Human Gene MUC4 (ENST00000463781.8) from GENCODE V44
Description: Homo sapiens mucin 4, cell surface associated (MUC4), transcript variant 1, mRNA. (from RefSeq NM_018406) RefSeq Summary (NM_018406): The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000463781.8 Gencode Gene: ENSG00000145113.22 Transcript (Including UTRs) Position: hg38 chr3:195,746,771-195,811,929 Size: 65,159 Total Exon Count: 25 Strand: - Coding Region Position: hg38 chr3:195,747,176-195,811,817 Size: 64,642 Coding Exon Count: 25
ID:MUC4_HUMAN DESCRIPTION: RecName: Full=Mucin-4; Short=MUC-4; AltName: Full=Ascites sialoglycoprotein; Short=ASGP; AltName: Full=Pancreatic adenocarcinoma mucin; AltName: Full=Testis mucin; AltName: Full=Tracheobronchial mucin; Contains: RecName: Full=Mucin-4 alpha chain; AltName: Full=Ascites sialoglycoprotein 1; Short=ASGP-1; Contains: RecName: Full=Mucin-4 beta chain; AltName: Full=Ascites sialoglycoprotein 2; Short=ASGP-2; Flags: Precursor; FUNCTION: May play a role in tumor progression. Ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. Has anti-adhesive properties. Seems to alter cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and in its ability to act as an intramembrane ligand for ERBB2. Plays an important role in cell proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. The MUC4-ERBB2 complex causes site-specific phosphorylation of the ERBB2 'Tyr-1248'. In polarized epithelilal cells segragates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. SUBUNIT: A heterodimeric complex, composed of a mucin-4 alpha chain and a cysteine-rich transmembrane mucin-4 beta chain. Mucin- 4 beta chain interacts with ERBB2 via the EGF-like domain 1. In nonpolarized cells, associates with ERBB2 and ERBB3 (By similarity). SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein (Potential). Secreted. Note=Isoforms lacking the Cys-rich region, EGF-like domains and transmembrane region are secreted. Secretion occurs by splicing or proteolytic processing. SUBCELLULAR LOCATION: Mucin-4 beta chain: Cell membrane; Single- pass membrane protein. SUBCELLULAR LOCATION: Mucin-4 alpha chain: Secreted. SUBCELLULAR LOCATION: Isoform 3: Cell membrane; Single-pass membrane protein. SUBCELLULAR LOCATION: Isoform 11: Secreted. SUBCELLULAR LOCATION: Isoform 15: Secreted. SUBCELLULAR LOCATION: Isoform 17: Cell membrane; Single-pass membrane protein. TISSUE SPECIFICITY: Expressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, and mammary and salivary glands. Expressed in carcinomas arising from some of these epithelia, such as lung cancers, squamous cell carcinomas of the upper aerodigestive tract, mammary carcinomas, biliary tract, colon, and cervix cancers. Minimally or not expressed in the normal pancreas or chronic pancreatitis, but is highly expressed in pancreatic tumors and pancreatic tumor cell lines. DEVELOPMENTAL STAGE: Expressed early in the primitive gut before respiratory and digestive epithelial cells have acquired their tissue and cell specificity. Expressed at the basal surface of the epithelium from week 14 to 26 weeks and then predominantly localized in only parietal cells. Immediately before birth, found in the cytoplasm of the mucous columnar epithelial cells. In the embryo expressed in skin, then disappears late in gestation. PTM: Proteolytically cleaved into 2 chains, mucin-4 alpha chain and mucin-4 beta chain. PTM: mucrnin-4 alpha chain is highly O-glycosylated. PTM: mucin-4 beta chain is predominantly N-glycosylated. MISCELLANEOUS: Expression is a very useful predictor of poor prognosis in patients with invasive ductal carcinoma and intrahepatic cholangiocarcinoma, mass forming type (IDC,ICC-MF). Patients with IDC or ICC-MF who have high MUC4 expression had a worse survival rate than those with low MUC4 expression. SIMILARITY: Contains 1 AMOP domain. SIMILARITY: Contains 2 EGF-like domains. SIMILARITY: Contains 1 NIDO domain. SIMILARITY: Contains 1 VWFD domain. SEQUENCE CAUTION: Sequence=AAA63230.1; Type=Miscellaneous discrepancy; Note=May be derived from an intron translation; Sequence=CAC14139.1; Type=Frameshift; Positions=1171; Sequence=CAC14141.1; Type=Frameshift; Positions=1256; WEB RESOURCE: Name=Mucin database; URL="http://www.medkem.gu.se/mucinbiology/databases/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MUC4ID41459ch3q29.