| CD104 | ITGB4(integrin β4 chain), TSP-180 (tumor specific protein 180-antigen- mouse) |
| Molecule Type | Antigen Expression | Molecular Weight Min / Max |
| Non-lineage Restricted Molecule Type 1 glycoprotein | Epithelia Schwann Cell Endothelial Cell Epithelial Cell Skin Gastrointestine Nerve T Lymphocyte | 205 / 205 |
Expression | ||||||||||||||||||||
| CD104 is expressed in conjunction with CD49f as the a6b4 integrin on the hemidesmosomes of stratified epithelia. It is also expressed on cells that do not have hemidesmosomes including simple epithelia and Schwann cells, and a subset of endothelial cells in the mouse. High expression is in the basal cell layer of epithelia including skin and gastrointestinal tract. Expression is on endothelium undergoing angiogenesis and in myelinating nerve fibers and in the immune system in double-negative pre-T lymphocytes. | ||||||||||||||||||||
Structure | ||||||||||||||||||||
| MOLECULAR FAMILY NAME: Belongs to the integrin b chain family. CD104 is a single-pass type-1822 aa glycoprotein. It contains a signal sequence, an extracellular domain which exhibits a 4-fold repeat of cysteine-rich motif and is normally conserved in the extracellular portion of integrin b subunits, a transmembrane domain and a large 1000 aa cytoplasmic domain which contains 4 fibronectin type-3 domains and an intervening 142 aa segment that can be tyrosine phophorylated. It is a member of a family of cell-surface proteins and is the integrin b4 subunit, which forms a heterodimer with the integrin a 6 subunit (CD49f). There are 3 alternative forms which have been identified by cDNA analysis. They contain either no inserts or insert-1 at position 1343, or insert-2 at position 1413. Both inserts are between the 2nd and 3rd fibronectin type-3 domains. cDNA isolated from the placenta contains a mixture of the short form with no inserts and 1 having only insert-2, whereas carcinoma cell lines appear to express only the form with insert-1. Immunoprecipitation studies suggest that the free b4 subunit may be present on carcinoma cell lines. MOLECULAR MASS
POST-TRANSCRIPTIONAL MODIFICATION Alternative splicing yields 5 different isoforms. POST-TRANSLATIONAL MODIFICATION: No information. | ||||||||||||||||||||
Ligands | ||||||||||||||||||||
| LIGANDS AND MOLECULES ASSOCIATED WITH CD104 CD104 combines with CD49f to form the a6b4 integrin, which is an integral component of hemidesmosomes in the stratified epithelia. CD104 binds laminins, keratin filaments and plectin. | ||||||||||||||||||||
Function | ||||||||||||||||||||
| Integrins are heterodimers comprised of α and β subunits. CD104 is involved in cell-cell and cell-matrix interactions, adhesion and migration and transduce signals that regulate gene expression and cell growth. CD104 encodes the β 4 subunit and tends to associate with α 6 subunit. Hemidesmosomal CD49f/CD104 (a6b4 integrin) plays an important role in the adhesion of epithelia to basement membranes, via interactions with laminin and/or kalinin anchoring filaments. The cytoplasmic domain is necessary for hemidesmosome formation. Unlike other integrins, CD49f/CD104 interacts with intracellular keratin filaments rather than the actin cytoskeleton. CD104 transduces signals through the interaction with laminin. It is expressed selectively in areas of proliferation and appears to be involved in cell activation and proliferation. BIOCHEMICAL ACTIVITY: No information. DISEASE RELEVANCE AND FUNCTION OF CD104 IN INTACT ANIMAL: CD104 likely plays a pivotal role in the biology of invasive carcinoma and functions in tumor metastasis. Increased CD104 expression is seen in squamous cell carcinomas and in thyroid, colorectal gastric and pancreatic carinomas. Decreased levels are found in breast, bladder and prostate tumors. Frameshift and deletion mutations have been identified with junctional epidermolysis bullosa with pyloric atresia. Knockout mice born with blistering of the gut and skin and absence of hemidesmosomes survive only a few hours. | ||||||||||||||||||||
Comments | ||||||||||||||||||||
| MOLECULAR INTERACTIONS- PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD104: No information. SUBSTRATES: No information. ENZYMES WHICH MODIFY CD104: No information. | ||||||||||||||||||||
Database accession numbers | ||||||||||||||||||||
Revised June 25, 2008
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