDGFA
	PPARG inhibits airway epithelial cell inflammatory response through a MUC1-dependent mechanism
	associates with BAX in human cancer cells (binds directly to the BAX BH3 domain and thereby blocks BAX function in activating the mitochondrial death pathway)
	MUC1 acts as a modulator of the hypoxic response in pancreatic cancer cells by regulating the expression/stability and activity of HIF1A
	interrelationship between MUC1–HIF1A oncogenic signaling networks serves to facilitate tumor growth and metastasis
	MUC1 drives MET-dependent migration and scattering
	SIGLEC9 expressed on immune cells may play a role as a potential counterreceptor for MUC1 and this signaling may be another MUC1-mediated pathway and function in parallel with a growth factor-dependent pathway
	binds to and activates MAPK8
	promotes FLT3 receptor activation in acute myeloid leukemia cells
	PPARG, an E3 ubiquitin ligase, is an inhibitor of MUC1-mediated cell proliferation, and induces MUC1 ubiquitination and degradation that is critical to terminate MUC1 signaling pathway-elicited cancer
	interactions between CTNND1 and MUC1, and these interactions modulate dynamic properties of cell adhesion, motility, and metastasis of pancreatic cancer cells
	binding of LGALS3 to MUC1 enhances likely the recruitment of SP1, leading to promotion of the transcription of TACSTD2

cell & other

ligand for Helicobacter pylori where it plays a role in gastric carcinogenesis

REGULATION

activated by

overexpressed by hypoxia and contributes to hypoxia-driven angiogenesis

ASSOCIATED DISORDERS

corresponding disease(s)

MCKD1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in esophageal squamous-cell carcinoma with poor prognosis tumoral     --over   in endometrial adenocarcinomas tumoral     --over   in hepatocellular and cholangiocarcinoma constitutional     --over   in severe preeclamptic placentas and MUC1 overexpression suppresses extravillous trophoblast (EVT) invasion mainly via modulating beta1-integrin signaling ( tumoral     --over   in up to 90 p100 of breast carcinomas tumoral     --other   expression of aberrantly glycosylated Mucin-1 in ovarian cancer tumoral     --over   aberrantly overexpressed in human breast cancer and other cancers tumoral     --over   in several carcinomas including pancreatic adenocarcinoma

Susceptibility

to the development of intestinal metaplasia preceding gastric carcinoma

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   inhibition of MUC1-C represents a potential therapeutic approach to induce terminal differentiation of acute myelogenous leukemia cells cancer lung   could be an effective target for the treatment of lung cancer. cancer digestive oesophagus MUC1 and MUC4 may be attractive targets for the selection of treatment methods in oral squamous cell carcinoma (OSCC)

ANIMAL & CELL MODELS