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF03782 - AMOP domain PF06119 - Nidogen-like PF00094 - von Willebrand factor type D domain
ModBase Predicted Comparative 3D Structure on Q99102
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AJ010901 - Homo sapiens MUC4 gene, 3' flanking region. AJ242541 - Homo sapiens partial mRNA for sv1-MUC4 apomucin. AJ242542 - Homo sapiens partial mRNA for sv2-MUC4 apomucin. AJ242543 - Homo sapiens partial mRNA for sv3-MUC4 apomucin. AJ242544 - Homo sapiens partial mRNA for sv4-MUC4 apomucin. AJ242545 - Homo sapiens partial mRNA for sv5-MUC4 apomucin. AJ242546 - Homo sapiens partial mRNA for sv6-MUC4 apomucin. AJ242547 - Homo sapiens partial mRNA for sv7-MUC4 apomucin. AJ242548 - Homo sapiens partial mRNA for sv8-MUC4 apomucin. AJ242549 - Homo sapiens mRNA for MUC4/Y apomucin. AJ242550 - Homo sapiens mRNA for MUC4/X apomucin. JD347848 - Sequence 328872 from Patent EP1572962. JD097720 - Sequence 78744 from Patent EP1572962. AJ276359 - Homo sapiens mRNA for mucin 4 (MUC4 gene). AJ277412 - Homo sapiens mRNA for mucin 4, variant V3 (MUC4 gene). AJ277505 - Homo sapiens mRNA for MUC4 splice variant sv11 (MUC4 gene). AJ400633 - Homo sapiens mRNA for MUC4 protein variant VI1. AJ400849 - Homo sapiens mRNA for MUC4 protein splice variant sv12 (MUC4 gene). AJ400850 - Homo sapiens mRNA for MUC4 protein splice variant sv13 (MUC4 gene). AJ400851 - Homo sapiens mRNA for MUC4 protein splice variant sv14 (MUC4 gene). AJ400852 - Homo sapiens mRNA for MUC4 protein splice variant sv15 (MUC4 gene). AJ400853 - Homo sapiens mRNA for MUC4 protein splice variant sv16 (MUC4 gene). AJ400854 - Homo sapiens mRNA for MUC4 protein splice variant sv17 (MUC4 gene). AJ400855 - Homo sapiens mRNA for MUC4 protein splice variant sv18 (MUC4 gene). AJ400856 - Homo sapiens mRNA for MUC4 protein splice variant sv19 (MUC4 gene). AJ400857 - Homo sapiens mRNA for MUC4 protein splice variant sv20 (MUC4 gene). AJ400858 - Homo sapiens mRNA for MUC4 protein splice variant sv21 (MUC4 gene). JD538908 - Sequence 519932 from Patent EP1572962. JD559797 - Sequence 540821 from Patent EP1572962. JD537628 - Sequence 518652 from Patent EP1572962. JD371762 - Sequence 352786 from Patent EP1572962. JD435310 - Sequence 416334 from Patent EP1572962. JD201174 - Sequence 182198 from Patent EP1572962. JD549021 - Sequence 530045 from Patent EP1572962. JD191264 - Sequence 172288 from Patent EP1572962. JD471900 - Sequence 452924 from Patent EP1572962. JD540856 - Sequence 521880 from Patent EP1572962. JD485006 - Sequence 466030 from Patent EP1572962. JD232486 - Sequence 213510 from Patent EP1572962. AK074437 - Homo sapiens cDNA FLJ23857 fis, clone LNG07164. JD173752 - Sequence 154776 from Patent EP1572962. JD274218 - Sequence 255242 from Patent EP1572962. JD504857 - Sequence 485881 from Patent EP1572962. JD043962 - Sequence 24986 from Patent EP1572962. JD428948 - Sequence 409972 from Patent EP1572962. JD162817 - Sequence 143841 from Patent EP1572962. JD492383 - Sequence 473407 from Patent EP1572962. JD492382 - Sequence 473406 from Patent EP1572962. JD158231 - Sequence 139255 from Patent EP1572962. JD150404 - Sequence 131428 from Patent EP1572962. JD475643 - Sequence 456667 from Patent EP1572962. JD560477 - Sequence 541501 from Patent EP1572962. JD432269 - Sequence 413293 from Patent EP1572962. JD213904 - Sequence 194928 from Patent EP1572962. JD276565 - Sequence 257589 from Patent EP1572962. JD561137 - Sequence 542161 from Patent EP1572962. JD066742 - Sequence 47766 from Patent EP1572962. JD409864 - Sequence 390888 from Patent EP1572962. JD438172 - Sequence 419196 from Patent EP1572962. JD411109 - Sequence 392133 from Patent EP1572962. JD408038 - Sequence 389062 from Patent EP1572962. JD057795 - Sequence 38819 from Patent EP1572962. JD114488 - Sequence 95512 from Patent EP1572962. JD522196 - Sequence 503220 from Patent EP1572962. JD254116 - Sequence 235140 from Patent EP1572962. JD162132 - Sequence 143156 from Patent EP1572962. JD465950 - Sequence 446974 from Patent EP1572962. JD424157 - Sequence 405181 from Patent EP1572962. JD478409 - Sequence 459433 from Patent EP1572962. JD407704 - Sequence 388728 from Patent EP1572962. JD213500 - Sequence 194524 from Patent EP1572962. JD128682 - Sequence 109706 from Patent EP1572962. JD458207 - Sequence 439231 from Patent EP1572962. JD120850 - Sequence 101874 from Patent EP1572962. JD287094 - Sequence 268118 from Patent EP1572962. EF091824 - Homo sapiens mucin 4 mRNA, complete cds. JD400749 - Sequence 381773 from Patent EP1572962. JD457070 - Sequence 438094 from Patent EP1572962. JD210017 - Sequence 191041 from Patent EP1572962. JD271201 - Sequence 252225 from Patent EP1572962. JD466582 - Sequence 447606 from Patent EP1572962. JD376126 - Sequence 357150 from Patent EP1572962. JD151686 - Sequence 132710 from Patent EP1572962. AF058804 - Homo sapiens clone G4-10-3 mucin 4 (MUC4) mRNA, partial cds. AF058804 - Homo sapiens clone G4-10-3 mucin 4 (MUC4) mRNA, partial cds. AF177925 - Homo sapiens mucin 4 (MUC4) mRNA, partial cds. AJ000281 - Homo sapiens mRNA for mucin protein, MUC4. AF177925 - Homo sapiens mucin 4 (MUC4) mRNA, partial cds. AF058803 - Homo sapiens clone G4-5-10 mucin 4 (MUC4) mRNA, partial cds. AK307054 - Homo sapiens cDNA, FLJ97002. JD423640 - Sequence 404664 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q99102 (Reactome details) participates in the following event(s):
R-HSA-913675 GALNTs transfer GalNAc from UDP-GalNAc to mucins to form Tn antigens R-HSA-5694487 A4GNT transfers GlcNAc to core 2 mucins R-HSA-6786012 CHST4 transfers SO4(2-) from PAPS to Core 2 mucins R-HSA-914012 GCNTs transfer GlcNAc from UDP-GlcNAc to Core 1 mucins R-HSA-977228 Sialyltransferase I can add sialic acid to the T antigen at the alpha 6 position R-HSA-981497 ST3GAL1-4 can add a sialic acid to the T antigen at the alpha 3 position R-HSA-981814 GalNAc alpha-2,6-sialyltransferase II can add a sialic acid to the T antigen at the alpha 6 position R-HSA-1964505 C1GALT1 transfers Galactose to the Tn antigen forming Core 1 glycoproteins (T antigens) R-HSA-914018 Addition of GlcNAc to Core 3 forms a Core 4 glycoprotein R-HSA-914010 Addition of GlcNAc to the Tn antigen forms a Core 3 glycoprotein R-HSA-1964501 Addition of galactose to Core 6 glycoprotein R-HSA-977071 Sialyltransferase I can add sialic acid to the Tn antigen at the alpha 6 position R-HSA-981809 ST6GALNAC3/4 can add a sialic acid to the sialyl T antigen to form the disialyl T antigen R-HSA-8858500 CLEC10A binds Tn-MUC1 R-HSA-913709 O-linked glycosylation of mucins R-HSA-5083636 Defective GALNT12 causes colorectal cancer 1 (CRCS1) R-HSA-5083625 Defective GALNT3 causes familial hyperphosphatemic tumoral calcinosis (HFTC) R-HSA-977068 Termination of O-glycan biosynthesis R-HSA-5083632 Defective C1GALT1C1 causes Tn polyagglutination syndrome (TNPS) R-HSA-5621480 Dectin-2 family R-HSA-5173105 O-linked glycosylation R-HSA-3906995 Diseases associated with O-glycosylation of proteins R-HSA-5621481 C-type lectin receptors (CLRs) R-HSA-597592 Post-translational protein modification R-HSA-3781865 Diseases of glycosylation R-HSA-168249 Innate Immune System R-HSA-392499 Metabolism of proteins R-HSA-1643685 Disease R-HSA-168256 Immune System
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